SAT0387 CONSISTENT EFFICACY IN PATIENT SUBGROUPS ACROSS BASELINE DEMOGRAPHICS AND DISEASE CHARACTERISTICS: RESULTS FROM A PHASE 2 STUDY OF GUSELKUMAB IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS
Authors: Iain McInnes, Philip Helliwell, Alice B. Gottlieb, Wolf-Henning Boehncke, Xie L. Xu, Stephen Xu, Yuhua Wang, Elizabeth C. Hsia, Atul Deodhar
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Guselkumab (GUS) is a monoclonal antibody targeting interleukin-23 that has demonstrated efficacy in a phase 2 trial of psoriatic arthritis (PsA).<sup>1</sup> <h3>Objectives</h3> Here subgroup analyses were conducted to evaluate the consistency of efficacy on the primary endpoint, ACR20 response. <h3>Methods</h3> In this randomized, double-blind, placebo-controlled, Phase-2 trial, pts with active PsA (≥3 tender, ≥3 swollen joints, C-reactive protein ≥3 mg/L, ≥3% body surface area [BSA] of plaque psoriasis) despite current or previous treatment with standard-of-care therapies were randomized 2:1 to subcutaneous GUS 100 mg (n=100) or placebo (PBO, n=49) at Wk0, Wk4, and every 8 wks (q8w) through Wk44. At Wk16, pts with &lt;5% improvement in both swollen and tender joints could escape early to open-label ustekinumab. Pts continuing PBO crossed-over to receive GUS 100mg at Wk 24, 28 then q8w through Wk44. The primary analysis was performed in a modified Intent-to-Treat (mITT) population which include all randomized subjects who received at least 1 administration of study agent based on their assigned treatment regardless actual treatment received. Pts who met treatment failure criteria, escaped early, or had missing data at Wk24 were considered non-responders for ACR20 at Wk24. Pre-planned subgroup analyses by demographic and disease characteristics at baseline and PsA medication use were performed, using the same data handling rules as in the primary analysis. <h3>Results</h3> At Wk24, 58/100 (58·0%) of pts in the GUS vs 9/49 (18.4%) in the PBO group achieved an ACR20 response (p&lt;0·001). Efficacy was consistently observed in subgroups defined by demographics (gender, age, weight, region), disease characteristics at baseline (disease duration, PsA subtypes, tender/swollen joint counts, HAQ-DI, CRP, presence of dactylitis or enthesitis, PASI, and BSA) or PsA medication use (prior use of DMARDs or anti-TNFs, concomitant use of MTX, oral corticosteroids, or NSAIDs) (Table). The treatment effect was statistically significant in the majority of subgroups with the lower bound of the 95% confidence interval of the difference between GUS and PBO exceeding 0 in favor of GUS. There are a few exceptions where small sample sizes of the subgroups limited the interpretation. All enrolled subjects were white; therefore, the effect of guselkumab in other racial groups could not be assessed. Among GUS-treated pts, pts with enthesitis, dactylitis, PASI ≥12, BSA &gt;10%, tender joint count ≤10 or swollen joint count ≤10 appeared to have numerically higher ACR20 response rate than those corresponding subgroups defined otherwise, although the sample size is small and the data should be interpreted with caution. <h3>Conclusion</h3> In this phase 2 trial of patients with PsA, GUS demonstrated efficacy consistently across subgroups of pts according to baseline demographics, disease characteristics, and PsA-medication use. The relationship between baseline characteristics and clinical outcome will be further explored in phase 3 studies with a larger PsA population. <h3>Reference</h3> [1] Deodhar A, et al. Lancet 2018;391: 2213–24. <h3>Disclosure of Interests</h3> Iain McInnes Grant/research support from: AstraZeneca, Celgene, Compugen, Novartis, Roche, UCB Pharma, Consultant for: AbbVie, Celgene, Galvani, Lilly, Novartis, Pfizer, UCB Pharma, Philip Helliwell Grant/research support from: Paid to charity: from AbbVie, Janssen and Novartis, Consultant for: Paid to charity: from AbbVie, Amgen, Pfizer, and UCB and Celgene. Paid to self: from Celgene and Galapagos, Alice B Gottlieb Grant/research support from: PI: Incyte Corporation, Janssen-Ortho Inc., Lilly ICOS LLC, Novartis, UCB, XBiotech, Consultant for: AbbVie, Dermira, Incyte Corporation, Lilly ICOS LLC, Novartis, Sun Pharmaceutical Industries Ltd., Avotres (unpaid), XBiotech (unpaid), Speakers bureau: AbbVie, Eli Lilly and Company, Janssen Biotech; advisory board: Bristol-Myers Squibb, Celgene Corporation, Janssen Biotech, Janssen-Ortho Inc., LEO Pharma, Novartis, UCB, Wolf-Henning Boehncke Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, Xie L Xu Employee of: Employee of Janssen Research &amp; Development, LLC, Stephen Xu Employee of: Employee of Janssen Research &amp; Development, LLC, Yuhua Wang Employee of: Employee of Janssen Research &amp; Development, LLC, Elizabeth C Hsia Employee of: Employee of Janssen Research &amp; Development, LLC, Atul Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB