Effect of a Self-Management Intervention for Patients Newly Diagnosed With Inflammatory Arthritis: Study Protocol for a Randomized Controlled NISMA Trial
Phase: NA
Conditions: Inflammatory Arthritis
Sponsor: Glostrup University Hospital, Copenhagen

 
 
Effect of a Self-Management Intervention for Newly Diagnosed Inflammatory 
Arthritis: study protocol for a randomized controlled trial {1} 
Luise Holberg Lindgren 1, Tanja Thomsen 1,2, Merete Lund Hetland 1,3, Mette Aadahl 2, 3, Annette de Thurah 4,5, 
Robin Christensen 6,7, Bente Appel Esbensen 1,3 
 
Mail corresponding author: luise.holberg.lindgren@regionh.dk 
 
ORCID: 
Luise Holberg Lindgren: 0000-0002-9393-4405 
Tanja Thomsen: 0000-0002-7112-2318 
Annette de Thurah: 0000-0003-0103-4328 
Mette Aadahl: 0000-0001-5904-9747 
Merete Lund Hetland: 0000-0003-4229-6818 
Robin Christensen: 0000-0002-6600-0631 
Bente Appel Esbensen: 0000-0001-5331-8221 
 
 
 

 
2 
 
ABSTRACT  
Background  
Patients newly diagnosed with inflammatory arthritis (IA) often face substantial physical, psychological, and 
social challenges despite advances in pharmacological management. 
Objective 
to investigate the efficacy of the “Newly diagnosed with Inflammatory arthritis—a Self-MAnagement 
intervention” (NISMA) and usual care, compared to usual care alone (control group),  in adults with newly 
diagnosed IA. 
Methods 
This pragmatic, multicenter randomized controlled trial (RCT) will enroll 130 adults with rheumatoid arthritis 
(RA), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) recruited consecutively from three Danish 
hospitals and randomized 1:1 to NISMA plus usual care or usual care alone. The control group receives 
ususal care which consists of planned consultations with a rheumatologist and access to nurses.  NISMA 
comprises three mandatory individual nurse-led sessions with two optional multidisciplinary group sessions 
delivered over 12 months. Assessments occur at baseline, 12 months (primary), and 24 months (extension). 
The primary outcome is the Health Education Impact Questionnaire (heiQ) ‘skill and technique acquisition’ 
domain. 
Statistical analysis  
Analyses follow the intention-to-treat principle. For the primary analysis, analysis of covariance (ANCOVA) 
adjusted for baseline, center, and diagnosis will estimate between-group differences with two-sided 95% CIs. 
Model assumptions (normality, homoscedasticity) will be checked (Q–Q plots, residual diagnostics). If 
violated, pre-specified alternatives (e.g., transformation, rank-based ANCOVA, or nonparametric tests) will 

 
3 
 
be used. Missing data will be addressed using multiple imputation. Key secondary endpoints will be assessed 
in a pre-specified hierarchical (gatekeeping) order; any post‑hoc analyses will be exploratory. Extension 
analyses at 24 months will use linear mixed-effects models. 
Discussion 
This randomized controlled trial will provide essential insights about the efficacy of a targeted self-
management intervention for newly diagnosed patients with inflammatory arthritis. If successful, the NISMA 
intervention could significantly enhance non-pharmacological management, providing a comprehensive 
approach to addressing both physical and psychological needs in caring for patients newly diagnosed with IA. 
Keywords 
Self-management; inflammatory arthritis; randomized controlled trial; patient‑centered care; quality of life; 
rheumatoid arthritis; psoriatic arthritis; axial spondyloarthritis. 
 
Administrative information  
Note: the numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers. The order of the 
items has been modified to group similar items (see http://www.equator-network.org/reporting-
guidelines/spirit-2013-statement-defining-standard-protocol-items-for-clinical-trials/). 
 
Title {1} 
Effect of a Self-Management Intervention for Newly Diagnosed 
Inflammatory Arthritis: study protocol for a randomized controlled 
trial {1} 
 
Trial registration {2a and 2b}. 
Clinicaltrials.gov, nr.: NCT06533423 
Protocol version {3} 
22.09.2025. Version 2.  
Funding {4} 
The NISMA trial is supported by grants from the Danish Rheumatism 
Association (grant nr.: R251-A9062), the Lundbeck Foundation, and 
the Novo Nordic Foundation (grant nr.: 0096696).  

 
4 
 
Author details {5a} 
1Copenhagen Center for Arthritis Research, Center for Rheumatology 
and Spine Diseases, Centre for Head and Orthopedics, Rigshospitalet, 
Glostrup, Denmark.  
2Center for Clinical Research and Prevention, Bispebjerg and 
Frederiksberg Hospital, Denmark.  
3Department of Clinical Medicine, University of Copenhagen, 
Denmark.  
4 Department of Rheumatology, Aarhus University Hospital, Denmark.  
5Department of Clinical Medicine, Aarhus University, Denmark.  
6Section for Biostatistics and Evidence-Based Research, the Parker 
Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, 
Denmark.  
7Research Unit of Rheumatology, Department of Clinical Research, 
University of Southern Denmark, Odense University Hospital, 
Denmark. 
Name and contact information for 
the trial sponsor {5b} 
Trial sponsor {5b}: There is no sponsor of this study. 
Role of sponsor {5c} 
Role of sponsor {5c}:  This study has no commercial sponsor, and all 
funding is provided solely by independent foundations that have no 
involvement in the study's design, data collection, management, 
analysis, or interpretation. Additionally, these foundations have no 
role in the writing of the report or the decision to submit it for 
publication. The research team maintains full independence and 
ultimate authority over all aspects of the study to ensure objectivity 
and scientific integrity.  
 
 
Introduction  
Background and rational {6a} 
Inflammatory arthritis (IA) (in this trial covering rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial 
spondyloarthritis (axSpA)) constitutes a group of acute and chronic joint diseases characterized by joint pain, 
swelling, and tenderness caused by underlying inflammation [1–3].  IA affects more than 2% of the 
population, with considerable variation worldwide [1–3], and can occur at any age and in both sexes. The 
etiology of IA is incompletely understood, but it involves both genetic and lifestyle factors [1,4,5]. IA mainly 
presents with joint inflammation, causing leading to pain and stiffness, but can also affect other connective 

