[Treatment of chronic inflammatory bowel diseases]

Marc Lémann
Bulletin de L'Académie Nationale de Médecine 2007, 191 (6): 1125-41; discussion 1141
The same drugs are used to treat hemorrhagic rectocolitis (HRC) and Crohn's disease (CD), although the aims are very different. Aminosalicylates are highly beneficial in HRC but virtually ineffective in CD, a disease in which immunosuppressants are more useful. Aminosalicylates exert their antiinflammatory effect directly on the lesions. Various oral and rectal preparations have been developed in order to deliver the active molecule to the intestinal target segment. These drugs are now known to act by stimulating the nuclear receptor PPAR-gamma, and this knowledge should help with the development of new agents. Chronic aminosalicylate treatment appears to diminish the risk of malignant transformation. Systemic steroids are still the mainstay of treatment for exacerbations of HRC and CD, yielding remissions in 60 to 90% of cases. In contrast, systemic steroids should not be used for maintenance therapy. Budesonide is a preparation that selectively releases steroids in the ileocolonic region, thereby reducing systemic adverse effects. Immunosuppressants such as azathioprine and 6-mercaptopurine, and also methotrexate in some cases, are used for maintenance therapy of steroid-dependent and highly recurrent forms. These drugs stabilize the disease in about half the patients who receive them. Treatment typically lasts several years and necessitates regular monitoring, especially of hematological status. Cyclosporine is used intravenously in severe HRC. Infliximab (RemicadeR), a chimeric monoclonal antibody targeting TNF is effective in acute forms and as maintenance therapy for CD. It was also recently shown to be effective in HRC. Infliximab is indicated in steroid-resistant forms and contraindicated in patients with latent systemic infections (tuberculosis, hepatitis B) and heart failure. Artificial nutrition is now only used in children with acute forms, in order to avoid the need for steroids. Probiotics might have a place in maintenance treatment of HRC. Surgical treatment of HRC consists of colectomy or, more radically, ileoprotectomy followed by ileoanal anastomosis with resection: however, the likely benefits and potential complications (especially nocturnal diarrhea) must be carefully weighed up. Surgical treatment of CD consists of resecting the worst-affected segments. As available medical and surgical treatments can only control these diseases, without curing them, patient management must be planned on a long-term basis. Control of exacerbations is judged on the basis of clinical parameters and biological markers of inflammation, rather than on lesion healing. The choice of maintenance therapy depends on the nature of the disease (HRC or CD) and its progressive nature. Surgery is reserved for patients with complicated and drug-resistant forms.

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