Treatment of stage IIII periodontitisThe EFP S3 level clinical practice guideline

Background:The recently introduced 2017 World Workshop on the classification of periodontitis, incorporating stages and grades of disease, aims to link disease classification with approaches to prevention and treatment, as it describes not only disease severity and extent but also the degree of complexity and an individual's risk. There is, therefore, a need for evidence-based clinical guidelines providing recommendations to treat periodontitis. Aim: The objective of the current project was to develop a S3 Level Clinical Practice Guideline (CPG) for the treatment of Stage I-III periodontitis. Material and Methods: This S3 CPG was developed under the auspices of the European Federation of Periodontology (EFP), following the methodological guidance of the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation (GRADE). The rigorous and transparent process included synthesis of relevant research in 15 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, the formulation of specific recommendations and consensus, on those recommendations, by leading experts and a broad base of stakeholders. Results: The S3 CPG approaches the treatment of periodontitis (stages I, II and III) using a pre-established stepwise approach to therapy that, depending on the disease stage, should be incremental, each including different interventions. Consensus was achieved on recommendations covering different interventions, aimed at (a) behavioural changes, supragingival biofilm, gingival inflammation and risk factor control; (b) supra-and sub-gingival instrumentation, with and without adjunctive therapies; (c) different types of periodontal surgical interventions; and (d) the necessary supportive periodontal care to extend benefits over time.Conclusion: This S3 guideline informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to treat periodontitis and to maintain a healthy dentition for a lifetime, according to the available evidence at the time of publication. | 5 SANZ et Al.

## | introduc ti on
1.1 | The health problem

## | definition
Periodontitis is characterized by progressive destruction of the tooth-supporting apparatus. Its primary features include the loss of periodontal tissue support manifest through clinical attachment loss (CAL) and radiographically assessed alveolar bone loss, presence of periodontal pocketing and gingival bleeding . If untreated, it may lead to tooth loss, although it is preventable and treatable in the majority of cases.

## | importance
Periodontitis is a major public health problem due to its high prevalence, and since it may lead to tooth loss and disability, it negatively affects chewing function and aesthetics, is a source of social inequality, and significantly impairs quality of life. Periodontitis accounts for a substantial proportion of edentulism and masticatory dysfunction, has a negative impact on general health and results in significant dental care costs [bib_ref] Impact of the global burden of periodontal diseases on health, nutrition and..., Tonetti [/bib_ref].

## | pathophysiology
Periodontitis is a chronic multifactorial inflammatory disease associated with dysbiotic dental plaque biofilms.

## | prevalence
Periodontitis is the most common chronic inflammatory non-communicable disease of humans. According to the Global Burden of Disease 2010 study, the global age-standardized prevalence (1990-2010) of severe periodontitis was 11.2%, representing the sixth-most prevalent condition in the world [bib_ref] Global burden of severe periodontitis in 1990-2010: A systematic review and meta-regression, Kassebaum [/bib_ref] , while in the Global Burden of Disease 2015 study, the prevalence of severe periodontitis was estimated in 7.4% [bib_ref] Global, regional, and national prevalence, incidence, and disability-adjusted life years for oral..., Kassebaum [/bib_ref]. The prevalence of milder forms of periodontitis may be as high as 50% [bib_ref] Age-dependent distribution of periodontitis in two countries: Findings from NHANES 2009 to..., Billings [/bib_ref].

## | consequences of failure to treat
Untreated or inadequately treated periodontitis leads to the loss of tooth-supporting tissues and teeth. Severe periodontitis, along with dental caries, is responsible for more years lost to disability than any other human disease (GBD 2017 Disease and Injury Incidence and Prevalence Collaborators, 2018). Furthermore, periodontal infections are associated with a range of systemic diseases leading to premature death, including diabetes , cardiovascular diseases 

## | economic importance
On a global scale, periodontitis is estimated to cost $54 billion in direct treatment costs and further $25 billion in indirect costs Disease and Injury Incidence and Prevalence Collaborators, 2018).
Periodontitis contributes significantly to the cost of dental diseases due to the need to replace teeth lost to periodontitis. The total cost of dental diseases, in 2015, was estimated to be of $544.41 billion, being $356.80 billion direct costs, and $187.61 billion indirect costs [bib_ref] Global-, regional-, and country-level economic impacts of dental diseases in 2015, Righolt [/bib_ref].

## | aim of the g u ideline
This guideline aims to highlight the importance and need for scientific evidence in clinical decision-making in the treatment of patients

## Clinical relevance
Scientific rationale for the study: Implementation of the new classification of periodontitis should facilitate the use of the most appropriate preventive and therapeutic interventions, depending on the stage and grade of the disease. The choice of these interventions should be made following a rigorous evidence-based decision-making process.
Principal findings: This guideline has been developed using strict validated methodologies for assuring the best available evidence on the efficacy of the interventions considered and the most appropriate recommendations based on a structured consensus process, including a panel of experts and representatives from key stakeholders.

## Practical implications: the application of this s3 level
Clinical Practice Guideline will allow a homogeneous and evidence-based approach to the management of Stage I-III periodontitis.
with periodontitis stages I to III. Its main objective is therefore to support the evidence-based recommendations for the different interventions used at the different steps of periodontal therapy, based on the best available evidence and/or expert consensus. In so doing, this guideline aims to improve the overall quality of periodontal treatment in Europe, reduce tooth loss associated with periodontitis and ultimately improve overall systemic health and quality of life. A separate guideline covering the treatment of Stage IV periodontitis will be published.

## | target users of the guideline
Dental and medical professionals, together with all stakeholders related to health care, particularly oral health, including patients.

## | targeted environments
Dental and medical academic/hospital environments, clinics and practices.

## | targeted patient population
People with periodontitis stages I to III.
People with periodontitis stages I to III following successful treatment.

## | exceptions from the guideline
This guideline did not consider the health economic cost-benefit ratio, since (a) it covers multiple different countries with disparate, not readily comparable health systems, and (b) there is a paucity of sound scientific evidence available addressing this question. This guideline did not consider the treatment of gingivitis (although management of gingivitis is considered as an indirect goal in some interventions evaluated), the treatment of Stage IV periodontitis, necrotising periodontitis, periodontitis as manifestation of systemic diseases and mucogingival conditions.

## | me thodology

## | general framework
This guideline was developed following methodological guidance To ensure adequate stakeholder involvement, the EFP established a guideline panel involving dental professionals representing 36 national periodontal societies within the EFP .
These delegates were nominated, participated in the guideline development process and had voting rights in the consensus conference. For the guideline development process, delegates were assigned to four Working Groups that were chaired by the members of the Organizing Committee and advised by the methodology consultants. This panel was supported by key stakeholders from European scientific societies with a strong professional interest in periodontal care and from European organizations representing key groups within the dental profession, and key experts from non-EFP member countries, such as North America .
In addition, EFP engaged an independent guideline methodologist to advise the panel and facilitate the consensus process (Prof. Dr.
med. Ina Kopp). The guideline methodologist had no voting rights.
EFP and the guideline panel tried to involve patient organizations but were not able to identify any regarding periodontal diseases at European level. In a future update, efforts will be undertaken to include the perspective of citizens/patients [bib_ref] How do we incorporate patient views into the design of healthcare services..., Brocklehurst [/bib_ref].

## | evidence synthesis

## | systematic search and critical appraisal of guidelines
To assess and utilize existing guidelines during the development of the present guideline, well-established guideline registers and the websites of large periodontal societies were electronically searched for potentially applicable guideline texts:
- Guideline International Network (GIN)
- www.Guide linec entral.com
- The National Institute for Health and Clinical Excellence (NICE)
- Canadian Health Technology Assessment (CADTH)
- European Federation for Periodontology (EFP)
- American Academy of Periodontology (AAP)
- American Dental Association (ADA)
The last search was performed on 30 September 2019. Search terms used were "periodont*," "Periodontal," "Guidelines" and "Clinical Practice Guidelines." In addition, content was screened by hand searches. See .
Only guidelines published in English and with full texts available were included. The methodological quality of these guideline texts was critically appraised using the AGREE II framework (https:// www.agree trust.org/agree -ii/).
Most of the identified guidelines/documents were considered not applicable due to (a) their age, (b) their methodological approach, or (c) their inclusion criteria. The recent German S3 guideline (Register Number 083-029) was found to be potentially relevant, scored highest in the critical appraisal using AGREE II and was, therefore, used to inform the guideline development process.

## | systematic search and critical appraisal of the literature
For this guideline, a total of 15 systematic reviews (SRs) were conducted to support the guideline development process [bib_ref] Resective surgery for the treatment of furcation involvement: A systematic review, Dommisch [/bib_ref] [bib_ref] The adjunctive use of host modulators in non-surgical periodontal therapy. A systematic..., Donos [/bib_ref] [bib_ref] Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review..., Figuero [/bib_ref] [bib_ref] Adjunctive effect of locally delivered antimicrobials in periodontitis therapy: A systematic review..., Herrera [/bib_ref] [bib_ref] Regenerative surgical treatment of furcation defects: A systematic review and Bayesian network..., Jepsen [/bib_ref] [bib_ref] The efficacy of pocket elimination/reduction compared to access flap surgery: A systematic..., Polak [/bib_ref] [bib_ref] Impact of risk factor control interventions for smoking cessation and promotion of..., Ramseier [/bib_ref] [bib_ref] Time between recall visits and residual probing depths predict long-term stability in..., Ramseier [/bib_ref] [bib_ref] Efficacy of access flap procedures compared to subgingival debridement in the treatment..., Sanz-Sanchez [/bib_ref] [bib_ref] Mechanical plaque removal of periodontal maintenance patients: A systematic review and network..., Slot [/bib_ref] [bib_ref] Adjunctive effect of systemic antimicrobials in periodontitis therapy. A systematic review and..., Teughels [/bib_ref] [bib_ref] Efficacy of alternative or additional methods to professional mechanical plaque removal during..., Trombelli [/bib_ref]. The corresponding manuscripts are published within this special issue of the Journal of Clinical Periodontology.
All SRs were conducted following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) framework [bib_ref] Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement, Moher [/bib_ref].

## | focused questions
In all 15 systematic reviews, focused questions in PICO(S) format were proposed by the authors in January 2019 to a panel comprising the working group chairs and the methodological consultants, in order to review and approve them .
The panel took great care to avoid overlaps or significant gaps between the SRs, so they would truly cover all possible interventions currently undertaken in periodontal therapy.

## Ta b l e 1 a guideline panel
Scientific society/ organization Delegate(s)

## | relevance of outcomes
A narrative review paper was commissioned for this guideline [bib_ref] Endpoints of active periodontal therapy, Loos [/bib_ref] to evaluate the possible outcome measures utilized to evaluate the efficacy of periodontal therapy in relation to true patient-centred outcomes like tooth retention/loss. The authors found that the commonly reported outcome variable with the best demonstrated predictive potential for tooth loss was the reduction in periodontal probing pocket depth (PPD). Therefore, for this guideline, PPD reduction was used as primary outcome for those systematic reviews not addressing periodontal regeneration, and where tooth survival data were not reported. When reviewing regenerative interventions, gains in clinical attachment were used as the primary outcome measure. To avoid introducing bias by including possibly spurious findings of studies with very short follow-up, a minimal follow-up period of six months was requested for all reviews.

## | search strategy
All SRs utilized a comprehensive search strategy of at least two different databases, supplemented by a hand search of periodontal journals and the reference lists of included studies.
In all SRs, the electronic and manual search, as well as the data extraction, was done in parallel by two different investigators.

## | quality assessment of included studies
In all SRs, the risk of bias of controlled clinical trials was assessed using the Cochrane risk of bias tool (https://metho ds.cochr ane.org/ bias/resou rces/rob-2-revis ed-cochr ane-risk-bias-tool-rando mized -trials). For observational studies, the Newcastle-Ottawa Scale was used http://www.ohri.ca/progr ams/clini cal_epide miolo gy/oxford. asp.

## | data synthesis
Where applicable, the available evidence was summarized by means of meta-analysis, or other tools aimed for pooling data (network meta-analysis, Bayesian network meta-analysis).

## | from evidence to recommendation: structured consensus process
The structured consensus development conference was held during the XVI European Workshop in Periodontology in La Granja de San Ildefonso Segovia, Spain, on 10-13 November 2019. Using the 15
SRs as background information, evidence-based recommendations were formally debated by the guideline panel using the format of a structured consensus development conference, consisting of small group discussions and open plenary were the proposed recommendations were presented, voted and adopted by consensus and [bib_ref] Consensus development methods, and their use in clinical guideline development, Murphy [/bib_ref].
In the small group phase, delegates convened in four working groups addressing the following subtopics: (a) "periodontitis stages I and II"; (b) "periodontitis Stage III"; (c) "periodontitis Stage III with intraosseous defects and/or furcations"; and (d) "supportive periodontal care." These working groups were directed by two chairpersons belonging to the EFP Workshop Committee. With the support of an expert in methodology in each working group, recommendations and draft background texts were generated | 9 SANZ et Al.
and subsequently presented, debated and put to a vote in the plenary of all delegates. During these plenary sessions, the guideline development process and discussions and votes were overseen and facilitated by the independent guideline methodologist (I.K.). The plenary votes were recorded using an electronic voting system, checked for plausibility in then introduced into the guideline text.
The consensus process was conducted as follows:  collection and merging of amendments by group chairs.
 initial voting within the working group on recommendations and guideline text to be presented as group result in the plenary.

## | plenary 2
- Presentation of working group results (draft recommendations and background text) by working group chairs.
- Invitation to formulate questions, statements and reasonable amendments of the plenary by the independent guideline methodologist/facilitator.
- Answering of questions by working group chairpersons.
- Collection and merging of amendments by independent moderator.
- Preliminary vote on all suggestions provided by the working groups and all reasonable amendments.
- Assessment of the strength of consensus.
- Opening debate, where no consensus was reached or reasonable need for discussion was identified.
- Formulation of tasks to be solved within the working groups.

## | working group phase 2
- Discussion of tasks and potential amendments raised by the plenary.
- Formulation of reasonable and justifiable amendments, considering the GRADE framework.
- Initial voting within the working group on recommendations and guideline text for plenary.

## | plenary 3
- Presentation of working group results by working group chairpersons.
- Invitation to formulate questions, statements and reasonable amendments of the plenary by the independent moderator.
- Collection and merging of amendments by independent moderator.
- Preliminary vote.
- Assessment of the strength of consensus.
- Opening debate, where no consensus was reached or reasonable need for discussion was identified.
- Formulation of reasonable alternatives.
- Final vote of each recommendation.

## | definitions: rating the quality of evidence, grading the strength of recommendations and determining the strength of consensus
For all recommendations and statements, this guideline makes transparent.
- the underlying quality of evidence, reflecting the degree of certainty/uncertainty of the evidence and robustness of study results
- the grade of the recommendation, reflecting criteria of considered judgement the strength of consensus, indicating the degree of agreement within the guideline panel and thus reflecting the need of implementation

## | quality of evidence
The quality of evidence was assessed using a recommended rating scheme [bib_ref] GRADE guidelines: 3. Rating the quality of evidence, Balshem [/bib_ref] Evidence in Guidelines, 2019).

## | strength of recommendations
The grading of the recommendations used the grading scheme ( In adult patients with periodontitis after initial non-surgical cause-related therapy and residual PPD of 5 mm or more, what is the efficacy of pocket elimination/reduction surgery in comparison with access flap surgery? [bib_ref] Adjunctive effect of systemic antimicrobials in periodontitis therapy. A systematic review and..., Teughels [/bib_ref] Adjunctive effect of systemic antimicrobials in periodontitis therapy. A systematic review and meta-analysis.
In patients with periodontitis, which is the efficacy of adjunctive systemic antimicrobials, in comparison with subgingival debridement plus a placebo, in terms of probing pocket depth (PPD) reduction, in randomized clinical trials with at least 6 months of follow-up. [bib_ref] Adjunctive effect of locally delivered antimicrobials in periodontitis therapy: A systematic review..., Herrera [/bib_ref] Adjunctive effect of locally delivered antimicrobials in periodontitis therapy. A systematic review and meta-analysis.
In adult patients with periodontitis, which is the efficacy of adjunctive locally delivered antimicrobials, in comparison with subgingival debridement alone or plus a placebo, in terms of probing pocket depth (PPD) reduction, in randomized clinical trials with at least 6 months of follow-up. [bib_ref] Resective surgery for the treatment of furcation involvement: A systematic review, Dommisch [/bib_ref] Resective surgery for the treatment of furcation involvement: A systematic review
What is the benefit of resective surgical periodontal therapy (i.e. root amputation or resection, root separation, tunnel preparation) in (I) subjects with periodontitis who have completed a cycle of non-surgical periodontal therapy and exhibit Class II and III furcation involvement (P) compared to individuals suffering from periodontitis and exhibiting class II and III furcation involvement not being treated with resective surgical periodontal therapy but were not treated at all, treated exclusively by subgingival debridement or access flap surgery (C) with respect to 1) tooth survival (primary outcome), 2) vertical probing attachment (PAL-V) gain and 3) reduction of probing pocket depth (PPD) (secondary outcomes) (O) evidenced by randomized controlled clinical trials, prospective and retrospective cohort studies and case series with at least 12 months of follow-up (survival, PAL-V, PPD) (S), respectively. In systemically healthy humans with dental plaque-induced gingival inflammation (with or without attachment loss, but excluding untreated periodontitis patients), what is the efficacy of agents used adjunctively to mechanical plaque control (either self-performed or professionally delivered), as compared to mechanical plaque control combined with a negative control, in terms of changes in gingival inflammation (through gingivitis or bleeding indices)? The grading of the quality of evidence and the strength of a recommendation may therefore differ in justified cases.

## | strength of consensus
The consensus determination process followed the recommendations by the German Association of the Scientific Medical Societies (AWMF) and Standing Guidelines Commission (2012). In case, consensus could not be reached, different points of view were documented in the guideline text. See .

## | editorial independence

## | funding of the guideline
The development of this guideline and its subsequent publication were financed entirely by internal funds of the European Federation of Periodontology, without any support from industry or other organizations. Management of conflict of interests (CoIs) was discussed in the working groups, following the principles provided by the Guidelines International Network [bib_ref] Guidelines international network: Principles for disclosure of interests and management of conflicts..., Schunemann [/bib_ref]. According to these principles, panel members with relevant, potential CoI abstained from voting on guideline statements and recommendations within the consensus process.

