Anti-infliximab antibodies in inflammatory bowel disease:  prevalence, infusion reactions, immunosuppression and response, a meta-analysis.
Infliximab is a chimeric monoclonal antibody directed against tumour necrosis factor-α. When used in inflammatory bowel disease, primary nonresponse is found 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 aim of the study was to determine in patients receiving infliximab the prevalence of ATIs, the effect of immunosuppressants on the prevalence of ATI, the effect of ATIs on the prevalence of infusion reactions and the effect of ATIs on the rates of remission. MEDLINE and EMBASE databases were searched from 1948 and 1980, respectively, to October 2011. 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. The rates of infusion reactions were significantly higher in patients with ATIs (relative risk: 2.07; 95% confidence interval, 1.61-2.67). Immunosuppressants resulted in a 50% reduction in the risk of developing ATIs (P<0.00001). However, the presence or absence of ATIs did not affect the rates of clinical remission. The prevalence of ATIs depends on the regimen of infliximab administration and the use of immunosuppressants. Patients who test positive for ATIs are at an increased risk of infusion reactions, but have similar rates of remission compared with patients who test negative for ATIs. Further analysis is required to determine whether loss of response is dependent on the titre of ATIs.
Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Lennard Y W
LY
Lee
Jeremy D
JD
Sanderson
Peter M
PM
Irving
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D005765:Gastrointestinal Agents / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology*; D000069285:Infliximab; D008297:Male; D015995:Prevalence; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab