Op0131 Occurrence and Predictors of Multiple Dmard Treatment Failure in Rheumatid Arthritis (Ra): Results From the Swedish Rheumatology Quality Register

Background: Thanks to breakthroughs in pharmacological treatment, earlier diagnosis, and improved treatment strategies the outcome of RA has improved markedly over the past few decades. However, a subgroup of patients remains difficult to treat. Previous studies have indicated that up to 20% of patients progress to a third biological disease modifying anti-rheumatic drug (bDMARD). 1,2 Estimation and early identification of this difficult-to-treat group of patients is crucial for optimal prevention and management. Objectives: To identify the occurrence and baseline predictors of multiple treatment switch of biological and targeted synthetic DMARDs (b/tsDMARDS) in RA. Methods: We designed an observational cohort study on adult patients diagnosed with RA between 2010-2019 based on data from the Swedish Quality Rheumatology register (SRQ). Patients were required to have at least three years of follow-up (maximum 13, i.e., until 2023) from the RA diagnosis. Three patient groups were defined: 1) patients followed from the RA diagnosis, 2) patients starting a first ever DMARD, and 3) patients starting a first ever b/tsDMARD. Baseline (start of follow-up) was defined as the time of RA diagnosis in the first group, start of a first ever DMARD in the next group, and start of a first ever b/tsDMARD in the last group. Only patients with a baseline visit were included in the analyses. We used two different definitions of the outcome ("multi-failing"): 1) 'Definition 1' was defined as failure of ≥3 b/tsDMARDs. 2) 'Definition 2' was defined as failure of ≥2 b/tsDMARDs with different mechanisms of action, which corresponds to the 1st criterion in the EULAR's definition of difficult to treat RA (D2T). Univariate and multivariable logistic regression analyses were conducted to investigate baseline factors associated with multi-switching. Results: A total of 17 780 (group 1), 18 038 (group 2) and 7957 (group 3) patients were identified. The proportions of patients reaching outcome 1 (failing ≥3 b/tsDMARDs) were 8%, 8% and 21% in group 1, 2 and 3, respectively. Outcome 2 (failure of ≥2 b/tsDMARD with different mechanisms of action) were observed in 10%, 11% and 26% in group 1, 2 and 3, respectively. Within 5 years from their baseline 5% of the patients in groups 1 and 2 and 16% among patients who started a first ever b/tsDMARD had failed ≥3 b/tsDMARDs. Within the same time period the risk of fulfilling definition 2 was 3% for groups 1 and 2, and 8% for group 3. In the univariate logistic regression analyses, female gender, younger age, higher pain, fatigue and HAQ, no concomitant conventional synthetic DMARD, seropositivity, high DAS28-ESR and a longer symptom duration before diagnosis were associated with outcome 1 in patient group 1. In the multivariable logistic regression model female gender, younger age, higher HAQ, fatigue, pain and seropositivity at baseline remained significantly associated with this outcome (Table 2). Similar associations were observed for outcome 2. When the corresponding analyses were performed in patient groups 2 and 3, higher disease activity, no concomitant csDMARD, ongoing treatment with glucocorticoids, but not pain, were significantly associated with outcome 1 (Table 2). Similar results were observed for outcome 2. Conclusion: Overall, around 8% of all patients diagnosed with RA have failed ≥3 b/tsDMARDs, with a median time to this failure of four years. Among patients who started a first ever b/tsDMARD, as many as 25% will have failed two or more b/tsDMARDs within three years. The risk of fulfilling the EULAR D2T criterion 1 was 2.3% during the first five years after RA diagnosis. Seropositivity, female gender, younger age, high disease activity, and high levels of HAQ, fatigue and pain at RA diagnosis are independent risk factors. REFERENCES: 1 Buch MH. Defining refractory rheumatoid arthritis. Ann Rheum Dis. 2018;77(7):966-9. 2 Kearsley-Fleet L, Davies R, De Cock D, Watson KD, Lunt M, Buch MH, et al. Biologic refractory disease in rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Ann Rheum Dis. 2018;77(10):1405-12. Acknowledgements: NIL. Disclosure of Interests: Emma Birgersson Wettersand: None declared, Daniela Di Giuseppe: None declared, Johan Askling Agreements between Karolinska Institutet (with JA as PI) and Abbvie, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, mainly for the national safety monitoring of rheumatology immunomodulators in Sweden (ARTIS)., Katerina Chatzidionysiou Support by Region Stockholm, clinical research appointment.