Background: Long-term remission is an important treatment goal for patients with Crohn's disease (CD). While anti-TNF inhibitors are effective at inducing and maintaining remission in patients with moderate to severe CD, a considerable proportion of patients do not respond or lose response to these therapies over time. Therapies with new MOAs are emerging to address this unmet need but clinical trials often do not include direct comparison of these agents. Better understanding of relative clinical efficacy and safety is needed to determine optimal positioning of biologic therapies in the treatment algorithm.
The aim of this analysis was to conduct an indirect comparison of efficacy of two novel MOA biologics: vedolizumab (VDZ), an anti-α4β7 integrin, and ustekinumab (UST), an antibody directed against the p40 subunit of IL-12 and IL-23, as therapy for patients with moderately to severely active CD.
Methods: Induction and maintenance data from Phase 3, randomized, double-blind, placebo-controlled studies were used in the analysis: GEMINI II  for VDZ and UNIT-1, UNIT-2, and IM-UNITI  for UST. Bayesian Network Meta Analysis comparing VDZ and UST was performed with OpenBUGS v3.2.2. A binomial likelihood and a logit link function in a fixed effect model were used to account for variability in the placebo (PLA) effect across trials. Week 6 induction data were extracted for PLA, VDZ 300mg, UST 6mg/kg. Week 52 maintenance data were extracted for PLA, VDZ 300mg Q8W and Q4W, UST 90mg Q12W and Q8W. Results were stratified by prior exposure to anti-TNFs (induction: non-anti-TNF refractory, anti-TNF refractory; maintenance: anti-TNF naïve, anti-TNF refractory). Clinical remission was defined as CDAI ≤150. Odds Ratios (ORs) were estimated for the probability of remission. Median and 95% credible intervals of the posterior distribution of each OR were calculated.
Results: The OR for clinical remission at 6 weeks of treatment of UST 6mg/kg vs VDZ 300mg was 0.99 for non-anti-TNF refractory and 1.63 for anti-TNF refractory patients. The OR for clinical remission at 52 weeks of treatment of UST 90mg Q8W vs VDZ 300mg Q8W was 0.67 for anti-TNF naive patients and 0.73 for anti-TNF refractory patients. None of the ORs were statistically significant. Results for other dosing regimens in the maintenance phase are shown in Table 1.
Conclusions: There appears to be a positive trend with VDZ demonstrating numerically superior odds of clinical remission vs UST in the maintenance phase of treatment. Direct head-to-head studies are required to confirm this trend.
This study was funded by Takeda Development Center Europe Ltd. No medical writing assistance was provided.
 Sandborn WJ et al. (2013), Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease, N Engl J Med, 711–721
 Feagan B et al. (2016), Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease, N Engl J Med, 1946–60