## | declaration of interests and management of potential conflicts

## | peer review
All 15 systematic reviews, and the position paper on outcome variables commissioned for this guideline, underwent a multistep peer review process. First, the draft documents were evaluated by members of the EFP Workshop Committee and the methodological consultants using a custom-made appraisal tool to assess (a) the methodological quality of the SRs using the AMSTAR 2 checklist [bib_ref] AMSTAR 2: A critical appraisal tool for systematic reviews that include randomised..., Shea [/bib_ref] , and (b) whether all PICO(S) questions were addressed as planned. Detailed feedback was then provided for the SR authors. Subsequently, all 15 systematic reviews and the position paper underwent the regular editorial peer review process defined by the Journal of Clinical Periodontology.
The guideline text was drafted by the chairs of the working groups, in close cooperation with the methodological consultants, and circulated in the guideline group before the workshop.
The methodological quality was formally assessed by an outside consultant using the AGREE framework. The guideline was subsequently peer-reviewed for its publication in the Journal of Clinical Periodontology following the standard evaluation process of this scientific journal.

## | implementation and dissemination plan
For this guideline, a multistage dissemination and implementation strategy will be actioned by the EFP, supported by a communication campaign.
This will include the following:
- Publication of the guideline and the underlying systematic reviews and position paper as an Open Access special issue of the The timeline of the guideline development process is detailed in .

## | validity and update process
The guideline is valid until 2025. However, the EFP, represented by the members of the Organizing Committee, will continuously assess current developments in the field. In case of major changes of circumstances, for example new relevant evidence, they will trigger an update of the guideline to potentially amend the recommendations.
It is planned to update the current guideline regularly on demand in form of a living guideline.

## | peri odontal d iag nos is and cl a ss ific ati on
Periodontal diagnosis has been followed according to the classification scheme defined in the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and
Conditions [bib_ref] Periodontal health and gingival diseases and conditions on an intact and a..., Chapple [/bib_ref] [bib_ref] Periodontal manifestations of systemic diseases and developmental and acquired conditions: Consensus report..., Jepsen [/bib_ref] [bib_ref] Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on..., Papapanou [/bib_ref].
According to this classification: - After the completion of periodontal therapy, a stable periodontitis patient has been defined by gingival health on a reduced periodontium (bleeding on probing in <10% of the sites; shallow probing depths of 4 mm or less and no 4 mm sites with bleeding on probing). When, after the completion of periodontal treatment, these criteria are met but bleeding on probing is pres-
[formula] - [/formula]

## | differential diagnosis
Periodontitis should be differentiated from the following clinical conditions (not an exhaustive list of conditions and diseases):
- Gingivitis - Vertical root fracture - Cervical decay - Cemental tears - External root resorption lesions - Tumours or other systemic conditions extending to the periodontium - Trauma-induced local recession - Endo-periodontal lesions [bib_ref] Acute periodontal lesions (periodontal abscesses and necrotizing periodontal diseases) and endo-periodontal lesions, Herrera [/bib_ref] - Periodontal abscess [bib_ref] Acute periodontal lesions (periodontal abscesses and necrotizing periodontal diseases) and endo-periodontal lesions, Herrera [/bib_ref] - Necrotizing periodontal diseases [bib_ref] Acute periodontal lesions (periodontal abscesses and necrotizing periodontal diseases) and endo-periodontal lesions, Herrera [/bib_ref] 

## | sequence for the treatment of periodontitis stages i, ii and iii
Patients, once diagnosed, should be treated according to a pre-established stepwise approach to therapy that, depending on the disease stage, should be incremental, each including different interventions.
An essential prerequisite to therapy is to inform the patient of the diagnosis, including causes of the condition, risk factors, treatment TA B L E 7 Periodontitis stage. Adapted from [bib_ref] Staging and grading of periodontitis: Framework and proposal of a new classification..., Tonetti [/bib_ref] Note: The initial Stage should be determined using CAL; if not available then RBL should be used. Information on tooth loss that can be attributed primarily to periodontitis -if available -may modify stage definition. This is the case even in the absence of complexity factors. Complexity factors may shift the Stage to a higher level, for example furcation II or III would shift to either Stage III or IV irrespective of the CAL. The distinction between Stage III and Stage IV is primarily based on complexity factors. For example, a high level of tooth mobility and/or posterior bite collapse would indicate a Stage IV diagnosis. For any given case only some, not all, complexity factors may be present, however, in general it only takes 1 complexity factor to shift the diagnosis to a higher Stage. It should be emphasized that these case definitions are guidelines that should be applied using sound clinical judgment to arrive at the most appropriate clinical diagnosis.
For post-treatment patients CAL and RBL are still the primary stage determinants. If a stage shifting complexity factor(s) were eliminated by treatment, the stage should not retrogress to a lower stage since the original stage complexity factor should always be considered in maintenance phase management.
Abbreviations: CAL, clinical attachment loss; RBL, radiographic bone loss.
TA B L E 8 Periodontitis grade. Adapted from [bib_ref] Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on..., Papapanou [/bib_ref] Grade should be used as an indicator of the rate of periodontitis progression. The primary criteria are either direct or indirect evidence of progression. Whenever available, direct evidence is used; in its absence indirect estimation is made using bone loss as a function of age at the most affected tooth or case presentation (radiographic bone loss expressed as percentage of root length divided by the age of the subject, RBL/age). Clinicians should initially assume Grade B disease and seek specific evidence to shift towards grade A or C, if available. Once grade is established based on evidence of progression, it can be modified based on the presence of risk factors. CAL, clinical attachment loss; HbA1c, glycated hemoglobin A1c; RBL, radiographic bone loss.
alternatives and expected risks and benefits including the option of no treatment. This discussion should be followed by agreement on a personalized care plan. The plan might need to be modified during the treatment journey, depending on patient preferences, clinical findings and changes to overall health.
1. The first step in therapy is aimed at guiding behaviour change by motivating the patient to undertake successful removal of supragingival dental biofilm and risk factor control and may include the following interventions:
- Supragingival dental biofilm control to the patient's needs, and in any of these recall visits, any patient may need re-treatment if recurrent disease is detected, and in these situations, a proper diagnosis and treatment plan should be reinstituted.
In addition, compliance with the recommended oral hygiene regimens and healthy lifestyles are part of supportive periodontal care.
In any of the steps of therapy, tooth extraction may be considered if the affected teeth are considered with a hopeless prognosis.
The first part of this document was prepared by the steering group with the help of the methodology consultants, and it was carefully examined by the experts participating in the consensus and was voted upon in the initial plenary session to form the basis for the specific recommendations.

## | clinic al recommendations: fir s t s tep of ther apy
The first step of therapy is aimed at providing the periodontitis patient with the adequate preventive and health promotion tools to facilitate his/her compliance with the prescribed therapy and the Strength of consensus strong consensus (0% of the group abstained due to potential CoI).
assurance of adequate outcomes. This step not only includes the implementation of patient's motivation and behavioural changes to achieve adequate self-performed oral hygiene practices, but also the control of local and systemic modifiable risk factors that significantly influence this disease. Although this first step of therapy is insufficient to treat a periodontitis patient, it represents the foundation for optimal treatment response and long-term stable outcomes.
This first step includes not only the educational and preventive interventions aimed to control gingival inflammation but also thevprofessional mechanical removal of the supragingival plaque and calculus, together with the elimination local retentive factors. We recommend that the same guidance on oral hygiene practices to control gingival inflammation is enforced throughout all the steps of periodontal therapy including supportive periodontal care.

## | intervention

## Supporting literature van der weijden and slot (2015)

## Grade of recommendation grade a-
Strength of consensus Strong consensus [3.8% of the group abstained due to potential conflict of interest (CoI)]

# Background

## Intervention
Supragingival dental biofilm control can be achieved by mechanical and chemical means. Mechanical plaque control is mainly performed by tooth brushing, either with manual or powered toothbrushes or with supplemental interdental cleaning using dental floss, interdental brushes, oral irrigators, wood sticks, etc. As adjuncts to mechanical plaque control, antiseptic agents, delivered in different formats, such as dentifrices and mouth rinses have been recommended.
Furthermore, other agents aimed to reduce gingival inflammation have also been used adjunctively to mechanical biofilm control, such as probiotics, anti-inflammatory agents and antioxidant micronutrients.

## Available evidence
Even though oral hygiene interventions and other preventive measurements for gingivitis control were not specifically addressed in the systematic reviews prepared for this Workshop to Develop
Guidelines for the treatment of periodontitis, evidence can be drawn from the XI European Workshop in Periodontology (2014) [bib_ref] Primary prevention of periodontitis: Managing gingivitis, Chapple [/bib_ref] and the systematic review on oral hygiene practices for the prevention and treatment of gingivitis (Van der Weijden & . This available evidence supports the following:
- Professional oral hygiene instructions (OHI) should be provided to reduce plaque and gingivitis. Re-enforcement of OHI may provide additional benefits.
- Manual or power tooth brushing are recommended as a primary means of reducing plaque and gingivitis. The benefits of tooth brushing out-weigh any potential risks.
- When gingival inflammation is present, inter-dental cleaning, preferably with interdental brushes (IDBs) should be professionally taught to patients. Clinicians may suggest other inter-dental cleaning devices/methods when the use of IDBs is not appropriate.

## R.1.2 | are additional strategies in motivation useful?

## Expert consensus-based recommendation (1.2)
We recommend emphasizing the importance of oral hygiene and engaging the periodontitis patient in behavioural change for oral hygiene improvement.

## Supporting literature carra et al. (2020)

## Grade of recommendation grade a-
Strength of consensus Strong consensus (1.3% of the group abstained due to potential CoI)

# Background

## Intervention
Oral hygiene instructions (OHI) and patient motivation in oral hygiene practices should be an integral part of the patient management during all stages of periodontal treatment . Different behavioural interventions, as well as communication and educational methods, have been proposed to improve and maintain the patient's plaque control over time [bib_ref] Scope, competences, learning outcomes and methods of periodontal education within the undergraduate..., Sanz [/bib_ref]. See additional information in the next section on "Methods of motivation."

## R.1.3 | are psychological methods for motivation effective to
improve the patient's compliance in oral hygiene practices?

# Evidence-based statement (1.3)
To improve patient's behaviour towards compliance with oral hygiene practices, psychological methods such as motivational interviewing or cognitive behavioural therapy have not shown a significant impact. [bib_ref] Promoting behavioural changes to improve oral hygiene in patients with periodontal diseases:..., Carra [/bib_ref] Quality of evidence Five randomized clinical trials (RCTs) (1716 subjects) with duration 6 months in untreated periodontitis patients [(4 RCTs with high and 1 RCT with low risk of bias (RoB)]

## Supporting literature

## Grade of recommendation statement-unclear, additional research needed

# Evidence-based statement (1.3)
Strength of consensus Strong consensus (1.3% of the group abstained due to potential CoI)

# Background

## Intervention
Several different psychological interventions based on social cognitive theories, behavioural principles and motivational interviewing (MI) have been applied to improve OHI adherence in patients with periodontal diseases. The available evidence has not demonstrated that these psychological interventions based on cognitive constructs and motivational interviewing principles provided by oral health professionals have improved the patient's oral hygiene performance as measured by the reduction of plaque and bleeding scores over time.

## Available evidence
The evidence includes two RCTs on MI (199 patients) and three RCTs on psychological interventions based on social cognitive theories and feedback (1,517 patients).

## Risk of bias
The overall body of evidence was assessed at high risk of bias (four RCTs high and one RCT low).

## Consistency
The majority of the studies found no significant additional benefit implementing psychological interventions in conjunction with OHI.

## Clinical relevance and effect size
The reported effect size was not considered clinically relevant.

## Balance of benefit and harm
Benefit and harm were not reported, and due to the fact that different health professionals were involved to provide interventions, no conclusion could be drawn.

## Economic considerations
These studies did not assess a cost-benefit evaluation in spite of the expected additional cost related to the psychological intervention.

## Patient preferences
No proper information was available to assess this issue.

## Applicability
A psychological approach needs special training to be effectively performed.

## | intervention: adjunctive therapies for gingival inflammation
Adjunctive therapies for gingival inflammation have been considered within the adjunctive therapies to subgingival debridement, and therefore, they have been evaluated within the second step of therapy.

## | intervention: supragingival dental biofilm control (professional)
R1.4 | What is the efficacy of supragingival professional mechanical plaque removal (PMPR) and control of retentive factors in periodontitis therapy?

## Expert consensus-based recommendation (1.4)
We recommend supragingival professional mechanical plaque removal (PMPR) and control of retentive factors, as part of the first step of therapy.
Supporting literature [bib_ref] Professional mechanical plaque removal for prevention of periodontal diseases in adults-systematic review..., Needleman [/bib_ref] ; [bib_ref] Effect of professional mechanical plaque removal performed on a long-term, routine basis..., Trombelli [/bib_ref] 

## Grade of recommendation grade a-
Strength of consensus Unanimous consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
The removal of the supragingival dental biofilm and calcified deposits (calculus) (here identified under the term "professional mechanical plaque removal" (PMPR) is considered an essential component in the primary and secondary prevention of periodontitis as well as within the basic treatment of plaque-induced periodontal diseases (van der
Weijden & Slot, 2011). Since the presence of retentive factors, either associated with the tooth anatomy or more frequently, due to inadequate restorative margins, are often associated with gingival inflammation and/or periodontal attachment loss, they should be prevented/eliminated to reduce their impact on periodontal health.

## Available evidence
Even though these interventions were not specifically addressed in the systematic reviews prepared for this Workshop to develop guidelines for the treatment of periodontitis, indirect evidence can be found in the 2014 European Workshop on Prevention, in which the role of PMPR was addressed both in primary prevention or in supportive periodontal care (SPC) [bib_ref] Effect of professional mechanical plaque removal performed on a long-term, routine basis..., Trombelli [/bib_ref]. Some additional evidence can be found to support both procedures, as part of periodontitis therapy. A split-mouth RCT, with a follow-up of 450 days in 25 subjects, concluded that the performance of supragingival debridement, before subgingival debridement, decreased subgingival treatment needs and maintained the periodontal stability over time [bib_ref] Supragingival treatment as an aid to reduce subgingival needs: A 450-day investigation, Gomes [/bib_ref]. In addition, supragingival debridement may induce beneficial changes in the subgingival microbiota [bib_ref] The effect of repeated professional supragingival plaque removal on the composition of..., Ximenez-Fyvie [/bib_ref]. Moreover, it has been established that retentive factors may increase the risk of worsening the periodontal condition [bib_ref] Dental restorations: A risk factor for periodontal attachment loss, Broadbent [/bib_ref] [bib_ref] Multilevel analysis of the association between posterior restorations and gingival health in..., Demarco [/bib_ref] [bib_ref] Clinical and microbiological effects of subgingival restorations with overhanging or clinically perfect..., Lang [/bib_ref].

## | intervention: risk factor control

## R1.5 | what is the efficacy of risk factor control in
periodontitis therapy?

## Evidence-based recommendation (1.5)
We recommend risk factor control interventions in periodontitis patients, as part of the first step of therapy.

## Supporting literature ramseier et al. (2020)

## Quality of evidence 25 clinical studies

## Grade of recommendation grade a-
Strength of consensus Strong consensus (1.3% of the group abstained due to potential CoI)

# Background

## Intervention
Smoking and diabetes are two proven risk factors in the etiopathogenesis of periodontitis , and therefore, their control should be an integral component in the treatment of these patients. Interventions for risk factor control have aimed to educate and advice patients for behavioural change aimed to reduce them and in specific cases to refer them for adequate medical therapy. Other relevant factors associated with healthy lifestyles (stress reduction, dietary counselling, weight loss or increased physical activities) may also be part of the overall strategy for reducing patient's risk factors.

## Available evidence
In the systematic review , the authors have identified 13 relevant guidelines for interventions for tobacco smoking cessation, promotion of diabetes control, physical exercise (activity), change of diet, carbohydrate (dietary sugar reduction) and weight loss. In addition, 25 clinical studies were found that assess the impact of (some of) these interventions in gingivitis/periodontitis patients.

## Risk of bias
It is explained specifically for each intervention.

## Consistency
The heterogeneity in study design precludes more consistent findings, but adequate consistency may be found for studies on smoking cessation and diabetes control.

## Clinical relevance and effect size
No meta-analysis was performed; effect sizes can be found in the individual studies.

## Balance of benefit and harm
In addition to periodontal benefits, all the tested interventions represent a relevant beneficial health impact.

## Economic considerations
The various studies do not indicate a cost-benefit evaluation. However, it cannot be discarded an additional cost related to the psychological intervention. However, the systemic health benefits that can be obtained from these interventions, if they are successful, would represent reduced cost of healthcare services in different comorbidities.

## Patient preferences
Interventions are heterogeneous, but the potential systemic health benefits may favour preference for them.

## Applicability
Demonstrated with studies testing large groups from the general population; the practicality of routine use is still to be demonstrated.

## R1.6 | what is the efficacy of tobacco smoking cessation interventions in periodontitis therapy?

## Evidence-based recommendation (1.6)
We recommend tobacco smoking cessation interventions to be implemented in patients undergoing periodontitis therapy. [bib_ref] Impact of risk factor control interventions for smoking cessation and promotion of..., Ramseier [/bib_ref] Quality of evidence Six prospective studies with, at least, 6-month follow-up

## Supporting literature

## Grade of recommendation grade a-
Strength of consensus Unanimous consensus (1.2% of the group abstained due to potential CoI)

# Background

## Intervention
Periodontitis patients may benefit from smoking cessation interventions to improve periodontal treatment outcomes and the maintenance of periodontal stability. Interventions consist of brief counselling and may include patient referral for advanced counselling and pharmacotherapy.

## Available evidence
In the systematic review , six prospective studies of 6-to 24-month duration and performed at university setting were
identified. Different interventions were tested (smoking cessation counselling, 5 A's [ask, advise, assess, assist, and arrange], cognitive behavioural therapy [CBT], motivational interview, brief interventions, nicotine replacement therapies). In three of the studies, the intervention was programmed in parallel with non-surgical periodontal therapy (NSPT) and followed by SPC, in one study SPC patients were included and, in another, patients in NSPT and in SPC were compared; in one study, it was unclear. The success of smoking cessation was considered as moderate (4%-30% after 1-2 years), except in one study. Two studies demonstrated benefits in periodontal outcomes, when comparing former smokers to smokers and oscillators.
Additional factors have been discussed in the overall evaluation of risk factor control.

