Background: Benefits of interventions are more likely to be published from randomized controlled trials (RCTs) than harms, and most information on side effects collected in RCTs is evaluated through the eyes of clinicians. However, patients and clinicians have different perspectives on side effects, and more than half of side effects reported in drug RCTs of rheumatic and musculoskeletal diseases (RMDs) are appropriate for patients’ own reports (1). Still, a suitable measurement instrument to assess the patient perspective on symptomatic treatment-related side effects in RMDs is lacking (2).

Objectives: This study evaluates what patients with inflammatory arthritis (i.e. rheumatoid arthritis [RA], psoriatic arthritis [PsA] and axial spondyloarthritis [AxSpA]) consider important to know about symptomatic side effects they may experience from a prescription drug if it gets to the market.

Methods: Patients over 18 years with inflammatory arthritis, who had one or more prescribed drugs for their disease for at least 12 months, participated in focus groups and individual interviews. All discussions were recorded, transcribed verbatim, anonymised, and analysed using reflexive thematic analysis.

Results: We conducted seven focus groups and 10 individual interviews with 34 participants across three continents: 14 were from Europe, 11 from North America, and 9 from Australia. They had a mean age of 58 (range 21-81) and a mean disease duration of 23 years (range 2-50). The majority were women ( n= 22, 65%), white ( n= 33, 97%), and currently taking biologic-DMARDs ( n= 24, 71%) or conventional-DMARDs ( n= 17, 50%). Nearly 60% had RA, 20% had PsA, and 20% had AxSpA.

Various aspects were important to patients in assessment of side effects from medical treatment (Figure 1). Safety-aspects appropriate for being directly collected and reported from patients included ‘impact on life’, which was connected to participants ‘daily life’, ‘family life’, ‘work life’, and ‘social life’. In the ‘psychological and physical aspects’ participants described ‘limitation to physical function’, ‘emotional dysregulation’ and ‘an overall mental state’. Extra tests, hospital visits and payment for medication were considered a ‘time, energy and financial burden’ of side effects. Other aspects should not be overlooked by clinicians and researchers but are less appropriate for patient’s self-reports. However, clinicians should know that patients accept a certain level of side effects with medication but weigh these up against their perceived benefits of treatment. This ‘benefit-harm-balance’ is essential to patients and includes the ‘cumulative burden’ of having several side effects at the same time and the persistence of side effects over time. Nevertheless, there was no clear way to measure the ‘benefit-harm-balance’ and the ‘cumulative burden’ of symptomatic side effects. Still, patients suggest ‘severity’, ‘frequency’, and ‘duration’ to be important measurement issues in assessment of side effects from drug treatments.

Conclusion: Patient perspectives on safety constitutes an outcome reflecting overall measures of the cumulative burden and the benefit-harm-balance. These findings contribute new evidence in support of a target domain - an outcome that represents the patient voice evaluating the symptomatic treatment-related adverse events for people with RMDs enrolled in clinical trials. Our findings will guide patient-centred care and future research of how to measure patients own reports of side effects.

REFERENCES: [1] Berthelsen DB, Woodworth TG, Goel N, Ioannidis JPA, Tugwell P, Devoe D, et al. Harms reported by patients in rheumatology drug trials: a systematic review of randomized trials in the cochrane library from an OMERACT working group. Semin Arthritis Rheum. 2021 Jun;51(3):607–17.

[2] Klokker L, Berthelsen DB, Woodworth T, Andersen KM, Furst DE, Devoe D, et al. Identifying possible out-come domains from existing outcome measures to inform an OMERACT core domain set for safety in rheumatology trials. J Rheumatol. 2019 May;46(9):1173–8.

Figure 1.

Patients’ perspective of important themes and sub-themes when assessing side effects in clinical trials.

Acknowledgements: The authors wish to thank all members of the OMERACT Safety Working Group for discussions in preparing this study and in the results of the study. We deeply thank our collaborators who helped to recruit for the study – a special thanks to Dan Furst (David Geffen School of Med. Division Rheuma-tology, UCLA), Catherine Hofstetter (Chair OMERACT PRP Support Team), Ben Horgan (East Metro Health Service, Western Australia), Maarten de Wit (EMGO+ research institute, Amsterdam), and Lyn March (University of Sydney) for their effort in trying to help us to “get the recruiting snowball running”. We gratefully thank all patients who participated in our online discussions and helped us to better understand side effects from the patients’ perspectives. Thanks to Peter M Brooks (University of Melbourne, Victoria, Australia) for chairing the Safety Working Group. Also, thanks to the OMERACT secretariat and executive for their ongoing support of our work, particularly Shawna Grosskleg for her administrative support.

Disclosure of Interests: None declared.