Cytomegalovirus reactivation in inflammatory bowel disease: an uncommon occurrence related to corticosteroid dependence

This study evaluated the efficacy and safety of adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody administered subcutaneously, in the maintenance of response and remission in patients with moderate to severe Crohn's disease (CD). Patients received open-label induction therapy with adalimumab 80 mg (week 0) followed by 40 mg (week 2). At week 4, patients were stratified by response (decrease in Crohn's Disease Activity Index > or =70 points from baseline) and randomized to double-blind treatment with placebo, adalimumab 40 mg every other week (eow), or adalimumab 40 mg weekly through week 56. Co-primary end points were the percentages of randomized responders who achieved clinical remission (Crohn's Disease Activity Index score <150) at weeks 26 and 56. The percentage of randomized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 (40%, 47%, and 17%, respectively; P < .001) and week 56 (36%, 41%, and 12%, respectively; P < .001). No significant differences in efficacy between adalimumab eow and weekly were observed. More patients receiving placebo discontinued treatment because of an adverse event (13.4%) than those receiving adalimumab (6.9% and 4.7% in the 40-mg eow and 40-mg weekly groups, respectively). Among patients who responded to adalimumab, both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks. Adalimumab was well-tolerated, with a safety profile consistent with previous experience with the drug.

Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas. We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization. The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009). Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks. Copyright 2004 Massachusetts Medical Society