## R1.7 | what is the efficacy of promotion of diabetes control interventions in periodontitis therapy?
Evidence-based recommendation (1.7)
We recommend diabetes control interventions in patients undergoing periodontitis therapy. [bib_ref] Impact of risk factor control interventions for smoking cessation and promotion of..., Ramseier [/bib_ref] Quality of evidence Two 6-month RCTs

## Supporting literature

## Grade of recommendation grade a-
Strength of consensus Consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
Periodontitis patients may benefit from diabetes control interventions to improve periodontal treatment outcomes and the maintenance of periodontal stability. These interventions consist of patient education as well as brief dietary counselling and, in situations of hyperglycaemia, the patient's referral for glycaemic control.

## Available evidence
In the systematic review , two studies on the impact of diabetes control interventions in periodontitis patients were identified, two of them 6-month RCTs, all of them performed at university settings. Periodontal interventions were not clearly defined. Different interventions were tested, including individual lifestyle counselling, dietary changes and oral health education. Some improvements were observed in the intervention groups, in terms of periodontal outcomes.
Additional factors have been discussed in the overall evaluation of risk factor control.

## R1.8 | what is the efficacy of increasing physical exercise
(activity) in periodontitis therapy?

## Evidence-based recommendation (1.8)
We do not know whether interventions aimed to increasing the physical exercise (activity) have a positive impact in periodontitis therapy.

## Evidence-based recommendation (1.8)
Supporting literature [bib_ref] Impact of risk factor control interventions for smoking cessation and promotion of..., Ramseier [/bib_ref] Quality of evidence One 12-week RCT, one 12-week prospective study

## Grade of recommendation grade 0-statement: unclear, additional research needed
Strength of consensus Consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
Overall evidence from the medical literature suggests that the promotion of physical exercise (activity) interventions may improve both treatment and the long-term management of chronic non-communicable diseases. In periodontitis patients, the promotion may consist of patient education and counselling tailored to the patients' age and general health.

## Available evidence
In the systematic review , two 12-week studies on the impact of physical exercise (activity) interventions in periodontitis patients were identified, one RCT (testing education with comprehensive yogic interventions followed by yoga exercises) and one prospective study (with briefing followed by physical exercises; the control group was a dietary intervention), performed at university settings. Periodontal interventions were not clearly defined, although in the yoga study, standard therapy was delivered (by not described) in periodontitis patients, while no periodontal therapy was provided in the second study. Both studies reported improved periodontal parameters, including bleeding scores and probing depth changes, after 12 weeks (although in the yoga study also, the influence on psychological stress could not be discarded).
Additional factors have been discussed in the overall evaluation of risk factor control.

## R1.9 | what is the efficacy of dietary counselling in
periodontitis therapy?

## Evidence-based recommendation (1.9)
We do not know whether dietary counselling may have a positive impact in periodontitis therapy. [bib_ref] Impact of risk factor control interventions for smoking cessation and promotion of..., Ramseier [/bib_ref] Quality of evidence Three RCTs, four prospective studies

## Supporting literature

## Grade of recommendation

# Background

## Intervention
Periodontitis patients may benefit from dietary counselling interventions to improve periodontal treatment outcomes and the maintenance of periodontal stability. These interventions may consist of patient education including brief dietary advices and in specific cases patient's referral to a nutrition specialist.

## Available evidence
In the systematic review , seven studies on the impact of dietary counselling (mainly addressing lower fat intake, less free sugars and salt intake, increase in fruit and vegetable in- In the systematic review , two studies specifically on the impact of dietary counselling aiming at carbohydrate (free sugars) reduction in gingivitis/periodontitis patients were identified, one 4-week RCT (including also gingivitis patients) and
one 24-week prospective study. Periodontal interventions were not clearly defined. Both studies reported improved gingival indices.
Additional factors have been discussed in the overall evaluation of risk factor control.

## R1.10 | what is the efficacy of lifestyle modifications aiming at weight loss in periodontitis therapy?
Evidence-based recommendation (1.10)
We do not know whether interventions aimed to weight loss through lifestyle modification may have a positive impact in periodontitis therapy.

## Supporting literature ramseier et al. (2020)

## Quality of evidence five prospective studies
Grade of recommendation Grade 0-Statement: unclear, additional research needed Strength of consensus Strong consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
Available evidence suggests that weight loss interventions may improve both the treatment and long-term outcome of chronic non-communicable diseases. In periodontitis patients, these interventions may consist of specific educational messages tailored to the patients' age and general health. These should be supported with positive behavioural change towards healthier diets and increase in physical activity (exercise).

## Available evidence
In the systematic review , five prospective studies, in obese gingivitis/periodontitis patients, on the impact of weight loss interventions were identified, with different follow-ups (18 months, 12 months, 24 weeks and two studies of 12 weeks).
Periodontal interventions were not clearly defined. Intensity of lifestyle modifications aiming at weight loss interventions ranged from a briefing, followed by counselling in dietary change, to an 8-week high-fibre, low-fat diet, or a weight reduction programme with diet and exercise-related lifestyle modifications. Three studies reported beneficial periodontal outcomes and, the other two, no differences.
Additional factors have been discussed in the overall evaluation of risk factor control.

## | clinic al recommendations: s econd s tep of ther apy
The second step of therapy (also known as cause-related therapy) is aimed at the elimination (reduction) of the subgingival biofilm and calculus and may be associated with removal of root surface (cementum).
The procedures aimed at these objectives have received in the scientific literature different names: subgingival debridement, subgingival scaling, root planning, etc. [bib_ref] Non-surgical periodontal therapy, Kieser [/bib_ref]. In this guideline, we have agreed to use the term "subgingival instrumentation" to all non-surgical procedures, either performed with hand (i.e. curettes) or power-driven (i.e. sonic/ultrasonic devices) instruments specifically designed to gain access to the root surfaces in the subgingival environment and to remove subgingival biofilm and calculus. This second step of therapy requires the successful implementation of the measures described in the first step of therapy.
Furthermore, subgingival instrumentation may be supplemented with the following adjunctive interventions:
- Use of adjunctive physical or chemical agents.
- Use of adjunctive host-modulating agents (local or systemic).
- Use of adjunctive subgingival locally delivered antimicrobials.
- Use of adjunctive systemic antimicrobials.

## | intervention: subgingival instrumentation

## R2.1 | is subgingival instrumentation beneficial for the treatment of periodontitis?
Evidence-based recommendation (2.1)
We recommend that subgingival instrumentation be employed to treat periodontitis in order to reduce probing pocket depths, gingival inflammation and the number of diseased sites. Evidence-based recommendation (2.1) Quality of evidence One 3-month RCT (n = 169 patients); 11 prospective studies (n = 258) 6 months

## Supporting literature

## Grade of recommendation grade a-
Strength of consensus Unanimous consensus (2.6% of the group abstained due to potential CoI)

# Background

## Intervention
Subgingival instrumentation aims at reducing soft tissue inflammation by removing hard and soft deposits from the tooth surface.
The endpoint of treatment is pocket closure, defined by probing pocket depth (PPD) 4 mm and absence of bleeding on probing (BOP).

## Available evidence
One RCT on 169 patients with 3-month outcomes addressed the PICOS question. Further 11 prospective studies (n = 258) with a follow-up of 6 months which considered baseline measures and post-treatment reductions in probing pocket depth (primary outcome) and bleeding on probing and percentage of closed pockets (secondary outcomes) were analysed.

## Risk of bias
Study quality assessment identified a low risk of bias in all but one study, which had a high risk of bias.

## Consistency
Evidence was consistent across all 11 studies that were included in the pre-and post-treatment analysis and was therefore considered strong. Patient-reported outcomes were inconsistently reported and adverse events, when reported, were rare. No indications of publication bias were observed but heterogeneity was high.

## Clinical relevance and effect size
The evidence suggested a mean reduction of PPD of 1.7 mm at 6/8 months, a mean proportion of closed pockets of 74% and a mean reduction of BOP of 63%. Deeper sites (>6 mm) demonstrated a greater mean PPD reduction of 2.6 mm.

## Balance of benefits and harm
An overall consideration of the benefit versus harm of subgingival instrumentation supports the strength of the recommendation.

# Ethical considerations
Evaluation of the efficacy of subgingival debridement is ethically challenging as it would entail comparison with no subgingival intervention. Due to the lack of relevant RCTs, prospective studies were included and their data analysed.

## Applicability
The majority of studies were conducted in well-controlled research environments and included specifically selected populations, that is those with no systemic disease. While results from studies involving populations with systemic diseases were not included in the systematic review, there is a consensus that subgingival instrumentation is efficacious in these groups , but the magnitude of the effect requires further study.
The evidence presented illustrates "efficacy" rather than "effectiveness"; therefore, generalizability to general dental practice settings is unclear.
R2.2 | Are treatment outcomes of subgingival instrumentation better after use of hand, powered (sonic/ ultrasonic) instruments or a combination thereof?

## Evidence-based recommendation (2.2)
We recommend that subgingival periodontal instrumentation is performed with hand or powered (sonic/ultrasonic) instruments, either alone or in combination.

## Supporting literature suvan et al. (2019)
Quality of evidence Four RCTs (n = 132) with a follow-up of 6 months.

## Grade of recommendation grade a-
Strength of consensus Unanimous consensus (6.2% of the group abstained due to potential CoI)

# Background

## Intervention
Numerous types of instruments are available to perform subgingival instrumentation.

## Available evidence
Four RCTs (n = 132) with a low overall risk of bias were included.
Findings were evaluated at 6/8 months for PPD reduction (primary outcome) and clinical attachment level (CAL) gain (secondary outcome).

## Risk of bias
Study quality assessment identified all four studies to be at low risk of bias.

## Consistency
The evidence demonstrated that outcomes of treatment were not dependent on the type of instrument employed. The evidence was considered strong and consistent. No indications of publication bias were observed but heterogeneity was high.

## Clinical relevance
No clinically or statistically significant differences were observed between the different types of instruments.

## Balance of benefits and harm
The use of all types of instruments is technique-sensitive and therefore requires specific training. Patient-reported outcomes and adverse events were inconsistently reported. If present, no obvious differences between hand and powered instruments in terms of post-operative sensitivity were noted.

# Ethical considerations
There is a potential ethical dilemma in that patient preference may conflict with the clinician's preference in terms of type of instrument. Patient autonomy should be respected.

## Economic considerations
Cost-effectiveness has not been evaluated in these studies.
Furthermore, there is no evidence that the use of one type of instrument is superior in terms of requisite treatment time.

## Applicability
The majority of studies were conducted in well-controlled research environments, in specifically selected populations and under local anaesthetic. Clinicians should be aware that new instrument choices (i.e. mini instruments) were not evaluated in the available studies.
The choice of instrument should be based upon the experience/skills and preference of the operator together with patient preference.

## R2.3 | are treatment outcomes of subgingival
instrumentation better when delivered quadrant-wise over multiple visits or as a full mouth procedure (within 24 hr)?

## Evidence-based recommendation (2.3)
We suggest that subgingival periodontal instrumentation can be performed with either traditional quadrant-wise or full mouth delivery within 24 hr. Quality of evidence Eight RCTs (n = 212) with a follow-up of 6 months.

## Supporting literature

## Grade of recommendation grade b-
Strength of consensus Strong consensus (3.8% of the group abstained due to potential CoI)

# Background
Intervention Subgingival instrumentation has traditionally been delivered during multiple sessions (e.g. quadrant-wise). As an alternative, full-mouth protocols have been suggested. Full-mouth protocols included single stage and two-stage therapy within 24 hr; however, protocols including antiseptics (full-mouth disinfection) were not included in this analysis.

## Available evidence
Eight RCTs (n = 212) with a follow-up of 6 months were included demonstrating a low risk of bias. Outcome measures reported were PPD reduction (primary outcome), CAL gain, BOP reduction and pocket closure (secondary outcomes).

## Risk of bias
Study quality assessment identified all eight studies at low risk of bias.

## Consistency
The evidence suggested that outcomes of treatment were not dependent on the type of delivery (protocol) employed. The evidence was considered strong and consistent. No indications of publication bias were observed, and heterogeneity was low. The results confirm the findings of a recent Cochrane systematic review [bib_ref] Full-mouth treatment modalities (within 24 hours) for chronic periodontitis in adults, Eberhard [/bib_ref].

## Clinical relevance
No substantial differences were observed between the two treatment modalities.

## Balance of benefits and harm
Clinicians should be aware that there is evidence of systemic implications (e.g. acute systemic inflammatory response) with full-mouth protocols. Thus, such an approach should always include careful consideration of the general health status of the patient.

# Ethical considerations
There is a potential ethical dilemma in that patient preference may conflict with the clinician's recommendation in terms of mode of treatment delivery. Patient autonomy should be respected.

## Legal considerations
Potential adverse systemic effects of full-mouth treatment protocols in certain risk patients should be considered.

## Economic considerations
Limited evidence on the cost-effectiveness of different modes of delivery is available.

## Patient preferences
Patient-reported outcomes were inconsistently reported, and there is no evidence supporting one approach over the other. Reports of increased discomfort and side effects, evident in studies on fullmouth disinfection, were not included in the present analysis.

## Applicability
The majority of studies were conducted in well-controlled environments, included specifically selected populations and were undertaken in a number of different continents.
6.2 | Intervention: Use of adjunctive physical agents to subgingival instrumentation R2.4 | Are treatment outcomes with adjunctive application of laser superior to non-surgical subgingival instrumentation alone?

## Evidence-based recommendation (2.4)
We suggest not to use lasers as adjuncts to subgingival instrumentation.
Supporting literature [bib_ref] Time between recall visits and residual probing depths predict long-term stability in..., Ramseier [/bib_ref] Quality of evidence Two RCTs (n = 46, wavelengths 2,780 nm and 2,940 nm) and 3 RCTs (n = 101, wavelength range 810-980 nm) with single laser application reporting 6-month outcomes. Two RCTs reported mean PPD changes.

## Grade of recommendation grade b-
Strength of consensus Simple majority (3.8% of the group abstained due to potential CoI)

# Background

## Intervention
Lasers offer the potential to improve outcomes of subgingival root surface treatment protocols when used as adjuncts to traditional root surface instrumentation. Depending upon the wavelength and settings employed, some lasers can ablate subgingival calculus and exert antimicrobial effects. The evidence reported to inform the current guidelines has grouped lasers into two main wavelength categories: lasers with a wavelength range of 2,780-2,940 nm and lasers with a wavelength range of 810-980 nm.

## Available evidence
Evidence was available from five RCTs (total n = 147) with a followup of 6 months and a single laser application. Only RCTs reporting mean PPD changes were considered and this recommendation is made in the light of this approach to the systematic review.

## Risk of bias
The majority of studies displayed unclear risk of bias.

## Consistency
Studies differed in terms of laser type, tip diameter, wavelength, mode of periodontal treatment, number of treated sites, population and several possible combinations of these parameters.

## Clinical relevance and effect size
There is insufficient evidence to recommend adjunctive application of lasers to subgingival instrumentation.

## Balance of benefits and harm
The majority of the studies did not report on potential harm/adverse effects.

## Economic considerations
Additional costs associated with adjunctive laser therapy may not be justified.

## Patient preferences
Patient-reported outcomes were rarely reported.

## Applicability
The majority of studies were conducted in university settings, included specifically selected populations and were undertaken in a number of different countries.

## R2.5 | are treatment outcomes with adjunctive antimicrobial
photodynamic therapy (aPDT) superior to non-surgical subgingival instrumentation alone?

## Evidence-based recommendation (2.5)
We suggest not to use adjunctive a PDT at wavelength ranges of either 660-670 nm or 800-900 nm in patients with periodontitis. [bib_ref] Time between recall visits and residual probing depths predict long-term stability in..., Ramseier [/bib_ref] Quality of evidence Five RCTs (n = 121, wavelength range 660-670 nm and wavelength range 800-900 nm) with single aPDT application reporting 6-month outcomes. Three RCTs reported mean PPD changes.

## Supporting literature

## Grade of recommendation grade b-
Strength of consensus Consensus (1.3% of the group abstained due to potential CoI)

# Background

## Intervention
Adjunctive antimicrobial photodynamic therapy (aPDT) is an approach used to improve the antimicrobial effects of traditional root surface decontamination methods. It functions by attaching a photosensitizing dye to the normally impermeable outer cell membrane of Gramnegative bacteria and then uses laser light to generate reactive oxygen species through the membrane-bound dye to locally destroy those bacteria.

## Available evidence
Evidence was available from five RCTs (n = 121) with a follow-up of 6 months and a single aPDT application. Only RCTs reporting mean PPD changes were included in the meta-analysis, and this recommendation is made in the light of this approach to the systematic review.

## Risk of bias
The majority of studies displayed unclear risk of bias.

## Consistency
Substantial heterogeneity across the studies was identified, in terms of laser type, photosensitizer, wavelength, mode of periodontal treatment, number of treated sites, population and several possible combinations of these parameters.

## Clinical relevance and effect size
No benefits were observed with the adjunctive application of aPDT.

## Balance of benefits and harm
The majority of the studies reported on adverse events with no harm associated with the adjunctive application of aPDT.

## Economic considerations
Additional costs associated with adjunctive laser therapy may not be justified.

## Patient preferences
Patient-reported outcomes were rarely reported, and there is no evidence supporting one approach over the other.

## Applicability
All studies were conducted in well controlled university settings or specialist centres, included specifically selected populations and were undertaken in a number of different countries.

## | intervention: use of adjunctive hostmodulating agents (local or systemic) to subgingival instrumentation
R2.6 | Does the adjunctive use of local statins improve the clinical outcome of subgingival instrumentation?

## Evidence-based recommendation (2.6)
We recommend not to use local administration of statin gels (atorvastatin, simvastatin, rosuvastatin) as adjuncts to subgingival instrumentation. [bib_ref] The adjunctive use of host modulators in non-surgical periodontal therapy. A systematic..., Donos [/bib_ref] Quality of evidence Twelve placebo-controlled RCTs (n = 753), for 1.2% atorvastatin (six RCTs, n = 180), 1.2% simvastatin gel (5 RCTs, n = 118) and 1.2% rosuvastatin gel (four RCTs, n = 122)

## Supporting literature

## Grade of recommendation grade a-

# Strength of consensus

## Available evidence
Twelve placebo-controlled RCTs (n = 753), all derived from the same research group, assessed the effect of local statin gels in adjunctive non-surgical therapy for infrabony or furcation Class II defects. PPD reduction (primary outcome) was reported at 6 and 9 months for 1.2% atorvastatin (6 RCTs, n = 180), 1.2% simvastatin gel (five RCTs, n = 118) and 1.2% rosuvastatin gel (four RCTs, n = 122). Meta-analysis was performed in nine RCTs (n = 607).

