Evidence map›Paper›PMID 31515290›Full record

ArticleNeurology2019

Risk of natalizumab-associated PML in patients with MS is reduced with extended interval dosing.

Lana Zhovtis Ryerson, John Foley, Ih Chang, Ilya Kister, Gary Cutter, Ryan R Metzger, Judith D Goldberg, Xiaochun Li, Evan Riddle, Karen Smirnakis and 5 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 2 pooled it
16.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 186 citations in OpenAlex.

  1. Pooled it
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  6. Immune reconstitution and tolerance-inducing therapies as promising therapeutic approaches in multiple sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Review
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  17. Changes in circulating pro-inflammatory lymphocytes and cortical excitability with extended-interval natalizumab dosing in multiple sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
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28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Lana Zhovtis RyersonFrom 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.
John FoleyFrom 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.
Ih ChangFrom 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.
Ilya KisterFrom 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.
Gary CutterFrom 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.ORCID 0000-0002-8455-980X
Ryan R MetzgerFrom 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.
Judith D GoldbergFrom 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.ORCID 0000-0003-3758-6976
Xiaochun LiFrom 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.
Evan RiddleFrom 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.
Karen SmirnakisFrom 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.
Rachna KasliwalFrom 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.
Zheng RenFrom 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.
Christophe HotermansFrom 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.
Pei-Ran HoFrom 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 CampbellFrom 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.
Biogen (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo 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).

methodsThis 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.

resultsThis 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,

conclusionNatalizumab 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.

Indexed as

AdultAntibodies, Monoclonal, HumanizedAntibodies, ViralFemaleHumansImmunosuppressive AgentsLeukoencephalopathy, Progressive MultifocalMaleMiddle AgedMultiple SclerosisNatalizumabRetrospective StudiesRisk FactorsAntibodies, Monoclonal, HumanizedAntibodies, ViralImmunosuppressive AgentsNatalizumab

Identifiers

PMID31515290
PMCPMC7010325
OpenAlexW2973164339

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.