Background: Antibiotics have been used to treat luminal Crohn’s disease (CD) with variable success. Rifaximin has a favorable safety profile given its limited systemic absorption. Studies suggest clinical improvement in patients with mild-moderate CD treated with rifaximin. Studies evaluating response to rifaximin in moderate-severe luminal CD are limited. Methods: We randomized 24 subjects eligible per protocol with moderate-severe CD (Crohn’s disease activity index (CDAI) 250-450) 1:1 to receive blinded rifaximin 550 mg PO BID or placebo for 8 weeks. Non-responders to placebo then received open label (OL) rifaximin 550 mg PO BID for 8 weeks. Assessments include disease activity by CDAI, quality of life by Inflammatory Bowel Disease Questionnaire (IBDQ), and biochemical assessments including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Adverse events were documented throughout the study and 8 weeks after the last dose. Results: Key characteristics of 24 subjects eligible per protocol are described in Table 1. After 8 weeks of blinded treatment, 38.5% of subjects reported clinical response by CDAI in the treatment arm, compared to 9.1% in the control population (P = 0.055 by non-parametric permutation test). Ten subjects with nonresponse to placebo received OL rifaximin. Five subjects completed the OL study. 1 subject withdrew consent and 4 discontinued early due to lack of efficacy. At week 8, 1 subject had clinical response and no subjects were in remission by CDAI. Adverse events were similar between groups. Conclusion: Rifaximin has a moderate impact on clinical disease activity in moderate-severe Crohn’s disease, even in patients with a significant disease burden and prior exposure to one or more biologic therapies. Quality of life and biochemical assessments were numerically improved. No new safety concerns were identified.
