Single centre experience of refractory rheumatoid arthritis

Abstract Objectives To evaluate the proportion of RA patients that are refractory to multiple targeted therapies in a real-world cohort of patients in a tertiary rheumatology referral centre. To describe patterns of drug sequencing associated with the development of RefRA. To identify if there is a subgroup of RefRA patients in whom successive drugs have shown primary lack of efficacy. Methods Patients at a single centre were defined as refractory if they had failed two or more classes of targeted therapy (TT) and were identified from a dedicated TT clinic database. Reasons for drug failure were recorded and patients categorised pragmatically as having mild (2 biologic DMARD (bDMARD) class failure), moderate (≥3 bDMARD class failure) or severe (≥2 bDMARD class and JAK inhibitor failure) refractory disease. Results 172 patients were identified as RefRA (>10% of our TT exposed cohort); median (IQR) TT exposures of 4 (2), 81.5% female, 82% seropositive, mean (SD) age of 63 (12.3) years. Detailed analysis of 60 patients showed a median (IQR) disease duration of 22 (10.75) years, median (IQR) time from diagnosis to initiation of first TT of 5 (10) years, and mean (SD) baseline DAS28CRP prior to starting 1st line TT of 5.91 (0.84). Among RefRA patients, 15% were severe refractory, and 6% had demonstrated no clinical response to any TT. Conclusion A small proportion of patients have “true” RefRA. Most patients fail multiple therapies due to a combination of inefficacy and adverse events.