 
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tissues [2,3,6]. If treated insufficiently, these diseases may progress with functional decline, irreversible joint 
damage, development of various comorbidities, and increased mortality [7,8]. Pharmacological treatment 
with disease-modifying anti-rheumatic drugs (DMARDs) early after diagnosis improves short- and long-term 
outcomes [9,10]. Approximately 60% of patients with RA achieve long-term disease remission [11,12], but 
even in remission, some patients with IA will experience symptoms, and due to the fluctuating nature of the 
arthritis, symptoms will come and go throughout life with varying intensity [10,13–15]. Thus, after more than 
two decades of progress in the pharmacological treatment, some aspects of having IA remain less well 
managed: patients with IA still confront physiological and psychological distress, impacting daily activities, 
and overall quality of life (QoL) at disease onset, but also later in the disease course, and even when clinical 
remission is achieved [15,16]. 
Patients newly diagnosed with IA are particularly challenged and vulnerable. They are about to begin a life 
with IA that may involve regular blood tests, lifelong pharmacological treatment, side-effects to treatment, 
symptoms such as pain, fatigue, sleep disturbances, and increased risk of developing co-morbidities such as 
depression, cardiovascular disease, diabetes, and osteoporosis [7]. Experiencing altered body image, and 
changes in the family, work, and social life is common [17–23]. Therefore, a crucial but often insufficient 
aspect of caring for patients with IA is empowering them to gain a thorough understanding of their condition 
and develop their capacity to effectively manage the practical, physical, and psychological effects of the 
disease [24]. Several studies have shown that newly diagnosed patients require regular consultations and 
support from health professionals (HPs) to deal with physical, emotional and social consequences of the 
arthritis [17–23]. In addition, they have a wide range of educational needs, such as knowledge and 
management of the arthritis, and lifestyle recommendations. Previous research suggests that increased self-
management - defined as the individual's ability to manage symptoms, treatments, physical and psychosocial 
consequences, and lifestyle changes inherent in living with a chronic condition [25], - can improve the QoL life 
in patients with chronic illness [26–30]. 

 
6 
 
Self-management in rheumatology has been applied across multiple clinical contexts, including symptom 
pacing for pain and fatigue; adherence to exercise and physical activity; medication adherence and shared 
decision‑making within treat‑to‑target care; and navigation of multidisciplinary services. Program formats 
range from brief nurse‑led education to structured group programs that integrate problem‑solving, 
goal‑setting, and action planning, with demonstrated benefits in patient‑reported outcomes and health 
service use [31,32]. 
As per recommendations from EULAR (European Alliance of Associations for Rheumatology) (10), self-
management should be included in daily rheumatology care to support patients to become active partners in 
handling the disease [24]. This should include patient education and e.g., key self-management approaches 
such as problem-solving, goal-setting and action planning. However, when reviewing the numerous 
systematic reviews of arthritis-specific self-management interventions [33–37], we found it challenging to 
compare the included studies due to their heterogeneous study designs, program foci, and outcomes. 
Furthermore, despite the well-documented need for patient guidance following diagnosis [34], we found no 
IA-specific self-management interventions that have been systematically and specifically developed with a 
focus on newly diagnosed patients and subsequently tested in a Randomized Controlled Trial (RCT). 
NISMA is a systematically developed, theory‑informed self‑management program for adults newly diagnosed 
with IA, described in detail elsewhere [38]. Development of NISMA followed the Medical Research Council 
framework, [39,40] with feasibility and process evaluations subsequently undertaken (manuscripts 
submitted [41,42]. The present RCT evaluates the program’s efficacy compared with usual care. 
The hypothesis is that the adapted NISMA intervention will be superior to usual care in increasing self-
management skills and techniques and thereby improve symptoms among others. Therefore, the next step 
will be to test this hypothesis in a randomized NISMA trial. Further, if the intervention proves to be effective, 
we will conduct a cost-effectiveness analysis subsequently. 
Rationale: Compared with usual care NISMA provides structured, individualized coaching with continuity 
from a dedicated nurse, explicit behavior‑change techniques (problem‑solving, goal‑setting, action planning), 

 
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and optional peer‑supported group sessions. Grounded in Social Cognitive Theory (SCT) and informed by 
Acceptance and Commitment Therapy (ACT) questioning techniques, NISMA targets self‑efficacy, adaptive 
coping, and healthcare service navigation—mechanisms expected to improve heiQ domains and 
downstream clinical and psychosocial outcomes. 
 
Objectives {7} 
The primary objective of this trial is to compare the short-term efficacy of the NISMA intervention and usual 
care, relative to usual care alone, on the HeiQ ’self-management skills and techniques’ domain in patients 
newly diagnosed with inflammatory arthritis, from baseline to 12 months from randomization.  
Our key secondary objectives are to compare the short-term efficacy of the NISMA intervention and usual 
care, relative to usual care on self-management skills, anxiety and depression, fatigue, pain self-efficacy, pain 
intensity, patient global assessment, medication adherence, quality of life, loneliness, and physical function 
from baseline to completion of the intervention (12 months from baseline). 
 
In the extension study we will explore the longer-term efficacy of the intervention relative to usual care on 
self-management skills, anxiety and depression, fatigue, pain self-efficacy, pain intensity, patient global 
assessment, medication adherence, quality of life, loneliness, and physical function at follow-up 24-months 
from baseline. 
Trial design {8} 
The trial is designed as a pragmatic, multicenter randomized trial with a two-group parallel design in a 
superiority framework. Participants will be allocated in a 1:1 ratio; after providing informed consent and 
completing baseline assessments, they will be randomized to either the NISMA intervention (experimental 
group) or usual care (control group) with no protocolized added treatment. 

 
8 
 
The protocol is approved by the Regional Committee on Health Research Ethics for the Capital Region of 
Denmark (H‑24046135) and the Danish Data Protection Agency (p‑2024‑15846). 
 
Methods  
Setting {9} 
Patients will be included from the following 3 centers: the Center for Rheumatology and Spine Diseases, 
Rigshospitalet University Hospital, Copenhagen, and the Department of Rheumatology and Spinal Diseases, 
Holbæk Hospital and Slagelse Hospital; all in Denmark. These three departments cover most of the Zealand, 
which covers an area of 2.5 million residents.  
 
Eligibility criteria {10} 
Inclusion Criteria 
Patients will be included if they are adults aged 18 years or older with one of the following conditions: 
• 
RA diagnosed within the last 6 months 
• 
PsA diagnosed within the last 6 months 
• 
AxSpA diagnosed within the last 12 months, and has initiated biological treatment 
 
Patients with axSpA will have unique inclusion criteria due to NSAIDs being the first-line pharmacological 
treatment [43]. For those effectively treated with NSAIDs and exercise, treatment is transitioned to their 
general practitioner. Therefore, we only those who has initiated biological treatment will be included. 
 
