Factors associated with the effectiveness and safety of Janus kinase inhibitors in rheumatoid arthritis: an 8-year observational study from the JAGUAR Registry.

OBJECTIVES: To identify factors associated with the effectiveness and safety of Janus kinase (JAK) inhibitors in patients with rheumatoid arthritis (RA), as reflected by treatment retention. METHODS: This retrospective cohort study used data from the JAGUAR Registry, a multicentre RA registry of JAK inhibitor treatments. At 1 and 4 years, reasons and rates of treatment discontinuation were assessed. Treatment retention was evaluated using Cox regression and Kaplan-Meier curves. Factors associated with treatment retention were analysed for the discontinuation reasons of lack of effectiveness and adverse drug reactions (ADRs). RESULTS: A total of 435 treatment episodes with JAK inhibitors (tofacitinib: 118, baricitinib: 181, upadacitinib: 80, filgotinib: 56) were included. At 1 year, discontinuation rates were: 23.0% due to lack of effectiveness, 17.0% due to ADRs and 2.3% due to other reasons. At 4 years, the corresponding discontinuation rates were: 32.9%, 19.5% and 5.5%, respectively. Chronic concomitant glucocorticoid (GC) treatment was associated with JAK inhibitor discontinuation due to lack of effectiveness (p=0.007). Discontinuation rates due to lack of effectiveness were higher in patients requiring GCs for >6 months versus ≤6 months (29.1% vs 18.8% at 1 year; 50.5% vs 32.5% at 4 years). Age was associated with JAK inhibitor discontinuation due to ADRs (p=0.003). Discontinuation rates due to ADRs were higher in patients aged ≥65 years versus <65 years (25.6% vs 14.5% at 1 year; 35.3% vs 17.4% at 4 years). CONCLUSIONS: In RA, chronic concomitant GC treatment and patient age are associated with JAK inhibitor discontinuation due to lack of effectiveness and ADRs, respectively.