Abstract Details

Title 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

Topic Multiple Sclerosis

Presentation(s) MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 201

Objective

Update the assessment of PML risk with natalizumab EID compared with every-4-week (Q4W) dosing using TOUCH data as of June 1, 2020.

Background Natalizumab treatment is associated with PML risk. Previous analyses of patient data in the TOUCH database have demonstrated that EID may be associated with lower risk of PML than Q4W dosing.

Design/Methods TOUCH data were used to determine whether EID is associated with lower PML risk compared with Q4W dosing in anti–JC virus antibody positive patients using 3 preplanned 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 <3 or >12 weeks were excluded. Hazard ratios (HRs) of PML with EID versus Q4W dosing were calculated using adjusted Cox regression models.

Results Compared to the previous analysis (June 1, 2019), the numbers of patients in the respective EID and Q4W groups increased by 16.3% and 4.5% in the primary analysis, by 12.4% and 3.8% in the secondary analysis, and by 16.5% and 5.2% in the tertiary analysis. For all analyses, the mean number of natalizumab infusions and mean treatment duration were greater with EID than with Q4W dosing. Unlike past analyses, which had no PML cases in the tertiary analysis EID group, PML cases occurred in all groups. All three analyses showed reduced risks for PML (P<0.0003) ranging from 63% (upper limit of 95% confidence interval) to 96% (point estimate).

Conclusions This updated analysis of TOUCH patient data reinforces previous conclusions that natalizumab EID is associated with a significantly lower PML risk than Q4W dosing to date. Continued follow-up will further quantitate the amount of risk reduction with EID.

Authors/Disclosures
Lana Zhovtis Ryerson, MD, FAAN (Jersey Shore University Medical Center) PRESENTER	Dr. Zhovtis Ryerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Zhovtis Ryerson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi.
John F. Foley, MD, FAAN (Rocky Mountain MS Clinic)	The institution of Dr. Foley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave. Dr. Foley has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Foley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics . The institution of Dr. Foley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. The institution of Dr. Foley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. Dr. Foley has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Foley has stock in InterPRO Bioscience. The institution of Dr. Foley has received research support from Biogen. The institution of Dr. Foley has received research support from Novartis. The institution of Dr. Foley has received research support from Octave. The institution of Dr. Foley has received research support from Genentech. The institution of Dr. Foley has received research support from Imstem. The institution of Dr. Foley has received research support from Aegir.
Ilya Kister, MD, FAAN (NYU School of Medicine)	Dr. Kister has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech-Roche. Dr. Kister has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. The institution of Dr. Kister has received research support from Genentech. The institution of Dr. Kister has received research support from Novartis. Dr. Kister has received publishing royalties from a publication relating to health care.
Gary R. Cutter, PhD (University of Alabama At Birmingham)	Dr. Cutter has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for onsulting or Advisory Boards: Alexion, Antisense Therapeutics/Percheron, Avotres, Biogen, Clene Nanomedicine, Clinical Trial Solutions LLC, Endra Life Sciences, Cognito Therapeutics, Genzyme, Genentech, Immunic, Klein-Buendel Incorporated, Kyverna Therapeutics, Inc. , Linical, Merck/Serono, Noema, Neurogenesis, Perception Neurosciences, Protalix Biotherapeutics, Regeneron, Revelstone Consulting, Roche, SAB Biotherapeutics, Sapience Therapeutics, Scott&Scott LLP, Tenmile.. Dr. Cutter has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Data and Safety Monitoring Boards: Applied Therapeutics, AI therapeutics, AMO Pharma, Argenx, Astra-Zeneca, Avexis Pharmaceuticals, Bristol Meyers Squibb, CSL Behring, Cynata Therapeutics, DiamedicaTherapeutics, Horizon Pharmaceuticals, Immunic, Inhibrix, Karuna Therapeutics, Kezar Life Sciences, Medtronic, Merck, Meiji Seika Pharma, Mitsubishi Tanabe Pharma Holdings, Prothena Biosciences, Novartis, Pipeline Therapeutics (Contineum), Regeneron, Sanofi-Aventis, Teva Pharmaceuticals, United BioSource LLC, University of Texas Southwestern.. Dr. Cutter has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JASN.
Ryan Metzger, PhD (RM Biosciences)	An immediate family member of Dr. Metzger has received personal compensation for serving as an employee of Neurocrine Biosciences. Dr. Metzger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Interpro Bioscience. An immediate family member of Dr. Metzger has stock in Ascendis. An immediate family member of Dr. Metzger has stock in Neurocrine Biosciences.
Judith Goldberg	No disclosure on file
Xiaochun Li	No disclosure on file
Evan Riddle, PhD	Dr. Riddle has received personal compensation for serving as an employee of Biogen. Dr. Riddle has received stock or an ownership interest from Biogen.
Karen Smirnakis	No disclosure on file
	No disclosure on file
Zheng Ren	Zheng Ren has received personal compensation for serving as an employee of Biogen.
Nolan Campbell	Nolan Campbell has received personal compensation for serving as an employee of Biogen. Nolan Campbell has stock in Biogen.

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