Exclusion criteria 

 
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• Severe mental illness that, in the investigator’s judgment, precludes participation 
• Pregnancy 
• Current chemotherapy for malignancy 
• Insufficient Danish language proficiency to participate (operationalized as inability to read the written 
information and explain study procedures in own words during consent; assessed via a brief comprehension 
check by the project manager) 
 
Who will take informed consent {26a} 
If patients meet the above criteria, the rheumatologist and/or other HPs will briefly inform patients about 
the trial and hand out written information. Interested patients will have the possibility to contact the project 
manager (LHL) by telephone or e-mail. Oral information about the trial will take place at the hospital or by 
telephone based on the patient’s preferences. The project manager will ensure that the information is given 
in an undisturbed setting if conducted at the hospital. Patients will be informed of their right to bring a 
relative to the information session. If still interested after oral information, a consent statement must be 
filled out. Based on the recruitment rates from the prior feasibility study, we estimate that recruitment will 
take 10-12 months. 
 
Additional consent provisions for collection and use of participant data and biological 
specimens {26b}  
This item does not apply as there will be no collection of biological specimens.  
 

 
10 
 
 
 

 
11 
 
The interventions  
Explanation for the choice of comparators {6b} 
Both groups will continually receive relevant treatment for her IA. There are no established standards for 
identifying and addressing self-management needs in rheumatology outpatient consultations. Participants 
allocated to the control group will receive usual care, which consists of planned sessions with a 
rheumatologist and occasionally a nurse, a physiotherapist, and an occupational therapist. Those who 
started DMARDs of any type had an appointment with a nurse and a follow-up phone call. All participants 
will have the possibility to contact the outpatient clinic and consult a nurse. Participants in the control group 
will be encouraged to maintain their usual daily routines and self-management practices until the follow-up 
assessment is conducted. Participants allocated to the intervention group will receive the NISMA 
Intervention in addition to usual care. See Table 1 for summary of interventions (NISMA vs usual care) 
Table 1. Summary of interventions (NISMA vs usual care) 
Arm 
Provider(s) 
Dose & format 
Session 
characteristics 
Core content 
Adherence & 
fidelity 
Medical 
management / 
usual care 
Usual 
care 
(control) 
Rheumatologi
st; nurse; 
PT/OT as 
clinically 
indicated 
Consultations 
per clinical 
need; for 
DMARD starts. 
Nurse 
education visit 
+ follow‑up 
phone call 
Routine 
outpatient 
consultations; 
ad‑hoc 
education/support
; access to 
clinic/nurse advice 
line as needed 
Guideline‑concordan
t medical 
management; 
opportunistic 
self‑management 
advice (no 
structured program) 
Not applicable 
(no structured 
program; routine 
attendance 
recorded in 
clinical systems) 
Treat‑to‑target 
DMARD 
management 
and monitoring 
per local 
practice 
Usual 
care + 
NISMA  
Usual care 
Nurse 
(individual). 
Nurse + 
physiotherapist  
+ occupational 
therapist  
co‑facilitate 
group sessions 
Usual care + 
3× individual 
(60–90 min) 
over 
12 months; 2× 
optional group 
(120 min; ~5–
8 participants) 
Usual care + 
Individual: 
consistent nurse; 
first session in 
person, then 
in‑person/online 
as appropriate. 
Group: fixed time 
points; rolling 
enrolment 
Usual care + 
Person‑centered 
coaching; 
problem‑solving; 
goal‑setting; action 
planning; 
ACT‑informed 
questioning; lifestyle 
& symptom 
management 
Attendance logs; 
session checklists 
in REDCap; ~10% 
session fidelity 
review with 
feedback; 
automated 
reminders and 
active 
rescheduling 
Usual care + 
Guideline‑conco
rdant care 
including 
DMARDs and 
access to nurse 
advice (as part 
of usual care) 

 
12 
 
 
The NISMA-intervention (experimental group) {11a} 
The NISMA intervention is a flexible intervention and comprises three mandatory individual sessions with a 
nurse, supplemented by two optional group sessions over a period of 12 months, to provide comprehensive 
support tailored to each participant's needs. 
In brief, the intervention is delivered by a registered nurse for the individual sessions, with a physiotherapist 
and an occupational therapist co-facilitating the group sessions. The planned dose and format are three 
individual sessions of 60–90 minutes over 12 months and two optional group sessions of 120 minutes with 
approximately five to eight participants. Core content includes person-centered coaching; structured 
problem-solving, goal-setting, and action planning; ACT–informed questioning; and guidance on lifestyle and 
symptom management. 
Adherence and fidelity are promoted through attendance logs, session checklists entered in REDCap, and 
independent reviews of approximately 10% of sessions, alongside automated reminders and active 
rescheduling. Usual care (control) comprises guideline-concordant medical management, including DMARDs 
and nurse access, without a structured self-management program. See Figure 2 for an overview of the 
session sequence and content. 
Our intervention is grounded in the theoretical framework SCT [44] and inspired by the questioning 
techniques in ACT [45,46]. These methods play a crucial role in helping participants enhance their self-
efficacy. The key components of our approach include: a person-centered approach by addressing 
challenges identified by each participant to foster self-efficacy through targeted problem-solving, goal-
setting, and action planning. This is utilized by interviewing techniques derived from ACT to assist 
participants in accepting and committing to self-management. The program is designed to last between 12 
months, allowing for gradual skill development and adaptation. 
 

 
13 
 
 
Fig. 2. The NISMA intervention  
 
The structured sessions are as follows: 
Individual sessions 
The first individual session focuses on what IA is, medical management, providing essential knowledge and 
strategies for managing the condition effectively.  
The second session addresses emotional management, recognizing the unique challenges faced by newly 
diagnosed patients. Our intervention places a particular emphasis on themes of crisis and acceptance 
management.  

 
14 
 
The third session aims to address role management, aiding participants in adjusting their roles in personal 
and professional life. 
The individual sessions are conducted by a specially trained registered nurse , who remains consistent 
throughout the individual sessions to provide continuity of care. Individual sessions can be conducted either 
as online meetings or face-to-face. However, the initial meeting will be in person to establish a solid 
foundation for the relationship. 
Group sessions (optional) 
Participants are invited to attend two optional group sessions (two hours each), each designed to 
accommodate five to eight individuals. The group sessions are scheduled at fixed time points. This 
arrangement enables participants to register for these sessions at their convenience., facilitating their active 
engagement in the program. Group sessions are co-facilitated by a team comprising a nurse, an occupational 
therapist, and a physiotherapist, offering a multidisciplinary approach to address various aspects of self-
management (see Fig. 2 for overview of sessions). 
Group sessions delve into lifestyle and symptom management, offering practical advice and peer support. 
The themes of symptom management and lifestyle adjustments are central to the group discussions, aiming 
to equip participants with practical strategies for day-to-day management of their condition.  
To ensure the fidelity of the intervention, we have developed a comprehensive manual, and to secure the 
validity of its content, our experts in rheumatology and self-management (members of the project group) 
have reviewed the manual. Further, to train the HPs to deliver the intervention, we have designed a 
competence development program, where the HPs will be trained in ACT questioning techniques and group 
facilitation and in addition get familiar with the manual. To further increase fidelity, we offered the HPs 
ongoing supervision with both the project manager (LHL) and a psychologist trained in ACT. 
 

