AAN: Rituximab Reduces MS Lesions and Relapses

BOSTON, May 2 -- Six months of rituximab (Rituxan) for relapsing-remitting multiple sclerosis lesions appears to reduce active lesions significantly and retard relapses, investigators reported here.

The improvements from a single course of rituximab, better known for its activity against B-cell non-Hodgkin's lymphoma, and more recently intractable rheumatoid arthritis, were shown on gadolinium-enhanced MRI, said Stephen Hauser, M.D., of the University of California San Francisco, and colleagues.

In a phase II study, patients randomly assigned to rituximab had significantly fewer lesions by week 12, compared with patients on placebo, and that continued through week 24 after the start of the drug, they said at the American Academy of Neurology meeting.

There were 58% fewer relapses among patients treated with rituximab compared with patients treated with placebo treated patients, Dr. Hauser added.

Rituximab, a selective CD20 inhibitor, is not approved for MS.

An MS specialist who was not involved in the study noted in an interview that while MS is thought to be largely a T-cell mediated disease, there is growing evidence that the B cells may play a role in mediating relapses.

"It appears that targeting the B cell has substantial and somewhat surprising effect on disease activity, which may tell us something about immunopathogenesis of multiple sclerosis that we didn't understand," said Brian Apatoff, M.D., Ph.D., of Weill Cornell Medical College in New York.

In the phase II study, 104 patients with relapsing-remitting MS were randomly assigned to either placebo or to a single course of rituximab, delivered in two IV infusions two weeks apart.

The primary study endpoint was the total number of gadolinium-enhancing T1 MRI lesions seen at weeks 12, 16, 20 and 24.

The authors found that the total numbers of lesions was significantly reduced in rituximab-treated patients compared with placebo-treated patients at each of the study time points. The mean number of lesions at week 24 in the active treatment group was reduced by 91 percent to 0.5, compared with 5.5 for controls.

The proportion of patients who had relapses during the study was 34.3% for controls, and 14.5% for patients on rituximab. This difference translated into a 58% reduction in relapses for rituximab (P=0.0238).

Adverse events associated with the first infusion were significantly higher among rituximab-treated patients compared with placebo-treated patients, at 78.3% versus 40%, respectively. More than 95% of the infusion reactions were mild to moderate and were successfully managed, Dr. Hauser said.

With the exception of the infusion associated adverse events, the percentage of patients with overall adverse events and serious adverse events were comparable between the two treatment groups during this 24-week period. There were 97.1% of patients in both treatment groups who had an adverse event, and 10.1% of Rituxan-treated patients compared with 14.3%of placebo-treated patients had a serious adverse event).

Infections occurred in 65.2% of patients on rituximab, and 62.9% of controls. The difference was not statistically significant.

In a related study, Amit Bar-Or, M.D., and colleagues at McGill University in Montreal, and colleagues, reported that in a phase I study looking at the safety and tolerability of rituximab in patients with relapsing-remitting MS over 72 weeks, there were no serious adverse events, and side effects were limited to mild-to-moderate infusion-associated events.

They also saw a significant reduction in the lesion count, as seen by gadolinium-enhancing T1 MRI, beginning at week four and continuing through week 48. Re-dosing at six months appeared to further reduce the lesion frequency, as gadolinium-enhancing T1 MRI, and number or relapses.

Common adverse reactions reported with the use of the drug in cancer and arthritis include infections, hematologic problems, cardiovascular complications, and, as seen with natalizumab (Tysabri) rare, scattered cases of JC virus infections resulting progressive multifocal leukoencephalopathy and death.