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.