#AANAM – Research Suggests Extended Interval Dosing of Tysabri Can Decrease Risk of PML

New data suggests that treatment with Tysabri (natalizumab) in an extended interval dosing regimen is associated with a significantly lower risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS), compared with the standard interval dosing.

The data was presented by Lana Zhovtis Ryerson, MD, on May 7 at the 2019 Annual Meeting of the American Academy of Neurology (AAN), in a presentation titled “Reduced risk of progressive multifocal leukoencephalopathy (PML) associated with natalizumab extended interval dosing (EID): updated analysis of the TOUCH Prescribing Program database.” Ryerson is an assistant professor in the Department of Neurology, NYU Langone Health, New York University.

PML is a rare brain disease caused by infection with the John Cunningham virus (JCV). Treatment with Tysabri (natalizumab, marketed by Biogen) — an approved therapy for the treatment of relapsing-remitting MS (RRMS) — has been associated with an increased risk of PML.

However, new research suggests this risk can be reduced by using extended interval dosing (EID), meaning extending the dosing intervals between Tysabri treatments. (The standard interval dosing (SID) typically used between Tysabri treatments (300 mg intravenous infusion each) is four weeks.)

In order to compare PML risk between SID and EID approaches, researchers assessed data from the TOUCH Prescribing Program, a U.S. database designed to better understand and mitigate the risk of developing PML among MS patients treated with Tysabri. Data as of June 1, 2018, were analyzed.

The average SIDs were 29-30 days (about four weeks), while EIDs were of 34-41 days (about five-six weeks).

Three types of analyses were performed. In the primary analysis, researchers compared patients who, in the 18 months prior to the analysis, were given Tysabri either EID (2,266 patients) or SID (14,305 patients). The secondary analysis looked at patients who had been given EID or SID for any stretch of time (3,726 and 16,648 patients, respectively).

The tertiary (third) analysis looked at patients who, over the course of their treatment, had been given primarily either Tysabri EID or SID (931 and 24,870 people, respectively). Of note, according to Ryerson, “most EID patients in the primary and secondary analyses had prior SID treatment.”

All patients included in the analyses were positive for antibodies against JCV, suggesting the presence of the virus and, consequently, the risk of PML.

Results showed that in all three analyses, patients who were treated with Tysabri EID were less likely to develop PML, compared to those given the standard regimen.

There was a “significant, robust reduction in PML risk” in patients receiving Tysabri EID, Ryerson said.

Notably, in the tertiary analysis, none of the patients who had primarily received the EID regimen developed PML. There was a “90% reduction in primary, 80% in secondary, and no PML cases in the tertiary analysis,” Ryerson noted.

Overall, the results suggest that Tysabri EID treatment might be more safe for RRMS patients, as it seems to decrease the risk of developing PML.

Ryerson emphasized that the TOUCH program “does not include effectiveness data; therefore, the effectiveness of EID compared with SID could not be evaluated in this analysis,” she said.

Biogen is currently conducting a Phase 3b trial, called NOVA (NCT03689972), to assess both the effectiveness and safety (including the associated PML risk) of Tysabri treatment given EID versus SID.