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 Kister3, Gary Cutter4, Ryan Metzger2, Judith Goldberg5, Xiaochun Li5, Evan Riddle6, Karen Smirnakis6, Liesel DSilva6, Susie Sinks6, Nolan Campbell6, Tyler Lasky6, Karthik Bodhinathan6
1Jersey Shore University Medical Center, 2Rocky Mountain MS Clinic, 3Department of Neurology, NYU Langone Health, New York University, 4University of Alabama At Birmingham School of Public Health, 5New York University Grossman School of Medicine, Division of Biostatistics, 6Biogen
Objective:
To update the assessment of PML risk with natalizumab EID in comparison with Q4W dosing using TOUCH data as of June 30, 2022.
Background:
Natalizumab treatment is associated with PML risk. Previous analyses of TOUCH data have demonstrated that natalizumab EID is associated with significantly lower PML risk than Q4W dosing in anti–JC virus (JCV) antibody-positive patients with multiple sclerosis.
Design/Methods:
TOUCH data were used to estimate PML risk for EID compared with Q4W dosing in anti-JCV antibody-positive patients using 3 prespecified analyses: primary (EID defined by the last 18 months of treatment), secondary (EID defined as any prolonged period of EID at any time during treatment), and tertiary (EID defined as a dosing history consisting primarily of EID). Hazard ratios (HRs) of PML with EID versus Q4W dosing were estimated using adjusted Cox regression models.
Results:
Compared with the previous analyses, patient numbers increased for all 3 analyses (EID: 9.9%–16.6%; Q4W: 2.2%–3.4%). For all analyses (EID vs Q4W), the mean number of natalizumab infusions (primary: 64.9 vs 56.4; secondary: 61.9 vs 39.8; tertiary: 41.9 vs 41.6), mean treatment duration (in months: primary, 74.5 vs 55.0; secondary, 68.3 vs 38.2; tertiary, 55.9 vs 41.2), and mean dosing interval (in days: primary, 36.5 vs 30.1; secondary, 35.4 vs 29.9; tertiary, 42.5 vs 30.8) were numerically greater with EID than Q4W dosing. All 3 analyses showed reduced risks of PML with EID vs Q4W (primary: 86% [HR=0.139 (95% confidence interval [CI], 0.066–0.294), P<0.0001]; secondary: 80% [HR=0.202 (0.113–0.361), P<0.0001]; tertiary: 96% [HR=0.040 (0.007–0.218)], P=0.0002).
Conclusions:
These results are consistent with all previous annual analyses of TOUCH patient data and demonstrate that natalizumab EID is associated with significantly lower PML risk than Q4W dosing. Continued follow-up will further quantify the amount of risk reduction with EID.