Severe infusion reactions to infliximab: aetiology, immunogenicity and risk factors in patients with inflammatory bowel disease
Open Access
- 3 May 2011
- journal article
- Published by Wiley in Alimentary Pharmacology & Therapeutics
- Vol. 34 (1), 51-58
- https://doi.org/10.1111/j.1365-2036.2011.04682.x
Abstract
International audienceBackground: Infliximab (IFX) elicits acute severe infusion reactions in about 5% of patients with inflammatory bowel disease (IBD). Aim: To investigate the role of anti-IFX antibodies (Ab) and other risk factors. Methods: The study included all IBD patients treated with IFX at a Danish university hospital until 2010 either continuously (IFX every 4-12 weeks) or episodically (reinitiation after >12 weeks). Anti-IFX Ab were measured by radioimmunoassay. Results: Twenty-five (8%) of 315 patients experienced acute severe infusion reactions. Univariate analysis showed that patients who reacted were younger at the time of diagnosis (19 vs 26 years, p=0.013) and at first IFX infusion (28 vs 35 years, p=0.012). Furthermore, they more often received episodic therapy (72 vs 31%, p<0.001), and logistic regression revealed this as the only significant predictor of reactions (OR 5 [2-13]; p<0.001). IFX reinitiation after 6 months intermission further increased the risk (OR 8 [3-20], p<0.001). Most reactions (n=14, 88%) occurred at 2nd infusion in the 2nd treatment series (p=0.006). Anti-IFX IgG Ab were highly positive in 19 of 20 patients (95%) shortly after the reactions (median 84 U/ml). Anti-IFX IgG Ab measured prior to the retreatment series were negative in 7 of 11 patients tested (64%). Anti-IFX IgE Ab were negative in all patients with reactions. Conclusion: Acute severe infusion reactions were strongly associated with development of anti-IFX IgG Ab, but not with anti-IFX IgE Ab. The risk was particularly high at the 2nd infusion in retreatment series. Negative anti-IFX Ab before reinitiation did not rule out reactionsKeywords
This publication has 30 references indexed in Scilit:
- Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn's diseaseScandinavian Journal of Gastroenterology, 2010
- The immunogenic part of infliximab is the F(ab')2, but measuring antibodies to the intact infliximab molecule is more clinically usefulGut, 2010
- Anti‐infliximab IgE and non‐IgE antibodies and induction of infusion‐related severe anaphylactic reactionsAllergy, 2010
- Infliximab safety profile and long‐term applicability in inflammatory bowel disease: 9‐year experience in clinical practiceAlimentary Pharmacology & Therapeutics, 2010
- Individual medicine in inflammatory bowel disease: Monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodiesScandinavian Journal of Gastroenterology, 2009
- Monitoring patients treated with anti-TNF- biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodiesRheumatology, 2007
- Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor α inhibitor infliximabArthritis & Rheumatism, 2006
- Successful induction of tolerance to infliximab in patients with Crohn's disease and prior severe infusion reactionsAlimentary Pharmacology & Therapeutics, 2006
- Clinical and biological consequences of immunization to infliximab in pediatric Crohn's diseaseClinical Immunology, 2005
- Infliximab Maintenance Therapy for Fistulizing Crohn's DiseaseNew England Journal of Medicine, 2004