Further confirmation has been reported that upon switching from natalizumab (Tysabri, Biogen Idec) to fingolimod (Gilenya, Novartis) in patients with multiple sclerosis (MS), the washout period should be less than 3 months.
The new study, published online in JAMA Neurology, was conducted by a group led by Mikael Cohen, MD, University Hospital of Nice, France.
The researchers note that this is the largest study on switching from natalizumab to fingolimod to date, with the study cohort representing close to 100% participation of French MS tertiary care centers.
They emphasize "2 important findings from the study that must be taken into consideration in clinical practice": the substantial risk for relapse during the washout period and an early relapse during fingolimod therapy.
They conclude that switching to fingolimod can be an option for patients with tolerance or efficacy issues during natalizumab therapy, but note that if the switch was motivated by the risk of developing progressive multifocal leukoencephalopathy (slightly >1% for patients in the highest risk category), the benefit-risk ratio between maintaining natalizumab therapy vs a switching strategy has to be carefully balanced. And in all cases, the washout period should be shorter than 3 months if a switch is chosen.
Dr. Cohen and coauthors explain that patients who test positive for JC polyomavirus antibodies while receiving natalizumab are advised to stop treatment with this agent, and fingolimod is a popular option for these patients. While a washout period between the 2 drugs is mandatory because of the immunosuppressive mechanisms of each agent, the optimal length of the washout period is not known.
The Enquête Nationale sur l'Introduction du Fingolimod en Relais au Natalizumab (ENIGM) study involved data from 333 patients switching from natalizumab to fingolimod. Patients had received a mean of 31 natalizumab infusions, and 71% were seropositive for the JC polyomavirus.
Results showed that MS disease activity was greater during the washout period, but not after fingolimod initiation. Relapses occurred in 27% of patients during the washout period, and a washout period shorter than 3 months was associated with a lower risk for relapse (odds ratio, 0.23; P = .001) and with less disease activity during the washout period (P = .03).
Patients who stopped natalizumab because of poor tolerance or lack of efficacy also had a higher risk for relapse (odds ratio, 3.20; P = .004). During the first 6 months of fingolimod therapy, 20% of patients relapsed, and 3% stopped fingolimod for efficacy, tolerance, or adherence issues.
In a multivariate analysis, the occurrence of relapse during the washout period was the only significant prognostic factor for relapse during fingolimod therapy (odds ratio, 3.80; P = .05).
The researchers note that, as expected, the risk for relapse during washout correlated with MS disease activity before natalizumab initiation and with the duration of the washout period, and the use of a short-term rescue or planned treatment (methylprednisolone or an immunomodulatory drug) did not mitigate the risk for relapse.
Similar observations were reported in 2 studies presented last fall at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), and reported by Medscape Medical News at that time, suggesting that even a slightly shorter washout period, as short as 4 to 8 weeks, was advisable to avoid relapse during the switch from natalizumab to fingolimod.
Dr. Cohen served as a consultant for Biogen Idec, Novartis, Teva Pharmaceuticals, sanofi-aventis, Merck Serono, and Bayer Schering Pharma.
JAMA Neurol. Published online February 24, 2014. Abstract
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Cite this: Shorter Washout Better for Natalizumab-to-Fingolimod Switch - Medscape - Mar 26, 2014.