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.
The Immunogenicity of Infliximab, Adalimumab and Etanercept in Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis, Crohn's Disease and Ulcerative Colitisa Quantitative and a Qualitative Review.
Garces1, Sandra, Demengeot2, Jocelyne, Wolbink3, Gj, Aarden4, L., Benito-Garcia5, Elizabeth
Instituto Gulbenkian Ciência; Hospital Garcia de Orta, Oeiras, Portugal
Instituto Gulbenkian Ciência, Oeiras, Portugal
Reade/Jan van Breemen Institute Research Center, Amsterdam, Netherlands
Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
BioEpi, Research Center, Oeiras, Portugal
Despite the beneficial effects of aTNF alpha agents on the systemic rheumatic and inflammatory bowel diseases, a significant proportion of patients cannot sustain a therapeutic response over time. An increasing body of literature highlights immunogenicity as one of the main factors behind therapeutic failure and infusion-related adverse events. Given the recent recommendations by the EMEA to monitor immunogenicity in clinical practice, it is important to reevaluate the impact of anti-biologic antibodies on drug efficacy and safety.
We conducted a meta-analysis to assess the influence antibodies against infliximab, adalimumab and etanercept on therapeutic efficacy/effectiveness and the influence of concomitant immunosuppression in anti-biologic antibodies production, in patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn`s disease and ulcerative colitis.
A systematic literature search of Medline, Embase and Cochrane Library was conducted trough May 2011, complemented with the reference lists of articles and consultation with experts. We included clinical trials and observational studies. Seventeen studies met our inclusion criteria. Fixed-effects models (Mantel-Haenszel method) were initially used for clustering results and random-effects models according to the Laird method were introduced whenever statistically significant heterogeneity existed, examined by calculating the c2 test for heterogeneity and the I2 measure of inconsistency. The effects of individual study and population characteristics were evaluated by meta-regression.
Overall, the presence of anti-biologic antibodies reduced the therapeutic response rate (RR, 95% CI varied from 0.05 to 0.53). Subgroup analysis revealed that the concomitant use of Methothrexate (MTX) was a significant source of heterogeneity. When high proportion of patients was receiving concomitant MTX (>=74%) the effect size reduction was smaller (RR 0.68, 95% CI 0.58 to 0.79) than in studies where a lower proportion of patients were co-treated with MTX (RR 0.20, 95% CI 0.11 to 0.35). The effect is independent of the type of the disease. The concomitant use of immunosupressors reduced the proportion of patients with detectable anti-biologic antibodies by about 50% (RR varied from 0.26 to 0.82). In the subgroup analysis we verified that when RIA was used to detect anti-biologic antibodies the effect size reduction was larger (RR 0.36, 95% CI 0.28 to 0.45) than in studies where the antibodies were detected by ELISA methods (RR 0.66, 95% CI 0.57 to 0.76).
There is evidence of an increased risk of therapeutic failure in patients with anti-biologic antibodies, which although modulated by MTX, remains very significant. Aside from clinical impact, immunogenicity can also alter drug safety profile. Concomitant immunosuppression reduces but do not abrogate anti-biological production. The type of assays employed to assess anti-biologic antibodies can influence the results. Routine assessment of immunogenicity will help us to design more cost-effective strategies, tailored to each patient.
To cite this abstract, please use the following information:
Garces, Sandra, Demengeot, Jocelyne, Wolbink, Gj, Aarden, L., Benito-Garcia, Elizabeth; The Immunogenicity of Infliximab, Adalimumab and Etanercept in Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis, Crohn's Disease and Ulcerative Colitisa Quantitative and a Qualitative Review. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :464