AB0753 COMPARING COMPOSITE MEASURES OF DISEASE ACTIVITY IN PSORIATIC ARTHRITIS: RESULTS FROM A RANDOMIZED PHASE 2 TRIAL WITH GUSELKUMAB
Authors: Philip Helliwell, Atul Deodhar, Alice B. Gottlieb, Wolf-Henning Boehncke, Xie L. Xu, Stephen Xu, Yuhua Wang, Elizabeth C. Hsia, Dafna D. Gladman, Christopher T. Ritchlin
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Psoriatic arthritiS Disease activity Score (PASDAS), GRAppa Composite scorE (GRACE) index, modified Composite Psoriatic Disease activity index (mCPDAI), and Disease activity index for PSoriatic arthritis (DAPSA) are composite indices recently developed to assess disease activity in psoriatic arthritis (PsA).1,2 Guselkumab (GUS) is a monoclonal antibody targeting interleukin-23 that has demonstrated efficacy in a phase 2 PsA trial.3 <h3>Objectives:</h3> To compare the effect of GUS on disease activity in psoriatic arthritis (PsA) as measured by these composite indices. <h3>Methods:</h3> In this Phase-2 trial, patients with active PsA (≥3 tender, ≥3 swollen joints, C-reactive protein ≥3 mg/L, ≥3% body surface area) were randomized 2:1 to subcutaneous GUS 100mg (n=100) or placebo (PBO, n=49) at Wk0, Wk4, and every 8 wks through Wk44. At Wk16, patients with &lt;5% improvement in swollen plus tender joints could early-escape (EE) to open-label ustekinumab. Patients continuing PBO crossed-over to receive GUS 100mg at Wks 24/28/36/44 (PBO to GUS). PsA composite indices PASDAS, GRACE, mCPDAI, and DAPSA were analyzed using last-observation-carried-forward for missing/post-EE data through Week24. Instruments were validated using SF-36 physical component summary (PCS) score as an anchor. Sensitivity was assessed via standardized mean differences (SMDs), effect size (ES) and standardized response means (SRMs). <h3>Results:</h3> Changes in SF-36 PCS score were consistent with disease activity states at Wk24 for each PsA composite index in guselkumab-treated patients. The SMD, ES and SRM indicated that guselkumab elicited a substantial effect in treating the diverse manifestations of PsA compared with placebo, regardless of composite index employed (Figure). PASDAS and GRACE indices appeared to be more sensitive than mCPDAI and DAPSA in detecting changes upon treatment and distinguishing guselkumab treatment effects relative to placebo. Residual disease activities among guselkumab-treated patients who achieved low disease activity at Week24 based on each PsA composite index are summarized in the Table. <h3>Conclusion:</h3> Regardless of the PsA-specific composite index employed, GUS significantly improved disease activity and achieved clinically meaningful therapeutic targets such as low/minimal disease activity or remission. PASDAS and GRACE indices were more sensitive than mCPDAI and DAPSA in detecting changes in disease activity by guselkumab treatment. <h3>References</h3> [1] Helliwell PS, et al. JRheumatol2014;41:1212-1217. [2] Scholes MM, et al. AnnRheumDis2016;75:811-818. [3] Deodhar a, et al. Lancet2018;391: 2213–24. <h3>Disclosure of interests:</h3> 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, 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, 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, Dafna D Gladman Grant/research support from: abbVie, amgen, Celgene, Lilly, Novartis, Pfizer, and UCB, Consultant for: abbVie, amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Christopher T. Ritchlin Grant/research support from: abbVie, amgen, UCB Pharma, Consultant for: abbVie, amgen, Lilly, Novartis, Pfizer, UCB Pharma