Risk of natalizumab-associated PML in patients with MS is reduced with extended interval dosing.
Adult
Antibodies, Monoclonal, Humanized
/ adverse effects
Antibodies, Viral
/ adverse effects
Female
Humans
Immunosuppressive Agents
/ adverse effects
Leukoencephalopathy, Progressive Multifocal
/ etiology
Male
Middle Aged
Multiple Sclerosis
/ drug therapy
Natalizumab
/ adverse effects
Retrospective Studies
Risk Factors
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
08 10 2019
08 10 2019
Historique:
received:
25
10
2018
accepted:
11
06
2019
pubmed:
14
9
2019
medline:
14
2
2020
entrez:
14
9
2019
Statut:
ppublish
Résumé
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). 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. 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, Natalizumab EID is associated with clinically and statistically significantly lower PML risk than SID. This study provides Class III evidence that for patients with MS, natalizumab EID is associated with a lower PML risk than SID.
Identifiants
pubmed: 31515290
pii: WNL.0000000000008243
doi: 10.1212/WNL.0000000000008243
pmc: PMC7010325
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antibodies, Viral
0
Immunosuppressive Agents
0
Natalizumab
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1452-e1462Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
Ann Clin Transl Neurol. 2015 May;2(5):570-4
pubmed: 26000328
Neurology. 2017 Oct 10;89(15):1584-1593
pubmed: 28916537
N Engl J Med. 2006 Mar 2;354(9):899-910
pubmed: 16510744
Neurology. 2015 Jul 7;85(1):29-39
pubmed: 26024899
Expert Rev Neurother. 2004 Jul;4(4):571-80
pubmed: 15853576
N Engl J Med. 2012 May 17;366(20):1870-80
pubmed: 22591293
CNS Drug Rev. 2007 Spring;13(1):79-95
pubmed: 17461891
Ther Adv Neurol Disord. 2014 Sep;7(5):227-31
pubmed: 25342976
J Neurol Neurosurg Psychiatry. 2016 Aug;87(8):885-9
pubmed: 26917698
J Neurol. 2017 Feb;264(2):284-294
pubmed: 27878443
J Pharmacokinet Pharmacodyn. 2017 Jun;44(3):263-275
pubmed: 28251386
J Neurol Neurosurg Psychiatry. 2014 Nov;85(11):1190-7
pubmed: 24532785
Mult Scler. 2012 Sep;18(9):1337-9
pubmed: 22389413
Neurology. 2014 Apr 29;82(17):1491-8
pubmed: 24682966
Lancet Neurol. 2017 Nov;16(11):925-933
pubmed: 28969984
N Engl J Med. 2003 Jan 2;348(1):15-23
pubmed: 12510038
Lancet Neurol. 2018 May;17(5):467-480
pubmed: 29656742
Neurodegener Dis Manag. 2015 Oct;5(5):399-402
pubmed: 26517599