Investigators present data from a new study showing that RHB-104 can effectively combat MAP infections for patients with moderately to severely active Crohn’s disease.
David Graham, MD
RHB-104 is being touted as an effective therapy to fight against mycobacterium avium paratuberculosis (MAP) infections for patients with moderate to severe Crohn’s disease (CD).
In research presented at the American College of Gastroenterology’s Annual Scientific Meeting (ACG 2019), a team of investigators, led by David Graham, MD, Baylor College of Medicine, tested the new drug in a global, multicenter, randomized trial called MAP US, comparing the efficacy and safety of RHB-104—a fixed-dose oral combination of clarithromycin, rifabutin, and clofazimine—with a placebo.
The study included 331 patients with active Crohn’s disease—as judged by a Crohn’s disease Activity Index (CDAI) score between 220-450—that failed with conventional therapies at 92 sites. The duration of the study was 52 weeks and permitted concomitant corticosteroids, immunosuppressive, and anti-tumor necrosis factor (TNF) therapies.
The primary endpoint of the study was clinical remission—a CDAI score of less than 150—at week 26. Secondary endpoints included clinical responses at week 26 as defined by a CDAI score decrease of at least 100 points, as well as early remission at week 16 and remission at week 52.
The team performed a population pharmacokinetic (PK) and exposure-response analysis based on PK assessments and remission at week 26. Also, a subset of patients underwent a colonoscopy at both baseline and week 26.
Overall, the study was deemed a success.
“The proportion achieving remission at [week] 26 (36.7% vs 23%, P =.007), remission at [week] 16 (42.2% vs 29.1%, P =.015) and response at [week] 26 (44% vs 30.9%, P =.017) were significantly greater with RHB-104 vs placebo,” the authors wrote. “The superiority of RHB-104 was more pronounced in patients receiving RHB-104 with concomitant anti-TNF or IS treatment.”
Despite a sample size of only 35 patients, a greater proportion of RHB-104 patients achieved endoscopic response by SES-CD 50 (28.6% vs 4.8%, P =.11).
The differences in fecal calprotectin (FCP) increased over time, while improvements in PRO-2 symptoms appeared by week 4 and reached significance by week 16.
The team also found a significantly greater proportion of patients receiving RHB-104 achieved clinical remission with at least a 50% reduction from baseline in either FCP or CRP concentration at week 16 (25.9% vs 9.7%, P =.0002).
The same held true at week 26 (21.1% vs 9.1%, p=.0003) and week 52 (16.9% vs 7.9%, P =.02).
Exposure-response modeling demonstrated the combination of the individual components of RHB-104 contributed to the higher rate of remission compared to placebo and that the probability of achieving remission was most sensitive to clofazimine.
“RHB-104 demonstrated meaningful improvement in efficacy and biomarkers of active inflammation, with exposure-response for each drug component, early onset of response and benefit in patients with and without concomitant anti-TNF or IS therapy,” the authors wrote.
The symposium, “RHB-104, a Fixed-Dose, Oral Antibiotic Combination Against Mycobacterium Avium Paratuberculosis (MAP) Infection, Is Effective in Moderately to Severely Active Crohn’s Disease,” was presented Wednesday, October 30, 2019, at the American College of Gastroenterology Annual Scientific Meeting (ACG 2019) in San Antonio, Texas.