Background Immunogenicity with therapeutic proteins has been linked to reduction in both efficacy and safety in patients (pts) with RA.1,2 We previously reported in clinical trials that IV abatacept (ABA) demonstrated low (∼3%) and transient immunogenicity that has no apparent impact on efficacy or safety.3
Objectives To evaluate immunogenicity in a large pt group with long-term (up to 8 yrs) IV ABA exposure.
Methods Data from 7 ABA RA clinical trials were included in immunogenicity assessments, including double-blind periods from 6 placebo-controlled studies (AIM, ATTEST, ATTAIN, ASSURE, 101 and 100) and 1 non-randomized, open-label study (ARRIVE), and their open-label, long-term extensions. Pts had active RA, inadequate response/intolerance to MTX/DMARDs or biologics and were treated with IV ABA (∼10 mg/kg) every 4 weeks. Anti-ABA antibodies were detected using two ELISA assays: one to whole ABA molecule (CTLA4 and IgG1), and one to CTLA4 “tip” region (T). Positive samples had titers≥400 for anti-ABA or ≥25 for anti-CTLA4-T. Persistent immunogenicity was defined as positive response on ≥2 consecutive visits. Data are as-observed for all ABA-treated pts.
Results 3985 pts were included with up to 8 yrs’ ABA exposure. A total of 6.3% of pts demonstrated immunogenicity; titers were low and did not increase with continued treatment. Persistent immunogenicity (2.4%) and immunogenicity with missed doses (3.8% for 1 and 4.6% for ≥2 missed doses) were also low. Serious adverse events (SAEs) attributed as being related to study drug were reported in 32/252 (12.7%) pts who experienced immunogenicity. No relationship was identified between immunogenicity and SAEs, peri-infusional, acute infusional or autoimmune events, or hypersensitivity reactions. No consistent relationship between immunogenicity and efficacy (measured by ACR20) was observed; 83% (55/66) of ACR20 responders maintained ACR20 vs 36% (10/28) of non-responders achieved ACR20 following positive antibody response.
Conclusions Abatacept demonstrated low immunogenicity in pts with RA and up to 8 yrs of abatacept exposure. Titers of anti-abatacept and anti-CTLA-4-T antibodies were low and did not persist nor increase with continued treatment. No consistent association was observed between antibody response and clinical efficacy or safety.
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Pascual-Salcedo D, et al. Rheumatology 2011;50:1445–52.
Haggerty HG, et al. J Rheum 2007;34:2365–73.
Disclosure of Interest M. Weinblatt Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, M. Genovese Consultant for: Bristol-Myers Squibb, M. Schiff Consultant for: Bristol-Myers Squibb, R. Westhovens Grant/Research support from: Roche, UCB, Inc., Consultant for: Bristol-Myers Squibb, Centocor, Inc., Roche, Schering-Plough, Speakers Bureau: Bristol-Myers Squibb, R. Alten Grant/Research support from: BMS, Merck Pharma GmbH, Wyeth Pharmaceuticals, Pfizer, Consultant for: Abbott Laboratories, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, Speakers Bureau: Abbott Laboratories, BMS, Horizon Pharma, Merck Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, I. Delaet Employee of: Bristol-Myers Squibb, M. Nys Employee of: Bristol-Myers Squibb, J. Manning Employee of: Bristol-Myers Squibb, J. Kremer Grant/Research support from: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb
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