Natalizumab Extended Interval Dosing (EID) is Associated with a Reduced Risk of Progressive Multifocal Leukoencephalopathy (PML) Compared With Every-4-Week (Q4W) Dosing: Updated Analysis of the TOUCH® Prescribing Program Database
Lana Zhovtis Ryerson1, John Foley2, Ilya Kister1, Gary Cutter3, Ryan Metzger2, Judith D. Goldberg4, Xiaochun Li4, Karen Smirnakis5, Liesel Dsilva5, Wai Chin5, Evan Riddle5
1Department of Neurology, NYU Langone Health, New York University, 2Rocky Mountain MS Clinic, 3University of Alabama School of Public Health, 4New York University Grossman School of Medicine, Division of Biostatistics, 5Biogen
Objective:
To update the assessment of PML risk with natalizumab EID in comparison with Q4W dosing using TOUCH data as of June 30, 2021.
Background:
Natalizumab treatment is associated with PML risk. Previous analyses of patient data in the TOUCH database have demonstrated that EID is associated with lower risk of PML than is Q4W dosing.
Design/Methods:
TOUCH data were used to determine whether EID is associated with lower PML risk in comparison with Q4W dosing in anti–JC virus antibody-positive patients using three prespecified analyses: primary analysis (EID defined by the last 18 months of treatment), secondary analysis (EID defined as any prolonged period of EID at any time during treatment), and tertiary analysis (EID defined as a dosing history consisting primarily of EID). Patients with any dosing interval of <3 or >12 weeks were excluded. Hazard ratios (HRs) of PML with EID versus Q4W dosing were estimated using adjusted Cox regression models.
Results:
Compared with the June, 2020 analysis, patient numbers increased for all three analyses (16.0%–21.0% increase for EID; 3.0%–4.0% increase for Q4W). The mean number of natalizumab infusions (primary: 63.9 vs 55.5 infusions; secondary: 60.6 vs 39.5 infusions; tertiary: 41.1 vs 40.7 infusions) and mean natalizumab treatment duration (primary: 73.1 vs 54.1 months; secondary: 66.8 vs 37.8 months; tertiary: 55.0 vs 40.3 months) were greater with EID than with Q4W dosing. All three analyses showed reduced risks of PML for EID vs Q4W (primary: 87% [HR =0.127]; secondary: 81% [HR =0.195]; tertiary: 96% [HR = 0.042]; all P ≤0.0003).
Conclusions:

This analysis is consistent with all previous annual analyses of TOUCH patient data and demonstrates that natalizumab EID is associated with a significantly lower PML risk than Q4W dosing. Continued follow-up will further quantitate the amount of risk reduction with EID.