Background In the Phase III ASTRAEA trial (NCT01860976), abatacept (ABA), a selective T-cell co-stimulation modulator, significantly increased ACR20 response (primary endpoint; PE) and had an overall beneficial effect vs placebo (PBO) on musculoskeletal symptoms in patients (pts) with active psoriatic arthritis (PsA) at 24 weeks (W).1
Objectives To analyse 1-year results from ASTRAEA.
Methods Pts with active disease (≥3 swollen and ≥3 tender joints), ≥2 cm target lesion of plaque psoriasis and inadequate response/intolerance to ≥1 non-biologic DMARD were randomized (1:1) to SC ABA 125 mg weekly or PBO for 24W, followed by open-label (OL) SC ABA up to 52W. Randomization was stratified by MTX use, prior TNF inhibitor (TNFi) use and skin involvement ≥3% of body surface area. Pts without ≥20% improvement in joint counts at W16 were switched to OL ABA (early escape; EE) for 28W (total study time: 44W). Pre-specified exploratory endpoints included: ACR20/50/70 responses at W44; adjusted mean changes from baseline (BL) in DAS28 (CRP; post hoc analysis) and HAQ-DI at W44 and PsA-modified total Sharp/van der Heijde score (SHS) at W44 (EE pts)/W52 (non-EE pts); complete resolution of BL enthesitis and dactylitis at W44 (EE pts)/W52 (non-EE pts); and Psoriasis Area and Severity Index (PASI) 50/75 responses at W44. Analyses used the ITT population with non-responder imputation for missing values and actual data at each time point for all pts (denominator at each time point equal to number of pts in ITT population). All missing responses were imputed as non-responders, except if the missing value was between 2 visits for which the pt was a responder. In that case the missing value was imputed as a responder.
Results Of 424 pts enrolled, 213 received ABA and 211 PBO. Most (>60%) pts had received prior TNFis. Of pts in the ABA and PBO groups, 76 (36%) and 89 (42%) were EE, 12 (6%) and 24 (11%) discontinued by PE of W24; 197 (92%) and 185 (88%) entered the OL period, of whom 165 (84%) and 162 (88%) completed. At W44, ACR responses at W24 were maintained for pts who continued ABA, and improved for those who switched from PBO to ABA (Figure). Continued improvements in DAS28 (CRP) and HAQ-DI after W24 were seen for ABA and PBO/ABA groups, with mean (SE) changes from BL to W44 of –1.81 (0.09) and –1.84 (0.10) in DAS28 (CRP) (changes to W24 were –1.35 [0.10] and –0.94 [0.11]) and –0.37 (0.04) and –0.38 (0.04) in HAQ-DI (changes to W24 were –0.33 [0.04] and –0.20 [0.05]), respectively. There was minimal progression based on mean (SE) change from BL in PsA-modified total SHS at W44/52 in the ABA and PBO/ABA groups: 0.18 (0.12) vs 0.30 (0.12). Complete resolution of BL enthesitis occurred in 48.6% and 43.9% and BL dactylitis in 68.9% and 60.0% of pts with ABA and ABA/PBO, respectively, at W44/52. At W44, for ABA and PBO/ABA, PASI 50 responses were 30.1% and 34.5%; PASI 75 responses were 19.9% and 16.9%. There were no new safety signals.
Conclusions Responses were maintained across musculoskeletal endpoints up to 1 year in a relatively refractory population of pts continuing on SC abatacept. Abatacept was well tolerated.
Mease P, et al. Arthritis Rheumatol 2016;68(Suppl 10):Abstract 1041.
Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, Corrona, Demira, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, Zynerba, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, Genentech, Janssen, Novartis, Pfizer, UCB, A. Gottlieb Grant/research support from: Centocor (Janssen), Amgen, Abbott (AbbVie), Novartis, Celgene, Pfizer, Lilly, Coronado, Levia, Merck, Xenoport, Dermira, Baxalta, Consultant for: Amgen Inc.; Astellas, Akros, Centocor (Janssen), Inc.; Celgene Corp., Bristol-Myers Squibb Co., Beiersdorf, Inc., Abbott Labs. (AbbVie), TEVA, Actelion, UCB, Novo Nordisk, Novartis, Dermipsor Ltd., Incyte, Pfizer, Canfite, Lilly, Coronado, Vertex, Karyopharm, CSL Behring Biotherapies for Life, GlaxoSmithKline, Xenoport, Catabasis, Meiji Seika Pharma Co., Ltd, Takeda, Mitsubishi Tanabe Pharma Development America, Inc, Genentech, Baxalta, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boeringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB, O. FitzGerald: None declared, A. Johnsen Employee of: Bristol-Myers Squibb, M. Nys Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Banerjee Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, D. Gladman Grant/research support from: AbbVie, Amgen, Celgene, Janssen, Novartis, Pfizer, UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB