FRI0191 Immunogenicity is low and transient with intravenous abatacept therapy
Authors: M.E. Weinblatt, M.C. Genovese, M.H. Schiff, R. Westhovens, R. Alten, I. Delaet, M. Nys, J. Manning, J.M. Kremer
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Immunogenicity with therapeutic proteins has been linked to reduction in both efficacy and safety in patients (pts) with RA.<sup>1,2</sup> 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.<sup>3</sup> <h3>Objectives</h3> To evaluate immunogenicity in a large pt group with long-term (up to 8 yrs) IV ABA exposure. <h3>Methods</h3> 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. <h3>Results</h3> 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. <h3>Conclusions</h3> 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. <h3>References</h3> Bartelds GM, et al. JAMA 2011;305:1460–8. Pascual-Salcedo D, et al. Rheumatology 2011;50:1445–52. Haggerty HG, et al. J Rheum 2007;34:2365–73. <h3>Disclosure of Interest</h3> 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