Natalizumab for Active Crohn’s Disease
There was also an Antegren/Crohn's Disease letter in the current issue of NEJM. In this case the conclusion was actually positive for Antegren (if anything). Credit for this one goes to myself.
to the editor:
In the study by Ghosh et al. (Jan. 2 issue),1 a regimen of two infusions of natalizumab at a dose of 6 mg per kilogram of body weight was associated with higher remission rates than was placebo at several intervals, except at week 6 (the primary end point). The failure to demonstrate a difference may be due in part to chance and to the use of a small study sample. Randomization is supposed to ensure equal distribution of base-line characteristics that may confound a clinical trial.
However, in this study, the randomization process assigned 63 patients to placebo and only 51 patients to two infusions of 6 mg of natalizumab per kilogram (a 19 percent difference). The authors attribute their failure to detect significant differences at week 6 to the unusually high remission rate in the placebo group. However, concomitant therapy with azathioprine or mercaptopurine was being given to a larger percentage of patients in the placebo group (35 percent) than in the group assigned to two infusions of 6 mg of natalizumab per kilogram (18 percent) (P=0.04). It appears that the shortcomings of randomization may have contributed to the reported null findings with regard to the primary study end point in this trial.
Edward A. Lew, M.D., M.P.H.
Elena Martinez Stoffel, M.D.
Brigham and Women’s Hospital
Boston, MA 02115
edward_lew@hms.harvard.edu
1.
Ghosh S, Goldin E, Gordon FH, et al. Natalizumab for active
Crohn’s disease. N Engl J Med 2003;348:24-32.
the authors reply:
We thank Drs. Lew and Stoffel for their discussion of base-line imbalances between the placebo group and the group receiving two infusions of 6 mg of natalizumab per kilogram and for their discussion of the potential effect of such imbalances on the analysis of the primary end point.
Subrata Ghosh, M.D.
Imperial College of Medicine
London W1Z 0NN, United Kingdom
s.ghosh@ic.ac.uk
Tanya Palmer, B.Sc.
Elan Pharmaceuticals
Stevenage SG1 2FU, United Kingdom |