 
15 
 
Criteria for discontinuing or modifying allocated intervention {11b} 
As this is a minimal-risk intervention, no modification or discontinuation of interventions is anticipated. 
Participants voluntarily participate in the intervention and can withdraw their consent and exit the trial at 
any time. If a participant in the intervention group is unable to attend a scheduled session due to unforeseen 
circumstances, a new individual session will be arranged at the earliest possible convenience. Patients who 
fail to attend the three individual sessions will be classified as non-completers.  
 
Strategies to improve adherence to the intervention {11c} 
Participants will receive SMS/e‑mail appointment reminders; missed sessions will be actively rescheduled. 
Interventionists will complete structured session checklists and upload to REDCap; a 10% sample of sessions 
will be reviewed for fidelity with feedback to providers. To enhance adherence throughout the trial period, 
several strategies will be employed. Participants will be encouraged to practice self-management skills 
through follow-ups during sessions. For the HPs delivering the intervention, we will monitor fidelity to 
research protocols by requiring HPs will complete an evaluation form after each session.  Also, the HPs will 
provide feedback on the delivery of the intervention, participant engagement, and report any adverse 
events. 
 
Relevant concomitant care permitted or prohibited during the trial {11d} 
No specific concomitant care is restricted during the trial. 
 
Provisions for post-trial care {30} 
Post-trial care is usual care.  

 
16 
 
Outcomes {12} 
Self-management is a complex concept that primarily has been utilized in the research of patients with 
chronic diseases. There is no consensus on how to measure self-management in IA (or any other chronic 
disease) [47]. Early IA presents multidimensional challenges (symptoms, function, mental health, 
self‑efficacy, service navigation). The outcome set captures these domains while prioritizing a single primary 
endpoint (heiQ ‘skill and technique acquisition’). Key secondary endpoints follow a pre‑specified hierarchy 
based on feasibility results; interpretation will consider heterogeneity of scales. 
 
 
Primary outcome and endpoint 
The primary outcome is self-management skills assessed with the heiQ “skill and technique acquisition” 
domain [48]. We consider the” self-management skill and technique acquisition” domain to best reflect the 
changes we aim to achieve through our intervention, and therefore it is considered our primary outcome. 
This domain captures knowledge-based skills and techniques used to manage disease-related symptoms and 
health problems. The heiQ comprises eight independent domains (health-directed activity; positive and 
active engagement in life; emotional wellbeing; self-monitoring and insight; constructive attitudes and 
approaches; skill and technique acquisition; social integration and support; health service navigation), each 
scored 1–4, where higher values reflect better self-management (note: emotional wellbeing is reverse-
scored). The heiQ demonstrates sound internal consistency, construct validity, and responsiveness across 
chronic-disease and rheumatology settings [49,50].  The primary endpoint is the between-group difference 
in least-squares means (LS-means) for the heiQ “skill and technique acquisition” score at 12 months from 
baseline, reported with two-sided 95% confidence intervals and p values (superiority defined as p<0.05). 
 

 
17 
 
Key secondary outcomes and endpoints 
Secondary outcomes are the following PROMs: 
• 
Self-management skills measured by seven of the heiQ domains: health-directed activity; positive and 
active engagement in life; emotional wellbeing; self-monitoring and insight; constructive attitudes and 
approaches; social integration and support, and health service navigation [49,50].  The corresponding 
endpoints is the between-group difference in least squares means from the 6 heiQ domains after 12 
months. Endpoints in the extension study are the between-group difference in least squares means in 
heiQ domain 1, 2, 3, 4, 5, 6, 7, and 8 after 24 months. 
• 
Anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS), that has good 
reliability and factorial validity across medical populations, including rheumatology [51,52]. The 
corresponding endpoint is the between-group difference in least squares means from HADS after 12 
months. Endpoint in the extension study is between group difference in HADS 24 months after baseline. 
• 
Fatigue measured by the Bristol Rheumatoid Arthritis Fatigue Numeric Rating Scale (BRAF-NRS), that is 
validated, including Danish versions, with good construct validity and responsiveness [53],  and VAS-
fatigue (0-100). The corresponding endpoint is the between-group difference in least squares means 
from VAS and BRAF-NRS after 12 months. Endpoint in the extension study is between group difference in 
VAS and BRAF-NRS 24 months after baseline. 
• 
Pain self-efficacy measured by the Arthritis specific Self-Efficacy measurement tool (ASES-pain). The 
scale has established internal consistency and predictive validity in arthritis [54,55]. The corresponding 
endpoint is the between-group difference in least squares means from ASES-pain after 12 months. 
Endpoint in the extension study is between group difference in ASES-pain 24 months after baseline. 
• 
Pain Intensity measured by VAS (0-100), a simple, reliable single-item measures with strong convergent 
validity in IA [56,57]The corresponding endpoint is the between-group difference in least squares means 
from VAS after 12 months. Endpoint in the extension study is between group difference in VAS 24 
months after baseline. 

 
18 
 
• 
Patient global assessment measured by VAS-Global, which is validated within rheumatology [58]. The 
corresponding endpoint is the between-group difference in least squares means from VAS after 12 
months. Endpoint in the extension study is between group difference in VAS 24 months after baseline. 
• 
Medication adherence will be measured by the Compliance Questionnaire Rheumatology (CQR)-5-item 
scale, that has acceptable reliability and criterion validity for identifying non-adherence [59,60] The 
corresponding endpoint is the between-group difference in least squares means from CQR after 12 
months. Endpoint in the extension study is between group difference in CQR 24 months after baseline. 
• 
Health Related Quality of Life measured by European Quality of Life (EQ5D-5L), that has validity 
supported across rheumatic diseases; Danish value set applied [61,62]. The corresponding endpoint is 
the between-group difference in least squares means from EQ5D-5L after 12 months. Endpoint in the 
extension study is between group difference in EQ5D-5L 24 months after baseline. 
• 
Loneliness will be measured by the Three Item Loneliness Scale, a short scale validated for measuring 
loneliness [63]. The corresponding endpoint is the between-group difference after 12 months. Endpoint 
in the extension study is between group difference 24 months after baseline. 
• 
Physical function measured by Modified Health Assessment Questionnaire (MD-HAQ) , is well-validated 
and responsive across rheumatology) [64]. The corresponding endpoint is the between-group difference 
in least squares means from MD-HAQ after 12 months. Endpoint in the extension study is between 
group difference in MD-HAQ 24 months after baseline. 
 
