Lana Zhovtis Ryerson1, John Foley1, Ih Chang1, Ilya Kister1, Gary Cutter1, Ryan R Metzger1, Judith D Goldberg1, Xiaochun Li1, Evan Riddle1, Karen Smirnakis1, Rachna Kasliwal1, Zheng Ren1, Christophe Hotermans1, Pei-Ran Ho1, Nolan Campbell2. 1. From the Department of Neurology (L.Z.R., I.K.), NYU Langone Health, New York University, New York; Rocky Mountain MS Clinic (J.F., R.R.M.), Salt Lake City, UT; Biogen (I.C., E.R., K.S., R.K., Z.R., C.H., P-R.H., N.C.), Cambridge, MA; University of Alabama School of Public Health (G.C.), Birmingham; and Division of Biostatistics (J.D.G., X.L.), New York University School of Medicine, New York. 2. From the Department of Neurology (L.Z.R., I.K.), NYU Langone Health, New York University, New York; Rocky Mountain MS Clinic (J.F., R.R.M.), Salt Lake City, UT; Biogen (I.C., E.R., K.S., R.K., Z.R., C.H., P-R.H., N.C.), Cambridge, MA; University of Alabama School of Public Health (G.C.), Birmingham; and Division of Biostatistics (J.D.G., X.L.), New York University School of Medicine, New York. nolan.campbell@biogen.com.
Abstract
OBJECTIVE: To use the large dataset from the Tysabri Outreach: Unified Commitment to Health (TOUCH) program to compare progressive multifocal leukoencephalopathy (PML) risk with natalizumab extended interval dosing (EID) vs standard interval dosing (SID) in patients with multiple sclerosis (MS). METHODS: This retrospective cohort study included anti-JC virus antibody-positive patients (n = 35,521) in the TOUCH database as of June 1, 2017. The effect of EID on PML risk was evaluated with 3 planned analyses using Kaplan-Meier methods stratified by prior immunosuppressant use. Risk of PML was analyzed by Cox regression adjusted for age, sex, prior immunosuppressants, time since natalizumab initiation, and cumulative number of infusions. RESULTS: This study included 35,521 patients (primary analysis: 1,988 EID, 13,132 SID; secondary analysis: 3,331 EID, 15,424 SID; tertiary analysis: 815 EID, 23,168 SID). Mean average dosing intervals were 35.0 to 43.0 and 29.8 to 30.5 days for the EID and SID cohorts, respectively. Hazard ratios (95% confidence intervals) of PML risk for EID vs SID were 0.06 (0.01-0.22, p < 0.001) and 0.12 (0.05-0.29, p < 0.001) for the primary and secondary analyses, respectively. Relative risk reductions were 94% and 88% in favor of EID for the primary and secondary analyses, respectively. The tertiary analysis included no cases of PML with EID. CONCLUSION: Natalizumab EID is associated with clinically and statistically significantly lower PML risk than SID. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with MS, natalizumab EID is associated with a lower PML risk than SID.
OBJECTIVE: To use the large dataset from the Tysabri Outreach: Unified Commitment to Health (TOUCH) program to compare progressive multifocal leukoencephalopathy (PML) risk with natalizumab extended interval dosing (EID) vs standard interval dosing (SID) in patients with multiple sclerosis (MS). METHODS: This retrospective cohort study included anti-JC virus antibody-positive patients (n = 35,521) in the TOUCH database as of June 1, 2017. The effect of EID on PML risk was evaluated with 3 planned analyses using Kaplan-Meier methods stratified by prior immunosuppressant use. Risk of PML was analyzed by Cox regression adjusted for age, sex, prior immunosuppressants, time since natalizumab initiation, and cumulative number of infusions. RESULTS: This study included 35,521 patients (primary analysis: 1,988 EID, 13,132 SID; secondary analysis: 3,331 EID, 15,424 SID; tertiary analysis: 815 EID, 23,168 SID). Mean average dosing intervals were 35.0 to 43.0 and 29.8 to 30.5 days for the EID and SID cohorts, respectively. Hazard ratios (95% confidence intervals) of PML risk for EID vs SID were 0.06 (0.01-0.22, p < 0.001) and 0.12 (0.05-0.29, p < 0.001) for the primary and secondary analyses, respectively. Relative risk reductions were 94% and 88% in favor of EID for the primary and secondary analyses, respectively. The tertiary analysis included no cases of PML with EID. CONCLUSION:NatalizumabEID is associated with clinically and statistically significantly lower PML risk than SID. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with MS, natalizumabEID is associated with a lower PML risk than SID.
Authors: Michael Auer; Angelika Bauer; Antonia Oftring; Dagmar Rudzki; Harald Hegen; Gabriel Bsteh; Franziska Di Pauli; Klaus Berek; Anne Zinganell; Thomas Berger; Markus Reindl; Florian Deisenhammer Journal: CNS Drugs Date: 2022-09-29 Impact factor: 6.497
Authors: Heinz Wiendl; Ralf Gold; Thomas Berger; Tobias Derfuss; Ralf Linker; Mathias Mäurer; Martin Stangel; Orhan Aktas; Karl Baum; Martin Berghoff; Stefan Bittner; Andrew Chan; Adam Czaplinski; Florian Deisenhammer; Franziska Di Pauli; Renaud Du Pasquier; Christian Enzinger; Elisabeth Fertl; Achim Gass; Klaus Gehring; Claudio Gobbi; Norbert Goebels; Michael Guger; Aiden Haghikia; Hans-Peter Hartung; Fedor Heidenreich; Olaf Hoffmann; Zoë R Hunter; Boris Kallmann; Christoph Kleinschnitz; Luisa Klotz; Verena Leussink; Fritz Leutmezer; Volker Limmroth; Jan D Lünemann; Andreas Lutterotti; Sven G Meuth; Uta Meyding-Lamadé; Michael Platten; Peter Rieckmann; Stephan Schmidt; Hayrettin Tumani; Martin S Weber; Frank Weber; Uwe K Zettl; Tjalf Ziemssen; Frauke Zipp Journal: Nervenarzt Date: 2021-07-23 Impact factor: 1.214