Authors: Hampson SJ, Parker MC, Saverymuttu SH, Joseph AE, McFadden JJ, Hermon-Taylor J.

Institution: Department of Surgery, St George's Hospital Medical School, London, UK.

Summary: Twenty patients with active Crohn's disease, the majority refractory to conventional therapy, were treated with rifampicin, ethambutol, isoniazid, and pyrazinamide or clofazamine for 9 months. After this period, 10 were in remission (Crohn's disease activity index less than 150).

Of the 10 not in remission, three had been at 6 months, but had relapsed on treatment. Nine of 10 patients on steroids at the beginning were off steroids at 9 months. Six patients came to surgery during the period, five for stricture formation without evidence of florid Crohn's disease outside the strictured segment. Three young patients with severe Crohn's disease facing total colectomy were spared surgery. No serious drug-related side-effects were encountered.

The results of this pilot study suggest that controlled trials of antimycobacterial chemotherapy, using four or more of the best agents available, are worthy of assessment in Crohn's disease.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2518848&query_hl=56&itool=pubmed_docsum

Authors: Gui GP, Thomas PR, Tizard ML, Lake J, Sanderson JD, Hermon-Taylor J.

Institution: University Department of Surgery, St George's Hospital Medical School, London, UK.

Summary:Fifty-two patients with severe Crohn's disease were enrolled in this study. Six (11.5%) were intolerant of the medication and had to be excluded. The remaining 46 patients were treated with rifabutin in combination with a macrolide antibiotic (clarithromycin or azithromycin).

Patients were treated for a mean of 18.7 (range 6-35) months and followed up for 25.1 (range 7-41) months. Of the 19 patients who were steroid dependent at the start of this study, only two continued to require steroids when treatment was established. A reduction in the Harvey-Bradshaw Crohn's disease activity index occurred after 6 months' treatment (P = 0.004, paired Wilcoxon test) and was maintained at 24 months (P < 0.001).

An improvement in inflammatory parameters was observed as measured by a reduction in erythrocyte sedimentation rate (P = 0.009) and C-reactive protein (P = 0.03) at 18 months compared with pretreatment levels, and an increase in serum albumin at 12 months (P = 0.04). When subsets of the study population were analysed, patients with pan-intestinal disease achieved better remission at 2 years than did those with less extensive involvement (P = 0.04, Mann-Whitney U-test).

No difference in treatment response by age, disease duration, the presence of granulomas on histology, or the occurrence of drug-induced side-effects, was observed. These data suggest that treatment with rifabutin and clarithromycin or azithromycin may result in a substantial clinical improvement in Crohn's disease and justify the conduct of a randomized controlled trial.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9096189&query_hl=53&itool=pubmed_docsum

Authors: Shafran I, Kugler L, El-Zaatari FA, Naser SA, Sandoval J.

Institution: Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, USA. ira@shafran.net

Background: Crohn's disease, an inflammatory bowel disease in humans, has a suspected aetiology of Mycobacterium avium subsp. Paratuberculosis.

Results: Seven patients (19.4%) withdrew from the study since they were unable to tolerate medications. Of the remaining 29 patients, 21 (58.3%) reached a sustained state of improvement, traditionally defined as a decrease of 70 points between their entrance and exit Crohn's disease activity index scores together with the absence of the need of all other Crohn's medications, such as immunosuppressants and corticosteroids. Three Crohn's disease patients [8. 3%) noticed significant improvements, but required other Crohn's medications, concurrently with rifabutin and macrolide antibiotic therapy, to achieve and sustain improvement. Only 5 Crohn's disease patients (13.8%) were non-responders, noticing no marked improvement while on rifabutin and macrolide antibiotic therapy.

Conclusion: The data add further evidence to support the role of rifabutin and macrolide antibiotic therapy in the treatment of Crohn's disease specifically in those patients with evidence of Mycobacterium avium subsp. Paratuberculosis infection. A large multi-centre clinical trial is needed to further explore these findings.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11930899&query_hl=51&itool=pubmed_docsum