## Risk of bias
There was a moderate overall risk of bias in the studies analysed.
Three of 12 studies presented with a high risk of bias in at least one domain. One study was moderately underpowered. While pharmaceutical companies provided the statins in the included studies, the level of involvement of industry in the analysis and interpretation of the results is unclear.

## Consistency

## Clinical relevance
Although the mean estimates suggested a clinically meaningful benefit from adding statin gels to subgingival instrumentation, there was a large prediction interval for PPD reduction at 6 months (0.08 mm to 3.74 mm) and the I 2 (95.1%) indicating wide heterogeneity of data and therefore caution needs to be adopted when assessing the efficacy of statins. While the prediction interval at 9 months (1.16-3.34 mm) improved over 6-month results, heterogeneity (I 2 statistic) of 65.4% still indicated moderate inconsistency in results. Since the outcomes of the different statin gels were considered as one group during the meta-analysis, it is not possible to draw definitive conclusions on which statin offered higher efficacy.

## Balance of benefits and harms
All studies included in the review reported that patients tolerated local statins well, without any complications, adverse reactions/side effects or allergic symptoms.

## Economic considerations
There is an additional cost associated with the use of statins that is borne by the patient.

## Ethical and legal considerations
The statin formulations included in the systematic review are "offlabel" and an approved formulation with appropriate good manufacturing practice quality control (Good Manufacturing Practice, GMP) and patient's safety validation is not available.

## Applicability
The same research group published all data within the RCTs, thereby restricting the generalizability of the results, which need to be confirmed in future larger (multicentre) RCTs by independent groups, with multilevel analyses to account for potential confounding factors (e.g. medical history, smoking history). In addition, future studies will need to clarify which type of statin is more effective.

## R2.7 | does the adjunctive use of probiotics improve the clinical outcome of subgingival instrumentation?

## Evidence-based recommendation (2.7)
We suggest not to use probiotics as an adjunct to subgingival instrumentation Supporting literature [bib_ref] The adjunctive use of host modulators in non-surgical periodontal therapy. A systematic..., Donos [/bib_ref] Quality of evidence Five placebo controlled RCTs (n = 176) testing preparations containing L. ramnosus SP1, L. reuteri or the combination of S. oralis KJ3, S. uberis KJ2 and S. rattus JH145.

## Grade of recommendation grade b-
Strength of consensus Consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
Probiotics are defined as "live microorganisms which, when administered in adequate amounts, confer a health benefit on the host" (FAO/WHO). It has been suggested that probiotics may alter the ecology of micro-environmental niches such as periodontal pockets, and as such, they may disrupt an established dysbiosis. This may re-establish a symbiotic flora and a beneficial interaction with the host via several mechanisms including modulation of the immuneinflammatory response, regulation of antibacterial substances and exclusion of potential pathogens via nutritional and spatial competition [bib_ref] Probiotics and periodontitis -A literature review, Gatej [/bib_ref]. This guideline does not include evidence on the use of probiotics in supportive periodontal therapy.

## Available evidence
Five placebo-controlled RCTs (n = 176) assessed the adjunctive effect of probiotics to subgingival instrumentation. Two studies from the same group used a preparation containing L. ramnosus SP1 (2  10 7 colony forming units). Two other RCTs from another research group used a preparation containing L. reuteri. One study evaluated a combination of S. oralis KJ3, S. uberis KJ2 and S. rattus JH145. Meta-analysis was performed on PPD reduction (primary outcome) at 6 months.

## Risk of bias
All studies had an overall low risk of bias. Two out of the five studies declared industrial sponsorship, and three received the probiotics from industry.

## Consistency
Meta-analysis of five RCTs demonstrated that, compared with placebo, treatment with probiotics resulted in a mean difference in PPD reduction of 0.38 mm (95% CI [0.14; 0.90]) at 6 months. The confidence interval and I 2 statistic (93.3%) suggested considerable heterogeneity for the effect of the treatment with the different formulations.

## Clinical relevance
The mean estimated difference in PPD reduction between probiotics and placebo was not statistically significant and of limited clinical relevance (difference < 0.5 mm). Moreover, two groups published four out of the five RCTs included each of them using a different probiotic formulation. Preparations containing
Lactobacillus reuteri were the only ones to demonstrate improved PPD reductions.
Given that probiotics embrace a broad range of micro-organisms and types of preparations, combining such data within the same meta-analysis poses an interpretational challenge.

## Balance of benefits and harms
All formulations appeared to be safe and patients did not report adverse effects.

## Economic considerations
There is an additional cost associated with the use of probiotics that is borne by the patient.

## Applicability
All studies were conducted in two countries, and no conclusions can be drawn on the effectiveness of probiotics as adjuncts to subgingival instrumentation.

## Risk of bias
One study was considered to be at high risk of bias and the remaining studies presented some concerns in certain domains. Of the five studies included in meta-analysis, three declared industrial sponsorship, one was sponsored by the academic institution, and the fifth did not declare funding.

## Consistency
The systematic review included data from eight RCTs, but metaanalysis was performed in five RCTs that stratified pockets into moderate (4-6 mm) versus deep (7 mm). The findings were consistent in all studies. The I 2 statistic was 0% (95% CI [0%; 64.1%])
for both moderate and deep pockets. Two out of five RCTs included did not report a power calculation. The strict experimental protocols employed by the five studies included in the meta-analysis limits the generalizability of the outcomes.

## Clinical relevance of outcomes and effect size
Additional PPD reductions reported following the use of SDD were 0.22 mm at 6 months and 0.3 mm at 9 months in moderate depth pockets. The mean prediction interval ranged from 0.06 mm to 0.38 mm at 6 months and from 0.15 mm to 0.45 mm at 9 months. At deep sites, the additional PPD reductions were more clinically relevant, with 0.68 mm mean additional PPD reductions at 6 months and 0.62 mm at 9 months. The mean prediction interval ranged from 0.34 mm to 1.02 mm at 6 months and from 0.28 mm to 0.96 mm at 9 months. Percentage of pocket closure was not reported.

## Balance of benefits and harm
Most studies in the SDD category did not report any serious adverse events or patient dropouts that were directly attributed to the medication. However, it is known that doxycycline may lead to elevations in liver enzymes, which was evident for some patients in the results of one RCT included in the systematic review [bib_ref] Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root..., Caton [/bib_ref] [bib_ref] Subantimicrobial dose doxycycline as an adjunct to scaling and root planing: Post-treatment..., Caton [/bib_ref]. The sustainability of the benefits or adverse events beyond the study period is unknown.

# Ethical considerations
Current health policies on antibiotic stewardship and related public health concerns surrounding increasing antibiotic resistance need to be taken into account. The systemic effects of a drug taken over a 6-to 9-month period during the initial phase of subgingival instrumentation require careful consideration when extrapolating outcomes from controlled research trials into general clinical practice.

## Legal considerations
SDD is not approved or available in some European countries.

## Economic considerations
There is a cost associated with the use of SDD that is borne by the patient.

## Applicability
SSD is mainly effective in deep sites (7 mm), although SDD is used as a systemic rather than a site-specific treatment. The clinical significance in deep sites (0.68 mm at 6 months and 0.62 mm at 9 months) is small, given that re-treatment with non-surgical root debridement might yield additional PPD reductions, and local drug delivery systems may yield similar effect sizes. Moreover, the five studies that did stratify results based upon pocket depth did not present an a priori statistical plan powered to stratify results in that manner.

## R2.9 | does the adjunctive use of systemic/local
bisphosphonates to subgingival instrumentation improve clinical outcomes?

## Evidence-based recommendation (2.9)
We recommend not to use locally delivered bisphosphonate (BP) gels or systemic BPs as an adjunct to subgingival instrumentation. [bib_ref] The adjunctive use of host modulators in non-surgical periodontal therapy. A systematic..., Donos [/bib_ref] Quality of evidence Seven placebo-controlled RCTs (n = 348), on local delivery of 1% alendronate gel (six studies) and 0.5% zolendronate gel (one study); two placebo-controlled RCTs (n = 90) on systemic administration of BPs (alendronic acid and risedronate).

## Supporting literature

## Grade of recommendation grade a-
Strength of consensus Strong consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
Bisphosphonates (BPs) are a class of antiresorptive agents that act mainly by inhibiting osteoclast activity. BPs can also directly inhibit host degradative enzymes like matrix metalloproteinases released by osteoclasts and other cells of the periodontium. There is also evidence that BPs reduce osteoblast apoptosis, thus increasing bone density as an overall therapeutic outcome. It is therefore rational to speculate that BPs may benefit the management of inflammationmediated alveolar bone resorption in periodontitis patients [bib_ref] Bisphosphonates in periodontal treatment: A review, Badran [/bib_ref].

## Available evidence
Seven placebo-controlled RCTs (n = 348), all from the same research group, on local delivery of 1% alendronate gel (six studies) and 0.5% zolendronate gel (one study) in infrabony or furcation Class II defects were identified.
A meta-analysis on PPD reduction at 6 months in five RCTs (n = 228) using either single or multiple sites per patient in infrabony defects was undertaken. Two placebo-controlled RCTs (n = 90) evaluated systemic administration of BPs (alendronate and risedronate).

## Risk of bias
Of the nine studies included, two were at high risk of bias and seven presented some concerns in at least one of the domains of the risk of bias assessment tool. One study was underpowered. All studies on local BPs were published by the same research group.
While pharmaceutical companies provided bisphosphonates for local application in the included studies, the level of involvement of industry in the analysis and interpretation of the results is unclear.

## Consistency

## Clinical relevance
The results of the two studies on systemic BPs were poorly comparable as they were undertaken in different populations and involved different confounding factors (e.g. smoking).
Although the mean estimates suggested adjunctive benefits from adjunctive use of BP gels, the combined use of studies considering single and multiple sites per patient in the meta-analysis should be taken into consideration.

## Balance of benefits and harm
Both systemic and local BPs were well-tolerated in the studies reported in the systematic review and were not associated with severe adverse reactions.

## Economic considerations
There is an additional cost associated with the use of bisphosphonates that is borne by the patient.

## Ethical and legal considerations
The balance of recognized potential severe risks (e.g. osteochemonecrosis of the jaws) versus benefits resulted in a consensus that systemic administration of BPs should not be recommended in the clinical management of periodontal bone loss. It is important to note that BP gel formulations are "off-label" and an approved formulation with appropriate quality control (GMP) and patient safety validation is not available.

## Applicability
The same research group/centre published all data on locally delivered BPs; therefore, the generalizability of the results requires substantiating in future larger (multicentre) RCTs, with multilevel analyses accounting for potential confounding factors (e.g. medical history, smoking history).

## R2.10 | does adjunctive use of systemic/local non-steroidal
anti-inflammatory drugs to subgingival instrumentation improve the clinical outcomes?

## Evidence-based recommendation (2.10)
We recommend not to use systemic or local non-steroidal anti-inflammatory drugs (NSAIDs) as an adjunct to subgingival instrumentation Supporting literature [bib_ref] The adjunctive use of host modulators in non-surgical periodontal therapy. A systematic..., Donos [/bib_ref] Quality of evidence Two placebo-controlled RCTs (n = 88) on local application (1% flurbiprofen toothpaste; irrigation with 200 ml buffered 0.3% acetylsalicylic acid); two placebo-controlled RCTs (n = 133) on systemic applications (celecoxib, diclofenac potassium)

## Grade of recommendation grade a-

# Strength of consensus

# Background

## Intervention
Periodontitis is an inflammatory disease in which altered immuneinflammatory responses to a dysbiotic biofilm drives connective tissue destruction and bone loss. It is reasonable therefore that nonsteroid anti-inflammatory drugs (NSAIDs), may be effective as adjunctive periodontal therapies.

## Available evidence
Two placebo-controlled RCTs (n = 88) on local application, one using 1% flurbiprofen toothpaste twice daily for 12 months and a second using subgingival daily irrigation with 200 ml buffered 0.3% acetylsalicylic acid, were identified. Two placebo-controlled RCTs (n = 133) on systemic applications, one RCT using systemic celecoxib (200 mg daily 6 months) and another using a cyclical regime of diclofenac potassium (50 mg 2-months, then 2 months off, then 2 months on), were included. All studies reported on PPD reduction at 6 months. No meta-analysis was performed due to the limited number of studies identified and their heterogeneity.

## Risk of bias
Two out of four studies were considered at high risk of bias. All studies on NSAIDs either did not provide information on sample size calculation or were underpowered. All studies declared industry funding.

## Consistency
It was not possible to undertake a meta-analysis of local or systemic NSAID administration as an adjunct to subgingival instrumentation because the studies were heterogeneous (not comparable) in terms of the medication employed and the modality of administration.

## Clinical relevance
Local NSAIDs did not enhance the clinical outcomes of subgingival instrumentation. Systemic NSAIDs exhibited limited clinical benefits, but their heterogeneity did not permit the drawing of clinically meaningful conclusions.

## Balance of benefits and harm
No serious adverse events were reported.

# Ethical considerations
Long-term use of systemic NSAIDs carries a well-known risk of unwanted side effects, which raises concerns over their use as adjuncts to subgingival instrumentation.

## Economic considerations
There would be a cost to using NSAIDs which would ultimately transfer to the patient.

## Evidence-based recommendation (2.11)
We recommend not to use omega3 PUFAs as an adjunct to subgingival instrumentation.

## Supporting literature donos et al. (2019)
Quality of evidence Three placebo-controlled RCTs (n = 160) with 6-month administration of omega-3 PUFAs.

## Grade of recommendation grade a-
Strength of consensus Consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
The recent discovery of pro-resolving lipid mediators by Serhan and colleagues [reviewed by [bib_ref] Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and..., Serhan [/bib_ref] ], some of which are produced by the metabolism of two major omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and
docosahexanoic acid (DHA) to E-and D-resolvins, respectively, raises the potential for essential dietary PUFAs as adjunctive hostmodulating therapeutics for non-surgical periodontal treatment.
However, few studies have investigated their efficacy in human trials.

## Available evidence
Three placebo-controlled RCTs (n = 160) with 6-month administration of omega-3 PUFAs. Heterogeneity in study designs precluded a meta-analysis. One RCT investigated low dose omega-3 PUFAs (6.25 mg eicosapentaenoic acid -EPA and 19.9mg docosahexaenoic acid -DHA) twice daily for 6 months; a second study employed high dose omega-3 PUFAs (3 g) in combination with 81 mg aspirin daily for 6 months; and a third study used 1 g omega-3 PUFAs twice daily for 6 months. All studies provided PPD reduction data at 6 months post-subgingival instrumentation. No meta-analysis was performed due to the limited number of studies identified and their heterogeneity.

## Risk of bias
One out of three studies was considered to be at high risk of bias.
One study reported industry support, one was supported by a University, and one did not disclose the funding source.

## Consistency
No meta-analysis could be performed due to the low number of available studies and study heterogeneity in terms of proposed regime and formulation.

## Clinical relevance
Since the three RCTs used different doses and preparations of omega-3 PUFAs and one out of three studies combined omega-3 with 81 mg aspirin, it was not possible to draw clinically meaningful conclusions from the data.

## Balance of benefits and harm
No adverse events were associated to the use of omega-3 PUFAs, and they are essentially a relatively safe dietary supplement.

## Economic considerations
There would be a cost to using omega-3 PUFAs which would ultimately transfer to the patient.

## Applicability
There is insufficient data to support or refute the use of omega-3
PUFAs, either as a monotherapy or as a combined therapeutic adjunct to subgingival instrumentation. The combination of omega-3 fatty acids and low-dose aspirin also warrants further assessment of its use as an adjunct in the management of periodontitis.

## R2.12 | does the adjunctive use of local metformin
improve the clinical outcome of subgingival instrumentation?

## Evidence-based recommendation (2.12)
We recommend not to use local administration of metformin gel as adjunct to subgingival instrumentation.

## Supporting literature donos et al. (2019)
Quality of evidence Six placebo-controlled RCTs (n = 313) on locally delivered 1% metformin gel

## Grade of recommendation grade a-
Strength of consensus Strong consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
Metformin is a second-generation biguanide used to manage type 2 diabetes mellitus. There is evidence suggesting that metformin decreases inflammation and oxidative stress and may also have an osteogenic effect by increasing the proliferation of osteoblasts and reducing osteoclast activity [bib_ref] Effects of metformin on inflammation, oxidative stress, and bone loss in a..., Araujo [/bib_ref]. It is therefore plausible that this medication may be beneficial in treating a chronic inflammatory disease like periodontitis.

## Available evidence
Six placebo-controlled RCTs (n = 313) from the same research group investigated locally delivered 1% metformin gel as an adjunct to subgingival instrumentation. All studies reported on PPD reduction at 6 months post-subgingival instrumentation, and a meta-analysis was undertaken combining the six RCTs.

## Risk of bias
Four out of six studies presented some concerns of risk of bias in most of the domains. All studies were published by the same research group. While pharmaceutical companies provided metformin, the level of involvement of industry in the analysis and interpretation of the results is unclear.

## Consistency
Meta-analysis of six studies (four considering single sites per patient and two considering multiple sites per patient) indicated that 1% metformin gel as adjunct to subgingival instrumentation led to an improved PPD reduction of 2.07 mm (95% CI [1.83; 2.31]) at 6 months. Heterogeneity between the studies was low (I 2 = 43%).

## Clinical relevance
All studies reported a benefit in terms of PPD reduction when 1% metformin gel was used as an adjunct to subgingival instrumentation. However, studies using single and multiple sites per patients were combined.

## Balance of benefits and harms
All studies included in the review reported that patients tolerated local metformin gel well, without any complications, adverse reactions/side-effects, or symptoms of hypersensitivity.

## Ethical and legal considerations
The metformin formulation included in the systematic review is "offlabel" and an approved formulation with appropriate quality control (GMP) and patient safety validation is not available.

## Economic considerations
There is an additional cost associated with the use of metformin that is borne by the patient.

## Applicability
The same research group published all data on local metformin; therefore, the generalizability of the results needs to be confirmed in future larger (multicentre) RCTs, with multi-level analyses accounting for potential confounding factors (e.g. medical history, smoking history).

