Concerns and side effects of azathioprine during adalimumab induction and maintenance therapy for Japanese patients with Crohn's disease: a sub-analysis of a prospective randomized clinical trial (DIAMOND study).

Background Combining a thiopurine with the human anti-tumor necrosis factor- monoclonal antibody adalimumab for Crohn's disease (CD) treatment is controversial with regard to efficacy and safety. By conducting a sub-analysis of a multicenter, randomized, prospective, open-label trial (the DIAMOND study, UMIN registration number 000005146), we studied the risk of discontinuation of thiopurine in combination with adalimumab. Methods In the preceding DIAMOND study, we analyzed the: (i) timing and reasons for dropout in the monotherapy group and combination group; (ii) risk factors for dropout in the combination group. Results There was no significant difference in the dropout rate up to week-52 between the monotherapy group and combination group (p = 0.325). The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group (Fisher's exact test, p < 0.001). Kaplan-Meier analyses revealed significantly earlier dropout in the combination group (log-rank test, p = 0.001). Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. Conclusion Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab-monotherapy group.