An open-label study of thalidomide for maintenance therapy in responders to infliximab in chronically active and fistulizing refractory Crohn's disease.

Abstract

Infliximab, a chimeric monoclonal antibody to tumour necrosis factor-alpha, is a new potent therapy for active Crohn's disease, but induces short-lived improvements. To evaluate the efficacy of thalidomide, a drug with anti-tumour necrosis factor-alpha activity, for the maintenance of infliximab-induced response in refractory Crohn's disease. Fifteen patients with severe, refractory disease (10 females, five males; mean age, 40 years; eight with luminal disease, two with fistulizing disease and five with both luminal and fistulizing disease) were started on thalidomide (100 mg daily), 29 +/- 10 days after they had responded to infliximab (5 mg/kg infusions). The median follow-up period was 238 days (range, 10-458 days) from the initiation of thalidomide and 265 days (range, 10-537 days) from the last infliximab infusion. The median Crohn's disease activity indices were 322 (range, 170-525), 119 (range, 24-503) and 35 (range, -60-360) before infliximab, at the initiation of thalidomide and at the end of follow-up, respectively. Remission rates on thalidomide were 92%, 83% and 83% at 3, 6 and 12 months, respectively, after the last infliximab infusion (Kaplan-Meier). Four patients (two in remission) stopped thalidomide for suspected adverse effects. Side-effects (drowsiness, rash and peripheral neuropathy) were mild and mostly transient. Thalidomide appears to be an effective and relatively safe drug to maintain response to infliximab in chronically active and fistulizing refractory Crohn's disease.