Other secondary outcomes and endpoints 
• 
Disease activity measured by the percentage improvement from baseline using various composite scores 
depending on the rheumatic diagnoses. For RA: Disease Activity Score in 28 joints (DAS28) [65], for 
axSpA: the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [66], and for PsA: the Disease 
Activity index for Psoriatic Arthritis (DAPSA) [67].These indices have established reliability, construct 

 
19 
 
validity, and responsiveness in their target populations, and are analyzed as between-group LS-means 
differences at 12 months; the extension study repeats these analyses at 24 months. 
 
All primary and secondary outcomes will be measured at baseline (t=0 months), 12 months after baseline.  
The extension study will report all outcomes, presenting the long-term effect and sustainability at 24 months 
from baseline. 
 
Participant timeline {13} 
The participant timeline is shown in Table 2. 
 
Sample size and power calculation {14} 
As no established thresholds exist for clinically relevant changes in heiQ domains, we refer to prior research 
[68,69]. I prior research in the skills acquisition domain, we found mean differences between groups ranging 
from 0.22 to 0.38. Therefore, we decided that a minimal important difference probably correspond to a 
target difference of 0.30 with a standard deviation (SD) of 0.55 for the heiQ ‘skill and technique acquisition’ 
domain (primary endpoint) from baseline to 12 months after baseline. To achieve a statistical power of 80% 
and a significance level set at an alpha of 0.05, our calculations indicated a need for 54 patients per group 
(i.e., enrolling 108 patients in the Intention to Treat Population (ITT)). Incorporating an anticipated dropout 
rate of 15% from our feasibility study [41], the sample size would correspond to 127. Consequently, we 
revised the necessary sample size to approximately 65 patients per group (i.e., 130 patients in the ITT 
population) to achieve a reasonable statistical power to identify a statistically significant difference between 
the intervention and control group (i.e., corresponding to a statistical power of 87% in the best-case 
scenario). 

 
20 
 
 
Recruitment {15} 
Eligible patients will be identified in the outpatient clinic, the rheumatologist and/or other HPs will briefly 
inform patients about the trial and hand out written information.  
 
Sequence generation {16a} and concealment mechanism {16b}  
Randomization in a 1:1 ratio will be performed after the patient has signed informed consent and completed 
baseline assessments. A computerized random number generator algorithm obtained from the Sealed 
Envelope website [70] will be used to provide customized randomization tables.  Randomization will be 
stratified by site (3 centers) and type of inflammatory condition (3 diagnoses). To facilitate this,  the 
customized randomization tables will be uploaded for each site to Research Electronic Data Capture 
(REDCap) [71] allowing for stratification across three individual IA conditions. The REDCap randomization 
module will be used for allocation generation and to securely maintain the sequence until the intervention is 
assigned. 
 
Implementation {16c} 
The project manager will enroll participants at the individual sites and inform them whether they have been 
allocated to the intervention group or the control group (see Fig. 1 for participants flow through the trial). 
For participants randomized to the intervention group, the first individual session will be scheduled as soon 
as possible after allocation.  
 

 
21 
 
Who will be blinded {17a} 
Due to the nature of the intervention, it is not possible to blind participants or HPs to the allocated 
intervention. Outcome assessors abstracting clinical indices from DANBIO/electronic records will be blinded 
to group allocation wherever feasible. Analyses will be performed with groups masked until the primary 
analysis is finalized. 
 
Procedure for unblinding if needed {17b} 
This item does not apply as participants and HPs knew the group allocation.  
  
Data collection and management 
Plans for assessment and collection of outcomes {18a} 
Socio-demographic and lifestyle data will be collected at baseline. For the primary analyses, outcomes will be 
measured at baseline and 12 months after baseline. An additional 24-month follow-up assessment will be 
included in the extension study (See Fig. 1 and Table 2). Diagnosis and disease duration will be obtained from 
the electronic Danish Rheumatology Database DANBIO [72–74]. Data on pharmacological treatment will be 
obtained from the electronic medical record (Sundhedsplatformen), and data on disease activity from 
DANBIO using the nearest value to the current measurement timepoint. Data will be extracted from 
DANBIO/electronic records by trained staff blinded to allocation; a 10% random sample will be re‑abstracted 
to evaluate agreement (kappa/ICC). 
The self-administered questionnaires will be entered by the participants into the electronic project manager 
tool REDCap [75]. Patients will have the flexibility to complete the questionnaire either on-site at the hospital 

 
22 
 
or through their official digital mailbox ('e-Boks'), based on their preference. All other data will be entered 
into REDCap by the project manager (LHL). 
 
Table 2. Diagram of enrolment, interventions, and assessments – study period 0-12 (and 24 months) 
 
Measurement 
 
Enrolment 
Baseline 
End of 
intervention 
(primary 
endpoint) 
Follow-up 
(extension 
study) 
Time point 
 
Before 
Baseline 
Week -2 to 0 
12 months 
after 
baseline 
24 months 
after 
baseline 
Enrolment 
 
 
Eligibility criteria 
 
X 
 
 
 
Informed consent 
 
X 
 
 
 
Allocation 
 
 
X 
 
 
Intervention 
 
NISMA-intervention 
 
 
X 
X 
 
Usual care 
 
 
X 
X 
 
Assessments 
 
Outcomes 
Primary outcome 
Self-management skills and 
technique measured by 
HeiQ1  
HeiQ: Domain 6: Skill and technique acquisition 
 
X 
X 
X 
Key secondary outcomes 
Self-management skills  
HeiQ: Domain 1: Health-directed activities 
 
X 
X 
X 
HeiQ:  Domain 2: Positive and active 
engagement in life 
 
X 
X 
X 
HeiQ:  Domain 3. Emotional distress 
 
X 
X 
X 
HeiQ: Domain 4: Self-monitoring and insight 
 
X 
X 
X 
HeiQ:  Domain 5: Constructive attitudes and 
approaches 
 
X 
X 
X 
HeiQ:  Domain 7: Social integration and support 
 
X 
X 
X 
HeiQ:  Domain 8: Health service navigation 
 
X 
X 
X 
Anxiety and depression 
HADS Anxiety  
 
X 
X 
X 
HADS Depression  
 
X 
X 
X 
Fatigue  
 
BRAF-NRS severity 
 
X 
X 
X 
BRAF-NRS impact 
 
X 
X 
X 
BRAF-NRS coping 
 
X 
X 
X 
VAS-fatigue 
 
X 
X 
X 
Pain self-efficacy  
ASES-pain 
 
X 
X 
X 
Pain intensity  
VAS-pain 
 
X 
X 
X 
Global assessment by  
VAS-global 
 
X 
X 
X 
Medication adherence  
CQR-5-item scale 
 
X 
X 
X 
Quality of life by  
EQ5D-5L 
 
X 
X 
X 
Loneliness by  
Three-Item Loneliness Scale 
 
X 
X 
X 
Physical function by  
MD-HAQ 
 
X 
X 
X 
Other Secondary outcomes  
Disease activity by 
condition 
 
DAS28 for RA 
 
X 
X 
X 
BASDAI for axSpA 
 
X 
X 
X 
DAPSA for PsA 
 
X 
X 
X 

 
23 
 
Acute phase reactant value  
C-reactive protein 
 
X 
X 
X 
Additional measures 
Age, sex, educational level, 
cohabitation, work status 
Questionnaire 
 
X 
 
 
Diagnoses 
Medical record 
 
X 
 
 
Pharmacological treatment 
of arthritis (DMARDS) 
Medical record 
 
X 
 
 
Use of pain medication 
Medical record 
 
X 
 
 
Use of glucocorticoids  
Medical record  
 
X 
 
 
Co-morbidity* 
Medical record and Questionnaire 
 
X 
 
 
Smoking 
Questionnaire 
 
X 
 
 
Alcohol 
Questionnaire 
 
X 
 
 
*Diabetes, hypertension, myocardial infarction, chronic obstructive pulmonary disease, cancer, osteoarthritis, osteoporosis, asthma, depression, or 
anxiety.   
 
