Cyclophosphamide pulse therapy followed by azathioprine or methotrexate induces long-term remission in patients with steroid-refractory Crohn's disease

Background In patients with steroid-refractory Crohn's disease, the therapeutic goal is to achieve both rapid remission and maintenance of clinical response. Aim To evaluate the long-term benefit in patients treated with cyclophosphamide pulse therapy and azathioprine or methotrexate, a combination shown to be effective in a recent pilot study. Methods Sixteen patients with acute steroid-refractory Crohn's disease participated in a prospective open-labelled uncontrolled pilot study between December 1998 and June 2003. All had a median number of 4 monthly pulses of intravenous cyclophosphamide (750 mg) and were followed until relapse of the disease. Results Thirteen of 16 patients (81%) achieved remission within 8 weeks after two pulses of cyclophosphamide in combination with azathioprine or methotrexate, with a Crohn's Disease Activity Index decrease from 294 to 111 (median). Remission sustained for 19 months (median, range: 1-45). Moreover, eight patients with pyoderma gangrenosum and erythema nodosum who responded to cyclophosphamide have maintained their remission for up to 30 months. Conclusions In steroid refractory patients with Crohn's disease, cyclophosphamide is highly effective to induce remission. This uncontrolled study indicates that cyclophosphamide-induced remission is long-lasting under standard immunosuppressive therapy.