title: Long-term combination therapy with infliximab plus azathioprine predicts sustained steroid-free clinical benefit in steroid-dependent ulcerative colitis.
abstract: BACKGROUND
  Infliximab (IFX) has demonstrated effectiveness for inducing 12-month steroid-free clinical remission in patients with steroid-dependent ulcerative colitis (UC), but long-term data are lacking. The aim of the study was to describe the long-term outcome of IFX treatment in steroid-dependent UC and investigate if predictors of sustained clinical response and colectomy could be identified.
  
  
  METHODS
  Consecutive patients with steroid-dependent UC treated with IFX were studied. The coprimary prespecified outcomes were sustained clinical response in patients who achieved clinical remission or response after IFX induction and colectomy-free survival. Secondary analyses were addressed to look for predictors of sustained clinical response and colectomy.
  
  
  RESULTS
  After induction, 76% (96/126) of patients achieved clinical benefit. The median duration of follow-up on IFX maintenance therapy was 41.5 months (interquartile range, 26-45). Sixty-four percent (46/96) of patients had sustained clinical response at median follow-up. Colectomy-free survival was 77% at median follow-up. Combination therapy of IFX with thiopurines was an independent predictor of sustained clinical response (P < 0.0001; hazard ratio [HR], 3.98; 95% confidence interval [CI], 1.73-9.14). Independent predictors of colectomy were Mayo endoscopic subscore of 3 at baseline (P = 0.04; HR, 2.77; 95% CI, 1.09-7.05) and high C-reactive protein after induction (P = 0.001; HR, 5.65; 95% CI, 2.03-15.7). Thiopurine naive status (P = 0.025; HR, 0.34; 95% CI, 0.13-0.87) was protective from colectomy.
  
  
  CONCLUSIONS
  Long-term IFX treatment is effective in inducing sustained clinical response in patients with steroid-dependent UC. Combination therapy is predictive of sustained clinical response in the long-term. Patients with more severe endoscopic lesions at baseline and high C-reactive protein after induction are at higher risk of colectomy. Conversely, thiopurine naive status is protective from colectomy.
authors.affiliation: *IBD Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy; and †IBD Center, Gastroenterology, IRCCS Humanitas, Rozzano, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Armuzzi
authors.forename: Daniela
authors.initials: D
authors.lastname: Pugliese
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
authors.forename: Gianluca
authors.initials: G
authors.lastname: Rizzo
authors.forename: Carla
authors.initials: C
authors.lastname: Felice
authors.forename: Manuela
authors.initials: M
authors.lastname: Marzo
authors.forename: Gianluca
authors.initials: G
authors.lastname: Andrisani
authors.forename: Gionata
authors.initials: G
authors.lastname: Fiorino
authors.forename: Olga Maria
authors.initials: OM
authors.lastname: Nardone
authors.forename: Italo
authors.initials: I
authors.lastname: De Vitis
authors.forename: Alfredo
authors.initials: A
authors.lastname: Papa
authors.forename: Gian Lodovico
authors.initials: GL
authors.lastname: Rapaccini
authors.forename: Luisa
authors.initials: L
authors.lastname: Guidi
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000401:mortality; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D012189:Retrospective Studies; D013256:Steroids / Q000008:administration & dosage*; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; D013256:Steroids; D000069285:Infliximab; D001379:Azathioprine