AB0763 SAFETY OF ABATACEPT TREATMENT OVER 2 YEARS IN A PHASE III ACTIVE PSORIATIC ARTHRITIS RANDOMIZED TRIAL (ASTRAEA)
Authors: Philip J. Mease, Alice B. Gottlieb, Désirée van der Heijde, Oliver Fitzgerald, Alyssa Johnsen, Marleen Nys, Subhashis Banerjee, Harris a. Ahmad, Dafna D. Gladman
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In the placebo (PBO)-controlled Phase III aSTRAEA study (ClinicalTrials.gov, NCT01860976) in psoriatic arthritis (PsA), abatacept (ABA) 125 mg SC weekly significantly increased the aCR20 response rate at Week 24 versus PBO (39.4% vs 22.3%, respectively; p&lt;0.001; primary endpoint).<sup>1</sup> Numerical benefits in physical function, enthesitis and dactylitis and a modest impact on psoriasis lesions were also seen at Week 24. Efficacy was maintained or improved up to Week 52.<sup>1</sup> <h3>Objectives</h3> To assess aBA safety up to 2 years in patients (pts) enrolled in aSTRAEA. <h3>Methods</h3> Pts with active PsA were randomised 1:1 to aBA or PBO for 24 weeks followed by 28 weeks' open-label (OL) aBA (total time on study: 52 weeks); pts without ≥20% improvement in joint counts at Week 16 (early escape) were switched to OL aBA (total time on study: 44 weeks).<sup>1</sup> Pts could subsequently receive OL aBA in a 52-week long-term extension (LTE; Year 2) for the collection of safety data. The proportions of pts in the cumulative aBA population (all pts who received ≥1 dose of aBA at any time in the study) with aEs (all aEs, serious aEs [SAEs], deaths, aEs leading to discontinuation), laboratory marked abnormalities and anti-ABA antibodies over the cumulative aBA period (date of first treatment dose to end of LTE) were recorded in 1-year and 6-month intervals. <h3>Results</h3> Overall, 398 pts were included in the analysis of the cumulative aBA period (213 received aBA from study Day 1; 185 completed initial randomisation to PBO and received aBA thereafter). Of these, 322 pts entered the LTE (initial randomisation: aBA, n=162; PBO, n=160) and continued to receive OL aBA beyond the 28-week OL period. Of 162 and 160 pts initially randomised to aBA and PBO, respectively, 19 (11.7%) and 21 (13.1%) pts discontinued aBA in the LTE. Median (range) number of aBA injections in the cumulative aBA period to end of LTE was 80 (1–133). Safety during the cumulative aBA period over 2 years is shown (Table 1); 6-month interval safety data will be available at time of presentation. In the LTE, there were 3 SAEs of infection (osteomyelitis, intervertebral discitis and cellulitis) and 3 pts discontinued due to infection (hepatitis a, Epstein-Barr virus, intervertebral discitis). No malignancies or deaths were reported, and no autoimmune events were reported as serious or led to aBA discontinuation during the LTE. AEs, SAEs and aEs of special interest occurred with a similar frequency regardless of concomitant MTX or prior TNF inhibitor (TNFi) use. The proportion of pts with anti-ABA antibodies during the cumulative aBA period was higher during the post-treatment period (≥22 days after last dose; 37.1% [91/245]) than in the on-treatment period (first treatment dose date to ≤21 days after last dose; 7.1% [28/392]). No apparent relationship between anti-ABA antibodies and efficacy in the on-treatment period or aEs suggestive of systemic immune reactions was seen. <h3>Conclusion</h3> Abatacept was well tolerated up to 2 years with no new safety signals during the LTE in this Phase III study in PsA. There was no impact of concomitant MTX use or prior TNFi exposure on the safety profile of abatacept. The occurrence of anti-abatacept antibodies had no impact on abatacept efficacy or safety. <h3>References</h3> [1] Mease PJ, et al. Ann Rheum Dis2017;76:1550–8. <h3>Acknowledgement</h3> Professional medical writing: andrea Plant, PhD, Caudex; funding: Bristol-Myers Squibb. <h3>Disclosure of interests</h3> Philip J Mease Grant/research support from: abbVie, amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: abbVie, amgen, BMS, Galapagos, Gilead Sciences, inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: abbVie, amgen, BMS, Celgene, Genentech, Janssen, Lilly, 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, Désirée van der Heijde Consultant for: abbVie, amgen, astellas, astraZeneca, Bristol-Myers Squibb, Boehringer ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Union Chimique Belge, Oliver FitzGerald: None declared, alyssa Johnsen Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Marleen Nys Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Subhashis Banerjee Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Harris a ahmad Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, 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