Abstract Details

Title Reduced risk of progressive multifocal leukoencephalopathy (PML) associated with natalizumab extended interval dosing (EID): updated analysis of the TOUCH® Prescribing Program database

Topic Multiple Sclerosis

Presentation(s) S26 - MS and CNS Inflammatory Disease: Clinical Considerations II (1:55 PM-2:06 PM)

Poster/Presentation
Number 006

Objective To update the assessment of PML risk with natalizumab EID compared with standard interval dosing (SID) using TOUCH data as of June 1, 2018.

Background Natalizumab treatment is associated with an increased risk of PML. A June 2017 analysis of the TOUCH dataset demonstrated that natalizumab EID was associated with significantly lower PML risk than SID in anti–JC virus (JCV) antibody positive multiple sclerosis patients.

Design/Methods TOUCH data as of June 1, 2018, were used to assess the effect of EID/SID on PML risk using the three pre-planned analyses specified for the 2017 study: primary analysis (EID/SID over the last 18 months of doing history); secondary analysis (prolonged period of EID/SID occurring at any time); tertiary analysis (dosing history consisting primarily of EID/SID). Anti-JCV seropositive patients with dosing intervals of ≥3 to ≤12 weeks were included. PML hazard ratios (HRs) for EID and SID were compared using adjusted Cox regression models and Kaplan-Meier estimates.

Results Compared with 2017, this update increased the number of patients in all 3 analysis groups (primary: 14,305 SID [8.9% increase] and 2266 EID [14.0% increase] patients; secondary: 16,648 SID [7.9% increase] and 3726 EID [11.9% increase] patients; tertiary: 24,870 SID [7.3% increase] and 931 [14.2% increase] EID patients). For all analyses, EID patients had longer median natalizumab exposure durations (months) (primary, 60 vs 44; secondary, 57 vs 26; tertiary, 43 vs 26) than SID patients. The PML HR (95% confidence interval) was 0.10 (0.03–0.27; P<0.001) for the primary analysis and 0.20 (0.10?0.41; P<0.001) for the secondary analysis (both in favor of EID). As in the 2017 analysis, no EID PML cases were observed in the tertiary analysis (Kaplan-Meier log-rank test P=0.011).

Conclusions Updated analyses of TOUCH data demonstrate that natalizumab EID is associated with significantly lower PML risk compared with SID.

Authors/Disclosures
Lana Zhovtis Ryerson, MD (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.
Ih Chang	Ih Chang has received personal compensation for serving as an employee of Cerevel. Ih Chang has received stock or an ownership interest from Cerevel Therapeutics.
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
Rachna Kasliwal	No disclosure on file
Zheng Ren	Zheng Ren has received personal compensation for serving as an employee of Biogen.
Christophe Hotermans, MD, PhD (Alexion)	No disclosure on file
Pei-Ran Ho	No disclosure on file
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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