Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 2-year results from a phase 3, multicenter, double-blind, placebo-controlled study

Objectives To evaluate long-term clinical/radiographic efficacy of subcutaneous UST 45/90 mg in patients with active psoriatic arthritis (PsA) through wk108 of the PSUMMIT 1 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. At wk16, pts with <5% improvement in TJC & SJC entered blinded early escape (PBO$→ $UST45mg; UST45mg$→ $90mg; 90mg$→ $90mg). PBO-treated patients subsequently crossed over to UST45mg at wk24. Patients received q12wks dosing to wk88, with final efficacy evaluation at wk100 and safety assessment at wk108. Stable concomitant MTX use was permitted but not mandated. Pts treated with prior anti-TNF agents were excluded. Primary endpoint was ACR20 response at wk24. Other efficacy measures included ACR50, 70 responses, changes in HAQ-DI, and changes in vdHS-S scores. Patients who discontinued study agent due to efficacy-related reasons or who initiated protocol-prohibited medications were counted as non-responders. Otherwise, missing data were not imputed. Patients randomized to 45mg group who entered early escape to receive 90mg at wk 16 were included in the 45mg group in analyses. Results Through wk108, 79.7% of pts (490/615) completed study agent administration; 20.3% discontinued study agent [including 5.0% for adverse events, and 6.5% for lack of efficacy]. At wk24, significantly larger proportions of UST 45/90 mg pts had ACR20/50/70 responses, and greater improvements in HAQ-DI than PBO patients. Clinical improvements were generally maintained through wk100 (Table). Of 440pts with ≥3% BSA involvement at baseline, 63.9%, 72.5% and 71.3% of PBO$→ $ 45mg, 45mg and 90mg groups achieved PASI 75 at wk100. Wk24 analysis of PSUMMIT 1 demonstrated that UST treatment significantly inhibited radiographic progression at wk24 compared with PBO. Inhibition of radiographic progression was maintained at wk 52 and wk100 (Table). Through wk108, with average follow-up of 91.9 wks, rates (per 100pt-years of f/u) of AEs and serious AEs were 160.60 and 7.10, respectively, in the combined UST group. Rates of serious infections, malignancies, and major adverse cardiovascular events (MACE) were 1.23, 0.38, and 0.66, respectively, in the combined UST-treated group. The proportion of UST injections with injection-site reactions was 0.4%. Conclusions In PSUMMIT 1, q12 wk maintenance injections for both UST 45mg and UST 90mg maintained clinical efficacy through wk100. Effects on inhibition of radiographic progression were maintained through wk100. UST continues to be well tolerated and demonstrated a safety profile similar to that seen in PsO patients. (Figure Presented).