BACKGROUND & AIMS: Multiple randomized controlled trials (RCTs) have been conducted to determine therapeutic efficacy of the biological agents for the inflammatory bowel diseases (IBD). However, the external validity of findings from RCTs might be compromised by their stringent selection criteria. We investigated the proportion of patients encountered during routine clinical practice who would qualify for enrollment into a pivotal RCT of biological agents for IBD. METHODS: We performed a retrospective cohort study of adult patients with moderate-severe IBD who presented to a tertiary referral center. Inclusion and exclusion criteria were extracted from published RCTs of biologics approved by the Food and Drug Administration and applied to the study population. RESULTS: Only 31.1% of 206 patients with IBD (34% with Crohn's disease [CD], 26% with ulcerative colitis) would have been eligible to participate in any of the selected RCTs. Patients would have been excluded because they had stricturing or penetrating CD, took high doses of steroids, had comorbidities or prior exposure to biologics, or received topical therapies. Of the trial-ineligible patients with ulcerative colitis, 23.3% had colectomies, and 31.7% received infliximab, with a 63.2% response rate. Approximately half (49.4%) of the 82 trial-ineligible patients with CD received biological therapies, with lower response rates (60%) than trial-eligible patients (89%; P = .03). CONCLUSIONS: Most patients with moderate-severe IBD evaluated in an outpatient practice would not qualify for enrollment in a pivotal RCT of biological reagents; this finding raises important questions about their therapeutic efficacy beyond the clinical trial populations. Additional evaluation of the transparency of RCT design and selection criteria is needed to determine whether trial results can be generalized to the population.
BACKGROUND & AIMS: Multiple randomized controlled trials (RCTs) have been conducted to determine therapeutic efficacy of the biological agents for the inflammatory bowel diseases (IBD). However, the external validity of findings from RCTs might be compromised by their stringent selection criteria. We investigated the proportion of patients encountered during routine clinical practice who would qualify for enrollment into a pivotal RCT of biological agents for IBD. METHODS: We performed a retrospective cohort study of adult patients with moderate-severe IBD who presented to a tertiary referral center. Inclusion and exclusion criteria were extracted from published RCTs of biologics approved by the Food and Drug Administration and applied to the study population. RESULTS: Only 31.1% of 206 patients with IBD (34% with Crohn's disease [CD], 26% with ulcerative colitis) would have been eligible to participate in any of the selected RCTs. Patients would have been excluded because they had stricturing or penetrating CD, took high doses of steroids, had comorbidities or prior exposure to biologics, or received topical therapies. Of the trial-ineligible patients with ulcerative colitis, 23.3% had colectomies, and 31.7% received infliximab, with a 63.2% response rate. Approximately half (49.4%) of the 82 trial-ineligible patients with CD received biological therapies, with lower response rates (60%) than trial-eligible patients (89%; P = .03). CONCLUSIONS: Most patients with moderate-severe IBD evaluated in an outpatient practice would not qualify for enrollment in a pivotal RCT of biological reagents; this finding raises important questions about their therapeutic efficacy beyond the clinical trial populations. Additional evaluation of the transparency of RCT design and selection criteria is needed to determine whether trial results can be generalized to the population.
Authors: Parambir S Dulai; Brigid S Boland; Siddharth Singh; Khadija Chaudrey; Jenna L Koliani-Pace; Gursimran Kochhar; Malav P Parikh; Eugenia Shmidt; Justin Hartke; Prianka Chilukuri; Joseph Meserve; Diana Whitehead; Robert Hirten; Adam C Winters; Leah G Katta; Farhad Peerani; Neeraj Narula; Keith Sultan; Arun Swaminath; Matthew Bohm; Dana Lukin; David Hudesman; John T Chang; Jesus Rivera-Nieves; Vipul Jairath; G Y Zou; Brian G Feagan; Bo Shen; Corey A Siegel; Edward V Loftus; Sunanda Kane; Bruce E Sands; Jean-Frederic Colombel; William J Sandborn; Karen Lasch; Charlie Cao Journal: Gastroenterology Date: 2018-05-30 Impact factor: 22.682
Authors: Edward L Barnes; Alison Goldin; Rachel W Winter; Emily Collins; Bonnie Cao; Madeline Carrellas; Anne Marie Crowell; Joshua R Korzenik Journal: Dig Dis Sci Date: 2016-09-17 Impact factor: 3.199
Authors: Christopher B Forrest; Wallace V Crandall; L Charles Bailey; Peixin Zhang; Marshall M Joffe; Richard B Colletti; Jeremy Adler; Howard I Baron; James Berman; Fernando del Rosario; Andrew B Grossman; Edward J Hoffenberg; Esther J Israel; Sandra C Kim; Jenifer R Lightdale; Peter A Margolis; Keith Marsolo; Devendra I Mehta; David E Milov; Ashish S Patel; Jeanne Tung; Michael D Kappelman Journal: Pediatrics Date: 2014-06-16 Impact factor: 7.124
Authors: Edward Shelton; Jessica R Allegretti; Betsy Stevens; Matthew Lucci; Hamed Khalili; Deanna D Nguyen; Jenny Sauk; Cosmas Giallourakis; John Garber; Matthew J Hamilton; Michal Tomczak; Fredrick Makrauer; Robert B Burakoff; Jonathan Levine; Punyaganie de Silva; Sonia Friedman; Ashwin Ananthakrishnan; Joshua R Korzenik; Vijay Yajnik Journal: Inflamm Bowel Dis Date: 2015-12 Impact factor: 5.325