Study: Extending dosing intervals reduces deadly side effect risk from MS drug

February 07, 2018
According to a new study led by MS specialists at NYU Langone Health, a commonly-prescribed multiple sclerosis infusion medication linked to a rare but serious side effect is safer to use when dosing intervals are extended. The findings showed that extending dosing of natalizumab from every four weeks to every five to 12 weeks significantly reduced the risk of developing a rare but potentially fatal brain infection called progressive multifocal leukoencephalopathy. The findings could influence how neurologists prescribe the medication.
Natalizumab, a monoclonal antibody, is used to prevent MS relapses, improve quality of life, and slow worsening disability. The medication is indicated to be prescribed in 300-milligram infusion doses every four weeks. Taking the medication longer than two years, however, may increase risk PML, which is caused by the John Cunningham virus. There have been 756 PML cases reported worldwide as of January 2018, with a global incidence rate of 4.19 per 1,000 PML cases in people treated with natalizumab. Patients who test JCV antibody-positive are typically either told to not to start natalizumab, or have had treatment stopped after two years, when risk was deemed to be too high. The new study, however, reports safety data through up to six years, when the extended dosing regimens were applied, with risk reduction for PML as high as 94 percent.

Researchers reviewed data on all patients who have been exposed to JCV who are enrolled in TOUCH, the U.S. Food and Drug Administration-mandated Risk Evaluation and Mitigation Strategy program for natalizumab that requires manufacturers to document all uses of a medication to ensure that the benefits of a drug outweigh its risks. Because the optimal extended dose schedule is not known, researchers chose to look at the data in multiple ways: with the primary definition looking at extended dose history in the last 18 months, the secondary definition looking at extended dose occurring at any time in the dosing history, and for tertiary definition looking primarily at how extended dose history affects PML risk. The results showed clinically and statistically significant risk reductions with all definitions.
The new study did not look at drug efficacy comparing extended to standard doses. However, previous research found extending the dose up to eight weeks did not negatively affect the medication's efficacy in a retrospective sample of 2,000 people. The authors are planning prospective efficacy studies of extended dose natalizumab.
Natalizumab is manufactured by Biogen Idec and Elan, and sold under the name Tysabri®. Biogen provided the researchers access to their data and statistical support.
The authors presented their findings at the Americas Committee for Treatment and Research in Multiple Sclerosis Forum 2018 in San Diego.

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