Adalimumab Is Effective in Patients with Fistulizing Crohnʼs Disease Who Were Primary Nonresponders to Infliximab Treatment

Abstract

Purpose: Adalimumab (ADA), a fully human anti-tumor necrosis factor monoclonal antibody, is approved for the induction and maintenance of remission in adults with moderate to severe Crohn's disease (CD). Fistula healing and response was demonstrated in the 1-year CHARM trial, in which one-third of patients (pts) with fistulas had complete healing at the end of 1 year.1 Methods: Fistula healing and response in the CHOICE trial, a U.S.-based, multicenter, open-label trial of pts with moderately or severely active CD who failed infliximab therapy, were examined in this analysis. Patients who had previously responded to infliximab were enrolled, as well as primary nonresponders to infliximab. After a minimum 8-week infliximab washout, pts received open-label ADA as induction (160/80 mg at Weeks 0/2) and maintenance (40 mg every other week) therapies. Minimum study duration was ≥8 weeks, continuing until ADA was commercially available for CD. At/after 8 weeks, pts could be switched to ADA 40 mg weekly for flare/nonresponse. Complete fistula healing was measured at Week 0 and at the final study visit or early termination by lack of draining with gentle compression. All ADA patients were analyzed as a single group using both nonresponder imputation (NRI) and observed cases. Data were also summarized for 2 subgroups relative to infliximab failure: primary nonresponders (PNR) and initial responders (IR) who developed intolerance of or loss of response to infliximab. Results: Of the 673 pts in CHOICE, 88 had fistulas at baseline and 83 had data available at the last visit (ranging from Weeks 4 to 36). Complete fistula healing at last visit is shown in the table. Of the pts with complete fistula healing, 35% (12 of 34) completed Week 12 and 65% (22 of 34) completed Weeks 24 or 36. Conclusion: ADA was effective in this difficult-to-treat population of pts who had fistulas and had failed infliximab. Forty percent of pts had complete fistula healing at their last visit. Fistula healing was similar among the hard-to-treat pts who were primary nonresponders to infliximab. Fistula data from CHOICE are consistent with the efficacy demonstrated in CHARM. This research was funded by Abbott Laboratories, Abbott Park, IL.Table: Complete Fistula Healing With Adalimumab Therapy.