Loss of Response to Vedolizumab and Ability of Dose Intensification to Restore Response in Patients With Crohn's Disease or Ulcerative Colitis: A Systematic Review and Meta-analysis

BACKGROUND & AIMS: Vedolizumab is effective and safe for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Little is known about the incidence rate of loss of response to vedolizumab maintenance therapy or whether dose intensification restores response to this drug. METHODS: We searched PubMed, Scopus and conference abstracts (Digestive Disease Week, European Crohn's and Colitis Organization, and United European Gastroenterology Week), through December 2017, for experimental or observational cohort studies of vedolizumab use in adult patients with CD or UC; we identified studies that provided sufficient data to determine the incidence rate of loss of response among initial responders and the ability of dose intensification to restore response. Two reviewers independently abstracted study data and outcomes and rated each study's risk of bias. The studies were evaluated for heterogeneity and publication bias. Summary estimates were calculated using random effects models. RESULTS: We analyzed data from 10 eligible cohorts; most patients had received prior treatment with a tumor necrosis factor antagonist. The pooled incidence rates of loss of response were 47.9 per 100 person-years of follow up (95% CI, 26.3. 87.0; I-2 = 74%) among patients with CD and 39.8 per 100 person-years of follow up (95% CI, 35.0. 45.3; I-2 = 0%) among patients with UC. Dose intensification restored response to the drug in 53.8% of secondary non-responders (95% CI, 21.8%. 82.9%; I-2 = 77%). CONCLUSIONS: In a systematic review and meta-analysis, we found high proportions of patients with CD or UC to lose responsiveness to vedolizumab maintenance therapy. Dose intensification restores responsiveness to more than half of these patients. Additional studies are warranted to inform clinical decision making.