Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Immunogenicity Is Low and Transient with Intravenous (IV) Abatacept Therapy: Results From a Large Pooled Analysis of 3985 Patients (pts) with Rheumatoid Arthritis (RA) and up to 8 Years' Exposure.
Weinblatt1, Michael E., Genovese2, Mark C., Schiff3, Michael H., Westhovens4, Rene, Alten5, Rieke, Delaet6, Ingrid, Nys6, Marleen
Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA
Stanford University, Palo Alto, CA
Rheumatology Division, University of Colorado, Denver, CO
University Hospital KU Leuven, Leuven, Belgium
Rheumatology Schlossparkklinik, Berlin, Germany
Bristol-Myers Squibb, Princeton, NJ
Albany Medical College and The Center for Rheumatology, Albany, NY
Immunogenicity with some biologics has been associated with loss of efficacy and occurrence of adverse events (AEs)1,2. IV abatacept (ABA) has demonstrated low and transient immunogenicity in clinical trials (~3%) that does not impact safety or efficacy3. We further explore immunogenicity to ABA using a large dataset of pts with up to 8 years' ABA exposure.
Data from seven ABA RA clinical trials were included in immunogenicity assessments, including the short-term (ST) periods (6- or 12-months) of six double-blind, placebo-controlled studies (AIM, ATTEST, ATTAIN, ASSURE, 101 and 100) and one 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 monthly IV ABA (~10 mg/kg). Samples on or before the day of first ABA dose were excluded. Anti-ABA antibodies were detected using two ELISAs: one to the whole ABA molecule (CTLA4 and IgG1), and one to the CTLA4 region (T). Positive samples had titers >=400 for anti-ABA or >=25 for anti-CTLA4-T. Immunogenicity was defined as proportion of pts with antibody response while on-treatment (<=42 days post-last dose) or post-treatment. Persistent immunogenicity was defined as positive response on >=2 consecutive visits. Data are as-observed for all ABA-treated pts.
3985 pts were included with up to 8 years' ABA exposure; 252/3985 (6.3%) pts demonstrated antibody response (Table). Antibody titers in positive pts were generally low (in the majority of pts, titers were less than 5000 for anti-ABA and less than 100 for anti-CTLA4-T) and did not appear to increase with continued treatment. Persistent immunogenicity and immunogenicity with missed doses was infrequent (Table); titers in these pts were also generally low. Serious adverse events (SAEs) related to study drug occurred in 32/252 pts who experienced immunogenicity, with no relationship identified between immunogenicity and SAEs, peri-infusional, acute infusional or autoimmune events, or hypersensitivity reactions. No consistent relationship with efficacy was identified; 83% (55/66) of ACR20 responders maintained this following positive antibody response, while 36% (10/28) of non-responders achieved ACR20 following positive antibody response.
Immunogenicity, n/N (%) patients with positive antibody response
ABA demonstrated low immunogenicity; any immunogenicity was transient and with low titer that did not increase upon continued dosing. No consistent association was observed between antibody response and safety or clinical efficacy, with previous observations in a pooled dataset demonstrating no association with pharmacokinetics3. These findings confirm previous observations3 in a large pt population with up to 8 years' exposure.
To cite this abstract, please use the following information:
Weinblatt, Michael E., Genovese, Mark C., Schiff, Michael H., Westhovens, Rene, Alten, Rieke, Delaet, Ingrid, et al; Immunogenicity Is Low and Transient with Intravenous (IV) Abatacept Therapy: Results From a Large Pooled Analysis of 3985 Patients (pts) with Rheumatoid Arthritis (RA) and up to 8 Years' Exposure. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2191