Ustekinumab Is Effective for the Induction and Maintenance of Response in Crohnʼs Disease: A Multi-center Cohort Study

Abstract

Introduction: While ustekinumab is not yet approved to treat Crohn's disease (CD), clinicians have begun to prescribe it off-label due to promising clinical trials. We assess the real-world efficacy of ustekinumab for induction of clinical response in CD patients. We also evaluate the proportion of ustekinumab primary responders who develop secondary loss of response during maintenance therapy. Methods: A retrospective multicenter cohort study was performed at two academic institutions on patients with CD who received ustekinumab between 2011-2016. The primary outcome was induction of clinical response at 3 months, defined by reduction in Harvey Bradshaw Index of >2 points and tapering off corticosteroids. Secondary loss of response was defined by clinical, endoscopic, or radiographic disease activity requiring dose escalation, rescue steroids/immunomodulators, surgical resection, or ustekinumab discontinuation. Patients were stratified by weight-adjusted induction dose (3 vs. 6mg/kg), method of induction (intravenous vs. subcutaneous), and initial maintenance regimen (q8 vs. 12 weeks). The proportion of patients on ustekinumab with clinical response was determined at 3, 6, and 12 months. Results: 82 CD patients met inclusion criteria. Median follow-up was 45.6 weeks (IQR 33.0-66.6). 75 patients (91.4%) had previously failed anti-TNF therapy and 61 patients (74.4%) had failed more than one biologic. 55 patients (67.1%) had clinical response to induction therapy at 3 months. Among 78 CD patients who were followed for or discontinued drug prior to 6 months, 67.9% (53/78) were still on treatment and in clinical response. 49.3% (33/67) of patients followed for 12 months or discontinuing drug prior to 12 months were on drugt and responding at 1 year. There were no differences in proportion of patients achieving response at 3, 6, or 12 months when stratified by induction dose (p=0.40-0.94), maintenance dose (p=0.30-0.75), or induction method (p=0.12-0.58). Among 55 primary induction responders, 60.0% (33/55) maintained response to end of follow-up. Median time to secondary loss of response was 45.6 weeks (IQR 33.0-66.6 weeks). Twenty-six patients (31.7%) experienced an adverse effect, predominantly arthralgias (11.0%) and infections (13.4%). Conclusion: In this cohort of CD outpatients, the majority of whom had previously failed multiple biologic agents, ustekinumab was effective for inducing clinical response and this response was maintained over long-term follow-up.Table 1: Baseline patient demographic and clinical characteristics of 82 patients treated with ustekinumab between 2011 and 2015