Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, or adalimumab in patients with active psoriatic arthritis and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs: OPAL Broaden, a randomized, placebo-controlled, phase 3 trial

Background: Tofacitinib is an oral Janus kinase inhibitor under investigation for psoriatic arthritis (PsA). We evaluated tofacitinib efficacy and safety vs placebo (PBO) in patients (pts) with active PsA and an inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drug (csDMARD). Methods: This was a randomized, PBO-controlled, double-blind, multicenter, Phase 3 study (NCT01877668). Eligible pts had a diagnosis of PsA for ≥6 months, meeting ClASsification criteria for Psoriatic ARthritis (CASPAR), active arthritis (≥3 tender/- painful and ≥3 swollen joints) and plaque psoriasis, IR to ≥1 csDMARD, and were tumor necrosis factor-inhibitor-naïve. Pts were randomized 2:2:2:1:1 to tofacitinib 5 mg twice daily (BID) (n = 107), tofacitinib 10 mg BID (n = 104), adalimumab (ADA) 40 mg SC injection once every 2 weeks (n = 106), PBO/tofacitinib 5 mg BID (n = 52), or PBO/tofacitinib 10 mg BID (n = 53). Pts who initially received PBO advanced to tofacitinib at Month (M) 3. Ongoing treatment with a stable dose of 1 csDMARD was required. Pts were followed through M12. M3 primary endpoints were American College of Rheumatology 20% improvement (ACR20) and change from baseline in Health Assessment Questionnaire Disability Index (DHAQ-DI). Secondary endpoints included 75% improvement from baseline Psoriasis Area and Severity Index (PASI75). Results: Of 422 randomized pts, 373 (88.4%) completed the study. Across treatment groups at baseline, mean age was 46.9-49.4 years, 47.2-59.6% were female, mean duration of PsA was 5.3-7.3 years, mean HAQ-DI was 1.1-1.2, and mean PASI was 8.3-10.1 (among pts with ≥3% BSA). Both tofacitinib 5 and 10 mg BID significantly improved ACR20 response rates vs PBO at M3 (50.5% [P ≤ .05] and 60.6% [P < .0001] vs 33.3%) and DHAQ-DI (-0.35 [P ≤ .05] and -0.40 [P <.001] vs -0.18); responses were maintained to M12. Greater efficacy was also observed for ADA vs PBO. Both tofacitinib doses significantly improved PASI75 response rates vs PBO at M3 (tofacitinib 5 mg BID 42.7%; tofacitinib 10 mg BID 44.3%; PBO 14.6%; both P< .0001). Over 12 months, the most common adverse events (AEs) were upper respiratory tract infection (7.5-10.6% of pts across groups), nasopharyngitis (7.5-11.5%), and headache (3.8-10.6%); serious AEs were reported by 3.8-8.5% of pts; 2.9-5.6% of pts discontinued due to AEs. Conclusion: Tofacitinib was superior to PBO in ACR20 response rate and DHAQ-DI at M3, which was maintained to M12. No new safety signals were identified.