FRI0227 Five-Year Safety and Efficacy of Subcutaneous Abatacept in Patients with Moderate To Severely Active RA and An Inadequate Response To MTX: Long-Term Extension of The Phase III, Double-Blind, Randomized Acquire Study

BackgroundThe ACQUIRE study demonstrated non-inferiority of the SC to the IV formulation.1ObjectivesTo assess the 5-yr safety and efficacy of SC ABA 125 mg/wk plus background MTX in the LT extension (LTE).MethodsThe 6-month, double-blind (DB) period was followed by an open-label LTE in which patients (pts) received SC ABA 125 mg/wk. Dose adjustments to MTX, corticosteroids and NSAIDs were permitted. Safety, efficacy and immunogenicity assessments were performed at 12-wk intervals. Safety and efficacy analyses included all pts who entered the LTE and received ≥1 dose of ABA.Results1373/1385 pts who completed the DB period entered the LTE, 427 (31.1%) had discontinued by end of Yr 5 (due to AE: 100 [7.3%]; lack of efficacy: 89 [6.5%]; withdrawal of consent: 81 [5.9%]). In the LTE, 1240 pts (90.3%) had an AE (Table), most (79.8%) were mild/moderate; most frequent non-serious AEs were infections. Overall, 353 pts (25.7%) had an SAE. The incidence rate/100 pt-yrs (95% CI) for SAEs decreased from 9.02 (6.31, 12.90) in the DB period to 7.73 (6.96, 8.58) during the LTE (332.6 and 4566.2 pt-yrs of exposure, respectively). Efficacy in the LTE was consistent with the DB phase and was maintained to 5 yrs in pts who remained on study: at Day 1821, 356/421 (84.6%), 277/423 (65.5%) and 191/425 (44.9%) had an ACR20, 50 or 70 response, respectively. ABA trough concentrations were stable over the LTE. Immunogenicity was low over 5 yrs (4.6/100 pt-yrs); there was no association between immunogenicity and ABA efficacy, safety or PK.Adverse eventAdverse events in 5-yr LTE (n=1373)n (%) of ptsAll AEs1240 (90.3) AE related to study drug632 (46.0) AE leading to discontinuation97 (7.1) SAEs353 (25.7) Death41 (3.0)AEs of special interest Infections962 (70.1) Serious infections85 (6.2) Opportunistic infections*4 (0.3) Systemic injection reactions161 (11.7) Autoimmune disorders†67 (4.9) Malignancies‡56 (4.1) Local injection-site reactions33 (2.4)*Peritoneal tuberculosis, fungal oesophagitis, fungal eye infection, fungal sinusitis (n=1 each); †Including psoriasis (n=13), chronic gastritis (n=11), Sjögren's syndrome (n=10), vasculitis (n=6); ‡Including basal cell carcinoma (CA) (n=15); breast cancer, squamous cell CA, squamous cell CA of skin (n=4 each); thyroid neoplasm (n=3); cervical CA Stage 0, invasive ductal breast CA, non-small cell lung cancer, prostate cancer (n=2 each).ConclusionsDuring this 5-yr LTE of the ACQUIRE study, the safety and efficacy of SC abatacept were consisten