Tofacitinib Improves Composite Endpoint Measures of Disease in Patients with Psoriatic Arthritis

Abstract

Aim To examine the effects of tofacitinib, an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA), on composite endpoints in patients with PsA.

Method In two Phase (P)3 studies, patients had active PsA and inadequate response (IR) to ≥1 csDMARD and were TNFi‐naïve (OPAL Broaden [N=422; 12 months; NCT01877668]), or IR to ≥1 TNFi (OPAL Beyond [N=394; 6 months; NCT01882439]). Patients were randomised to tofacitinib 5 mg BID, tofacitinib 10 mg BID, placebo (advancing to tofacitinib 5 or 10 mg BID at Month [M]3) or adalimumab 40 mg subcutaneous injection Q2W (OPAL Broaden only), with a single, stable csDMARD. Composite endpoints assessed: Psoriatic Arthritis Disease Activity Score (PASDAS), Disease Activity Score using 28 joints with C‐reactive protein (DAS28‐3[CRP]), Disease Activity Index for Reactive Arthritis/Psoriatic Arthritis (DAREA/DAPSA) and Composite Psoriatic Disease Activity Index (CPDAI) score.

Result Mean baseline values were generally similar across treatment arms and studies (OPAL Broaden/Beyond: PASDAS, 5.92–6.03/5.97–6.43; DAS28‐3[CRP], 4.38–4.56/4.40–4.67; DAREA/DAPSA, 38.52–45.55/42.64–51.54; CPDAI, 9.7–10.0/9.6–10.7). Both tofacitinib doses improved composite endpoints vs placebo at M3 in both studies. Effect size among composite endpoints (based on patients with available data for all endpoints) was highest for PASDAS and typically lowest for DAREA/DAPSA; this rank order of effect size was similar across treatment arms and studies. At M3 in OPAL Broaden/Beyond, respectively, effect sizes in tofacitinib‐treated patients ranged from 0.90/0.81 (both DAREA/DAPSA, 5 mg BID) to 2.40/1.84 (both PASDAS, 10 mg BID). Standardised response means generally followed the same pattern as effect size across studies and tofacitinib doses.

Conclusions In two P3 studies, tofacitinib 5 and 10 mg BID improved composite endpoint scores vs placebo over 3 months in patients with PsA. Effect sizes and standardised response means were highest for PsA‐specific composite measures and were consistent across studies.