OP0174 Efficacy and Safety of Ustekinumab in Psoriatic Arthritis Patients with Spondylitis and Peripheral Joint Involvement: Results from a Phase 3, Multicenter, Double-Blind, Placebo-Controlled Study

Background

IL-23 may be implicated in spondylitis. A substantial number of pts with spondylitis and peripheral joint involvement were enrolled in PSUMMIT.

Objectives

We evaluated the efficacy of SC UST 45/90 mg in a subgroup of psoriatic arthritis (PsA) pts with physician diagnosed spondylitis and peripheral joint involvement through wk108, from PSUMMIT 1.

Methods

Adult PsA patients (n=615) with active disease (≥5 SJC and ≥5 TJC;CRP≥0.3mg/dL) despite DMARD and/or NSAIDs were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12wks. Pts treated with prior anti-TNF agents were excluded. Stable concomitant MTX was permitted but not mandated. At wk16, pts with <5% improvement in TJC & SJC entered blinded early escape (PBO→UST45mg; UST45mg→90mg; 90mg→90mg). PBO pts subsequently crossed over to UST45mg at wk24. Pts received q12w dosing to wk88, with final efficacy evaluation at wk100 and safety assessment at wk108. Pts with spondylitis and peripheral joint involvement as their primary arthritis presentation of PsA also had BASDAI assessments at wks12 and 24.

Results

186 randomized pts (70 PBO, 116 UST combined) had spondylitis with peripheral joint involvement at baseline (30% of overall population); mean baseline characteristics were similar to the overall population (age 45.6yrs, weight 82.8kg, PsA duration 6.3yrs, SJC/TJC 14.3/24.1, HAQ-DI 1.3; BASDAI 6.5, and 26% were HLAB27 positive. Mean baseline scores among pts with dactylitis (n=100), enthesitis (148), and skin disease (147) were 8.3, 5.6, and PASI 14.2, respectively. At wk24, greater proportions of combined UST45/90mg treated pts had improvements in dactylitis/enthesitis measurements, HAQ-DI and ACR20/50/70 responses than PBO (Table). Clinical improvements were generally maintained through wk100. A significantly higher proportion of UST-treated pts achieved BASDAI20/50/70 responses vs. PBO at wk24 (54.1%/27.9%/14.4% vs. 26.2%/13.1%/0.0%). Peripheral structural damage assessed by total vdH-S mean change from baseline also showed improvement in the UST groups vs PBO at wk24. Of the 135 patients with ≥3% BSA involvement and spondylitis with peripheral arthritis at baseline, PASI75 responses were also maintained through wk100. During the PBO-controlled period, the proportion of pts with AEs were comparable between the PBO and combined UST-treated groups (AEs 32.9% vs 24.1%; SAEs 1.4% vs 0.9%; discontinuations due to AEs 2.9% vs 0.9%; serious infections 14.3% vs 7.8%). Through 2yrs, safety observations were consistent with the overall PsA population.

Conclusions

In this post-hoc subgroup analysis, UST significantly improved signs and symptoms, and demonstrated improvements in BASDAI and peripheral radiographic progression compared with PBO through wk24; efficacy was maintained through wk100. UST was well-tolerated and demonstrated a safety profile similar to that observed in the overall PsA study population.

Disclosure of Interest

A. Kavanaugh Grant/research support from: AbbVie, Amgen, Janssen, and UCB., L. Puig Grant/research support from: AbbVie, Amgen, Boehringer, Celgene, Eli Lilly, Janssen, Leo-Pharma, Merck/Schering-Plough, Merck-Serono, Novartis, Pfizer, Sandoz, and VBL., A. Gottlieb Grant/research support from: Amgen, AbbVie, Celgene, Coronado, Eli Lilly, Janssen, Levia, Merck, and Pfizer., Consultant for: AbbVie, Actelion, Akros, Amgen, Astellas, Bristol Myers Squibb, Canfite, Catabasis, Celegene, CSL Behring Biotherapies for Life, Coronado, Dermipsor, Eli Lilly, GlaxoSmithKline, Incyte, Janssen, Karyopharm, Novartis, Novo Nordisk, Pfizer, Sanofi Aventix, UCB, Vertex, and Xenoport., C. Ritchlin Grant/research support from: Amgen, Janssen, and UCB., Consultant for: AbbVie, Amgen, Janssen, Regeneron, Roche, and UCB., Y. You Employee of: Janssen R&D, LLC., Y. Wang Employee of: Janssen R&D, LLC., A. Mendelsohn Employee of: Janssen R&D, LLC., M. Song Employee of: Janssen R&D, LLC., P. Rahman Grant/research support from: AbbVie, Amgen, Janssen, Pfizer, and Novartis., I. McInnes Grant/research support from: AbbVie, BMS, Janssen, Pfizer, Roche, Merck/Schering-Plough, and UCB.