Reasons for multiple biologic and targeted synthetic DMARD switching and characteristics of treatment refractory rheumatoid arthritis

Switching biologic and targeted synthetic DMARD (b/tsDMARD) medications occurs commonly in RA patients, however data are limited on the reasons for these changes. The objective of the study was to identify and categorize reasons for b/tsDMARD switching and investigated characteristics associated with treatment refractory RA. In a multi-hospital RA electronic health record (EHR) cohort, we identified RA patients prescribed ≥1 b/tsDMARD between 2001-2017. Consistent with the EULAR "difficult to treat" (D2T) RA definition, we further identified patients who discontinued ≥2 b/tsDMARDs with different mechanisms of action. We performed manual chart review to determine reasons for medication discontinuation. We defined "treatment refractory" RA as not achieving low disease activity (<3 tender or swollen joints on <7.5mg of daily prednisone equivalent) despite treatment with two different b/tsDMARD mechanisms of action. We compared demographic, lifestyle, and clinical factors between treatment refractory RA and b/tsDMARD initiators not meeting D2T criteria. We identified 6040 RA patients prescribed ≥1 b/tsDMARD including 404 meeting D2T criteria. The most common reasons for medication discontinuation were inadequate response (43.3%), loss of efficacy (25.8%), and non-allergic adverse events (13.7%). Of patients with D2T RA, 15% had treatment refractory RA. Treatment refractory RA patients were younger at b/tsDMARD initiation (mean 47.2 vs. 55.2 years, p<0.001), more commonly female (91.8% vs. 76.1%, p=0.006), and ever smokers (68.9% vs. 49.9%, p=0.005). No RA clinical factors differentiated treatment refractory RA patients from b/tsDMARD initiators. In a large EHR-based RA cohort, the most common reasons for b/tsDMARD switching were inadequate response, loss of efficacy, and nonallergic adverse events (e.g. infections, leukopenia, psoriasis). Clinical RA factors were insufficient for differentiating b/tsDMARD responders from nonresponders.