Ustekinumab in active psoriatic arthritis including patients previously treated with anti-TNF agents: Results of a Phase 3, multicenter, double-blind, placebo-controlled study

Background/Purpose: Assess efficacy & safety of UST in reducing signs & symptoms of active PsA, including pts with & without previous anti-TNF experience, in PSUMMIT 2.

Methods:   Adult PsA pts (n=312) with active disease (≥5 SJC & ≥5 TJC;CRP≥0.3mg/dL) despite DMARD &/or NSAID &/or exposure to anti-TNF’s (≥8 wks of exposure to etanercept, golimumab, adalimumab or certolizumab pegol, or 14 wks exposure to infliximab, &/or documented evidence of anti-TNF intolerance/toxicity with exposure <8-14wks;n=180/312) were randomized to UST45mg, UST90mg, or PBO at wks 0, 4, & q12wks. At wk16, pts with <5% improvement in TJC & SJC entered blinded EE (PBO→UST45mg; UST45mg→90mg; 90mg→90mg). Stable MTX was permitted but not mandated. Primary endpt was ACR20 at wk24. Secondary endpts at wk24 included: ACR 50/70 & DAS28-CRP responses, change from BL in HAQ-DI, PASI75 (in pts with ≥3% BSA psoriatic involvement at BL), & % change from BL in enthesitis & dactylitis scores. Stat testing adjusted for BL MTX status. AEs reported through PBO-controlled period (wk16) & wk24.

Results: BL disease characteristics were generally comparable across grps.  Median BL disease characteristics among all pts were:  PsA duration 5.08 yrs, CRP 9.32mg/L, SJC/TJC 11/22, pain VAS 6.8, pt global assessment VAS 6.2, PGA 7.1, HAQ-DI 1.3. BL disease characteristics among anti-TNF experienced pts:  PsA duration 6.7 yrs, CRP 10.6 mg/L, SJC/TJC 12/24, pain VAS 7.2, pt global assessment VAS 6.4, PGA 7.4, HAQ-DI 1.4. Sig greater prop of UST vs PBO pts had ACR20 response at wk24. Sig improvements were also observed in DAS28-CRP response at wk12 & wk24 for both UST grps vs PBO. Clinically meaningful change from BL in HAQ-DI (≥0.3) was observed in 34.0%, 38.1%, & 16.3% of UST45mg, 90mg, & PBO pts, resp (p=0.003, p<0.001). Nearly half used MTX; ACR responses were greater with UST vs PBO regardless of MTX.  Among pts with enthesitis (n=221), median % improvements in the enthesitis score (MASES) were 33.3%, 48.3%, & 0.0% for the UST45mg (p=0.098), 90mg (p=0.008), & PBO grps, resp. Among pts with dactylitis at BL (n=117), median % improvements in dactylitis scores were 0.0%, 65.0%, & 0.0% of pts in the UST 45mg, 90mg, & PBO grps (not stat sig).Through wk16, pts with ≥1 AE were 63.1%, 60.6% & 54.8% for the UST 45mg, UST 90mg, & PBO grps, resp, with infections being most common AE (28.2%, 26.0%, & 23.1%). Serious AEs were reported in 0.0%, 1.0%, & 4.8%, resp. Through wk24, no deaths, opportunistic infections, TB, or major adverse CV events were reported. 1 serious infection (interstitial lung disease, PBO) & 1 malignancy [squamous cell Ca in situ of skin (uncovered from cleared PsO plaque), UST90mg] were reported.

Conclusion: UST reduced signs & symptoms, improved physical fxn, enthesitis & improved plaque PsO. Safety profiles were similar between UST & PBO.