ASES (Arthritis Self-Efficacy Scale); axSpA (axial spondyloarthritis); BASDAI (Bath Ankylosing Spondylitis Disease Activity Index); BRAF-NRS (Bristol 
Rheumatoid Arthritis Fatigue Numerical Rating Scale); CQR-5 (Compliance Questionnaire Rheumatology, 5-item); DAS28 (Disease Activity Score in 28 
joints); DAPSA (Disease Activity in Psoriatic Arthritis); DMARDs (disease-modifying antirheumatic drugs); EQ5D-5L (EuroQol 5 Dimensions 5 Levels); 
HADS (Hospital Anxiety and Depression Scale); heiQ (Health Education Impact Questionnaire); MD-HAQ (Modified Health Assessment Questionnaire); 
PsA (psoriatic arthritis); RA (rheumatoid arthritis); VAS (visual analogue scale). 
 
Plans to promote participants retention and complete follow-up {18b} 
To promote participant retention and ensure complete follow-up participants will be thoroughly informed 
about the data collection process and timepoints and the importance of data completeness for the project. 
Further, questionnaires will be re-sent after two weeks.  
 
Data management {19}  
Collected data will be stored securely, physically, and digitally, anonymized using a unique participant 
research ID, and accessed only by the team members trained in data management.  
 
Confidentiality {27}  
Data will be stored on password-protected computers and entered into a computer database (REDCap). For 
all analyses, subjects will be identified by their unique study ID. Limited information will be retained on 

 
24 
 
patients who are pre-screened and do not qualify, or who are approached and decline participation, to 
generate a CONSORT flow diagram.  
 
Plans for collection, laboratory evaluation, and storage of biological specimens 
for genetic or molecular analysis in this trial/future use {33}  
This item does not apply as no biological specimens will be collected. 
 
Statistical methods for primary and secondary outcomes {20a} 
Descriptive statistics for baseline data will be reported in a Table 1 format; reported separately for each 
treatment group. These descriptive statistics will summarize the characteristics of participants at baseline, 
including demographic information and outcome variables relevant to the trial. Descriptive statistics include 
the mean and standard deviation (SD), or median and interquartile ranges (if applicable). For categorical data 
we will report the count and percentages. 
If ANCOVA assumptions are not met, we will consider rank‑based ANCOVA (aligned ranks) or transformation 
as pre‑specified alternatives; any post‑hoc analyses will be labeled exploratory. 
The primary endpoint will be based on the change in heiQ from baseline to 12 after baseline, estimated as 
the difference between least squares means. In our main analyses, estimations of between-group 
differences for all continuous outcomes will be conducted after 12 months. The primary endpoint will be 
analyzed using analysis of covariance (ANCOVA), adjusting for baseline values, trial site, and type of IA 
diagnosis as covariates. The analyses of the secondary endpoints will be performed and interpreted in 
sequence until one of the analyses fails to show the statistically significant difference, or until all analyses 
have been completed at a statistical significance level of 0.05 (P<0.05). All analyses in the statistical hierarchy 
will be based on the treatment policy estimand (the primary estimand, i.e., the ITT principle), which quantify 
the average treatment effect regardless of adherence to treatment or initiation of rescue interventions 

 
25 
 
between baseline and month 12. Key assumptions for statistical tests, including normality of residuals in 
ANCOVA, will be assessed using studentized residuals scattered against the predicted values, and other 
graphical methods (e.g., Q-Q plots, histograms). If assumptions are violated, alternative methods such as 
nonparametric tests (e.g., Wilcoxon rank-sum test) or transformation of variables will be considered.  
 
The extension study  
Given the availability of repeated measures in the extension study, missing data will be addressed implicitly 
using repeated-measures mixed-effects models. The primary and key secondary (continuous) outcomes will 
be analyzed using linear mixed-effects models (LMMs) with repeated measures, incorporating: Treatment 
group (2 levels: intervention, control), time (0, 12, and 24 months after baseline [3 levels]), group × time 
interaction, baseline values of the respective outcome as a covariate, and stratification factors: center (3 
levels) and diagnosis (3 levels) 
This approach ensures that all intergroup differences at each timepoint are adjusted for baseline levels, 
thereby minimizing random variation. Least squares means (LSMs), and their standard errors will be reported 
for each group, with between-group differences presented as adjusted LSM differences with two-sided 95% 
CIs and P values. Superiority will be defined as P < 0.05. 
 
Interim analyses {21b}  
This item does not apply as there will be no interim analyses.  
 
Methods for additional analyses (e.g., subgroup analyses) {20b}  
This item does not apply as no additional analyses are planned.  
 

 
26 
 
Methods in analysis to handle protocol non-adherence and any statistical methods 
to handle missing data {20c} 
The main analyses will be based on the ITT population, i.e., including all randomized patients with a baseline 
measure available [76]. The ITT principle asserts the effect of a treatment policy (that is, the planned 
treatment regimen), rather than the actual treatment given (i.e., it is independent of treatment adherence) 
[9].  Accordingly, participants allocated to a treatment group (NISMA and Control, respectively) will be 
followed up, assessed, and analyzed as members of that group, irrespective of their adherence to the 
planned course of treatment (i.e., independent of withdrawals and cross-over phenomena). 
All 95% confidence intervals and P values will be two sided. We will not apply explicit adjustments for 
multiplicity, rather we will analyze the key secondary outcomes and interpret these as endpoints in a 
prioritized order (e.g., “gatekeeping procedure”). 
A multiple imputation approach will be used in which missing data are imputed from month 12 
measurements from participants in the same treatment group. A series of complete data sets will be 
generated and analyzed, and the results will be combined using the Rubin formula [77] to obtain overall 
estimates. While binary outcomes will be analyzed and initially reported using Odds Ratios with 
95%confidence intervals (95%Cis), all between-group differences 95%Cis for continuous outcomes will be 
based on the least square means, adjusted for baseline levels and stratifying factors to minimize random 
variation [78].  
Continuous outcome measures will be analyzed using analysis of covariance, with randomized treatment, 
trial site, and type of IA diagnoses as factors, and baseline (pre-exposure) value as a covariate. Categorical 
end points will be analyzed using logistic regression, with the same factors and covariates.  
 

