Open label trial of oral clarithromycin in active Crohn's disease.

Abstract

Crohn's disease seems likely to be due in some way to bacteria. Clarithromycin is a broad spectrum macrolide antibiotic with good penetration into macrophages and may be effective in eradicating the organisms that are presumed to be at the centre of the granulomatous reaction in Crohn's disease. Twenty-five patients with active Crohn's disease were treated with oral clarithromycin 250 mg b.d. in an open label study. Treatment was for an initial 4-week period, continued to 12 weeks in patients who had shown a partial or complete response. The patients had a median age of 30 years (range 17-72), and disease duration of 5 years (range 2 months-28 years); 14 had ileocolonic, four small bowel, seven colonic disease and 10 had previous resections. Twenty patients were receiving a 5-ASA preparation, 15 corticosteroids (prednisolone median dose 10 mg range 2-30 mg) and nine azathioprine. All patients receiving corticosteroids or azathioprine had been on unchanged treatment for at least 12 weeks. Median pre-treatment Harvey Bradshaw index (HBI) was 9 (range 5-16) and median serum C-reactive protein was 21.5 mg/L (range < 5-117). By 4 weeks the median HBI had decreased to 5 (range 0-18) (P < 0.001) and median CRP to 17 mg/L (range < 5-157) (P=0.16). Sixteen patients (64%) had at least a 3 point fall in HBI and remission (defined as a HBI less than or equal to 4) was achieved in 12 patients (48%). By 12 weeks median HBI was 5 (range 0-18) (P < 0.001) and median CRP was 14.5 mg/L (range < 5-157) (P=0.05). Eleven of the 25 patients studied continued on oral clarithromycin after 12 weeks for a median of 28 weeks (range 20-60). Eight (73%) remained in remission on treatment. When treatment with clarithromycin was stopped three remained in remission and five relapsed after a median of 5 months (range 4-9). Two patients withdrew due to non-serious side-effects. Treatment was well tolerated in the remaining patients. This open label study has shown an impressive response to clarithromycin in a group of patients with active Crohn's disease, many of whom had been resistant to other therapy. A formal randomized controlled trial of clarithromycin in active Crohn's disease is needed.