COMFI - a COMbined Fatigue Intervention

Background: Inflammatory arthritis (IA) encompasses chronic autoimmune rheumatic diseases, such as rheumatoid arthritis (RA) and spondyloarthritis (which includes psoriatic arthritis, PsA, and axial spondyloarthritis, axSpA). In Denmark, the prevalence of people living with RA, PsA, or axSpA is approximately 50,000, 25,000, and 5,000 respectively. The characteristics of IA-related symptoms encompass swollen joints, stiffness, loss of physical function, pain, fatigue, sleep problems, and emotional distress. Despite advances in pharmacological treatment over the last decades and treat-to-target strategies aiming to reduce disease activity for people with IA, many still struggle with the substantial impact of fatigue on their everyday lives. Fatigue is highly prevalent in people with IA with 41-57% suffering from severe fatigue. The patients describe fatigue as overwhelming, unpredictable, disabling, challenging to manage, and affecting all areas of everyday life, including their health-related quality of life (HRQOL), performance of activities, and participation in daily living. Participation includes workability, which is important for a person's identity to be able to work, and it provides a sense of purpose and quality of life. Patients expressed the need for support to manage the impact of IA-related fatigue on everyday life. Besides the individual burden of living with fatigue, the high levels of absenteeism, and work disability contribute to societal and economic costs. Thus, from both a patient and a societal perspective, interventions aiming to reduce the impact of fatigue in people with IA are needed.

To encompass the complex and multidimensional nature of fatigue, a management approach incorporating pharmacological and non-pharmacological interventions is needed. Reviews on non-pharmacological interventions for fatigue in people with RA have shown that psychosocial and physical activity interventions can reduce fatigue severity. Additionally, studies have documented that interventions with physical activity or a cognitive behavioral approach significantly reduced fatigue severity and/or impact in people with IA compared to usual care. One of those, the Lessening the Impact of Fatigue in Inflammatory Rheumatic Disease Trial (LIFT) study compared three arms: 1) usual care 2) usual care and a cognitive behavioral approach, and 3) usual care and a personalized exercise program. Both a cognitive behavioral approach and a personalized exercise program, in addition to usual care, reduced fatigue severity and impact compared to usual care only. In the Reducing Arthritis Fatigue: clinical Teams using CB approaches (RAFT) study, a cognitive behavioral approach was delivered in a face-to-face group intervention by trained members of the rheumatology team in addition to usual care significantly reduced fatigue impact and increased self-efficacy compared to usual care only. Additionally, the study showed high patient satisfaction and attendance in the cognitive behavioral approach group. To include both a cognitive behavioral approach and a personalized exercise program may reduce the severity and impact of fatigue further, but to date, no studies have investigated the combined effect of a cognitive behavioral approach and physical activity on fatigue severity and impact in patients with IA.

Thus, the aim of this study is to evaluate the feasibility (acceptability, dose, and fidelity) and preliminary outcomes of the developed COMFI, which combines a cognitive behavioral approach and physical activity support for people with IA to improve the management of fatigue and to reduce fatigue severity and -impact among patients with IA in Soenderborg, Denmark and Lund, Sweden.

Methods The testing of COMFI will be guided by the UK Medical Research Council (MRC) framework for developing and evaluating Complex Interventions.

This feasibility study is a single-arm interventional study to assess the COMFI intervention, which is a newly developed 24-week group-based outpatient fatigue intervention consisting of 1) Six group sessions based on a cognitive behavioral approach covering topics such as fatigue and related factors, physical activity, trying out physical activity, energy management, and enhancing peer support 2) a seventh group session intended as a booster session in week 24, 3) one optional individual session in week 6-9 of COMFI, and 4) a support line in week 13-23 of COMFI. Additionally, the participants will participate in 2 focus group interviews after the sixth and seventh sessions to enable a qualitative evaluation of the intervention.

The groups in the intervention will consists of 8-10 participants, and the intervention will be tested in two groups in each site (four in total), which means 16-20 patients with IA from each of the involved hospitals will be included in this feasibility test.

Recruitment in Denmark: Before clinical consultations, the patient completes questionnaires in the Danish Rheumatology Quality Database (DANBIO), including. VAS fatigue. If VAS fatigue ≥60, a text appears on the screen with information about the project and the opportunity to add their phone number for further contact. The research department then contacts eligible patients to provide more information about the project and request written consent for participation and accessing medical records and data in DANBIO. Eligible patients receive written information and consent material electronically or via postal mail.

Recruitment in Sweden: Manually check in Swedish Rheumatology Quality Register (SRQ) for eligible patients and contact them to inquire if they are interested in participating in the project. The following procedure will be the same as in Denmark.

Data collection: Outcomes will be measured at baseline (week 0), end of intervention (week 12), after the booster session (week 24), and at follow-up (week 52). Patient-reported outcomes will be collected through the software program RedCap, and the databases DANBIO and SRQ. Physical measurements or tests will be imputed into REDCap. Additionally, Information on attendance, time use, etc. will be recorded by the health professionals in a "logbook".

Ethics The project is conducted in line with the Helsinki Declaration, and the Danish and Swedish codex for research. The project is registered at the Danish Data Protection Agency and the local regional scientific ethical committee in the Region of Southern Denmark declared that the project does not need formal approval (case number: S-20232000 - 110). Ethical approval from The Swedish Ethical Review Authority has been obtained. All participants will receive oral and written information about the study and provide written consent to participate. Data will be pseudo-anonymized and measures to protect the integrity of the participants will be taken. Data storage and management in Open Patient Data Explorative Network (OPEN) (a secure application in the Region of Southern Denmark), which is a secure application in the Region of Southern Denmark which complies with the European General Data Protection Regulation (GDPR) and Danish law for data protection.

• Physical activity - objectively measured [Срок оценки: Baseline and at 6-month follow-up]
• Physical activity - Diary [Срок оценки: Baseline and at 6-month follow-up]
• Physical activity - Physical fitness test [Срок оценки: Baseline]
• Physical activity - Patient-reported [Срок оценки: At Baseline, and 3, 6, and 12-month follow-up]
• Health-related quality of life [Срок оценки: At Baseline, and 3, 6, and 12-month follow-up]
• Health-related quality of life visual analog scale (VAS) [Срок оценки: At Baseline, and 3, 6, and 12-month follow-up]
• Mental Well-being [Срок оценки: At Baseline, and 3, 6, and 12-month follow-up]
• Stress [Срок оценки: At Baseline, and 3, 6, and 12-month follow-up]
• Pain level [Срок оценки: At Baseline, and 3, 6, and 12-month follow-up]
• Disease impact [Срок оценки: At Baseline, and 3, 6, and 12-month follow-up]
• Sleep [Срок оценки: At Baseline, and 3, 6, and 12-month follow-up]
• Physical function [Срок оценки: Baseline]