## | intervention: use of adjunctive chemical agents to subgingival instrumentation

## R2.13 | does the adjunctive use of adjunctive

## Chemotherapeutics (antiseptics) improve the clinical outcome of subgingival instrumentation?

## Expert consensus-based recommendation (2.13)
Adjunctive antiseptics may be considered, specifically chlorhexidine mouth rinses for a limited period of time, in periodontitis therapy, as adjuncts to mechanical debridement, in specific cases.

# Background

## Intervention
In order to control gingival inflammation during periodontal therapy, the adjunctive use of some agents has been proposed. Chlorhexidine mouth rinses have been frequently tested in this indication and frequently used in different clinical settings.

## Available evidence
In the systematic reviews of the present European Workshop, the role of antiseptics in active periodontal therapy has not been directly addressed. However, some evidence is available based on studies on the role of chlorhexidine use after subgingival instrumentation (da [bib_ref] Chlorhexidine mouthwash as an adjunct to mechanical therapy in chronic periodontitis: A..., Da Costa [/bib_ref].
In addition, other factors should be considered:
- It is unclear whether this should be a general recommendation for initial therapy.
- It may be necessary to optimize mechanical plaque control before considering adjunctive chlorhexidine as an adjunct to subgingival instrumentation.
- Specific considerations can be made when used in conjunction with full-mouth disinfection approaches and/or with systemic antimicrobials.
- The medical status of the patient.
- Adverse effects (staining) and economical costs should be considered.

## | intervention: use of adjunctive locally administered antiseptics to subgingival instrumentation

## R2.14 | do adjunctive locally administered
antiseptics improve the clinical outcome of subgingival instrumentation?

## Evidence-based recommendation (2.14)
Locally administered sustained-release chlorhexidine as an adjunct to subgingival instrumentation in patients with periodontitis may be considered. [bib_ref] Adjunctive effect of locally delivered antimicrobials in periodontitis therapy: A systematic review..., Herrera [/bib_ref] Quality of evidence Nine RCTs, 6-9 months. 718/719 patients. High risk of bias and heterogeneity among studies.

## Supporting literature

## Grade of recommendation grade 0-
Strength of consensus Consensus (10.5% of the group abstained due to potential CoI)

# Background

## Intervention
There is insufficient evidence on the benefits of locally administered sustained-release antiseptics as an adjunct to subgingival debridement in patients with periodontitis.

## Available evidence
The systematic review revealed results from studies on products containing chlorhexidine (Periochip n = 9, Chlosite n = 2). One product (Periochip) demonstrated statistically significantly greater PPD reduction following single or multiple applications as an adjunct to subgingival debridement on short-term follow-up (6-9 months) (weighted mean difference (WMD) = 0.23, 95% CI [0.12; 0.34], p < .001 and significant heterogeneity). There are no long-term data available. No significant differences were found regarding CAL. Data on BOP were insufficient and no data on pocket closure or on number needed to treat (NNT) were provided.

## Risk of bias
High risk of bias and heterogeneity among studies.

## Clinical relevance and effect size
Effect size estimated for all PPD categories indicates an increased effect of about 10% in PPD reduction.

## Balance of benefit and harm
No increase in adverse effects or differences in patient-reported outcome measures (PROMs) were observed.

## Economic considerations
The cost for the product and the limited availability of products in European countries need to be considered.

## | intervention: use of adjunctive locally administered antibiotics to subgingival instrumentation

## R2.15 | do adjunctive locally administered antibiotics improve the clinical outcome of subgingival instrumentation?

## Evidence-based recommendation (2.15)
Specific locally administered sustained-release antibiotics as an adjunct to subgingival instrumentation in patients with periodontitis may be considered. [bib_ref] Adjunctive effect of locally delivered antimicrobials in periodontitis therapy: A systematic review..., Herrera [/bib_ref] Quality of evidence PPD reduction (6-9 months): Atridox n = 2, 19/19 patients; Ligosan: n = 3, 232/236 patients; Arestin: n = 6, 564/567 patients. High risk of bias and heterogeneity in the majority of studies.

## Supporting literature

## Grade of recommendation grade 0-
Strength of consensus Consensus (7.8% of the group abstained due to potential CoI)

# Background

## Available evidence
Of the products available on the European market, the systematic review revealed statistically significantly improved PPD reduction of locally applied antibiotics as an adjunct to subgingival debridement on short-term follow-up (6-9 months) for indicates an increased effect of 10%-30% in PPD reduction.

## Risk of bias
High risk of bias and heterogeneity in the majority of studies.

## Balance of benefit and harm
No increase in adverse effects or differences in PROMs were observed. Harm versus benefit considerations on the use of antibiotics need to be considered.

## Economic considerations
High economic costs and limited availability of products in European countries need to be considered.

## | intervention: use of adjunctive systemically administered antibiotics to subgingival instrumentation

## R2.16 | does adjunctive systemically administered
antibiotics improve the clinical outcome of subgingival instrumentation?

## Evidence-based recommendation (2.16)
A Due to concerns about patient's health and the impact of systemic antibiotic use to public health, its routine use as adjunct to subgingival debridement in patients with periodontitis is not recommended. B The adjunctive use of specific systemic antibiotics may be considered for specific patient categories (e.g. generalized periodontitis Stage III in young adults). [bib_ref] Adjunctive effect of systemic antimicrobials in periodontitis therapy. A systematic review and..., Teughels [/bib_ref] Quality of evidence RCTs (n = 28) with a double-blind, placebocontrolled, parallel design. Risk of bias was low for 20 of the studies, while seven studies had a high risk. PPD reduction at 6 months; MET + AMOX: n = 8, 867 patients. PPD reduction at 12 months; MET + AMOX: n = 7, 764 patients, MET: n = 2, 259 patients.

## Supporting literature

## Evidence-based recommendation (2.16) a grade of recommendation grade a- b grade of recommendation grade 0-
A Strength of consensus Consensus (0% of the group abstained due to potential CoI) B Strength of consensus Consensus (0% of the group abstained due to potential CoI)

# Background

## Available evidence
While the results from the meta-analysis (

## Risk of bias
Low risk of bias and low heterogeneity among studies.

## Consistency
High consistency of results.

## Clinical relevance and effect size
Effect size estimation on PPD reduction as opposed to subgingival debridement alone indicates an increased effect of about 40%-50%.

## Balance of benefit and harm
While the MET + AMOX combination had the most pronounced

## Applicability
Due to concerns to patient's health and the impact of systemic antibiotic use to public health, its routine use as adjunct to subgingival debridement in patients with periodontitis is not recommended.
Based on the available evidence, however, its adjunctive use may be considered for special patient categories (e.g. generalized periodontitis Stage III in young adults).

## | clinic al recommendations: third s tep of ther apy

## | intervention: access flap procedures
The first relevant question to evaluate the relative efficacy of the surgical interventions in the third step of therapy, for the treatment of Stage III periodontitis patients with residual pockets after the second step of periodontal therapy, is whether access flap procedures are more efficacious than subgingival re-debridement for achieving the endpoints of therapy [probing depth (PD) 4 mm without BOP].

## R3.1 | how effective are access flaps as compared to
repeated subgingival instrumentation?

## Evidence-based recommendation (3.1)
In the presence of deep residual pockets (PPD  6 mm) in patients with Stage III periodontitis after the first and second steps of periodontal therapy, we suggest performing access flap surgery.
In the presence of moderately deep residual pockets (4-5 mm), we suggest repeating subgingival instrumentation. [bib_ref] Efficacy of access flap procedures compared to subgingival debridement in the treatment..., Sanz-Sanchez [/bib_ref] Quality of evidence Thirteen RCTs (500 patients) with moderate-tohigh risk of bias. Five studies were restricted to pockets associated with intrabony defects. Limited number of studies presented data for quantitative analyses. High consistency of results. - open flap debridement with intra-sulcular incisions (OFD);

## Supporting literature

## Grade of recommendation grade b-

# Strength of consensus
- flaps with para-marginal incisions, such as modified Widman flap (MWF) and
- papilla preservation flaps.

## R3.2 | how effective are the different access flap
procedures?

## Evidence-based recommendation (3.2)
In cases of deep (PPD  6 mm) residual pockets and intrabony defects in patients with Stage III periodontitis after adequate first and second steps of periodontal therapy, there is insufficient evidence for a recommendation on the choice of flap procedures. Access periodontal surgery can be carried out using different flap designs. [bib_ref] Efficacy of access flap procedures compared to subgingival debridement in the treatment..., Sanz-Sanchez [/bib_ref] Quality of evidence Three RCTs compared MWF with OFD. One RCT compared the efficacy of papilla preservation flaps (single flap approach versus OFD) in the presence of intrabony pockets. Two RCTs compared minimally invasive surgery with conventional surgery. Moderate to high risk of bias. Limited available data.

## Supporting literature

## Grade of recommendation grade 0-

# Strength of consensus
Consensus (0% of the group abstained due to potential CoI)

# Background

## Available evidence
Out of three available studies comparing MWF with OFD, only one showed statistically significantly greater PPD reduction for MWF than OFD. There were no statistically significant differences in % PPD reduction in deep infrabony pockets between papilla preservation flap (single flap approach) and conventional flaps (one study). Two studies comparing minimally invasive surgery with conventional surgery did not demonstrate a significant added value in PPD reduction or CAL gain.

## | intervention: resective flap procedures
The third relevant question was whether resective flap procedures (those that, in addition to gaining access for subgingival debridement, aim to change the architecture of the hard and/or the soft tissues to attain shallow probing depths) are more efficacious than conservative surgical procedures in achieving the endpoints of periodontal in the treatment of patients with Stage III periodontitis.

## R3.3 | what is the efficacy of pocket elimination/reduction surgery in comparison with access flap surgery?

## Evidence-based recommendation (3.3)
In cases of deep (PPD  6 mm) residual pockets in patients with Stage III periodontitis after an adequate second step of periodontal therapy, we suggest using resective periodontal surgery, yet considering the potential increase of gingival recession. [bib_ref] The efficacy of pocket elimination/reduction compared to access flap surgery: A systematic..., Polak [/bib_ref] Quality of evidence Nine RCTs (four could be used for the quantitative analysis). High risk of bias. Limited available data.

## Supporting literature

## Grade of recommendation grade b-

# Strength of consensus
Simple majority (2.6% of the group abstained due to potential CoI)

# Background

## Available evidence
Resective periodontal surgery attained statistically significantly higher

## Risk of bias
High risk of bias, scarcity of quantitative data (only 4 RCTs).

## Clinical relevance and effect size
The paucity of the data on percentage of shallow pockets or incidence of re-treatment prevents assessments of the clinical relevance of the differences.

## Balance of benefit and harm
Data on PROMs, the percentage of residual pockets or the need of re-treatment were not reported in any of the studies.

## | general recommendations for periodontal surgical procedures

## R3.4 | what is the level of care required for management of deep residual pockets with or without presence of intrabony defects or furcation involvement after completion of steps
1 and 2 of periodontal therapy?

## Expert consensus-based recommendation (3.4)
Surgical treatment is effective but frequently complex, and we recommend that it is provided by dentists with additional specific training or by specialists in referral centres. We recommend efforts to improve access to this level of care for these patients.

## Supporting literature expert opinion

## Grade of recommendation grade a-
Strength of consensus Consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
Advanced periodontal surgery (regenerative and furcation management) is beyond the scope and competence of education in general dental practice [bib_ref] Scope, competences, learning outcomes and methods of periodontal education within the undergraduate..., Sanz [/bib_ref]. Dental curricula include knowledge and familiarity with the approach but are not designed to provide competence to conduct such treatment:
Additional specific training is required and is available through continuing professional development and periodontal learned societies in most countries. Post-graduate periodontal education, on the other hand, is specifically designed to provide competence and proficiency towards the resolution of such complex problems [bib_ref] Periodontology as a recognized dental speciality in Europe, Sanz [/bib_ref] Velden & Sanz, 2010).

## R3.5 | if expertise is not available or referral is not an
option, what is the minimum level of primary care required for management of residual pockets associated with or without intrabony defects or furcation involvement after completion of steps 1 and 2 of periodontal therapy?

## Expert consensus-based recommendation (3.5)
As a minimum requirement, we recommend repeated scaling and root debridement with or without access flap of the area in the context of high-quality step 1 and 2 treatment and a frequent program of supportive periodontal care including subgingival instrumentation.
Supporting literature Expert opinion [and systematic reviews for access flaps [bib_ref] Clinical performance of access flap surgery in the treatment of the intrabony..., Graziani [/bib_ref] ]

## Grade of recommendation grade a-

## Expert consensus-based recommendation (3.5)
Strength of consensus Consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
Dental services are organized differently in various countries.
Some are structured in both primary care and specialist care (usually delivered by referral to dental hospitals or specialist practices/centres); in other countries, dental services are based on a single level of care and interested general practitioners acquire broader periodontal skills through continuing professional development. Optimal management of Stage III and Stage IV periodontitis remains limited in most health systems with significant inequalities in availability and access to advanced/specialist periodontal care. There is an urgent need to improve patient access to the appropriate level of care given the high burden and costs associated with the sequelae of unmanaged severe (stages III and IV) periodontitis.

## R3.6 | what is the importance of adequate selfperformed oral hygiene in the context of surgical periodontal treatment?

## Expert consensus-based recommendation (3.6)
We recommend not to perform periodontal (including implant) surgery in patients not achieving and maintaining adequate levels of self-performed oral hygiene.

## Supporting literature expert opinion

## Grade of recommendation grade a-
Strength of consensus Strong consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
Proof-of-principle studies conducted in the 1970s have pointed to the negative effects (clinical attachment loss) of performing periodontal surgery in subjects with inadequate plaque control [bib_ref] Periodontal surgery in plaque-infected dentitions, Nyman [/bib_ref] [bib_ref] The healing potential of the periodontal tissues following different techniques of periodontal..., Rosling [/bib_ref] 

## Evidence-based recommendation (3.7)
We recommend treating teeth with residual deep pockets associated with intrabony defects 3 mm or deeper with periodontal regenerative surgery. Quality of evidence Twenty-two RCTs (1,182 teeth in 1,000 patients)-four studies at low risk of bias-there is consistency of direction of benefit but high heterogeneity for superiority of regeneration over open flap debridement.

## Supporting literature

## Grade of recommendation grade a-
Strength of consensus Consensus (10% of the group abstained due to potential CoI)

# Background
Intervention See previous sections. An algorithm for clinical decision-making in the treatment by regenerative surgical therapy of intrabony defects and residual pockets is depicted in .

## Available evidence
The evidence base includes 22 RCTs with 1,000 patients. The quality of the evidence was rated as high.

## Risk of bias

## Balance of benefit and harm
No serious adverse event was reported in any of the studies included in the systematic review. The adverse events associated with regenerative therapy included local adverse events (wound failure) and post-operative morbidity. No specific harm has been reported after regenerative surgery. Potential risk for disease transmission from well-documented human-derived or animal-derived regenerative biomaterials is considered extremely low.

# Ethical considerations
The perception that regenerative treatment of deep intrabony de-

## Regulatory consideration
It is important to emphasise that only few classes of regenerative materials are registered in Europe. In each class, only few materials satisfy the evidence base criteria set forth by these guidelines and the considerations should not be applied to materials that have not been adequately tested. Implementation of the new EU medical device regulations will prove useful.

## Economic considerations
Regenerative surgery is more expensive than access flap surgery but cheaper than tooth replacement necessary as a consequence of tooth loss. In the absence of health-economic data in RCTs included in the review, a pilot study has indicated that the initial increase in cost of regeneration is associated with lower cost of managing recurrence over a 20-year period [bib_ref] Periodontal regeneration compared with access flap surgery in human intra-bony defects 20-year..., Cortellini [/bib_ref].

## Patient preferences
No data are available about patient preference or acceptability.
Religious issues may be present for segments of the population since some of the regenerative materials are of porcine or bovine origin.
While the use for medical reasons is generally acceptable and has been approved by religious leaders, the sensitivity of individual subjects may pose a barrier.

## R3.8 | what is the adequate choice of regenerative
biomaterials for promoting healing of residual deep pockets associated with a deep intrabony defect?

## Evidence-based recommendation (3.8)
In regenerative therapy, we recommend the use of either barrier membranes or enamel matrix derivative with or without the addition of bone-derived grafts* Supporting literature Quality of evidence Twenty RCTs (972 patients)-four studies at low risk of bias-moderate-to-high heterogeneity for superiority of these biomaterials

## Grade of recommendation grade a-
Strength of consensus Consensus (18.1% of the group abstained due to potential CoI) * Clinicians should select a specific biomaterial to be used to promote regeneration at intrabony defects (or Class II furcation involvements) based on satisfaction of all of the following criteria (Proceedings of the, 1996 World Workshop in Periodontics, 1996): (a) availability of solid preclinical research identifying plausible mechanism(s) of action leading to periodontal regeneration; (b) human histological evidence of regeneration in the specific application; and (c) evidence of efficacy in applicable, high-quality randomized controlled clinical trials. While there are biomaterials that satisfy all these criteria, it must be understood that many biomaterials do not meet them in spite of being CE ("Conformite Europeene") marked or Food and Drug Administration (FDA)-approved/cleared.

# Background

## Intervention
See previous sections.

## Available evidence
The evidence base includes 20 RCTs with 972 patients. The quality of the evidence was considered to be high.

## Risk of bias
Study quality assessment identified four studies at low risk of bias and 15 studies at unclear risk of bias.

## Consistency

## Clinical relevance and effect size
The mean adjunctive benefit in term of CAL gain was 1.

## R3.9 | what is the adequate choice of surgical flap design
for the regenerative treatment of residual deep pockets associated with an intrabony defect?

## Evidence-based recommendation (3.9)
We recommend the use of specific flap designs with maximum preservation of interdental soft tissue such as papilla preservation flaps. Under some specific circumstances, we also recommend limiting flap elevation to optimize wound stability and reduce morbidity. [bib_ref] Clinical performance of access flap surgery in the treatment of the intrabony..., Graziani [/bib_ref] ; Quality of evidence Ancillary evidence arising from systematic reviews and expert opinion.

## Supporting literature

## Grade of recommendation grade a-
Strength of consensus Consensus (2.8% of the group abstained due to potential CoI)

# Background
Intervention See previous sections.

## Available evidence
The evidence base includes two systematic reviews.

## Risk of bias
Study quality assessment identified five studies at low risk of bias and 15 studies at unclear risk of bias.

