Optimizing the benefit to risk ratio of medical therapy of inflammatory bowel diseases.

Despite the progress in the treatment of Crohn's disease and ulcerative colitis, there is a dire need to improve the benefit to risk ration of clinical care for young patients with chronic diseases. Most of the effective therapies for IBD are immunosuppressants and carry a burden of toxicity. The present work has focused on improving the tolerance of medical therapy while preserving efficacy. We have demonstrated that a reduction of the i.v. cyclosporine dose to 2 mg/kg preserves clinical efficacy and opens the perspective to a reduced toxicity. This study has been internationally implemented in treatment guidelines. In a case of progressive multifocal leukencephalopathy, al lethal brain infection caused by JC virus, in a patient with Crohn's disease, we were able to link JC reactivation to a specific therapy inhibiting leukocyte trafficking. We took this observation further and attempted to develop a screening algorithm for early detection of JC viral replication. Although further studies are needed this may be a first step to safer treatment with anti integrin therapies. Finally we have demonstrated that patients with myenteric plexitis at the ileal resection margins at surgery for ileocolonic Crohn's disease have a higher endoscopic relapse rate throughout one year. Myenteric plexitis is the first histological marker guiding prophyalictic therapy in the postoperative setting.