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The management of refractory severe inflammatory bowel disease (IBD) is still unresolved. We read with interest the article by Stallmach et al on the safety and efficacy of intravenous pulse cyclophosphamide in acute steroid refractory IBD (Gut 2003;52:377–82).
In common with other disease, the aims of therapy in IBD fall into three categories:
induction of remission;
maintenance of remission; and
prevention of relapse, all of which should be undertaken with minimal mortality and morbidity either from the disease itself or from therapy.
Based on previous observations of improvement in autoimmune diseases (that is, vasculitides), cyclophosphamide can be a primary cytotoxic drug: pulse intravenous cyclophosphamide is probably equally effective as oral cyclophosphamide in inducing remission and this remission is usually maintained by continuing cyclophosphamide for 3–6 months before changing to a combination of other oral therapies. Therapy must be continued to prevent relapse and for maintenance.1
We would like to report on some other cases. In our cohort, we included patients with Crohn’s disease (CD) and ulcerative colitis (UC). Four patients with CD and four with UC were diagnosed according to standard criteria. They did not respond to conventional therapy and therefore we administered pulse cyclophosphamide therapy monthly (for six months, 800 mg each time). Most patients went into remission after the second/third cyclophosphamide pulse. Disease activity decreased, there were no side effects, no toxicity, and all patients achieved long lasting remission. For maintenance, patients with CD were treated with methotrexate (10 mg/week) and patients with UC were given azathioprine (100 mg/day). Remission appears to be stable.
These findings suggest that aggressive immunosuppressive therapy may be useful in some refractory patients, and further controlled study should be considered in order to fully evaluate this type of treatment as a potential therapy in IBD.
IBD continue to pose a challenge to clinicians. Over the past few years there have been significant advances in our understanding of pathogenesis and treatment. These advances will hopefully lead to more specific and targeted treatments, with consequent improvement in clinical outcomes. Intravenous pulse cyclophosphamide may be a safe and effective treatment in patients with severe IBD unresponsive to “conventional” treatment. It is also recommended as a firstline adjunct to, or replacement for, systemic corticosteroids in the treatment of IBD.
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