## Consistency
No conclusion can be drawn.

## Clinical relevance and effect size
Papilla preservation flaps have been shown to lead to increased CAL gain and PD reduction as well as reduced post-surgical recession compared with OFD.

## Balance of benefit and harm
No serious adverse event has been reported after application of papilla preservation flaps in regenerative periodontal surgery performed by adequately trained clinicians. The added complexity of the surgery requires additional training.

## Applicability
Anatomical considerations related to the width of the interdental space advise on the choice of the preferred flap design to access the interdental area [bib_ref] The modified papilla preservation technique. A new surgical approach for interproximal regenerative..., Cortellini [/bib_ref] [bib_ref] A minimally invasive surgical approach for periodontal regeneration: Surgical technique and observations, Harrel [/bib_ref]. Location and configuration of the intrabony defect advise on the possibility to (a) minimize flap extension [bib_ref] A minimally invasive surgical technique with an enamel matrix derivative in the..., Cortellini [/bib_ref] [bib_ref] A minimally invasive surgical approach for periodontal regeneration: Surgical technique and observations, Harrel [/bib_ref] , and (b) raise a single flap or the need to fully elevate the interdental papilla [bib_ref] Improved wound stability with a modified minimally invasive surgical technique in the..., Cortellini [/bib_ref] [bib_ref] Singleflap approach with buccal access in periodontal reconstructive procedures, Trombelli [/bib_ref].

## | intervention: management of furcation lesions

## R3.10 | what is the adequate management of molars with
Class II and III furcation involvement and residual pockets?

## Evidence-based recommendation and statement (3.10)
A We recommend that molars with Class II and III furcation involvement and residual pockets receive periodontal therapy. B Furcation involvement is no reason for extraction.

## Supporting literature

## Available evidence
The evidence base includes 20 RTCs with 575 patients (Class II buccal/lingual mandibular and maxillary buccal furcation involvement) and seven observational studies with 665 patients (Class II interproximal and Class III). Previous systematic reviews have addressed the clinical performance of periodontal therapy of teeth with furcation involvement [bib_ref] The effect of periodontal therapy on the survival rate and incidence of..., Huynh-Ba [/bib_ref] [bib_ref] Tooth loss in molars with and without furcation involvement -A systematic review..., Nibali [/bib_ref].

## Risk of bias
High quality of evidence of RCTs. Low quality of evidence for observational studies.

## Consistency
Following treatment, moderate to substantial heterogeneity in the size of the effect (wide ranges of tooth survival) was observed. The reasons cannot be determined from the existing data.

## Clinical relevance and effect size
Following treatment, reasonable survival rates were observed over 4-30.8 years. Overall, the observed tooth survival rates were better in Class II furcation involvement than Class III.

## Balance of benefit and harm
We did not identify data about harm directly related to procedures.

## Economic considerations
Simulations based on the German health system have indicated that tooth retention after complex periodontal therapy of teeth with furcation involvement is more cost-effective than their extraction and replacement with an implant supported fixed partial denture [bib_ref] Retaining or replacing molars with furcation involvement: A cost-effectiveness comparison of different..., Schwendicke [/bib_ref]. A study assessing the actual cost of retention of molars in the same health system showed that cost for retaining periodontally compromised molars were minimal [bib_ref] Retention costs of periodontally compromised molars in a German population, Schwendicke [/bib_ref].

## Patient preferences
There is a strong patient preference for tooth retention .

## Applicability
The guideline can be applied since it is independent of availability of materials and a segment of the dental workforce has been trained or can be trained to deliver surgical furcation treatment in the different European health systems.

## R3.11 | what is the adequate management of residual deep pockets associated with mandibular class ii furcation involvement?

## Evidence-based recommendation (3.11)
We recommend treating mandibular molars with residual pockets associated with Class II furcation involvement with periodontal regenerative surgery.

## Supporting literature jepsen et al. (2019)
Quality of evidence 17 RCTs 12 months (493 patients).

## Grade of recommendation grade a-
Strength of consensus Consensus (7.6% of the group abstained due to potential CoI)

# Background

## Intervention
See previous sections.

## Available evidence
The evidence base includes 17 RCTs with 493 patients. The quality of the evidence for the statement was assessed according to GRADE and considered to be high. In the systematic review underlying this recommendation , a standard meta-analysis grouping all regenerative techniques versus OFD was performed altogether with ancillary analysis. Results indicated that regenerative therapies had a significant benefit over OFD in terms of both primary and surrogate outcomes.

## Risk of bias
Study quality assessment identified an unclear risk of bias for the majority of the studies. Bearing in mind that six papers failed to disclose support and seven papers reported industry funding for the research.

## Consistency
Regenerative treatment consistently demonstrated added benefits (in terms of furcation improvement, horizontal bone gain, horizontal and vertical attachment gain, pocket reduction) in comparison with OFD.

## Clinical relevance and effect size
The mean adjunctive benefit of a regenerative treatment is clinically relevant (1.3 mm vertical CAL and greater PPD reduction), and the effect size is significant as furcation improvement showed an odds ratio (OR) of 21 (Bayesian credible interval 5.8-69.4) in favour of regenerative techniques.

## Balance of benefit and harm
The benefit of regenerative therapies to promote tooth retention outweighs the adverse events which consist mainly of local wound failure.

## F i g u r e 1 regenerative surgical therapy of intrabony defects and residual pockets [colour figure can be viewed at wileyonlinelibrary.com]

# Ethical considerations
The perception is that regenerative therapies to promote tooth retention are preferred over tooth extraction or open flap debridement.

## Regulatory consideration
All the studies reported FDA-or CE-approved devices.

## Economic considerations
Regenerative surgery has additional costs, which appear to be justified by the added benefits (furcation improvements).

## Patient preferences
Minimal data are available.

## Applicability
Teeth presenting with favourable patient, tooth and defect-related conditions.

## R3.12 | what is the adequate management of residual deep
pockets associated with maxillary buccal Class II furcation involvement?

## Evidence-based recommendation (3.12)
We suggest treating molars with residual pockets associated with maxillary buccal Class II furcation involvement with periodontal regenerative surgery.

## Supporting literature jepsen et al. (2019)
Quality of evidence Three RCTs 12 months (82 patients).

## Grade of recommendation grade b-
Strength of consensus Consensus (8.5% of the group abstained due to potential CoI)

# Background
Intervention See previous sections.

## Available evidence
The evidence base includes three RCTs with 82 patients [bib_ref] Comparison of a bioabsorbable GTR barrier to a non-absorbable barrier in treating..., Garrett [/bib_ref] [bib_ref] Treatment of class II furcation involvements in humans with bioresorbable and nonresorbable..., Hugoson [/bib_ref] [bib_ref] The response of human buccal maxillary furcation defects to combined regenerative techniques-two..., De Santana [/bib_ref]. The quality of the evidence for the statement was assessed according to GRADE and considered to be moderate. Of these studies only one [bib_ref] The response of human buccal maxillary furcation defects to combined regenerative techniques-two..., De Santana [/bib_ref] had a clear comparison towards OFD indicating an added benefit.

## Risk of bias
Study quality assessment identified an unclear/high risk of bias.

## Consistency
Regenerative treatment demonstrated added benefits.

## Clinical relevance and effect size
It cannot be extrapolated.

## Balance of benefit and harm
The benefit of regenerative therapies to promote tooth retention outweighs the adverse events which consist mainly of local wound failure.

# Ethical considerations
The expert perception is that regenerative therapies to promote tooth retention are preferred over tooth extraction or open flap debridement.

## Regulatory consideration
All the studies reported FDA-or CE-approved devices.

## Economic considerations
Regenerative surgery has additional costs which appear to be justified by the added benefits (furcation improvements).

## Patient preferences
No data are reported.

## Applicability
Teeth presenting with favourable patient, tooth and defect-related conditions.

## R3.13 | what is the adequate choice of regenerative
biomaterials for the regenerative treatment of residual deep pockets associated with Class II mandibular and maxillary buccal furcation involvement?

## Evidence-based recommendation (3.13)
We recommend treating molars with residual pockets associated with mandibular and maxillary buccal Class II furcation involvement with periodontal regenerative therapy using enamel matrix derivative alone or bone-derived graft with or without resorbable membranes* [bib_ref] Regenerative surgical treatment of furcation defects: A systematic review and Bayesian network..., Jepsen [/bib_ref] Quality of evidence Seventeen RCTs 12 months (493 patients) for mandibular class II, 3 RCTs 12 months (82 patients) for maxillary buccal Class II, and support from indirect evidence, expert opinion.

## Supporting literature

## Grade of recommendation grade a-
Strength of consensus Simple majority (12.7% of the group abstained due to potential CoI) *Clinicians should select a specific biomaterial to be used to promote regeneration at intrabony defects (or class II furcation involvements) based on satisfaction of all of the following criteria (Proceedings of the, 1996 World Workshop in Periodontics, 1996): (a) availability of solid preclinical research identifying plausible mechanism(s) of action leading to periodontal regeneration; (b) human histological evidence of regeneration in the specific application; and (c) evidence of efficacy in applicable, high-quality randomized controlled clinical trials. While there are biomaterials that satisfy all these criteria, it must be understood that many biomaterials do not meet them in spite of being CE marked or FDA-approved/cleared.

# Background

## Intervention
See previous sections.

## Available evidence
The evidence base includes 17 RCTs with 493 patients for mandibular Class II and three RCTs with 82 patients for maxillary buccal Class II. The quality of the evidence for the statement was assessed according to GRADE and considered to be high/moderate. In the systematic review underlying this recommendation , a Bayesian network meta-analysis was performed to assess which treatment modalities demonstrated the highest likelihood of success. For the outcome such as HBL, the highest-ranked groups were bone replacement graft, GTR with a bone replacement graft or enamel matrix derivative.

## F i g u r e 2 periodontal surgery: molars with furcation involvement (classes ii and iii) and residual pockets [colour figure can be viewed at wileyonlinelibrary.com]

## Risk of bias
Study quality assessment identified an unclear risk of bias for the majority of the studies. There is a mix of researcher and industryinitiated studies.

## Consistency
The procedures with the highest ranking for horizontal bone gain are bone-replacement graft, bone-replacement graft with resorbable membranes or enamel matrix derivative.

## Clinical relevance and effect size
It cannot be extrapolated among the therapies.

## Balance of benefit and harm
The benefit of regenerative therapies to promote tooth retention outweighs the adverse events which consist mainly of local wound failure.

# Ethical considerations
The perception is that regenerative therapies to promote tooth retention are preferred over tooth extraction and open flap debridement.

## Regulatory consideration
All the studies reported FDA-or CE-approved devices.

## Economic considerations
Regenerative surgery has additional costs, which appear to be justified by the added benefits (furcation improvements).

## Patient preferences
Enamel matrix derivative showed less postoperative swelling and pain than non-resorbable membranes.

## Applicability
Teeth presenting with favourable patient, tooth and defect-related conditions.

## R3.14 | what is the adequate management of maxillary interdental class ii furcation involvement?
Evidence-based recommendation (3.14)
In maxillary interdental Class II furcation involvement non-surgical instrumentation, OFD, periodontal regeneration, root separation or root resection may be considered. [bib_ref] Resective surgery for the treatment of furcation involvement: A systematic review, Dommisch [/bib_ref] [bib_ref] The effect of periodontal therapy on the survival rate and incidence of..., Huynh-Ba [/bib_ref] [bib_ref] What is the effect of guided tissue regeneration compared with surgical debridement..., Jepsen [/bib_ref] Quality of evidence Six observational studies (633 patients) with low quality of evidence for non-regenerative approaches and two systematic reviews with low quality of evidence for regenerative treatment.

## Supporting literature

## Grade of recommendation grade 0-

## Evidence-based recommendation (3.14)
Strength of consensus Consensus (4.3% of the group abstained due to potential CoI)

# Background
Intervention See previous sections.

## Available evidence
Six observational studies with 633 patients (Class II interproximal).

## Risk of bias
Low quality of evidence for observational studies.

## Consistency
Following non-regenerative treatment of maxillary interproximal Class II furcation involvement, moderate to substantial heterogeneity in the size of the effect (wide ranges of tooth survival) was observed. The reasons cannot be determined from the existing data.

## Clinical relevance and effect size
Following non-regenerative treatment of maxillary interproximal Class II furcation involvement, reasonable survival rates were observed over 4-30.8 years.

## Balance of benefit and harm
We did not identify data about harm directly related to procedures.
Regarding tooth survival, a benefit of root amputation/resection, root separation or tunnelling compared to SRP or OFD cannot be currently stated. For the individual choice of procedure, however, the clinician should consider criteria beyond class of furcation involvement (e.g. bone loss, jaw).

## Economic considerations
Simulations based on the German health system have indicated that tooth retention after complex periodontal therapy of teeth with furcation involvement is more cost-effective than their extraction and replacement with an implant supported fixed partial denture [bib_ref] Retaining or replacing molars with furcation involvement: A cost-effectiveness comparison of different..., Schwendicke [/bib_ref]. A study assessing the actual cost of retention of molars in the same health system showed that cost for retaining periodontally compromised molars were minimal [bib_ref] Retention costs of periodontally compromised molars in a German population, Schwendicke [/bib_ref].

## Patient preferences
There is a strong patient preference for tooth retention .

## Applicability
The guideline can be applied since it is independent of availability of materials and a segment of the dental workforce has been trained or can be trained to deliver surgical furcation treatment in the different European health systems.

## R3.15 | what is the adequate management of maxillary class
III furcation involvement?

## Evidence-based recommendation (3.15)
In maxillary Class III and multiple Class II furcation involvement in the same tooth nonsurgical instrumentation, OFD, tunneling, root separation or root resection may be considered. [bib_ref] Resective surgery for the treatment of furcation involvement: A systematic review, Dommisch [/bib_ref] Quality of evidence Six observational studies (633 patients) with low quality of evidence.

## Supporting literature

## Grade of recommendation grade 0-

# Strength of consensus
Strong consensus (0% of the group abstained due to potential CoI)

# Background
Intervention See previous sections.

## Available evidence
Six observational studies with 633 patients.

## Risk of bias
Low quality of evidence for observational studies.

## Consistency
Following treatment of maxillary Class III furcation involvement, moderate to substantial heterogeneity in the size of the effect (wide ranges of tooth survival) was observed. The reasons cannot be determined from the existing data.

## Clinical relevance and effect size
Following treatment of maxillary Class III furcation involvement, reasonable survival rates were observed over 4-30.8 years.

## Balance of benefit and harm
We did not identify data about harm directly related to procedures.
Regarding tooth survival, a benefit of root amputation/resection, root separation or tunnelling compared to SRP or OFD cannot be currently stated. For the individual choice of procedure, however, the clinician should consider criteria beyond class of furcation involvement (e.g. bone loss, jaw).

## Economic considerations
Simulations based on the German health system have indicated that tooth retention after complex periodontal therapy of teeth with furcation involvement is more cost-effective than their extraction and replacement with an implant supported fixed partial denture [bib_ref] Retaining or replacing molars with furcation involvement: A cost-effectiveness comparison of different..., Schwendicke [/bib_ref]. A study assessing the actual cost of retention of molars in the same health system showed that cost for retaining periodontally compromised molars were minimal [bib_ref] Retention costs of periodontally compromised molars in a German population, Schwendicke [/bib_ref].

## Patient preferences
There is a strong patient preference for tooth retention .

## Applicability
The guideline can be applied since it is independent of availability of materials and a segment of the dental workforce has been trained or can be trained to deliver resective treatment in the different European health systems.

## R3.16 | what is the adequate management of mandibular
Class III furcation involvement?

## Evidence-based recommendation (3.16)
In mandibular Class III and multiple Class II furcation involvement in the same tooth nonsurgical instrumentation, OFD, tunneling, root separation or root resection may be considered. [bib_ref] Resective surgery for the treatment of furcation involvement: A systematic review, Dommisch [/bib_ref] Quality of evidence Seven observational studies (665 patients) with low quality of evidence.

## Supporting literature

## Grade of recommendation grade 0-

# Strength of consensus
Unanimous consensus (0% of the group abstained due to potential CoI)

# Background
Intervention See previous sections.

## Available evidence
Seven observational studies with 665 patients (with mandibular class III furcation).

## Risk of bias
Low quality of evidence for observational studies.

## Consistency
Following treatment mandibular Class III furcation involvement, moderate to substantial heterogeneity in the size of the effect (wide ranges of tooth survival) was observed. The reasons cannot be determined from the existing data.

## Clinical relevance and effect size
Following treatment of mandibular Class III furcation involvement, reasonable survival rates were observed over 4-30.8 years.

## Balance of benefit and harm
We did not identify data about harm directly related to procedures.
Regarding tooth survival a benefit of root amputation/resection, root separation or tunnelling compared to SRP or OFD cannot be currently stated. For the individual choice of procedure, however, the clinician should consider criteria beyond class of furcation involvement (e.g. bone loss, jaw).

## Economic considerations
Simulations based on the German health system have indicated that tooth retention after complex periodontal therapy of teeth with furcation involvement is more cost-effective than their extraction and replacement with an implant supported fixed partial denture [bib_ref] Retaining or replacing molars with furcation involvement: A cost-effectiveness comparison of different..., Schwendicke [/bib_ref]. A study assessing the actual cost of retention of molars in the same health system showed that cost for retaining periodontally compromised molars were minimal [bib_ref] Retention costs of periodontally compromised molars in a German population, Schwendicke [/bib_ref].

## Patient preferences
There is a strong patient preference for tooth retention .

## Applicability
The guideline can be applied since it is independent of availability of materials and a segment of the dental workforce has been trained or can be trained to deliver resective treatment in the different European health systems.

## | clinic al recommendations: supp ortive periodontal c are
Following completion of active periodontal therapy, successfully treated periodontitis patients may fall in one of two diagnostic categories: periodontitis patients with a reduced but healthy periodontium or periodontitis patients with gingival inflammation [bib_ref] Periodontal health and gingival diseases and conditions on an intact and a..., Chapple [/bib_ref] We recommend that supportive periodontal care visits should be scheduled at intervals of 3 to a maximum of 12 months and ought to be tailored according to patient's risk profile and periodontal conditions after active therapy.

