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Previous Volume 348:24-32 January 2, 2003 Number 1 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by von Andrian, U. H. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background In chronic inflammatory conditions such as Crohn's disease, the migration of leukocytes from the circulation into the parenchyma and their activation within inflammatory sites are mediated in part by ₄ integrins.

Methods We conducted a double-blind, placebo-controlled trial of the ₄ integrin–specific humanized monoclonal antibody natalizumab in 248 patients with moderate-to-severe Crohn's disease. Patients were randomly assigned to receive one of four treatments: two infusions of placebo; one infusion of 3 mg of natalizumab per kilogram of body weight, followed by placebo; two infusions of 3 mg of natalizumab per kilogram; or two infusions of 6 mg of natalizumab per kilogram. Infusions were given four weeks apart. Outcomes included changes in scores for the Crohn's Disease Activity Index (higher scores indicate more severe disease), the health-related quality of life, and C-reactive protein levels.

Results The group given two infusions of 6 mg of natalizumab per kilogram did not have a significantly higher rate of clinical remission (defined by a score of less than 150 on the Crohn's Disease Activity Index) than the placebo group at week 6 (the prospectively defined primary end point in the efficacy analysis). However, both groups that received two infusions of natalizumab had higher remission rates than the placebo group at multiple time points. Natalizumab also produced a significant improvement in response rates (defined by a reduction of at least 70 points in the score on the Crohn's Disease Activity Index). The highest remission rate was 44 percent and the highest response rate was 71 percent (at week 6 in the group given two infusions of 3 mg per kilogram). Overall, the two infusions of 6 mg of natalizumab per kilogram and of 3 mg per kilogram had similar effects. The quality of life improved in all natalizumab groups; C-reactive protein levels improved in groups receiving two infusions of natalizumab. The rates of adverse events were similar in all four groups.

Conclusions Treatment with the selective adhesion-molecule inhibitor natalizumab increased the rates of clinical remission and response, improved the quality of life and C-reactive protein levels, and was well tolerated in patients with active Crohn's disease.

Source Information

From the Western General Hospital, Edinburgh, United Kingdom (S.G.); Hadassah University Hospital, Jerusalem, Israel (E.G.); Royal Free Hospital, London (F.H.G.); Klinikum Leverkusen, Leverkusen, Germany (H.A.M.); Herlev Hospital, Copenhagen, Denmark (J.R.-M.); University Hospital, Leuven, Belgium (P.R.); Nemocnice Pardubice, Pardubice, Czech Republic (P.V.); Kralovske Vinohrady, Prague, Czech Republic (Z.Z.); and Elan Pharmaceuticals, Stevenage, United Kingdom (T.P., S.D.).

Address reprint requests to Dr. Ghosh at Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom, or at s.ghosh{at}ic.ac.uk.

Full Text of this Article

Related Letters:

Natalizumab for Active Crohn's Disease
Lew E. A., Stoffel E. M., Ghosh S., Palmer T.
Extract | Full Text | PDF  
N Engl J Med 2003; 348:1599, Apr 17, 2003. Correspondence

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