Ustekinumab in patients with active psoriatic arthritis: Results of the phase III, multicenter, double-blind, placebo-controlled PSUMMIT i study

Objective: To assess the efficacy and safety of ustekinumab (UST) in patients (pts) with psoriatic arthritis (PsA). Methods: Adult PsA pts (n = 615) with active disease (≥ 5 SJC and ≥ 5 TJC; CRP ≥ 0.3 mg/dL) despite DMARDs and/or NSAIDs were randomized to UST 45 mg (UST 45 mg), UST 90 mg (UST 90 mg), or PBO at weeks 0, 4, and q12 weeks. At week 16, pts with < 5% improvement in TJC and SJC entered blinded early escape (PBO -» UST 45 mg; UST 45 mg-»90 mg; 90 mg-»90 mg). Stable concomitant methotrexate (MTX) was permitted but not mandated. Patients treated with previous anti-TNF agents were excluded. Primary endpoint was ACR 20 response at week 24; secondary endpoints included: ACR 50 response, ACR 70 response, DAS28-CRP response, change from baseline in HAQ-DI, PASI 75 response (in pts with ≥ 3% BSA), and percent change from baseline in enthesitis and dactylitis scores (in pts affected at baseline). Results: At week 24, ACR 20 responses were 42.4%, 49.5%, and 22.8% for the UST 45 mg, UST 90 mg, and PBO groups, respectively (P < .001). Significant improvements were also observed with UST 45 mg and 90 mg vs PBO for ACR 50, ACR 70 and DAS28-CRP responses (all P < .001). Changes from baseline in HAQ-DI at week 24 were significantly greater in the UST vs PBO groups, and significantly greater proportions of UST-treated pts had a clinically meaningful change from baseline in HAQ-DI (≥0.3; all P < .001). Nearly half of the pts used concomitant MTX at baseline; this did not alter the benefit of UST vs PBO. While ACR responses were greater with UST vs PBO, regardless of MTX use, differences were numerically larger among pts not taking MTX. Of 440 pts with ≥ 3% BSA involvement at baseline, PASI 75 was achieved in 572%, 62.4%, and 11.0% in the UST 45 mg, UST 90 mg, and PBO groups, respectively (P <.001). Among pts with enthesitis (n = 425) or dactylitis (n = 286) at baseline, greater improvements in enthesitis and dactylitis were observed at week 24 in the UST groups vs PBO (P < .001, for each). Through week 16 (PBO-controlled period), proportion of pts with ≥ 1 AE was similar between UST (41.8%) and PBO (42.0%), with infections being the most common AE; 1.7% (UST) and 2.0% (PBO) had ≥ 1 serious AE. No malignancies, serious infections, TB, opportunistic infections, or deaths occurred through week 24. Conclusion: UST significantly reduced the signs and symptoms of arthritis, improved physical function, enthesitis and dactylitis, and plaque psoriasis vs PBO-treated pts at week 24. Safety profiles were similar between UST and PBO. Supported by Janssen Services, LLC.