Randomized, Double-Blind, Placebo-Controlled Study of Anti-Mycobacterial Therapy (RHB-104) in Active Crohn's Disease

Area of Science:

• Gastroenterology
• Microbiology
• Clinical Pharmacology

Background:

• Crohn's disease is a chronic inflammatory bowel disease with complex etiology.
• Mycobacterium avium subspecies paratuberculosis (MAP) is a suspected, though unproven, causative agent in Crohn's disease.
• Existing treatments for Crohn's disease have limitations, necessitating novel therapeutic approaches.

Purpose of the Study:

• To evaluate the efficacy and safety of a triple antimicrobial therapy (RHB-104) targeting MAP in patients with active Crohn's disease.
• To test the hypothesis that anti-MAP therapy can favorably impact Crohn's disease activity and progression.

Main Methods:

• A double-blind, multicenter, randomized controlled trial (Clinicaltrials.gov: NCT01951326) involving 331 adult patients with active Crohn's disease.
• Patients received either RHB-104 (clarithromycin, rifabutin, clofazimine) or a placebo for up to 52 weeks, alongside standard-of-care treatment.
• Primary endpoint was remission (Crohn's Disease Activity Index [CDAI] < 150) at week 26; secondary endpoints included clinical response and fecal calprotectin (FCP) levels.

Main Results:

• A significantly greater proportion of patients in the RHB-104 group achieved remission at week 26 (36.7%) compared to placebo (22.4%) (p=0.0048).
• Clinical response rates at weeks 26 and 52 were also significantly higher in the RHB-104 group.
• RHB-104 treatment led to a statistically significant decline in FCP levels at multiple time points, with similar rates of serious adverse events between groups.

Conclusions:

• Triple antimicrobial therapy targeting MAP (RHB-104) demonstrated significant efficacy in improving clinical and laboratory measures of active Crohn's disease.
• The study supports the role of MAP as a potential factor in Crohn's disease pathogenesis and the utility of anti-MAP therapy.
• RHB-104 offers a potentially valuable new therapeutic option for Crohn's disease patients with an acceptable safety profile.