title: Severe infusion reactions to infliximab: aetiology, immunogenicity and risk factors in patients with inflammatory bowel disease.
abstract: BACKGROUND
  Infliximab (IFX) elicits acute severe infusion reactions in about 5% of patients with inflammatory bowel disease (IBD).
  
  
  OBJECTIVE
  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 using 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.
  
  
  CONCLUSIONS
  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 reactions.
authors.affiliation: Department of Medical Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev, Denmark. steenholdt@brygge.dk
authors.forename: C
authors.initials: C
authors.lastname: Steenholdt
authors.forename: M
authors.initials: M
authors.lastname: Svenson
authors.forename: K
authors.initials: K
authors.lastname: Bendtzen
authors.forename: O Ø
authors.initials: OØ
authors.lastname: Thomsen
authors.forename: J
authors.initials: J
authors.lastname: Brynskov
authors.forename: M A
authors.initials: MA
authors.lastname: Ainsworth
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000097:blood* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000097:blood / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D000069285:Infliximab