Efficacy and Safety of Open Label Rifaximin in the Treatment of Mild-Moderate Crohnʼs Disease (CD) Refractory to Multiple Medical Therapies

Abstract

Purpose: Rifaximin is a nonabsorbable antibiotic with broad-spectrum activity against intestinal pathogens, and is approved for traveler's diarrhea. We have previously reported the results of the use of rifaximin in 30 patients with mild-moderate CD, and found an overall response rate of 56%. Here, we report the results of our continued use of rifaximin in patients with mild-moderate disease CD refractory to multiple medical therapies. Methods: We reviewed the medical records of 60 patients from a single group practice, with mild-moderate CD treated with open label rifaximin (including the results of 30 patients previously reported). Rifaximin was dosed as 200 mg TID in 10 patients, 400 mg BID in 46 patients, and 400 mg TID in 4 patients. Patient outcome was assessed by 4 weeks using the Present-Korelitz score with scores of 0 = no clinical improvement, +1 = mild clinical improvement, +2 = modest clinical improvement, and +3 = clinical remission. Results: The mean age of the patients was 39 years old, mean duration of disease of 13.4 years. Concomitant medications were aminosalicylates in 33 of 60 patients (55%); ciprofloxacin or metronidazole in 21 of 60 patients (35%); budesonide in 21 of 60 patients (35%) (mean dose = 6.7 mg/d); prednisone in 14 of 60 patients (23%) (mean dose = 21mg/d), and immunomodulators (6-MP, azathioprine, or methotrexate) in 26 of 60 patients (43%). Prior to the initiation of rifaximin, patients were on a mean of 3.1 CD drugs/d. 27 patients (45%) had isolated small bowel disease, 23 (38%) had ileocolitis, and 10 (17%) had isolated colonic involvement. Overall, the response rate was 55%; response rates varied by disease location: 13 of 27 patients (48%) with ileitis improved, while 14 of 23 (61%) ileocolitis patients improved, and 6 of 10 (60%) of colitis patients improved. The only drug-related adverse events were oral thrush in 1 patient, and nausea in 3 patients. Conclusions: In this open label series, rifaximin therapy in doses of 600–1200 mg/day was effective by 4 weeks in 55% of patients in patients with mild-moderate Crohn's disease, despite being refractory to multiple other therapies. These results are consistent with randomized controlled trials with other antibiotics in mild-moderate CD, in which the benefit was greatest in patients with colonic involvement. Dose-ranging, placebo-controlled trials of rifaximin in CD are warranted.