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P100. Formation and effects of anti-infliximab antibodies: A meta-analysis

L.Y. Lee1, J. Sanderson2, P. Irving1

1Guy's and St. Thomas' NHS Foundation Trust, Gastroenterology, London, United Kingdom; 2St Thomas' Hospital, Dept. of Gastroenterology, London, United Kingdom

Background: Infliximab is a chimeric monoclonal antibody directed against tumour necrosis factor alpha. When used in inflammatory bowel disease (IBD), primary non-response is seen in at least 10% of patients with secondary loss of response occurring in a further 10–15% per year. It has been suggested that this may in part be a result of the development of anti-infliximab antibodies (ATIs). The prevalence of ATIs varies according to the frequency of administration of infliximab and the use of immunosuppressants. ATIs have also been linked with infusion and hypersensitivity reactions. We aimed to perform a meta-analysis of the prevalence of ATIs in people with IBD receiving infliximab, the effect of immunosuppressive drugs on prevalence of ATIs and the effects of ATIs on infusion reactions and remission rates.

Methods: MEDLINE and EMBASE databases were systematically searched from 1948 and 1980 respectively to October 2011. Inclusion criteria included randomized controlled trials, cohort studies or case series reporting on anti-infliximab antibodies in adult or juvenile IBD. Data from eligible studies were extracted into a standardized form and a meta-analysis performed.

Results: Eighteen studies involving 3326 patients were included. The prevalence of ATIs was 45.8% when episodic infusions of infliximab were given and 12.4% when maintenance infliximab was given. Rates of infusion reactions were significantly higher in patients with ATIs (RR: 2.07, 95% CI 1.61–2.67). Immunosuppressants resulted in a 50% risk reduction in prevalence of ATIs. The prevalence of ATIs was 17.5% in patients using immunosuppressants and 37.7% in those who were not (RR: 0.50, 95% CI 0.42–0.59).

Effect of immunosuppression on number of ATIs
 Number of ATIs95% CIRelative Risk
Episodic Infliximab95/128 (74.2%)0.66–0.81
 + immunosuppression77/171 (45.0%)0.38–0.530.60
Maintenance Infliximab148/423 (35.0%)0.31–0.40
 + immunosuppression32/315 (10.2%)0.07–0.140.31

However, the presence or absence of ATIs did not significantly affect rates of clinical remission, which was 46.5% in patients with ATIs and 60.2% in those without (p = 0.10).

Conclusions: The prevalence of ATIs depends on the regimen of infliximab administration and the use of immunosuppressants. Patients who develop ATIs are at increased risk of infusion reactions, but the presence of ATIs does not, by itself, have an effect on rates of clinical remission.