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 (csDMARDs): A randomised, placebo-controlled, phase 3 trial

Background: Tofacitinib is an oral Janus kinase inhibitor under investigation for treatment of psoriatic arthritis (PsA). Objectives: To assess the efficacy and safety of tofacitinib vs placebo (PBO) in patients (pts) with active PsA. Methods: Eligible pts in this randomised, PBO- and active-controlled, 12-month Phase 3 trial had ≥6-months' PsA diagnosis, fulfilled CASPAR criteria, had active arthritis (≥3 tender/painful and ≥3 swollen joints) and active plaque psoriasis at screening, inadequate response to ≥1 csDMARD, and were tumour necrosis factor-inhibitor (TNFi)-naïve. 422 pts were randomised 2:2:2:1:1 to tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg subcutaneous injection every 2 weeks, or PBO (advancing to tofacitinib 5 or 10 mg BID at Month [M]3). Stable treatment with 1 csDMARD was required. Primary endpoints comparing tofacitinib vs PBO were ACR20 response rate and change from baseline in Health Assessment Questionnaire Disability Index (ΔHAQ-DI) at M3. Secondary endpoints included: ACR20 response rates and ΔHAQ-DI through M12; pts achieving ACR50, ACR70, ≥75% improvement of PASI and PsARC at all time points; and changes from baseline in LEI, Dactylitis Severity Score and SPARCC Enthesitis Index. Radiographic progression was assessed by van Der Heijde-modified Total Sharp Score (mTSS). Results: 96.9% of pts were white and 53.3% were female; mean age was 47.9 years. 96.2% and 88.4% of pts completed M3 and M12, respectively. At M3, tofacitinib 5 and 10 mg BID significantly improved ACR20 response rates (50.5% [p≤0.05] and 60.6% [p<0.0001] vs 33.3%; Fig 1A) and ΔHAQ-DI (-0.35 [p≤0.05] and -0.40 [p<0.001] vs -0.18; Fig 1B) vs PBO, with responses maintained to M12 (Fig 1C&D). Greater efficacy was also seen for adalimumab vs PBO. Tofacitinib 5 and 10 mg BID were superior to PBO for ACR20 response rates at Week 2 (22.4% [p<0.001] and 31.7% [p<0.0001] vs 5.7%; Fig 1C). Secondary endpoints supported primary findings (data not shown). >91% of pts were radiographic non-progressors at M12 (defined as an increase from baseline in mTSS ≤0.5). M12 safety findings were similar between groups (Fig 1E). The most common adverse events were upper respiratory tract infection (7.5-10.6%), nasopharyngitis (7.5-11.5%) and headache (3.8-10.6%). (Figure Presented) Conclusions: In TNFi-naïve pts with active PsA, tofacitinib was superior to PBO in ACR20 response rates and ΔHAQ-DI at M3, with superiority vs PBO as early as Week 2 for ACR20, which was maintained to M12. No new safety risks were identified vs previous studies in other indications.