Extending Multiple Sclerosis Drug Dosing Plummets Adverse Event Risk

Although a commonly used multiple sclerosis (MS) drug has been linked to a rare, serious adverse event, the risk may be mitigated by extending dosing intervals, according to a new study presented at the Americas Committee for Treatment and Research in Multiple Sclerosis Forum 2018.

The authors discovered that switching the dosing of intravenous natalizumab from every 4 weeks to every 5 to 12 weeks reduced the risk of progressive multifocal leukoencephalopathy (PML).

These results may change the way these treatment regimens are prescribed, according to the study.

“Neurologists have been looking for safer ways to administer natalizumab infusions to their patients, but there hasn’t been clear data on whether decreasing dosing frequency improves safety,” said first study author Lana Zhovtis Ryerson, MD. “Our safety findings are clinically and statistically significant, and we believe that extending the dosing schedule of natalizumab is practice changing and may save lives.”

Natalizumab is a monoclonal antibody indicated to prevent relapses and inhibit disease progression. The treatment is prescribed in 300-mg doses administered every 4 weeks, according to the authors.

However, use of natalizumab for more than 2 years may increase the risk of developing PML, a brain infection caused by the John Cunningham virus (JCV). The authors reported that the global incidence rate is 4.19 per 1000 PML cases in patients treated with the drug.

Patients with JCV antibodies are typically not prescribed natalizumab or stop treatment before 2 years.

Over a period of 72 years, extending the dosing regimens was found to reduce the risk of PML by as much as 94%, according to the study.

In the study, the authors reviewed data from the TOUCH study, a REMS program for natalizumab.

Currently, the optimal extended dosing schedule is unknown, so the authors examined multiple avenues. The primary definition evaluated extending dose history in the last 18 months; the secondary definition evaluated extended the dose at any point in dosing history; and the third definition looked at how extended dose history may affect the risk of PML.

The authors found that there were clinically and statistically significant reductions in the risk of PML associated with all definitions.

Although the current study did not examine the efficacy of extended doses compared with standard doses, the team previously found that extending the dose up to 8 weeks did not affect efficacy in 2000 patients with MS.

To confirm their findings and the safety of dose extension, the authors next plan to conduct a prospective trial of natalizumab.