## Supporting literature

## Grade of recommendation grade a-
Strength of consensus Strong consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
Although not addressed directly in the systematic reviews underlying this guideline, different evidence supports the concept of defined intervals to perform SPC visit every 3-4 months are recommended in studies selected by [bib_ref] Efficacy of alternative or additional methods to professional mechanical plaque removal during..., Trombelli [/bib_ref].
- SPC every 3 months may be sufficient to control periodontitis progression after periodontal surgery [bib_ref] The efficacy of pocket elimination/reduction compared to access flap surgery: A systematic..., Polak [/bib_ref].

## - in addition, the conclusions of the 2014 european workshop on
Prevention, based on the review by [bib_ref] Effect of professional mechanical plaque removal performed on a long-term, routine basis..., Trombelli [/bib_ref] , concluded that the recommended interval ranges 2-4 times per year and that it could be optimized if it is tailored according to patient's risk .
- A recent study [bib_ref] Time between recall visits and residual probing depths predict long-term stability in..., Ramseier [/bib_ref] , over 883 patients, reflected on the importance of SPC and the factors involved in its success.

## R4.2 | is adherence to supportive periodontal care
important?

## Expert consensus-based recommendation (4.2)
We recommend that adherence to supportive periodontal care should be strongly promoted, since it is crucial for long-term periodontal stability and potential further improvements in periodontal status.
Supporting literature [bib_ref] Tooth loss in individuals under periodontal maintenance therapy: 5-year prospective study, Costa [/bib_ref] , [bib_ref] Effect of professional mechanical plaque removal on secondary prevention of periodontitis and..., Sanz [/bib_ref] , [bib_ref] Effect of professional mechanical plaque removal performed on a long-term, routine basis..., Trombelli [/bib_ref] Grade of recommendation Grade A-

## Expert consensus-based recommendation (4.2)
Strength of consensus Unanimous consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
Although not addressed directly in the systematic reviews underlying this guideline, different evidence supports the importance of complying with SPC visit, in which PMPR is performed:
- Greater rates of tooth loss and disease progression in patients with irregular compliance, versus patients with regular compliance [bib_ref] Tooth loss in individuals under periodontal maintenance therapy: 5-year prospective study, Costa [/bib_ref].
- The conclusions of the 2014 European Workshop on Prevention, based on the review by [bib_ref] Effect of professional mechanical plaque removal performed on a long-term, routine basis..., Trombelli [/bib_ref] , concluded that compliance with the preventive professional intervention is crucial, based also on retrospective observational studies .

## | intervention: supragingival dental biofilm control (by the patient)

## R4.3 | are oral hygiene instructions important? how
should they be performed?

## Expert consensus-based recommendation (4.3)
We recommend repeated individually tailored instructions in mechanical oral hygiene, including interdental cleaning, in order to control inflammation and avoid potential damage for patients in periodontal SPC. [bib_ref] Mechanical plaque removal of periodontal maintenance patients: A systematic review and network..., Slot [/bib_ref] 

## Supporting literature

## Grade of recommendation grade a-
Strength of consensus Unanimous consensus (0% of the group abstained due to potential CoI)

# Background
Intervention All surfaces exposed to the formation of intraoral biofilm have to be cleaned mechanically. Some of them will not be reached by toothbrushes even under optimized conditions. Interproximal cleaning therefore is essential in order to maintain interproximal gingival health, in particular for secondary prevention. It may be achieved using different devices, primarily inter-dental brushes (IDB, which are not single-tufted brushes), rubber/elastomeric cleaning sticks, wood sticks, oral irrigators and floss. However, all devices have the potential of side effects and their use has to be monitored not only with respect to efficacy but also with respect to early signs of trauma (e.g. onset of non-carious cervical lesions).

## Available evidence
Due to the scarcity of studies that met the inclusion criteria for each of the oral hygiene devices and the low certainty of the resultant evidence, no strong "evidence based" conclusion can be drawn concerning any specific oral hygiene device for patient self-care in periodontal maintenance. The evidence that emerged from the search provided 16 papers reporting on 13 CCTs/RCTs, which included 17 comparisons. The differences of powered versus manual toothbrushes were evaluated in five comparisons, an interdental device was used as an adjunct to toothbrushing in five comparisons, and seven comparisons evaluated two different interdental devices. In total, the studies evaluated 607 patients.

## Risk of bias
Study quality assessment identified one study at low risk of bias and 10 studies at high risk and two of an unclear risk of bias.

## Consistency
The summary of findings table shows that the body of evidence is rather consistent.

## Clinical relevance and effect size
Variable, depending on the comparisons established.

## Balance of benefit and harm
The adverse events were not evaluated. There is a moderate risk of trauma due to the use of interdental cleaning devices, when not used properly. Therefore, individual instruction and adoption to the individual situation by professionals are crucial. In any case, the benefits overweigh the risks by far.

## Economic considerations
A manual toothbrush is less expensive than a power toothbrush.
Interdental brushes and oral irrigators are more expensive than dental floss, wood sticks and rubber and silicon interdental bristle cleaners.

## Patient preferences
No data on patient preference arrive from the current review.

## Applicability
The guideline can be applied to patients attending a periodontal maintenance program. There is an abundance of mechanical oral hygiene products available.

## R4.4 | how should we choose an appropriate design of manual, powered toothbrushes and interdental cleaning
devices?

## Expert consensus-based recommendation (4.4)
We recommend taking into account patients' needs and preferences when choosing a toothbrush design, and when choosing an interdental brush design.

## Expert consensus-based recommendation (4.4)
Supporting literature [bib_ref] Mechanical plaque removal of periodontal maintenance patients: A systematic review and network..., Slot [/bib_ref] 

## Grade of recommendation grade a-
Strength of consensus Strong consensus (6.9% of the group abstained due to potential CoI)

# Background
Intervention See previous section.

## Available evidence
Scarcity or a lack of evidence does not necessarily imply that products may not be effective. Dental care professionals in clinical practice should tailor the best oral hygiene devices and methods according to patients' skill levels and preferences because patient acceptance is crucial for sustained long-term use [bib_ref] Short-term clinical study comparing supragingival plaque removal and gingival bleeding reduction of..., Steenackers [/bib_ref]. Clinical evidence indicates that the efficacy of interdental brushes depends on the relation between the size of the brush and the size and shape of the interdental space. Interdental spaces underlay a high variety regarding size and morphology, and interdental brushes have to be selected specific to the individual interdental space. The number of devices has to be limited to a certain number with respect to the ability of the patient to cope with this diversity. To reach this goal, compromises have to be found to achieve the individual optimum.

## R4.5 | should we recommend a powered or a manual toothbrush?
Evidence-based recommendation (4.5)
The use of a powered toothbrush may be considered as an alternative to manual tooth brushing for periodontal maintenance patients. [bib_ref] Mechanical plaque removal of periodontal maintenance patients: A systematic review and network..., Slot [/bib_ref] Quality of evidence Five RCTs (216 patients) with high risk of bias

## Supporting literature

## Risk of bias
Study quality assessment showed that all studies at high risk of bias.

## Consistency
The summary of findings table shows that the body of evidence is rather consistent.

## Clinical relevance and effect size
No differences could be found. The statistically established clinical evidence was calculated for one study and showed no clinically relevant effect size.

## Balance of benefit and harm
The adverse events were not evaluated.

## Economic considerations
A manual toothbrush is less expensive than a power toothbrush.

## Patient preferences
No data on patient preference arrive from the current review.

## Applicability
The guideline can be applied to patients attending a periodontal maintenance program. There is an abundance of toothbrushes available.

## R4.6 | how should interdental cleaning be performed?

## Evidence-based recommendation (4.6)
If anatomically possible, we recommend that tooth brushing should be supplemented by the use of interdental brushes. [bib_ref] Mechanical plaque removal of periodontal maintenance patients: A systematic review and network..., Slot [/bib_ref] Quality of evidence Seven comparisons from four RCTs (290 patients) with low to unclear risk of bias

## Supporting literature

## Grade of recommendation grade a-
Strength of consensus Unanimous consensus (5.4% of the group abstained due to potential CoI)

# Background

## Intervention
See previous sections.

## Available evidence
The underlying systematic review [bib_ref] Mechanical plaque removal of periodontal maintenance patients: A systematic review and network..., Slot [/bib_ref] 

## Risk of bias
Low to unclear.

## Consistency
High.

## Clinical relevance and effect size
Considered as clinically relevant.

## Balance of benefit and harm
There is a moderate risk of trauma due to the use of interdental brushes, when not used properly. Therefore, individual instruction and adaptation to the individual situation by professionals are crucial. In any case, the benefits overweigh the risks by far.

## Economic considerations
Not considered.

## Patient preferences
There is clinical evidence supporting that patients with open interdental spaces prefer the use of interdental brushes over the use of dental floss.

## Applicability
The guideline can be applied since appropriate quantities and varieties of interdental brushes are available on the European market.

## R4.7 | what is the value of dental flossing for interdental
cleaning in periodontal maintenance patients?

## Evidence-based recommendation (4.7)
We do not suggest flossing as the first choice for interdental cleaning in periodontal maintenance patients. [bib_ref] Mechanical plaque removal of periodontal maintenance patients: A systematic review and network..., Slot [/bib_ref] Quality of evidence Six comparisons from four RCTs (162 patients) with unclear to high risk of bias

## Supporting literature

## Grade of recommendation grade b-
Strength of consensus Consensus (5.6% of the group abstained due to potential CoI)

# Background
Intervention See previous sections.

## Available evidence
The underlying systematic review [bib_ref] Mechanical plaque removal of periodontal maintenance patients: A systematic review and network..., Slot [/bib_ref] found evidence for a significantly better cleaning effect of interdental brushes than of flossing. Both the descriptive analysis and the NMA indicate that
IDBs are the first choice for periodontal maintenance patients. Six comparisons from four RCTs (162 patients) were identified.

## Risk of bias
High to unclear.

## Consistency
High.

## Clinical relevance and effect size
Considered as clinically relevant.

## Balance of benefit and harm
There is a moderate risk of trauma due to the use of interdental brushes or flossing, when not used properly. Therefore, individual instruction and adaptation to the individual situation by professionals are crucial.

## Economic considerations
Not considered.

## Patient preferences
There is clinical evidence supporting that patients with open interdental spaces prefer the use of interdental brushes over the use of dental floss.

## Applicability
The guideline can be applied since appropriate quantities and varieties of interdental brushes are available on the European market.

## R4.8 | what is the value of other interdental devices for interdental cleaning in periodontal maintenance patients?
Expert consensus-based recommendation (4.8)
In interdental areas not reachable by toothbrushes, we suggest supplementing tooth brushing with the use of other interdental cleaning devices in periodontal maintenance patients. [bib_ref] Mechanical plaque removal of periodontal maintenance patients: A systematic review and network..., Slot [/bib_ref] Grade of recommendation Grade B- Strength of consensus Consensus (4.1% of the group abstained due to potential CoI)

## Supporting literature

# Background

## Intervention
Other interdental cleaning devices include rubber/elastomeric cleaning sticks, wood sticks, an oral irrigator or dental floss. Although there are very small and fine interdental brushes available on the market, it must be realized that not all interdental spaces are readily accessible with interdental brushes.

## Available evidence
The underlying systematic review [bib_ref] Mechanical plaque removal of periodontal maintenance patients: A systematic review and network..., Slot [/bib_ref] 

## Risk of bias
High.

## Consistency
Not evaluated.

## Clinical relevance and effect size
Considered as moderate.

## Balance of benefit and harm
Up to now no adverse effects have been reported.

## Economic considerations
Not considered.

## Patient preferences
Rubber/elastomeric cleaning sticks are highly accepted by patients as are oral irrigators.

## Applicability
The guideline can be applied since appropriate quantities and varieties of interdental cleaning devices are available on the European market.

## R4.9 | what additional strategies in motivation are useful?
Expert consensus-based recommendation (4.9)
We recommend utilizing the "First Step of Therapy" section of this guideline. [bib_ref] Promoting behavioural changes to improve oral hygiene in patients with periodontal diseases:..., Carra [/bib_ref] Strength of consensus Strong consensus (0% of the group abstained due to potential CoI)

## Supporting literature

# Background
Background information and the discussion of additional factors can be found in the section dealing with patients in active periodontal therapy (first step of therapy).

## | intervention: adjunctive therapies for gingival inflammation
R4.10 | What is the value of adjunctive antiseptics/ chemotherapeutic agents for the management of gingival inflammation?
Expert consensus-based recommendation (4.10)
The basis of the management of gingival inflammation is selfperformed mechanical removal of biofilm. Adjunctive measures, including antiseptic, may be considered in specific cases, as part of a personalized treatment approach.
Supporting literature [bib_ref] Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review..., Figuero [/bib_ref] Grade of recommendation Grade 0- Strength of consensus Consensus (11.8% of the group abstained due to potential CoI)

# Background

## Intervention
In order to control gingival inflammation during periodontal maintenance, the adjunctive use of some agents has been proposed. These agents are mainly antiseptics agents, and can be delivered as dentifrices, as mouth rinses or both.

## Available evidence
A systematic review [bib_ref] Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review..., Figuero [/bib_ref] [bib_ref] The use of a triclosan/copolymer dentifrice may retard the progression of periodontitis, Rosling [/bib_ref].

## Risk of bias
The great majority of these studies were industry-funded, and there was a high risk of bias both within and across studies.

## Consistency
Highly consistent across studies, 72 comparisons were included in the primary analysis.

## Clinical relevance and effect size
Considered as clinically relevant.

## Balance of benefit and harm
At least 31 studies assessed adverse events and PROMs and staining was the only relevant finding.

## Economic considerations
The issue has not been addressed. For dentifrices, it may not be relevant, since a dentifrice has to be used combined with mechanical tooth brushing; for mouth rinse, the extra cost should be taken into consideration. It should also be noted that the evidence base contains studies using products that may no longer be available.

## Patient preferences
Both dentifrices and mouth rinses are widely accepted by the population.

## Applicability
Demonstrated with studies testing large groups from the general population. The adjunctive use of some agents has been proposed in those subjects who are not able to effectively remove supragingival biofilms by the sole use of mechanical procedures, but there is no direct evidence to support this statement.

## R4.11 | should adjunctive chemotherapeutics be recommended for patients in supportive periodontal

## Care?
Evidence-based recommendation/statement (4.11)
A. The use of adjunctive antiseptics may be considered in periodontitis patients in supportive periodontal care in helping to control gingival inflammation, in specific cases. B. We do not know whether other adjunctive agents (such as probiotics, prebiotics, anti-inflammatory agents, antioxidant micronutrients) are effective in controlling gingival inflammation in patients in supportive periodontal care.

## Supporting literature

# Background

## Intervention
In order to control gingival inflammation during supportive periodontal care, the adjunctive use of some agents has been proposed.
These agents are mainly antiseptics but some other agents, such as probiotics, prebiotics, anti-inflammatory agents and antioxidant micronutrients, can be found in the literature. These products are mainly delivered as dentifrices or mouth rinses.

## Available evidence
See also previous section. The adjunctive use of antiseptic agents has been proposed in those subjects who are not able to effectively remove supragingival biofilms by the sole use of mechanical procedures. Actually, the recommendations of the XI European Workshop in Periodontology (2014) highlighted that [bib_ref] Primary prevention of periodontitis: Managing gingivitis, Chapple [/bib_ref] "For the treatment of gingivitis and where improvements in plaque control are required, adjunctive use of anti-plaque chemical agents may be considered. In this scenario, mouth rinses may offer greater efficacy but require an additional action to the mechanical oral hygiene regime". Recommending adjunctive antiseptics, to mechanical supragingival biofilm control, in a specific patient group, instead in the general population, is plausible, but there is no supporting evidence to defend it. Most studies assessing the adjunctive benefits of antiseptic formulations have been performed in general populations, with statistically significant benefits in plaque and gingival indices [bib_ref] Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review..., Serrano [/bib_ref]. Therefore, different factors may be considered when deciding whether to recommend the use of an adjunctive agent to control gingival inflammation in patients in supportive periodontal care. It is noted that all patients need to use a toothbrush with a fluoride toothpaste. However, in those subjects who are not able to effectively control supragingival biofilms and/or gingival inflammation by the sole use of mechanical procedures, a decision is then made whether or not to utilise a toothpaste and/or a mouth rinse that contains a specific active agent (in addition to fluoride). This decision would follow a personalized approach to patient care and would need to consider two aspects:
- Local factors consider levels of gingival inflammation related to plaque level, accessibility for cleaning, anatomical factors, etc.
- General factors consider systemic factors, general health status, frailty, limited dexterity, etc., some of which may be more relevant in elderly patients.
The most frequent delivery format for antiseptic agents is dentifrices and mouth rinses, or even they can be delivered in both, simultaneously. The obvious benefit of dentifrice delivery is that no other delivery format is needed, and a dentifrice is going to be used anyway. Mouth rinse delivery offers a better distribution around the mouth [bib_ref] Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review..., Serrano [/bib_ref] and better pharmacokinetic properties [bib_ref] Delivery of antiplaque agents from dentifrices, gels, and mouthwashes, Cummins [/bib_ref]. Some evidence suggests that the adjunctive use of mouth rinses may provide better outcomes than that of dentifrices. However, the evidence is conflictive and significant differences were only observed for the secondary outcome [bib_ref] Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review..., Figuero [/bib_ref]. In addition, direct comparisons between similar agents/formulations, delivered either as dentifrice or mouth rinse, are not available.
The decision to select a specific toothpaste or a mouth rinse should be also based on a combination of factors:
- Patient preferences including cost, taste, etc.
- Unwanted effects including staining, burning sensation during use, etc.
- Potential negative impacts on beneficial aspects of the oral microbiome highlighted in recent evidence (e.g. impact on nitric oxide pathway) [bib_ref] Effects of Chlorhexidine mouthwash on the oral microbiome, Bescos [/bib_ref].
- Potential negative impacts on blood pressure: one short-term (7days) study suggested a non-statistically significant "trend" for chlorhexidine mouth rinse to cause a small elevation in systolic blood pressure from 103 mmHg to 106 mHg [bib_ref] Effects of Chlorhexidine mouthwash on the oral microbiome, Bescos [/bib_ref].
The clinical significance of this is unknown.
- Depending on the specific agent already selected, a decision must be made regarding their frequency and duration of use.

## R4.12 | which antiseptic is the most effective in dentifrices?
Evidence-based recommendation (4.12)
If an antiseptic dentifrice formulation is going to be adjunctively used, we suggest products containing chlorhexidine, triclosancopolymer and stannous fluoride-sodium hexametaphosphate for the control of gingival inflammation, in periodontitis patients in supportive periodontal care. [bib_ref] Efficacy of adjunctive anti-plaque chemical agents: A systematic review and network meta-analyses..., Escribano [/bib_ref] 

## Supporting literature

# Background

## Intervention
In order to control gingival inflammation during supportive periodontal care, the adjunctive use of some agents has been proposed.
These products can be delivered as dentifrices.

