In the January issue of the New England Journal of Medicine, Ghosh et al. describe a double-blinded, randomized trial comparing natalizumab, a recombinant humanized monoclonal antibody against as integrin, with placebo inthe treatment of moderate-to-severe Crohn's disease. Patients 18 yr or older with Crohn's Disease Activity Index (CDAI) scores from 220 to 450 were screened for eligibility at 35 centers in Europe and Israel. Disqualifiers included previous antibody treatment of any kind, methotrexate, cyclosporin, prednisone dose >25 mg (or equivalent), increasing doses of azathioprine or 6 mercaptopurine, symptoms caused by mainly fibrotic disease, and surgery anticipated in the near future. Each patient was to receive two infusions 4 wk apart. Enrollees were randomly assigned to one of four schedules: 1) placebo/placebo, 2) natalizumab 3 mg/placebo. 3) natalizumab 3 mg/natalizumab 3 mg, and 4) natalizumab 6 mg/ natalizumab 6 mg. Outcome measures were remission (CDAI score 70), improvement in the Inflammatory Bowel Disease Questionnaire score, decline in C-reactive protein level, and adverse events. Patients were assessed at 2, 4, 6, 8, and 12 wk. The investigators screened 301 patients and enrolled 248. All 248 subjects were included in the intention-to-treat analysis, and 244 were included in the safety data anaylysis (four patients were disenrolled before receiving any intervention.) The four randomized groups were similar in terms of demographics, baseline medications, and disease severity indices. Efficacy results showed statistically significant improvements in remission at 4 wk in all three groups receiving natalizumab at the initial infusion. The group receiving natalizumab 3 mg at both infusions had statistically significant improvement in remission at 4, 6, 8, and 12 wk. The group receiving natalizumab 6 mg at both infusions had statistically significant improvement at 4, 8, and 12 wk. (This group did not reach significant improvement in remission at 6 wk, the predetermined primary end point.) Statistically significant improvement in response was seen at week 4, 6, and 8 in the group receiving natalizumab 3 mg only at the first infusion. In the group receiving natalizumab 6 mg at both infusions, improvement in response was seen at week 4, 6, 8, and 12. Improvement in response was seen at week 2, 4, 6, 8, and 12 in the group receiving natalizumab 3 mg at both infusions. All three groups receiving natalizumab at the initial infusion had scores on the Inflammatory Bowel Disease Questionnaire that were significantly improved as compared with the placebo group. By week 12, only the two groups receiving natalizumab at the second infusion maintained significantly better scores. The C-reactive protein levels tended to decrease compared with placebo in the groups receiving natalizumab, but the decrease only reached statistical significance at week 6 and 8 in the group receiving 3 mg at both infusions, and at week 6 in the group receiving 6 mg at both infusions. Serious adverse events occurred in 9-12% of the subjects (11% in the placebo group), but they were not believed to be related to natalizumab infusions. The total number of adverse events ranged from 78-88% (81% in the placebo group), and included abdominal pain, arthralgia, colitis, influenza syndrome, headache, infection, nausea, pain, and pharyngitis.