Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial.

BACKGROUND: Adalimumab induced clinical remission after four weeks in patients with active Crohn's disease in the CLASSIC I trial. OBJECTIVE: To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn's disease in a follow-on randomised controlled trial (CLASSIC II). METHODS: In the preceding CLASSIC I trial, 299 patients with moderate to severe Crohn's disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg, or placebo, at weeks 0 and 2. In all, 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 (week 4 of CLASSIC I) and 2; 55 patients in remission at both weeks 0 and 4 were re-randomised to adalimumab 40 mg every other week, 40 mg weekly, or placebo for 56 weeks. Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week. With non-response or flare, these patients could have their dosages increased to 40 mg weekly. Patients in the randomised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly. The primary end point was maintenance of remission (CDAI <150) in randomised patients through week 56. RESULTS: Of 55 patients randomised at week 4, 79% who received adalimumab 40 mg every other week and 83% who received 40 mg weekly were in remission at week 56, v 44% for placebo (p<0.05). In all, 204 patients entered the open-label arm. Of these, 93 (46%) were in clinical remission at week 56. Adalimumab was generally well-tolerated in all patients. CONCLUSIONS: Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn's disease naive to anti-TNF treatment.

A meta-analysis of antimycobacterial therapy for Crohn's disease.

OBJECTIVE: Various therapies have been studied for the treatment of Crohn's disease, including antimycobacterial therapy. Meta-analysis was used to evaluate the effect of antimycobacterial therapy in patients with Crohn's disease. METHODS: Randomized, controlled trials comparing antimycobacterial therapy with placebo were identified. Key outcome data were abstracted and the results were pooled to yield odds ratios for maintenance of remission in treated versus control groups. RESULTS: A total of eight randomized trials were identified. Six trials were fully published and were included in the primary analysis. Two trials used antimycobacterial therapy in combination with corticosteroids to induce remission in patients with active Crohn's disease, followed by maintenance therapy with antimycobacterial agents. In these trials, control patients received corticosteroids to induce remission but no antimycobacterial therapy. Pooling of these trials yielded an odds ratio of maintenance of remission in treatment versus control of 3.37 (95% confidence interval [CI], 1.38-8.24) in favor of antimycobacterial therapy. The remaining four trials used antimycobacterial therapy combined with standard therapy in patients with Crohn's disease. In these trials, control patients received standard therapy alone. Pooling of these trials yielded an odds ratio of maintenance of remission in treatment versus control of 0.69 (95% CI, 0.39-1.21) in favor of standard therapy. CONCLUSIONS: These results suggest that antimycobacterial therapy is effective in maintaining remission in patients with Crohn's disease after a course of corticosteroids combined with antimycobacterial therapy to induce remission. Treatment of Crohn's disease with antimycobacterial therapy does not seem to be effective without a course of corticosteroids to induce remission. Because of the small number of studies included in this meta-analysis, the results should be interpreted with caution.

Is rectal biopsy necessary in irritable bowel syndrome?

Many physicians obtain a rectal biopsy from patients with irritable bowel syndrome (IBS) in order to exclude melanosis coli and collagenous or microscopic colitis. To determine the value of routine rectal biopsy in IBS, 89 patients and 59 controls were administered a bowel questionnaire, and a rectal biopsy was obtained at sigmoidoscopy. IBS patients were 82% female and averaged 44 yr. Eighty-nine percent fulfilled three or more Manning criteria, and 84% fulfilled the Rome criteria for IBS. The 59 control subjects were 37% female, and averaged 57 yr. Only 15% fulfilled three or more Manning criteria, and 5% the Rome criteria. The 148 rectal biopsies were examined histologically by a pathologist whose methods were validated by a second pathologist. Although minor changes previously reported with phosphate enemas were observed, not a single subject had melanosis coli or fulfilled criteria for microscopic or collagenous colitis. Thus, patients with an endoscopically normal colon and a diagnosis of IBS made by established criteria are unlikely to have histologic abnormalities in the rectum. Rectal biopsies are costly and unnecessary in the investigation of IBS.