Pulse cyclophosphamide in steroid‐resistant inflammatory bowel disease

Abstract

SIRS, The Review Article by Drs Creed and Probert discusses steroid resistance in inflammatory bowel disease (IBD) - mechanisms and therapeutic strategies. 1 They underline the use of alternative immunosuppressants for the treatment of steroid-resistant IBD, but do not discuss a potential role for cyclophosphamide. Based on previous observations in autoimmune diseases (i.e., vasculitides), cyclophosphamide can be the primary cytotoxic drug and pulse intravenous cyclophosphamide is probably equally effective as oral cyclophosphamide at inducing and maintaining remission. 2-4 Cyclophosphamide can be administered intravenously at 500-1000 mg/m 2 pulses monthly. The optimal duration of treatment has not been determined for IBD, but treatment for 6 months with monthly pulses would be typical, followed by maintenance therapy with azathioprine or methotrexate. Recently, we reported an uncontrolled prospective study with pulse cyclophosphamide therapy for IBD patients.5' 6 The aim of this study was to examine the effect of this therapy both on UC and CD. Patients entered into remission after the second/third cyclophosphamide pulse, disease activity decreased without side effects and toxicity. For the maintenance, patients with Crohn's disease were treated with methotrexate (15 mg/week) and patients with ulcerative colitis were treated with azathioprine (2.5 mg/kg body weight/day). This study and others' indicates that cyclophosphamide-induced remission is long-lasting under standard immunosuppressive therapy.7'8 Because cyclophosphamide is effective for other inflammatory conditions and is relatively less expensive than some other agents, it is considered in the treatment of IBD. Intravenous pulse cyclophosphamide therapy may be a safe and effective treatment for patients with severe IBD unresponsive to conventional treatment as a first-line adjunct to or replacement of systemic corticosteroids in the treatment of IBD. However, larger placebo-controlled studies in more diverse patient population are warranted. 7