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Study Shows Natalizumab (Tysabri) Plus Interferon Beta-1a (Avonex) Reduces Disease Activity: Presented at ECTRIMS

By Bruce Sylvester

THESSALONIKI, GREECE -- October 4, 2005 -- The addition of natalizumab (Tysabri) to interferon beta-1a (IFNb-1a, Avonex) over 2 years of treatment significantly enhances the reduction of lesion formation compared with Avonex monotherapy in patients with multiple sclerosis (MS), researchers reported here on September 30^th at the 21^st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Ernst Radue, MD, professor of neuroradiology and head, department of neuroradiology, University Hospital, Basel, Switzerland, said the introduction of natalizumab cotherapy in patients treated with Avonex had a significant reduction of active brain lesions.

"So this means that even those who are on regular therapy with Avonex, the introduction of natalizumab reduced the activity of the disease significantly, about 86% for total lesion development beyond the effect of monotherapy," he added.

Immunomodulatory agents currently in use for MS are only partially effective, so that inflammation and demyelination continue to occur in patients treated with these agents, as seen on cranial magnetic resonance imaging (MRI) scans, the researchers explained.

The Safety and Efficacy of Antegren in Combination with Interferon beta-1a in Subjects with Relapsing-Remitting MS (SENTINEL) study was conducted to evaluate the efficacy and safety of natalizumab added to Avonex in patients who experienced disease activity during treatment with IFNb-1a monotherapy.

For this randomised, double-blind, placebo-controlled, multicentre, phase 3 trial, the investigators enrolled 1171 subjects who had received Avonex monotherapy for at least 12 months.

During the trial, subjects continued to take weekly treatment with intramuscular Avonex 30 mcg and were randomised to either natalizumab 300 mg (n = 589) or placebo (n = 582) by intravenous infusion every 4 weeks.

Of the total, 1003 subjects completed 120 weeks on the study.

Endpoints for 1 year were the number of new or enlarging T2-hyperintense lesions and the number of gadolinium-enhancing (Gd+) lesions on MRI. Endpoints for year 2 were the number and volume of new or enlarging T2-hyperintense lesions, the number and volume of Gd+, and the number and volume of T1-hypointense lesions on MRI.

Combination therapy reduced the mean number of GD+ lesions compared with monotherapy by 88% at year 1 (P < .001) and 89% at year 2 (P < .001). Mean GD+ lesion volume was reduced by 92% (P < .001) at both year 1 and year 2.

Patients on combination treatment also had an 83% reduction in the mean number of new or enlarging T2-hyperintense lesions over 2 years compared with monotherapy (P < .001). Over 2 years, the mean T2-hyperintense lesion volume decreased with combination treatment and increased with monotherapy (P < .001).

Combination treatment over 2 years reduced the mean number of new T-1 hypointense counts by 44% compared with monotherapy (P < .001) and significantly reduced mean T-1 hypointense lesion volume over 2 years compared with monotherapy (P < .005).

The percentage of patients with no disability progression, no relapses, and no lesion activity (Gd+ lesions, new or enlarging T-2 hyperintense lesions, and new T-2 hypointense lesions) was 16% in the combination arm and 5% in the monotherapy arm (P < .001).

The marketer of Tysabri -- Biogen Idec and Elan Corporation -- voluntarily removed the drug from the market after 3 cases were reported of progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal disease of the central nervous system (N Engl J Med. July 28, 2005).

Acknowledging the drug's voluntary removal from the market, Dr. Radue added, "But I foresee that it will return to the market with a monotherapy indication for MS, and I think that it will continue to prove to be an excellent drug for MS patients. Our data in this study is suggestive for its potential value as a combination therapy."

"We have now looked at all subjects from all relevant studies and have found no more cases of PML," he added. "I think that it will be the most effective treatment for MS when it returns to the market."

The study was supported by Biogen Idec, Inc. and Elan Pharmaceuticals, Inc.


[Presentation title: Natalizumab Added to Interferon Beta-1a Reduces Lesion Formation as Measured By Magnetic Resonance Imaging in Patients With Relapsing Multiple Sclerosis. Poster 582]

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