Background/Purpose: Efficacy and safety of IV ABA is well established in RA. The ACQUIRE trial showed comparable safety and efficacy in SC vs IV ABA over 6 mths1; here, we present 18-mth data from the long-term extension (LTE).
Methods: ACQUIRE was a Phase IIIb, 6-mth, double-blind (DB) double-dummy study of pts with active RA (³10 swollen and ³12 tender joint count [TJC and SJC], CRP ≥0.8 mg/dL) refractory to MTX. Pts were randomized to SC ABA (125 mg/week) with IV ABA loading (~10 mg/kg) on Day 1 or IV ABA (~10 mg/kg) on Days 1, 15, 29 and every 4 wks for 6 mths; all pts received MTX. After 6 mths pts could enter the open-label LTE to receive SC ABA 125 mg/week. Safety, immunogenicity (by electrochemiluminescence), and efficacy (ACR 20, 50 and 70 and HAQ-DI responses [improvement from baseline (BL) ≥0.3]) were assessed for pts treated with ≥1 dose of ABA in the LTE. Efficacy data are as-observed; not all pts reached later timepoints at time of analyses.
Results: Of 1372 pts entering the LTE, 1222 (89.1%) remained on therapy at time of reporting. Overall mean BL RA duration was 8 yrs, TJC and SJC were 30 and 20, and HAQ-DI was 1.7; characteristics were similar between groups. Median (SD) ABA exposure was 22 (3.8) mths. The IR (events/100 pt–yrs) of SAEs in the LTE was comparable with that seen with SC ABA in the DB period (9.00 [95% CI: 7.69–10.55] and 9.02 [6.31–12.90], respectively) and did not increase with increasing exposure (not shown). The IR of overall and serious infections in the LTE did not increase vs the DB period (47.64 [44.01–51.58] vs 84.62 [74.50–96.11] and 1.97 [1.41–2.74] vs 1.48 [0.62–3.56] respectively) and did not increase with increasing exposure (not shown). Opportunistic infections in the LTE included 3 TB cases and 2 candidiasis cases; no opportunistic infections were observed in the DB period. Injection site reactions occurred in 24 (1.7%) pts in the LTE (none serious). ABA-induced antibodies occurred in 39/1365 (2.9%) pts in the LTE; 4/11 pts with anti-CTLA4 antibodies eligible for testing were positive for neutralizing antibody. Immunogenicity did not affect efficacy, safety or ABA pharmacokinetics (data not shown). ACR responses up to Mth 24 were maintained from Mth 6 and comparable between original SC vs IV groups (Fig). DAS28 remission rates (95% CIs) were 24 (21–27) [n=685] vs 25% (22–28) [n=688] at Day 169 and 32 (22–42) [n=85] vs 31% (20–41) [n=72] at Day 729 in the original SC vs IV groups, respectively. HAQ responses (95% CIs) were 73 (69–76) [n=691] and 68% (65–72) [n=672] at Day 169 and 63 (53–73) [n=87] and 56% (45–67) [n=77] at Day 729 in the original SC and IV groups, respectively. At the time of analyses, most patients had not completed the later timepoints (Days 617, 729).
Conclusions: Over 24 mths, SC ABA showed acceptable safety, with high pt retention, similar to the IV experience. Efficacy was comparable between SC and IV groups; ACR and HAQ responses and DAS28 remission rates were maintained in the LTE.
1Genovese et al. A&R 2011;DOI:10.1002/art.30463
Disclosure: M. C. Genovese, Bristol-Myers Squibb, 5 ; A. Covarrubias Cobos, BMS, Pfizer, Lilly ICOS, 9, UNIDAD REUMATOLOGICA LAS AMERICAS SCP, 4 ; G. Leon, None; E. F. Mysler, Bristol-Myers Squibb, 5, Bristol-Myers Squibb, 8, Bristol-Myers Squibb, 9 ; M. W. Keiserman, Abbott Laboratories, Bristol-Myers Squibb, MSD, 5, Abbott Laboratories, Biogen Idec, Bristol-Myers Squibb, Eli Lilly and Company, Human Genome Sciences, Inc., MSD, Pfizer Inc, Roche, UCB, Inc, Novartis, 2, Bristol-Myers Squibb, MSD, 9 ; R. M. Valente, Pfizer, UCB, BMS, Roche, Takeda, and Lilly, 2 ; P. T. Nash, Bristol-Myers Squibb, 5, Bristol-Myers Squibb, 2, Bristol-Myers Squibb, 8, Bristol-Myers Squibb ; J. A. Simon Campos, None; W. Porawska, None; J. H. Box, Bristol-Myers Squibb, 5, Bristol-Myers Squibb, 8, Box Arthritis and Rheumatology of the Carolinas PLLC, 4 ; C. W. Legerton III, Bristol-Myers Squibb, 2 ; E. L. Nasonov, None; P. Durez, Bristol-Myers Squib, 8 ; R. Pappu, Bristol-Myers Squibb, 1, Bristol-Myers Squibb, 3 ; I. Delaet, Bristol-Myers Squibb, 1, Bristol-Myers Squibb, 3 ; J. Teng, Bristol-Myers Squibb, 1, Bristol-Myers Squibb, 3 ; R. Alten, Bristol-Myers Squibb, Merck Pharma GmbH, Wyeth Pharmaceuticals, Pfizer, 2, Abbott Laboratories, Bristol-Myers Squibb, Horizon Pharma, Merck Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, 8, Abbott Laboratories, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, 5, Abbott Laboratories, Bristol-Myers Squibb, Novartis Pharmaceuticals Corporation, Roche, 6 .