PT - JOURNAL ARTICLE AU - Ryerson, Lana Zhovtis AU - Foley, John AU - Chang, Ih AU - Kister, Ilya AU - Cutter, Gary AU - Metzger, Ryan AU - Goldberg, Judith AU - Li, Xiaochun AU - Riddle, Evan AU - Smirnakis, Karen AU - Kasliwal, Rachna AU - Ren, Zheng AU - Hotermans, Christophe AU - Ho, Pei-Ran AU - Campbell, Nolan TI - Reduced risk of progressive multifocal leukoencephalopathy (PML) associated with natalizumab extended interval dosing (EID): updated analysis of the TOUCH® Prescribing Program database (S26.006) DP - 2019 Apr 09 TA - Neurology PG - S26.006 VI - 92 IP - 15 Supplement 4099 - http://n.neurology.org/content/92/15_Supplement/S26.006.short 4100 - http://n.neurology.org/content/92/15_Supplement/S26.006.full SO - Neurology2019 Apr 09; 92 AB - 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.Disclosure: Dr Zhovtis Ryerson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Teva, Genezyme, Biogen and Celgene. Dr Zhovtis Ryerson received research support from Biogen. Dr. Foley has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, EMDSerono. Dr. Foley holds stock and/or stock options in Abreos Biosciences. Dr. Foley has received research support from Biogen, Mallinckrodt, Adamas, Genentech and Novartis. Dr. Chang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Chang holds stock and/or stock options in Biogen. Dr. Kister has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with ad board consulting for Biogen. Dr. Kister has received research support from research fundings from Biogen, Sanofi Genzyme, and Genentech. Dr. Cutter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AMO Pharmaceuticals, Biolinerx, Horizon Pharmaceuticals, Hisun Pharmaceuticals, Merck, Merck/Pfizer, Opko Biologics, Neurim, Novartis, Ophazyme, Sanofi-Aventis, Reata Pharmaceuticals, Receptos/Celgene, Teva pharmaceuticals, NHLBI, NICHD, Atara Biotherapeutics, Axon, Biogen, Argenix, Brainstorm Cell Therapeutics, Charleston Labs Inc, Click Therapeutics, Genzyme, Genentech, GW Pharma, Klein-Buendel Incorporated, Medimmune, Medday, Novartis, Roche, Scifluor, Somahlution, Teva pharmaceuticals, TG Therapeutics, UT Houston. Dr. Cutter has received personal compensation in an editorial capacity for Statistical editor for the Journal of the American Society of Nephrology. Dr. Cutter has received research support from Via MGFA. Dr. Metzger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Metzger holds stock and/or stock options in Biogen, which sponsored research in which Dr. Metzger was involved as an investigator. Dr. Goldberg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Statistical Science and Technology Associates, Inc., Actavis and Mylan Relistor. 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 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 as an employee of Biogen. Dr. Smirnakis owns stock in Biogen, which sponsored research in which Dr. Smirnakis was involved as an investigator. Dr. Kasliwal has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Ren has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Ren holds stock and/or stock options in Biogen. Dr. Ren has received research support from 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. 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 Biogen. Dr. Campbell holds stock and/or stock options in Biogen.