title: Combination of C-reactive protein, infliximab trough levels, and stable but not transient antibodies to infliximab are associated with loss of response to infliximab in inflammatory bowel disease.
abstract: BACKGROUND
  Antibodies to infliximab [ATI] and trough levels to infliximab [TRI] are associated with loss of response in inflammatory bowel diseases [IBD]. The best way to predict loss of response [LOR] to infliximab [IFX] is unknown.
  
  
  METHODS
  We conducted a prospective observational cohort study enrolling all IBD patients who were in clinical remission at Week 14 after IFX treatment initiation. TRI, ATI and C-reactive protein [CRP] level were measured at Week 22 [T1] and thereafter at every other IFX infusion. Loss of clinical response was defined by a flare requiring therapeutic change [IFX dose intensification, initiation of another drug class, and/or surgery].
  
  
  RESULTS
  A total of 93 patients [59 Crohn's disease, mean duration of follow-up 17.2 months] were included; 32 patients [34.4%] lost clinical response during follow-up. Cumulative probability of LOR was 50% at 20 months. Mean TRI at T1 was significantly lower in IBD patients with stable ATI as compared with those with transient ATI or without ATI [0.052, 3.34 ,and 4.29 µg/ml, respectively; p = 0.001 between no ATI vs stable ATI, and p = 0.005 between stable and transient ATI] [p = 0.0001]. Three independent factors were predictive of LOR after Cox proportional hazards modelling: TRI > 5.5 µg/ml (hazard ratio [HR]: 0.21; 95% confidence interval [CI]: 0.05-0.89;p = 0.034) at T1, CRP > 5mg/l [HR: 2.5; 95% CI: 1.16-5.26; p = 0.019] at T1, and stable ATI defined by two consecutive ATI > 20ng/ml [HR: 3.77; 95% CI: 1.45-10.0; p = 0.007]. Transient ATI did not influence LOR.
  
  
  CONCLUSIONS
  LOR can be predicted based on a combination of CRP, TRI and stable ATI with a high degree of accuracy.
authors.affiliation: Department of Gastroenterology, F-42055, CHU Saint Etienne, France xavier.roblin@chu-st-etienne.fr.
authors.forename: X
authors.initials: X
authors.lastname: Roblin
authors.affiliation: Department of Rheumatology, F-42055, CHU Saint Etienne, France.
authors.forename: H
authors.initials: H
authors.lastname: Marotte
authors.affiliation: Department of Gastroenterology, F-42055, CHU Saint Etienne, France.
authors.forename: M
authors.initials: M
authors.lastname: Leclerc
authors.affiliation: Department of Gastroenterology, F-42055, CHU Saint Etienne, France.
authors.forename: E
authors.initials: E
authors.lastname: Del Tedesco
authors.affiliation: Department of Gastroenterology, F-42055, CHU Saint Etienne, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Phelip
authors.affiliation: Inserm U954 and Department of Gastroenterology, Université de Lorraine, Nancy, France.
authors.forename: L
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.affiliation: Department of Immunology, F-42055, CHU Saint Etienne, France.
authors.forename: S
authors.initials: S
authors.lastname: Paul
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D004361:Drug Tolerance; D005260:Female; D005765:Gastrointestinal Agents / Q000097:blood* / Q000276:immunology; D006801:Humans; D000069285:Infliximab / Q000097:blood* / Q000276:immunology; D008297:Male; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000906:Antibodies; D005765:Gastrointestinal Agents; D002097:C-Reactive Protein; D000069285:Infliximab
keywords: Crohn’s disease; Infliximab; antibodies to infliximab; inflammatory bowel disease; kinetics; loss of response; ulcerative colitis