Natalizumab extended interval dosing (EID) is associated with a reduced risk of progressive multifocal leukoencephalopathy (PML) than every-4-week (Q4W) dosing: Updated analysis of the TOUCH® Prescribing Program database (1988)

Objective: Update the assessment of PML risk with natalizumab EID compared with Q4W dosing using TOUCH data as of June 1, 2019.

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 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 specified for the 2017 study: a primary analysis (EID defined by the last 18 months of exposure), secondary analysis (EID defined as any prolonged period of EID in exposure history at any time), and tertiary analysis (EID defined as a dosing history consisting primarily of EID). Patients with average dosing intervals <3 or >12 weeks were excluded. Hazard ratios (HRs) of PML with EID and Q4W dosing were compared using adjusted Cox regression models and Kaplan-Meier estimates.

Results: The updated analyses included more patients than the original 2017 study (primary: 2639 EID [32.7% increase] and 15,159 Q4W [15.4% increase]; secondary: 4237 EID [27.2% increase] and 17,493 Q4W [13.4% increase]; tertiary: 1048 EID [28.6% increase] and 26,540 Q4W [14.6% increase]). For all analyses, the mean number of natalizumab infusions and mean treatment duration were greater with EID than with Q4W dosing. Average dosing intervals were unchanged from 2017. The PML HR (95% confidence interval) was 0.11 (0.05–0.28; P<0.0001) for the primary analysis and 0.20 (0.11–0.40; P<0.0001) for the secondary analysis, both favoring EID. As in previous TOUCH analyses, no EID PML cases were observed in the tertiary analysis (Kaplan-Meier log-rank test P=0.006).

Conclusions: This updated analysis of TOUCH patient data continues to demonstrate that natalizumab EID is associated with a significantly lower PML risk than Q4W dosing.

Disclosure: Dr. Zhovtis Ryerson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Zhovtis Ryerson has received personal compensation for serving on speaker bureau for Biogen, Teva, Genentech and advisory board for Biogen and Celgene. Dr. Zhovtis Ryerson has received research support from Biogen. Dr. Foley has nothing to disclose. Dr. Chang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employees of and hold stock/stock options in Biogen. Dr. Chang holds stock and/or stock options in Biogen, stock greater than 10K which sponsored research in which Dr. Chang was involved as an investigator. Dr. Kister has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Has served on advisory boards of Biogen, Genentech.Dr. Cutter has received personal compensation from AMO Pharma, Argenix, Atara Bio-therapeutics, Axon, Biogen, BioLineRx, Bio-therapeutics, Brainstorm Cell Therapeutics, Charleston Laboratories, Inc., Click Therapeutics, Genentech, Genzyme, GW Pharma, Horizon Pharmaceuticals, Klein Buendel Inc., MedDay, MedImmune, Merck, Merck/Pfizer, Neurim, Novartis OPKO Biologics, Orphazyme, Pythagoras, Inc, Reata Pharmaceuticals, Receptos/ Celgene, Sanofi- Aventis, Roche, SciFluor, Somahlution, Teva Pharma-ceuticals, TG Therapeutics, UTHealth Houston Teva Neuroscience Dr. Metzger holds stock and/or stock options in Family member owns stock in Biogen which sponsored research in which Dr. Metzger was involved as an investigator. Dr. Goldberg has nothing to disclose. Dr. Li has nothing to disclose. Dr. Riddle has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of and hold stock and/or stock options in Biogen. Dr. Riddle holds stock and/or stock options in Biogen which sponsored research in which Dr. Riddle was involved as an investigator. Dr. Smirnakis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of and hold stock and/or stock options in Biogen. Dr. Smirnakis holds stock and/or stock options in employee%20of%20and%20holds%20stock%2Fstock%20options%20in%20Biogen which sponsored research in which Dr. Smirnakis was involved as an investigator. Dr. Smirnakis holds stock and/or stock options in employee%20of%20and%20holds%20stock%2Fstock%20options%20in%20Biogen. Dr. Ren has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of and hold stock and/or stock options in Biogen. Dr. Hotermans has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Hotermans holds stock and/or stock options in Biogen which sponsored research in which Dr. Hotermans was involved as an investigator.Dr. Ho has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Ho holds stock and/or stock options in Biogen.Dr. Campbell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Campbell has received compensation for serving on the Board of Directors of Received stock as employee of Biogen. Dr. Campbell holds stock and/or stock options in Biogen.