Ustekinumab in Patients with Active Psoriatic Arthritis: Results of the Phase 3, Multicenter, Double-blind, Placebo-Controlled PSUMMIT I Study

Background/Purpose: To assess efficacy and safety of ustekinumab (UST) in reducing signs and symptoms of active psoriatic arthritis (PsA) in a large, multicenter, double-blind, placebo (PBO)-controlled, Phase 3 trial.

Methods:   Adult PsA pts (n=615) with active disease (≥5 SJC and ≥5 TJC;CRP≥0.3mg/dL) despite DMARD and/or NSAID therapy were randomized to receive UST45mg, 90mg, or PBO at wks 0, 4, and q12wks, thereafter. At wk16, pts with <5% improvement in TJC & SJC entered blinded early escape (PBO→UST45mg; UST45mg→90mg; 90mg→90mg). Stable concomitant MTX use was permitted but not mandated. Pts treated with prior anti-TNF agents were excluded. Primary endpoint was ACR20 response at wk24. Secondary endpoints at wk24 included: ACR 50/70, DAS28-CRP response, change from baseline (BL) in HAQ-DI, PASI75 response (in pts w/ ≥3% BSA involvement), and percent change from baseline in enthesitis and dactylitis scores (in pts affected at baseline). Adverse events (AE) are reported through the PBO-controlled period (wk16) and through wk24.

Results: Significantly greater proportions of UST-treated vs PBO–treated pts had ACR20 response at wk24 (Table). Significant improvements were also observed with UST45mg and 90mg for ACR50/70 responses and DAS28-CRP responses at wk24 vs PBO. The changes from baseline in HAQ-DI at wk24 were significantly greater in the UST than PBO grp, and significantly greater proportions of UST-treated pts had a clinically meaningful change from baseline in HAQ-DI (≥0.3). Nearly half used concomitant MTX at baseline; this did not alter the likelihood of benefit of UST vs PBO. While ACR responses were greater with UST than PBO regardless of MTX use, differences were numerically larger among pts not taking MTX. Of 440pts with ≥3% BSA involvement at baseline, significantly larger proportion of UST pts achieved PASI 75 at wk24. Among pts affected with enthesitis (n=425) or dactylitis (n=286) at baseline, significantly greater improvements in enthesitis and dactylitis were observed at wk24 in the UST grp than PBO. Through wk16, the proportion of pts with ≥1 AE was similar between pts receiving 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 wk24.

Conclusion: In pts with active PsA, UST significantly reduced the signs and symptoms of arthritis, improved physical function, enthesitis and dactylitis, and improved plaque psoriasis vs PBO-treated pts at wk24. Safety profiles were similar between UST-and PBO-treated pts.

  Table:  PSUMMIT efficacy results at Wk 24

*Among pts affected at baseline.; p<0.001 for all parameters vs PBO