Background: Several studies have reported on the efficacy of combination therapy with infliximab and immunomodulators (IM) in patients with Crohn's disease (CD). Here, we investigated the efficacy of IM in long-term treatment with infliximab in Japanese patients with CD.
Methods: Retrospective data were collected from luminal CD patients treated with 5 mg/kg of infliximab for ≥14 weeks between January 2003 and December 2015 at two institutions. The efficacy of infliximab maintenance treatment was evaluated by the rate of sustained clinical benefit, which was estimated using the Kaplan–Meier method. Sustained clinical benefit was defined as the lack of treatment failure. Treatment failure was defined as the discontinuation of infliximab, dose escalation, or surgery for CD. Combination therapy with infliximab and IM was defined as the initiation of IM within 6 weeks from the first administration of infliximab and continuation until 14 weeks. Combination therapy was divided into IM naïve and IM exposed group. IM naïve and IM exposed group were defined as receiving IM treatment for less and more than 3 months prior to infliximab administration, respectively. Sustained clinical benefits of infliximab according to the type of IM treatment were investigated using the log-rank test.
Results: A total of 341 patients were included in this study. Of these, 243 patients received combination therapy. Of the 243 patients, 211 and 32 patients were administered azathioprine (AZA) and 6-mercaptopurine (6-MP), respectively. Of these, 83 and 126 patients were treated with 25 and 50 mg of AZA once a day, respectively. In addition, 23 patients were treated with 30 mg of 6-MP once a day. There were 190 patients in the IM naïve group and 53 patients in the IM exposed group. The 5 and 10-year cumulative sustained clinical benefit rates in all patients were 49% and 39%, respectively. Sustained clinical benefit rates were significantly higher in patients receiving a combination of infliximab and AZA than in those receiving infliximab monotherapy. Whereas, there was no significant difference in sustained clinical benefit rates between patients receiving a combination of infliximab and 6-MP and infliximab monotherapy. Patients receiving a combination of infliximab and AZA in IM naïve, but not IM exposed group achieved a significantly higher clinical benefit than those receiving infliximab monotherapy. Sustained clinical benefit in patients receiving a combination of infliximab and either 25 or 50 mg of AZA was significantly higher than that in patients treated with infliximab monotherapy.
Conclusions: Our data suggested that the combination of infliximab and low dose AZA (25 or 50 mg) as early as possible resulted in the better clinical outcome in Japanese patients with CD.