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
Year: 2025
Type: article
Abstract: 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.
Source: ACR Open Rheumatology
DOI: 10.1002/acr2.70097
Authors: Nicolino Ruperto, Daniel J. Lovell, Olga Synoverska, Carlos Abud‐Mendoza, Alberto Spindler, Yulia Vyzhga, Iris Reyhan, Lyudmila Grebenkina, Irit Tirosh, Lisa Imundo, Peter Chiraseveenuprapund, Daniel J Kingsbury, Betul Sozeri, Sheetal S. Vora, Sampath Prahalad, Elena Zholobova, Kevin D. Roberts, Gosford Sawyerr, Andreas Blum, Andrea Shapiro, Annette Diehl, Abbas Ebrahim, Pascal Klaus, Alberto Martini, Hermine I. Brunner
Institutions: Paediatric Rheumatology INternational Trials Organization (PRINTO), University of Milano-Bicocca, Cincinnati Children's Hospital Medical Center, University of Cincinnati, National Pirogov Memorial Medical University, Vinnytsya, University of Southern California, Children's Hospital of Los Angeles, Tel Aviv University, Sheba Medical Center, Edmond and Lily Safra Children's Hospital, Columbia University Irving Medical Center, University of Utah, Randall Children's Hospital at Legacy Emanuel, Ümraniye Eğitim ve Araştırma Hastanesi, Levine Children's Hospital, Wake Forest University, Emory University, Children's Healthcare of Atlanta, Sechenov University, Pfizer (United States), Pfizer (Germany), University of Genoa
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,550
Funder: Pfizer
Award: G1588314721
OpenAlex ID: W4414926661