title: Sequential Combination Therapy Versus Monotherapy: A Lack of Benefit in Time to Inflammatory Bowel Disease-Related Surgery.
abstract: The benefits of combination therapy with infliximab and azathioprine have been demonstrated in clinical trials of patients with ulcerative colitis (UC) and Crohn's disease (CD). Concerns remain regarding the ideal duration and benefits of adding therapies in a sequential manner.
  
  
  
  We aim to compare long-term outcomes among patients with inflammatory bowel disease (IBD) treated with sequentially added combination therapy or monotherapy strategies .
  
  
  
  We performed a retrospective cohort study involving adult patients with UC and CD. One cohort included patients treated with infliximab, adalimumab, or a thiopurine as monotherapy. A second cohort included patients treated with sequentially added combination therapy including infliximab or adalimumab and a thiopurine. The primary outcome was the rate of IBD-related surgery.
  
  
  
  Among 462 patients, 181 (39 %) were treated with combination therapy. 12 % of patients treated with combination therapy underwent an IBD-related surgery compared to 18 % of patients treated with monotherapy (p = 0.091), with no overall difference in time to IBD-related surgery demonstrated (log-rank test, p = 0.063). When evaluating the subtypes of IBD, there was a significant benefit in time to IBD-related surgery among patients with CD treated with sequentially added combination therapy (HR 0.46, 95 % CI 0.25-0.85) but not UC (HR 0.82, 95 % CI 0.30-2.22).
  
  
  
  The benefits of sequentially added combination therapy seem blunted when evaluating long-term clinical outcomes. This may be due to a decreased effectiveness of sequential combination therapy, a loss of benefit over time, or a differential effect between subtypes of IBD.
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. elb799@mail.harvard.edu.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Barnes
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Goldin
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Winter
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Collins
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Cao
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Madeline
authors.initials: M
authors.lastname: Carrellas
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Crowell
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Korzenik
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use*; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D016022:Case-Control Studies; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D003251:Constriction, Pathologic; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D013505:Digestive System Surgical Procedures / Q000706:statistics & numerical data; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use*; D007415:Intestinal Obstruction / Q000209:etiology / Q000601:surgery; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D018501:Antirheumatic Agents; D000069285:Infliximab; D000068879:Adalimumab; D001379:Azathioprine
keywords: Adalimumab; Azathioprine; Combination therapy; Inflammatory bowel disease; Infliximab