 
27 
 
Plans to give access to the full protocol, participant-level data, and statistical code 
{31c}  
Any changes to eligibility criteria, outcomes, or analyses during the study will be reported to 
ClinicalTrials.gov, and participants as needed. 
Due to the Italian data protection laws and GDPR regulations, access to participant-level data is restricted. 
The full study protocol and statistical analysis plan will be made available upon reasonable request to 
authorized regulatory authorities, ethics committees, and academic institutions in compliance with legal and 
ethical requirements. 
 
Oversight and monitoring  
Composition of the coordinating center and trial steering committee {5d} 
We have established a project group to ensure the timely execution, progress, and quality of the project. The 
group consists of one patient research partners, a professor in rheumatology nursing and self-management, 
a professor in rheumatology, a professor in rheumatology nursing and epidemiology, a professor in 
physiotherapy, a professor in biostatistics, a postdoc in occupational therapy and a postdoc in nursing. The 
project group has expertise within rheumatology, patients with chronic diseases, patient education, 
rehabilitation, health promotion, coping and telemedicine. The group expertise represents extended 
experience of RCT’s, qualitative research, and epidemiology. 
 
Composition of the data monitoring committee, its role and reporting structure {21a}  
Data monitoring committee is not required for this study. 

 
28 
 
 
Adverse event reporting and harms {22} 
This is a non-drug intervention trial using educational elements, behavioral therapies, and self-efficacy 
training strategies – all elements included in the daily work of many HPs and clinical practice. Participants will 
be monitored throughout the period of the intervention in order to detect any unintended events and to 
optimize security.  Adverse events occurring in the sessions will be reported and registered by the HPs. All 
serious adverse events will be reported to the Research Ethics Committee [79].  
 
Frequency and plans for auditing trial conduct {23} 
There are no procedures for auditing trial conduct.  
 
Plans for communicating important protocol amendments to relevant parties (e.g., 
trial participants, ethical committees) {25} 
All protocol amendments must be submitted to the Danish Ethical Committee for approval before 
implementation in the ongoing trial. The Principal Investigator (PI) is responsible for communicating these 
amendments and obtaining the necessary approvals. Once approved, an updated version of the protocol will 
be distributed to all study sites. The PI will ensure that amendments are reflected by updating the protocol’s 
date and version number. Additionally, all amendments will be documented within the protocol, and clinical 
trial registries will be updated accordingly to maintain transparency and compliance. 
 

 
29 
 
Dissemination plans {31a} 
The dissemination of results from our trial will be comprehensive and multifaceted, ensuring broad visibility 
irrespective of the results’ alignment with the initial hypothesis—whether they support the intervention, 
favor the comparator, or are ambiguous. Our communication strategy includes the publication of scientific 
papers in peer-reviewed journals and presentations at pertinent academic conferences. Additionally, we aim 
to engage a wider audience by leveraging news outlets, social media platforms, and both online and offline 
educational resources, including multimedia materials and printed literature. These efforts will be 
complemented by oral presentations and articles in popular science magazines to make our research 
accessible to the public. 
In terms of authorship, our policy aligns with the guidelines set forth by the International Committee of 
Medical Journal Editors (ICMJE), ensuring that all contributors who meet these criteria are recognized 
appropriately. Every author will be granted full access to the study data, promoting transparency and 
collaboration. 
Should there be any significant modifications to the trial protocol, these changes will be formally 
communicated to the Committee on Health Research Ethics for The Capital Region of Denmark. Moreover, 
all amendments will be duly registered on ClinicalTrials.gov and detailed in the primary report of the RCT, 
maintaining the integrity and transparency of the research process. 
 
Patient involvement 
This trial is designed with a solid patient focus. From the very beginning, three patients were involved in the 
initial design and development of the NISMA intervention (reported elsewhere [38]). During the feasibility 
testing and process evaluation (Phase 2), all patients were interviewed to include their views on the 
intervention [42]. We have also involved a patient with RA as research partner in the project group in all 

 
30 
 
project phases of NISMA. Studies have shown that this supports maintain the patient perspective, the 
relevance of the project focus and structure, and the results and implementation [80]. 
 
Discussion 
Several studies have highlighted the need for targeted interventions for newly diagnosed patients with IA 
[17–23]. Newly diagnosed patients are considered as a particularly vulnerable group and strengthening their 
self-management skills from the outset can lead to better long-term outcomes and increased self-
management abilities. However, evidence on effective intervention components remains limited. The NISMA 
RCT is designed to address this gap by evaluating a systematically developed intervention ) within the 
framework of the Medical Research Council [39,40].  Building on our prior feasibility study [81] and a 
comprehensive process evaluation [42] that examined contextual influences on delivery, fidelity, 
mechanisms of impact, and acceptability. Together, these preparatory studies indicate that the intervention 
is relevant, acceptable, and feasible to implement in routine care, providing a clear rationale for definitive 
evaluation in an RCT. Compared with conventional care—which typically prioritizes rapid pharmacologic 
control alongside variable, often ad hoc education—NISMA offers a structured, manualized program 
delivered early after diagnosis, integrating group facilitation with individual goal-setting, action planning, 
problem-solving, and cognitive-behavioral strategies.  
This targeted timing and method are intended to accelerate patient activation, improve navigation of 
services, and embed sustainable behaviors within routine clinical pathways, potentially yielding benefits 
beyond symptom control (e.g., mental health, coping, and engagement with care) [30,82]. 
Plausible mechanisms span both psychosocial, and physical domains. Reducing threat appraisal and stress 
reactivity, improving sleep, and increasing regular physical activity may modulate central pain processing and 
fatigue, supporting better symptom control. Psychosocially, gains in self-efficacy, insight, constructive 
attitudes, and social integration (as captured by heiQ domains) can enhance coping, resilience, and shared 

