Dose Intensification of Vedolizumab in Nonresponders With Active Crohn's Disease: Lessons From LOVE‐CD

ABSTRACT Background Dose intensification of vedolizumab (VDZ) in patients with Crohn's disease (CD) with secondary loss of response has been reported to be effective. However, evidence for its effectiveness in primary nonresponders is inconsistent and largely based on retrospective studies. In this analysis of the LOVE‐CD study, we investigated the effect of VDZ dose intensification in endoscopic nonresponders after 26 weeks of standard dosing. Methods In LOVE‐CD, patients with early and late CD with moderate‐to‐severe disease activity and ulcers at baseline endoscopy were treated with standard VDZ intravenously with an additional 300 mg dose at Week 10 in case of clinical nonresponse. Halfway through the trial, after 130 patients (50%) had been included, the protocol was amended by introducing VDZ dose intensification from 300 mg IV every 8 weeks to every 4 weeks in patients without endoscopic response (ΔSES‐CD < 50%) after 26 weeks. The primary outcome was deep remission, defined as both steroid‐free clinical (CDAI ≤ 150) and endoscopic remission (SES‐CD ≤ 3) at Week 52. Results At Week 26, 82 patients (31.5%) were endoscopic nonresponders. In total, 78 patients were included: 44 patients before and 34 patients after the dose intensification amendment. Disease severity and disease duration at baseline were comparable between the two groups. The dose intensification group had significantly higher VDZ serum concentrations compared to the standard dosing group (mean 32.6 vs. 10.3 μg/mL at Week 46, p < 0.001). However, there was no significant difference in deep remission, endoscopic remission, and clinical remission rates at Week 52. Rates of severe adverse events were similar between groups. Conclusion VDZ dose intensification in endoscopic nonresponders after 6 months of standard dosing was not effective in improving clinical and endoscopic outcomes at Week 52. Trial Registration EudraCT 2014‐005376‐29