The number of prevalent cases of IBD currently stands at about 1.5 million in the major pharmaceutical markets. This patient population is set to expand by up to 0.5% each year until 2008 contributing to the growth of the IBD market. Currently in excess of $0.5 billion, IBD related sales have been forecasted to increase by 3-10% each year over this period. Of the total number of IBD patients, just over 0.5 million are believed to suffer from Crohn's disease (CD). Although hotly debated, accumulating microbiological, immunological, molecular and epidemiological evidence is tipping the scales in favor of Mycobacterium avium subspecies paratuberculosis (Map) as the primary etiological agent in at least a proportion of patients with CD. This evidence includes positive culture and polymerase chain reaction (PCR) detection of Map in resected specimens of CD patients; the ability of Map to cause ileocolitis in primates; and a reported immunological responses to Map in Crohn's sufferers. Despite this supportive evidence, many studies have failed to establish a firm relationship between Map and CD and hence the wider scientific community remains sceptical towards its causative role. Part of the reason for this skepticism is trials using standard anti-tuberculous therapies for CD have generally yielded poor results. Given that Map is more closely related to Mycobacterium avium complex (MAC) than Mycobacterium tuberculosis this is perhaps not surprising. However, recent advances in the treatment of MAC infection and the availability of novel antimycobacterial agents have opened opportunities to combat Map and to continue the debate as to the cause of CD. Specifically, the chemical derivative of rifamycin antibiotics, rifabutin, and the macrolide clarithromycin, have good activity against MAC and Map in vitro both alone and in combination with other agents such as Clofazimine. More recently, Australian field-leaders have launched a long-term pilot trial designed to investigate the efficacy of triple-therapy. Twelve patients with severe, obstructive or penetrating CD and failing maximal therapy were commenced prospectively on a combination of rifabutin, clarithromycin and clofazimine. Six out of twelve patients experienced a full response to the anti-Map combination achieving complete clinical, colonoscopic and histologic remission of CD, while a further two experience partial response. Side effects included transient arthralgia and leucopenia, dry skin and vitiligo. No patient ceased therapy due to adverse drug reactions. These convincing data strongly support the need for larger studies designed to determine the effectiveness of antimycobacterial therapy in the treatment of CD and for pharmaceutical companies to develop improved antimicrobial agents with this indication in mind.

Adapted from Borody et al, Dig Liver Dis 2002 Jan;34(1):29-38

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