 
31 
 
decision-making. Physically, improved adherence, joint protection, pacing, and graded activity may preserve 
function and reduce flares. Together, these pathways are hypothesized to translate into fewer 
complications, lower symptom burden, and better quality of life [36,83], with potential downstream 
reductions in unplanned care and hospitalizations [84]. 
In line with EULAR recommendations, it foregrounds the role of HPs in symptom control, patient-reported 
outcomes, and psychosocial/lifestyle support, with training in group facilitation, problem-solving, goal-
setting, action planning, and cognitive-behavioral techniques [85,86]. This skill set strengthens 
multidisciplinary collaboration, streamlines workflows, and enables more personalized care, improving 
patient experience and clinician satisfaction [86]. 
The trial also incorporates an economic evaluation to inform scalability and adoption. When the NISAM trial 
is completed, we will conduct a cost-utility analysis using EQ5D-5L (Danish value set) to estimate QALYs, 
alongside a cost-consequence summary of key outcomes, from the healthcare payer perspective over 12 and 
24 months, with prespecified sensitivity analyses  [87]. If efficacy is confirmed, implementation work will 
examine feasibility, workforce requirements (including HP upskilling), reach, and sustainability across 
settings, supporting routine integration and equitable access [88,89].  
The trial’s scope and implications extend beyond IA symptom management. If NISMA proves effective and 
cost-effective, it will support embedding structured self-management at the diagnostic window as standard 
practice, strengthen multidisciplinary collaboration, and provide a replicable training model for HPs. Findings 
will also clarify which components and mechanisms matter most, guiding adaptation for heterogeneous IA 
phenotypes and informing policy and service design in rheumatology. 
In sum, NISMA has the potential to improve outcomes that matter to patients and to the health system, 
while providing robust evidence on effectiveness, and value for money. 

 
32 
 
Limitations  
Key limitations include the risk of contamination between arms within shared services, variability in disease 
trajectories early after diagnosis, and reliance on PROMs that may be influenced by expectancy and context. 
We mitigate these through a manualized curriculum, fidelity monitoring and supervision, prespecified 
analyses (including sensitivity and mediation analyses), and triangulation with clinical indices. Generalizability 
will be examined across participating sites, with attention to implementation contexts. Concomitant care 
was not restricted or systematically recorded; however, we trust that randomization distributed such 
practices evenly across groups, thereby minimizing the risk of systematic bias. Due to the nature of the 
NISMA intervention blinding of participants is impossible. However, the outcome assessor will be blinded, 
and participants will be asked not to disclose their group to the assessor. Second, spillover effect can be 
occurring, the participants in the control group may be receiving intervention fragments in the outpatient 
clinic or seek for additional support e.g., patient organizations. Moreover, the dose and content of usual care 
may be different among participants. Also, we cannot report the precise intervention content delivered to 
each participant, as the intervention is individually adjusted to individual challenges. 
 
Trial status 
The latest protocol version approval date is September 2025. Recruitment began 09-12-2024 with an 
expected completion date in December 2025. Therefore, the last patient first visit is expected to be around 
30-12-2025.  
Abbreviations  
ACT — Acceptance and Commitment Therapy 
ANCOVA — analysis of covariance 
ASES / ASES-pain — (Arthritis) Self-Efficacy Scale / pain subscale 
axSpA — axial spondyloarthritis 
BASDAI — Bath Ankylosing Spondylitis Disease Activity Index 
BRAF-NRS — Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scale 

 
33 
 
CONSORT — Consolidated Standards of Reporting Trials 
CQR-5 / CQR-5-item — Compliance Questionnaire Rheumatology (5-item) 
DANBIO — Danish nationwide rheumatology registry 
DAPSA — Disease Activity in Psoriatic Arthritis 
DAS28 — Disease Activity Score in 28 joints 
DMARDs — disease-modifying anti-rheumatic drugs 
EQ5D-5L — EuroQol 5 Dimensions, 5 Levels 
EULAR — European Alliance of Associations for Rheumatology 
GDPR — General Data Protection Regulation 
HADS — Hospital Anxiety and Depression Scale 
heiQ / HeiQ — Health Education Impact Questionnaire 
HPs — health professionals 
IA — inflammatory arthritis 
ICC — intraclass correlation coefficient 
ITT — intention-to-treat 
LHL — Luise Holberg Lindgren 
LS-means — least-squares means 
MD-HAQ  — Modified Health Assessment Questionnaire 
NISMA — Newly diagnosed with Inflammatory arthritis — a Self-MAnagement intervention 
PI — Principal Investigator 
PROMs — patient-reported outcome measures 
PsA — psoriatic arthritis 
PT / OT — physiotherapist / occupational therapist 
QALYs — quality-adjusted life years 
Q–Q (plots) — quantile–quantile (plots) 
QoL — quality of life 
RA — rheumatoid arthritis 
RCT — randomized controlled trial 
REDCap — Research Electronic Data Capture 
SCT — Social Cognitive Theory 
SD — standard deviation 
SPIRIT — Standard Protocol Items: Recommendations for Interventional Trials 
VAS / VAS-Global — visual analogue scale / patient global assessment by VAS 
 
 
Acknowledgements 
We would like to thank all patients and HPs who contributed to the development and feasibility test of the 
NISMA intervention, which laid the foundation for the final RCT design. 

 
34 
 
We also thank the patient research partner Sara Danshøj Christensen who approved the participant 
information, contributed to discussions on trial concept and collaborated on the intervention in NISMA as 
recommended by the European League Against Rheumatism. 
 
Authors’ contributions {31b} 
All authors contributed to the trial concept and the design. LHL and BAE performed the draft. All the authors 
(LHL, TT, AT, MA, MLH, RC, and BAE) read, critically revised, and approved the final version of the 
manuscript. All the authors are accountable for all aspects of the work. 
 
Funding {4} 
The NISMA trial is supported by grants from the Danish Rheumatism Association (grant nr.: R251-A9062), the 
Lundbeck Foundation, and the Novo Nordic Foundation (grant nr.: 0096696).  
 
Availability of data and material {29} 
All requests of data will be made available at reasonable request to the PI. 
 
Declarations  
Ethics approval and consent to participate {24} 
The trial was approved by the Regional Committee on Health Research Ethics for the Capital Region of 
Denmark nr H-24046135. Furthermore, the RCT was approved by the Danish Data Protection Agency of the 
Capital Region of Denmark (Nr.: p-2024-15846) and was registered at ClinicalTrials.gov. nr.: NCT06533423. 

 
35 
 
All data will be treated confidentially and in accordance with EU legislation and data security regulations, and 
legislation (GDPR). The principles of the Declaration of Helsinki will be followed. We will secure informed 
consent from participants. The trial sponsor and the project manager will secure that all information 
collected during the study will be kept confidential in accordance with Danish Data Protection Agency rules.  
This trial protocol has been prepared as outlined in the PREPARE guide [90], and reported according to the 
Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist [91]. 
 
All potential patients will receive oral and written information about the trial. Participation is voluntary, and 
participants can at any time and without justification leave the trial without affecting their rheumatological 
their treatment. The participants will give the primary investigator and project manager permission to obtain 
data from the patients' journals in the informed consent. Informed consent material is available in Danish.  
Consent for publication {32} 
The informed consent form is available from the corresponding author on request. 
Competing interests {28} 
The authors declare that they have no competing interests. 
 

 
36 
 
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