Impact of Concomitant Methotrexate Use and Prior Biologic Disease‐Modifying Antirheumatic Drug Exposure on Tofacitinib Efficacy and Safety in Patients with Polyarticular Course Juvenile Idiopathic Arthritis: Post Hoc Analysis of a Phase 3 Randomized Withdrawal Trial

Objective We evaluate tofacitinib efficacy and safety in patients with juvenile idiopathic arthritis (JIA) stratified by concomitant methotrexate and prior biologic disease‐modifying antirheumatic drug (bDMARD) treatment. Methods In this two part, double‐blind, randomized withdrawal Phase 3 trial (NCT02592434), patients (2–<18 years) with JIA received open‐label tofacitinib (5 mg twice daily/weight‐based equivalent) in Part 1 (Day 1–Week 18). Those eligible were randomized to continue tofacitinib or switch to placebo in Part 2 (Weeks 18–44). In this post hoc analysis, patients were stratified by concomitant methotrexate (MTX+/−) and prior bDMARD treatment (bDMARD+/−). Efficacy outcomes included JIA disease flare, JIA/American College of Rheumatology (ACR) 50/70 response rates, and JIA/ACR clinical inactive disease (CID). Safety was assessed throughout the trial. Results Of 225 patients in Part 1, 147 (65.3%) were MTX+; 85 (37.8%) were bDMARD+. Across subgroups, JIA flare rate at Week 44 was lower with tofacitinib than placebo: patients who were MTX+ (29.8% vs 47.5%), patients who were MTX− (32.3% vs 73.1%), patients who were bDMARD+ (29.0% vs 70.4%), patients who were bDMARD− (31.6% vs 48.3%). Greater JIA/ACR50/70 and JIA/ACR‐CID responses with tofacitinib than with placebo were observed across subgroups. In tofacitinib‐treated patients, adverse events (AEs) were more common in the subgroups of patients who were MTX− (85.9%) and patients who were bDMARD+ (81.2%) than the subgroups of patients who were MTX+ (74.1%) and patients who were bDMARD− (76.4%). Similar findings were observed with serious AEs/discontinuations due to AEs. Conclusion Tofacitinib was efficacious for patients regardless of baseline concomitant MTX treatment or prior bDMARD exposure; MTX may have a protective effect for flare upon tofacitinib withdrawal. Safety was consistent with the known tofacitinib profile, and no new risks were identified in these subgroups.