## Available evidence
In the systematic review [bib_ref] Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review..., Figuero [/bib_ref] , the adjunctive use of 14 different dentifrice formulations was evaluated for controlling gingival inflammation, with a clear heterogeneity in the number of available studies for each product. The magnitude of effect in gingival indices changes, in formulations with more than one study available, was headed by stannous fluoride with sodium hexametaphosphate (n = 2, S-WMD = 1.503), followed by triclosan and copolymer (n = 18, S-WMD = 1.313), and chlorhexidine (n = 2, S-WMD = 1.278, not statistically significant), although comparing the formulations was not a specific objective of the review. Effects on plaque levels were best with chlorhexidine at high concentrations (n = 3, S-WMD = 1.512) and triclosan and copolymer (n = 23, S-WMD = 1.164). In a previously published network meta-analyses, chlorhexidine and triclosan and copolymer were the most effective agents for plaque reduction, but no clear differences were observed for gingival index control [bib_ref] Efficacy of adjunctive anti-plaque chemical agents: A systematic review and network meta-analyses..., Escribano [/bib_ref] [bib_ref] Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review..., Figuero [/bib_ref].
Additional factors have been discussed in the overall evaluation of adjunctive agents.

## R4.13 | which antiseptic is the most effective in mouth
rinses?

## Evidence-based recommendation (4.13)
If an antiseptic mouth rinse formulation is going to be adjunctively used, we suggest products containing chlorhexidine, essential oils and cetylpyridinium chloride for the control of gingival inflammation, in periodontitis patients in supportive periodontal care. Quality of evidence CoE Class I-24 RCTs with, at least, 6-month follow-up

## Supporting literature

## Grade of recommendation grade b-
Strength of consensus Consensus (17.9% of the group abstained due to potential CoI)

# Background

## Intervention
In order to control gingival inflammation during supportive periodontal care, the adjunctive use of some agents has been proposed.
These products can be delivered as mouth rinses.

## Available evidence
In the systematic review [bib_ref] Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review..., Figuero [/bib_ref] , the adjunctive use of 11 different mouth rinse formulations were evaluated for controlling gingival inflammation, with a clear heterogeneity in the number of available studies for each product. The magnitude of effect in gingival indices changes, in formulations with more than one study available, ranged from S-WMD = 2.248 (essential oils, n = 10), to S-WMD = 1.499 (cetylpyridinium chloride, n = 5), and to S-WMD = 1.144 (chlorhexidine at high concentrations, n = 5), although comparing the formulations was not a specific objective of the review. In a previously published network metaanalyses (a statistical technique which allows the integration of data from direct and indirect comparisons, namely treatments compared among trials through a common comparator treatment), chlorhexidine and essential oil mouth rinses were ranked as the most efficacious agents in terms of changes in plaque and gingival indices [bib_ref] Efficacy of adjunctive anti-plaque chemical agents: A systematic review and network meta-analyses..., Escribano [/bib_ref] [bib_ref] Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review..., Figuero [/bib_ref].
Additional factors have been discussed in the overall evaluation of adjunctive agents.

## | intervention: supragingival dental biofilm control (professional)
R4.14 | What is the value of professional mechanical plaque removal (PMPR) as part of SPC?
Expert consensus-based recommendation (4.14)
We suggest performing routine professional mechanical plaque removal (PMPR) to limit the rate of tooth loss and provide periodontal stability/improvement, as part of a supportive periodontal care program. [bib_ref] Effect of professional mechanical plaque removal performed on a long-term, routine basis..., Trombelli [/bib_ref] Grade of recommendation Grade B- Strength of consensus Strong consensus (1.4% of the group abstained due to potential CoI)

## Supporting literature

# Background

## Intervention
Professional mechanical plaque removal (PMPR) administered on a routine basis (i.e. at specific, predetermined intervals) as an integral part of supportive periodontal care has been shown to result in low rates of tooth loss and limited attachment level changes in both the short-and long-term in patients treated for periodontitis [bib_ref] Supportive periodontal care: The effect of periodic subgingival debridement compared with supragingival..., Heasman [/bib_ref] [bib_ref] Effect of professional mechanical plaque removal performed on a long-term, routine basis..., Trombelli [/bib_ref]. In most of the studies, PMPR in SPC was often combined with other procedures (e.g. reinforcement of oral hygiene instruction, additional active treatment at sites showing disease recurrence), thus making it difficult to isolate information on the magnitude of the mere effect of PMPR on tooth survival and stability of periodontal parameters [bib_ref] Effect of professional mechanical plaque removal performed on a long-term, routine basis..., Trombelli [/bib_ref].

## Available evidence
This issue has not been directly addressed in the systematic reviews prepared for this Workshop; however, ample evidence is available to support this statement. It has been demonstrated that professional mechanical plaque removal (PMPR), performed at defined intervals, together with the other interventions of supportive periodontal care may result in lower rates of tooth loss and attachment level changes. In a systematic review [bib_ref] Effect of professional mechanical plaque removal performed on a long-term, routine basis..., Trombelli [/bib_ref] , presented at the 2014 European Workshop, a weighted mean yearly rate of tooth loss of 0.15 and 0.09 for follow-up of 5 years or 12-14 years, respectively, was reported; the correspondent figures for mean clinical attachment loss lower than 1 mm at follow-up ranging from 5 to 12 years. Information from this review, and also from other systematic reviews, collectively supports that patients with a history of treated periodontitis can maintain their dentition with limited variations in periodontal parameters when regularly complying with a SPC regimen based on routine PMPR .

## Risk of bias
The methodological quality was assessed with a specifically designed scale for the evaluation of non-randomized observational studies, with a quality level ranging from 3 to 7, in a 9-point scale, with 9 representing the highest quality (lowest risk of bias).

## Consistency
Although no meta-analysis was possible, the primary outcome (tooth loss) was reported in 12 studies, showing no or low incidence. Clinical attachment level (CAL) changes were reported in 10 studies, which consistently showed limited modifications in CAL, frequently as a slight CAL loss.

## Clinical relevance and effect size
A weighted mean yearly rate of tooth loss of 0.15 for follow-up of 5 years, and 0.09 for follow-up of 12-14 years, can be considered as relevant.

## Balance of benefit and harm
PROMs were not reported in the included studies.

## Economic considerations
Ethics and legal aspects are not relevant for this intervention; economic aspects have not been frequently addressed. In a study in a private practice in Norway, it was demonstrated that regular maintenance was associated with less tooth loos than not regular maintenance, with follow-ups of 16-26 years; the yearly cost of maintaining a tooth was estimated in 20.2 euro [bib_ref] Applying quality assurance in real time to compliant long-term periodontal maintenance patients..., Fardal [/bib_ref].

## Patient preferences
Demonstrated with compliance in long-term studies.

## Applicability
Demonstrated with studies testing large groups from the general population.
R4.15 | Should alternative methods be used for professional mechanical plaque removal (PMPR) in supportive periodontal care?

## Evidence-based recommendation (4.15)
We suggest not to replace conventional professional mechanical plaque removal (PMPR) with the use of alternative methods (Er:YAG laser treatment) in supportive periodontal care. [bib_ref] Efficacy of alternative or additional methods to professional mechanical plaque removal during..., Trombelli [/bib_ref] Quality of evidence One RCT

## Supporting literature

## Grade of recommendation grade b-
Strength of consensus Strong consensus (1.4% of the group abstained due to potential CoI)

# Background

## Intervention
The systematic review [bib_ref] Effect of professional mechanical plaque removal performed on a long-term, routine basis..., Trombelli [/bib_ref] was retrieving available RCTs on any given alternative intervention to conventional PMPR (the latter including supragingival and/or subgingival removal of plaque, calculus and debris performed with manual and/or powered instruments) in the maintenance of periodontitis patients with a follow-up of at least 1 year following the first administration of intervention/control treatment.

## Available evidence
In the systematic review [bib_ref] Efficacy of alternative or additional methods to professional mechanical plaque removal during..., Trombelli [/bib_ref] , only one RCT was identified, assessing Er:YAG laser as an alternative method to conventional PMPR. No statistically significant differences were found (Krohn-Dale, Boe, Enersen, & Leknes, 2012).

## Economic considerations
Cost-benefit or cost-effective analyses are missing and may be very relevant when considering this specific treatment option. The same is true for PROMs.

## R4.16 | should adjunctive methods be used for professional mechanical plaque removal (pmpr) in supportive periodontal
care?

## Evidence-based recommendation (4.16)
We suggest not to use adjunctive methods (sub-antimicrobial dose doxycycline, photodynamic therapy) to professional mechanical plaque removal (PMPR) in supportive periodontal care. [bib_ref] Efficacy of alternative or additional methods to professional mechanical plaque removal during..., Trombelli [/bib_ref] Quality of evidence Two RCTs

## Supporting literature

## Grade of recommendation grade b-
Strength of consensus Strong consensus (2.7% of the group abstained due to potential CoI)

# Background

## Intervention
The systematic review [bib_ref] Effect of professional mechanical plaque removal performed on a long-term, routine basis..., Trombelli [/bib_ref] was retrieving available RCTs on any given additional intervention to conventional PMPR (the latter including supragingival and/or subgingival removal of plaque, calculus and debris performed with manual and/or powered instruments) in the maintenance of periodontitis patients with a follow-up of at least 1 year following the first administration of intervention/control treatment.

## Available evidence
In the systematic review [bib_ref] Efficacy of alternative or additional methods to professional mechanical plaque removal during..., Trombelli [/bib_ref] , two RCTs were identified, one testing sub-antimicrobial dose (20 mg b.i.d.) of doxycycline [bib_ref] Efficacy of sub-antimicrobial dose doxycycline in post-menopausal women: Clinical outcomes, Reinhardt [/bib_ref] , another evaluating photodynamic therapy (PDT) with a 0.01% methylene blue as photosensitizer and a diode laser (wavelength of 660 nm) [bib_ref] Antimicrobial photodynamic effect to treat residual pockets in periodontal patients: A randomized..., Carvalho [/bib_ref]. No statistically significant differences were observed in any study, although

## Economic considerations
For the adjunctive use of SDD, adverse effects and cost-benefit ratio have to be considered. For the adjunctive use of PDT, a previous systematic review [bib_ref] Clinical efficacy of photodynamic therapy adjunctive to scaling and root planing in..., Xue [/bib_ref] , which included 11 RCTs, found better results for PDT, but only after 3 months, with 0.13 mm of additional impact in PPD reduction. No increase in adverse events were reported. Cost-benefit or cost-effective analyses are missing and may be very relevant when considering this specific treatment option.

## | intervention: risk factor control

## R4.17 | what is the value of risk factor control in spc?
Expert consensus-based recommendation (4.17)
We recommend risk factor control interventions in periodontitis patients in supportive periodontal care. [bib_ref] Impact of risk factor control interventions for smoking cessation and promotion of..., Ramseier [/bib_ref] 

## Supporting literature

## Grade of recommendation grade a-
Strength of consensus Strong consensus (0% of the group abstained due to potential CoI)

# Background

## Intervention
Periodontitis patients benefit from additional risk factor control interventions to improve the maintenance of periodontal stability.
Interventions include patient education which be staged and adapted according to individual needs ranging from single brief advice to patient referral for advanced counselling and pharmacotherapy. Smoking and diabetes are two of the main risk factors for periodontitis, and they are currently included in the grading of periodontitis . Controlling these risk factors therefore would be critical for treatment response and for long-term stability. In addition, other relevant factors, part a healthy life-style counselling, are considered, including dietary counselling, physical exercise or weight loss. These interventions, together with those for tobacco cessation and diabetes control, are not direct responsibility of oral health professionals, and they may want to refer the patients to other health professionals.
However, the direct/indirect role of oral health professionals in these interventions should be emphasized.

## Available evidence
In the systematic review , the authors have identified 13 relevant guidelines for interventions for smoking cessation, diabetes control, physical exercise (activity), change of diet, carbohydrate (dietary sugar reduction) and weight loss. In addition, 25 clinical studies were found that assess the impact of (some of) these interventions in gingivitis/periodontitis patients. However, only some of them included patients in supportive periodontal care.
Additional factors have been discussed in the evaluation of risk factor control in patients in active periodontal therapy.

## R4.18 | what is the role of tobacco smoking cessation interventions in spc?

## Evidence-based recommendation (4.18)
We recommend tobacco smoking cessation interventions to be implemented in periodontitis patients in supportive periodontal care. [bib_ref] Impact of risk factor control interventions for smoking cessation and promotion of..., Ramseier [/bib_ref] Quality of evidence Six prospective studies with, at least, 6-month follow-up

## Supporting literature

## Grade of recommendation grade a-
Strength of consensus Strong consensus (0% of the group abstained due to potential CoI)

# Background
Background information and the discussion of additional factors can be found in the section dealing with patients in active periodontal therapy.

## R4.19 | what is the role of promotion of diabetes control
interventions in SPC?

## Expert consensus-based recommendation (4.19)
We suggest promotion of diabetes control interventions in patients in maintenance therapy. [bib_ref] Impact of risk factor control interventions for smoking cessation and promotion of..., Ramseier [/bib_ref] Grade of recommendation Grade B- Strength of consensus Consensus (0% of the group abstained due to potential CoI)

## Supporting literature

# Background

## Intervention
Periodontitis patients may benefit from the promotion of diabetes control interventions to improve the maintenance of periodontal stability. The promotion may consist of patient education including brief dietary counselling and possibly patient referral for glycaemic control.

## Available evidence
In the systematic review , none of the identified studies was performed in patients in supportive periodontal care. Indirect evidence (see section on active periodontal therapy)
suggests that diabetes control interventions ought to be implemented in supportive periodontal care patients.
Background information and the discussion of additional factors can be found in the section dealing with patients in active periodontal therapy.
R4.20 | What is the role of physical exercise (activity), dietary counselling or lifestyle modifications aiming at weight loss in SPC?

# Evidence-based recommendation/statement (4.20)
We do not know whether physical exercise (activity), dietary counselling or lifestyle modifications aiming at weight loss are relevant in supportive periodontal care. [bib_ref] Impact of risk factor control interventions for smoking cessation and promotion of..., Ramseier [/bib_ref] Grade of recommendation Grade 0-Statement: unclear, additional research needed Strength of consensus Strong consensus (0% of the group abstained due to potential CoI)

## Supporting literature

# Background

## Intervention
Overall evidence from the medical literature suggests that the promotion of physical exercise (activity) interventions may improve both treatment and long-term management of non-communicable diseases. In periodontitis patients, the promotion may consist of patient education specifically target to the patients' age and general health.

## Available evidence
In the systematic review , none of the identified studies was performed in patients in supportive periodontal care.
Background information and the discussion of additional factors can be found in the section dealing with patients in active periodontal therapy [bib_ref] Age-dependent distribution of periodontitis in two countries: Findings from NHANES 2009 to..., Billings [/bib_ref].

## Ack n owled g em ents
The authors express their gratitude to all reviewers involved in the preparation of the systematic reviews. In addition, the organizations which accepted to participate in the guideline development process are also kindly and sincerely acknowledged: European

## Co n fli c t o f i nte r e s t
Workshop participants filed detailed disclosure of potential con-
[fig] R2. 8 |: Does the adjunctive use of systemic sub-antimicrobial dose doxycycline (SDD) to subgingival instrumentation improve clinical outcomes? Evidence-based recommendation (2.8) We suggest not to use systemic sub-antimicrobial dose doxycycline (SDD) as an adjunct to subgingival instrumentation. Supporting literature Donos et al. (2019) Quality of evidence Eight placebo-controlled RCTs (14 publications, n = 610). Meta-analysis on PPD reduction was performed in five RCTs (n = 484) Evidence-based recommendation (2.8) Grade of recommendation Grade B- Strength of consensus Consensus (1.3% of the group abstained due to potential CoI) Background Intervention Sub-antimicrobial dose doxycycline (up to 40 mg a day) is a systemic drug employed specifically for its anti-inflammatory as opposed to its antimicrobial properties. The formulation offers anti-collagenolytic activity, which may have utility in reducing connective tissue breakdown and augmenting healing responses following subgingival instrumentation in periodontitis patients. Available evidence Eight placebo-controlled RCTs (14 publications, n = 610) reported on the systemic use of a sub-antimicrobial dose doxycycline (SDD) (up to 40 mg a day) in combination with subgingival instrumentation. Meta-analysis on PPD reduction (primary outcome) at 6 months post-subgingival instrumentation was performed in five RCTs (n = 484). [/fig]
[fig] Applicability: We do not encourage everyday clinical use of systemic NSAIDs or to conduct future studies to test these medications in their current standard formulations or dosage regimes. No meaningful conclusions could be made regarding use of local NSAIDs. Based on the current limited evidence, local NSAIDs did not provide a clinical benefit. [/fig]
[fig] Figure 2: Dommisch et al. (2020); Jepsen et al. (2019) Quality of evidence Regenerative treatment: 20 RCTs (575 patients) Resective treatment: Seven observational studies (665 patients) with low quality of evidence Grade of recommendation A. Grade A- B. Statement A. Strength of consensus Strong consensus (1.5% of the group abstained due to potential CoI) B. Strength of consensus Consensus (1.5% of the group abstained due to potential CoI) Background Intervention See previous sections. An algorithm for clinical decision-making in the treatment by periodontal surgery of molars with furcation involvement (Class I, Class II) and residual pockets is depicted in [/fig]
[table] Table 4: by the German Association of the Scientific Medical #1. In patients with periodontitis, what is the efficacy of subgingival instrumentation performed with hand or sonic/ultrasonic instruments in comparison with supragingival instrumentation or prophylaxis in terms of clinical and patient reported outcomes?#2. In patients with periodontitis, what is the efficacy of nonsurgical subgingival instrumentation performed with sonic/ultrasonic instruments compared to subgingival instrumentation performed with hand instruments or compared to the subgingival instrumentation performed with a combination of hand and sonic/ultrasonic instruments in terms of clinical and patient-reported outcomes?#3. In patients with periodontitis, what is the efficacy of full mouth delivery protocols (within 24 hr) in comparison with quadrant or sextant wise delivery of subgingival mechanical instrumentation in terms of clinical and patient-reported outcomes? [/table]