A Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis
ABSTRACT
Background
In patients with multiple sclerosis, inflammatorybrain lesions appear to arise from autoimmune responses involvingactivated lymphocytes and monocytes. The glycoprotein integrinis expressed on the surface of these cells and plays a criticalpart in their adhesion to the vascular endothelium and migrationinto the parenchyma. Natalizumab is an integrin antagonistthat reduced the development of brain lesions in experimentalmodels and in a preliminary study of patients with multiplesclerosis.
Methods
In a randomized, double-blind trial, we randomly assigneda total of 213 patients with relapsing–remitting or relapsingsecondary progressive multiple sclerosis to receive
3 mg ofintravenous natalizumab per kilogram of body weight (68 patients),
6 mg per kilogram (74 patients), or
placebo (71 patients) every28 days for 6 months.
The primary end point was the number ofnew brain lesions on monthly gadolinium-enhanced magnetic resonanceimaging during the six-month treatment period. Clinical outcomesincluded relapses and self-reported well-being.
Results
There were marked reductions in the mean number of newlesions in both natalizumab groups:
9.6 per patient in the placebogroup,
as compared with 0.7 in the group given 3 mg of natalizumabper kilogram (P<0.001) and
1.1 in the group given 6 mg ofnatalizumab per kilogram (P<0.001).
Twenty-seven patientsin the placebo group had relapses, as compared with
13 in thegroup given 3 mg of natalizumab per kilogram (P=0.02) and
14in the group given 6 mg of natalizumab per kilogram (P=0.02).
The placebo group reported a slight worsening in well-being(a mean decrease of 1.38 mm on a 100-mm visual-analogue scale),whereas the
natalizumab groups reported an improvement (meanincrease of 9.49 mm in the group given 3 mg of natalizumab perkilogram and 6.21 mm in the group given 6 mg of natalizumabper kilogram).
Conclusions
In a placebo-controlled trial, treatment with natalizumabled to fewer inflammatory brain lesions and fewer relapses overa six-month period in patients with relapsing multiple sclerosis.