THU0092 USING EVIDENCE-BASED RESEARCH TO DESIGN A RANDOMISED TRIAL ON PERIODONTAL TREATMENT FOR INDIVIDUALS WITH RHEUMATOID ARTHRITIS: A SYSTEMATIC REVIEW PUTTING EXISTING RESEARCH INTO CONTEXT
Authors: D. Santos Silva, F. Costa, I. Poiares Baptista, T. Santiago, H. Lund, S. Tarp, J. A. P. Da Silva, R. Christensen
Journal: Annals of the Rheumatic Diseases (2020)

Background: It has been suggested that RA is triggered by genetic and environmental factors that lead to a breakdown of immune tolerance at mucosal surfaces (e.g. periodontium) (1, 2). The theory that Periodontitis (PD) affects RA process/measurement has deep implications: PD treatment might improve disease activity and/or prevent overtreatment. It is urgent to confirm available evidence and design research strategies to cover knowledge gaps.(3) Objectives: To gauge the evidence of non-surgical periodontal therapy (NSPT) impact upon measures of disease activity and inflammatory burden in individuals with RA and derive recommendations for research needed to address the knowledge gaps. Methods: Based on a prespecified Protocol (CRD42018103359), a search for RA and Periodontitis and controlled or randomised trials was conducted on the 7th April 2019 in PubMed, Cochrane Library (CENTRAL), Embase, ClinicalTrials.gov and WHO ICTRP portal. Two independent reviewers screened titles and abstracts and selected papers were full text reviewed. Outcome domains were those OMERACT-endorsed for RA CTs: disease activity (DAS28, SDAI, CDAI), life impact (patient-reported outcome measures) and inflammation markers (CRP, ESR). We summarised continuous outcomes using standardised mean differences (SMDs) with 95% confidence intervals (95% CIs). We evaluated inconsistency using the I 2 statistic, and combined SMDs using the standard inverse variance random effects for the meta-analyses; fixed-effect meta-analysis was applied for the purpose of sensitivity. Results: From 1909 studies identified, 9 reports (5 RCTs, 4 NRSIs) were eligible for quantitative synthesis (n=388). The evidence suggested a moderate effect on the disease activity domain in response to NSPT in RA patients (SMD -0.59 [95% CI, -1.21 to 0.03], n = 311; Figure 1). Using GRADE approach, as judged from the study’s Risk of bias, imprecision around the estimate, and the results’ inconsistency (I 2 = 83%), the evidence was rated down to ‘very low certainty evidence’ indicating that any possible effect of NSPT is likely to change as more prospective evidence is provided. A RCT in PD-RA patients would need a sample size of at least 90 individuals, randomised 1:1 (80% power) to detect an effect size of 0.59. Anticipating withdrawals and attrition, a more adequate sample size would be 120 (90% power). Conclusion: Our results summarise the current evidence on the likely impact of NSPT on RA outcomes. There is an urgent need to assemble a well designed RCT, or prospective (multicenter) cohorts of RA-PD patients using rigorous protocols, standardized diagnosis criteria, data collection and duration of follow-up. References: [1]Wegner N, Wait R, Sroka A, Eick S, Nguyen KA, Lundberg K, et al. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and alpha-enolase: implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum. 2010;62(9):2662-72. [2]Mikuls TR, Payne JB, Deane KD, Thiele GM. Autoimmunity of the lung and oral mucosa in a multisystem inflammatory disease: The spark that lights the fire in rheumatoid arthritis? Journal of Allergy and Clinical Immunology. 2016;137(1):28-34. [3]Lund H, Brunnhuber K, Juhl C, Robinson K, Leenaars M, Dorch BF, et al. Towards evidence based research. BMJ: British Medical Journal (Online). 2016;355. Disclosure of Interests: Daniela Santos Silva: None declared, Flavio Costa: None declared, Isabel Poiares Baptista: None declared, Tânia Santiago: None declared, Hans Lund: None declared, Simon Tarp: None declared, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Robin Christensen: None declared