title: Evaluating Study Withdrawal Among Biologics and Immunomodulators in Treating Ulcerative Colitis: A Meta-analysis of Controlled Clinical Trials.
abstract: BACKGROUND
  We conducted a systematic review and meta-analysis to evaluate the efficacy and adverse event (AE)-associated tolerability of treatment with immunomodulators and biologics in ulcerative colitis clinical trials.
  
  
  METHODS
  We performed a literature search of PubMed and the Cochrane databases to identify randomized placebo-controlled trials of immunomodulators and biologics. Tolerability was defined through study withdrawal due to AEs and efficacy through clinical response in induction trials and clinical remission in maintenance trials. We performed meta-analyses using a random-effects model to determine relative risks (RRs) of efficacy and study withdrawal. Number needed to treat (NNT) and number needed to stop (NNS) were determined. The ratio of NNS/NNT was calculated, with a higher ratio indicating a greater number of patients in remission for every AE study discontinuation.
  
  
  RESULTS
  We examined 13 single-agent trials representing biologics (infliximab, adalimumab, golimumab, and vedolizumab) and immunomodulators (tacrolimus and azathioprine). Induction therapy did not result in excess study withdrawal with immunomodulators (RR = 0.9, 95% CI 0.1-12.0) or biologics (RR = 0.7, 95% CI 0.3-1.8), therefore the NNS/NNT ratio could not be assessed because of high tolerability. Maintenance immunomodulator therapy resulted in a NNS of 14 (RR = 2.8, 95% CI 0.7-10.5) and NNS/NNT ratio of 2.4 in 2 trials. Biologics did not result in excess study withdrawal in maintenance (RR = 0.7, 95% CI 0.3-1.7) or combined induction-and-maintenance (RR = 0.6, 95% CI 0.4-1.0) trials.
  
  
  CONCLUSIONS
  Biologics were not associated with a higher RR of study withdrawal due to AE than placebo. There were insufficient data to compare these results with immunomodulators.
authors.affiliation: *Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California; †Section of Gastroenterology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; and ‡Department of Veterans Affairs, Los Angeles, California.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Shah
authors.forename: Corey A
authors.initials: CA
authors.lastname: Siegel
authors.forename: Kelly
authors.initials: K
authors.lastname: Chong
authors.forename: Gil Y
authors.initials: GY
authors.lastname: Melmed
mesh_terms: D001688:Biological Products / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D011379:Prognosis; D028761:Withholding Treatment
chemical_list: D001688:Biological Products; D007155:Immunologic Factors