Evidence map›Paper›PMID 29669908›Full record

ArticleNeurology2018

Progressive multifocal leukoencephalopathy after fingolimod treatment.

Joseph R Berger, Bruce A Cree, Benjamin Greenberg, Bernhard Hemmer, Brian J Ward, Victor M Dong, Martin Merschhemke

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

Article in Neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 2 pooled it
7.4field-weighted citation impact, top 2% 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

76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 143 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Review
  6. Article
  7. JC Polyomavirus Infection: A Narrative Review.Infectious diseases and therapy · 2025
    Review
  8. Article
  9. Choosing initial MS therapy; personal, disease, and medication factors.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review

16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

Joseph R BergerFrom the Department of Neurology (J.R.B.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Multiple Sclerosis Centre (B.A.C.), University of California, San Francisco; University of Texas Southwestern Medical Center (B.G.), Multiple Sclerosis Program, Dallas, TX; Department of Neurology (B.H.), Klinikum Rechts der Isar, Technical University of Munich; Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Infectious Diseases Division (B.J.W.), Research Institute of the McGill University Health Centre, Montreal, Canada; Novartis Pharmaceuticals Corporation (V.M.D.), East Hanover, NJ; and Novartis Pharma AG (M.M.), Basel, Switzerland. joseph.berger@uphs.upenn.edu.
Bruce A CreeFrom the Department of Neurology (J.R.B.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Multiple Sclerosis Centre (B.A.C.), University of California, San Francisco; University of Texas Southwestern Medical Center (B.G.), Multiple Sclerosis Program, Dallas, TX; Department of Neurology (B.H.), Klinikum Rechts der Isar, Technical University of Munich; Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Infectious Diseases Division (B.J.W.), Research Institute of the McGill University Health Centre, Montreal, Canada; Novartis Pharmaceuticals Corporation (V.M.D.), East Hanover, NJ; and Novartis Pharma AG (M.M.), Basel, Switzerland.
Benjamin GreenbergFrom the Department of Neurology (J.R.B.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Multiple Sclerosis Centre (B.A.C.), University of California, San Francisco; University of Texas Southwestern Medical Center (B.G.), Multiple Sclerosis Program, Dallas, TX; Department of Neurology (B.H.), Klinikum Rechts der Isar, Technical University of Munich; Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Infectious Diseases Division (B.J.W.), Research Institute of the McGill University Health Centre, Montreal, Canada; Novartis Pharmaceuticals Corporation (V.M.D.), East Hanover, NJ; and Novartis Pharma AG (M.M.), Basel, Switzerland.
Bernhard HemmerFrom the Department of Neurology (J.R.B.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Multiple Sclerosis Centre (B.A.C.), University of California, San Francisco; University of Texas Southwestern Medical Center (B.G.), Multiple Sclerosis Program, Dallas, TX; Department of Neurology (B.H.), Klinikum Rechts der Isar, Technical University of Munich; Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Infectious Diseases Division (B.J.W.), Research Institute of the McGill University Health Centre, Montreal, Canada; Novartis Pharmaceuticals Corporation (V.M.D.), East Hanover, NJ; and Novartis Pharma AG (M.M.), Basel, Switzerland.
Brian J WardFrom the Department of Neurology (J.R.B.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Multiple Sclerosis Centre (B.A.C.), University of California, San Francisco; University of Texas Southwestern Medical Center (B.G.), Multiple Sclerosis Program, Dallas, TX; Department of Neurology (B.H.), Klinikum Rechts der Isar, Technical University of Munich; Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Infectious Diseases Division (B.J.W.), Research Institute of the McGill University Health Centre, Montreal, Canada; Novartis Pharmaceuticals Corporation (V.M.D.), East Hanover, NJ; and Novartis Pharma AG (M.M.), Basel, Switzerland.
Victor M DongFrom the Department of Neurology (J.R.B.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Multiple Sclerosis Centre (B.A.C.), University of California, San Francisco; University of Texas Southwestern Medical Center (B.G.), Multiple Sclerosis Program, Dallas, TX; Department of Neurology (B.H.), Klinikum Rechts der Isar, Technical University of Munich; Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Infectious Diseases Division (B.J.W.), Research Institute of the McGill University Health Centre, Montreal, Canada; Novartis Pharmaceuticals Corporation (V.M.D.), East Hanover, NJ; and Novartis Pharma AG (M.M.), Basel, Switzerland.
Martin MerschhemkeFrom the Department of Neurology (J.R.B.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Multiple Sclerosis Centre (B.A.C.), University of California, San Francisco; University of Texas Southwestern Medical Center (B.G.), Multiple Sclerosis Program, Dallas, TX; Department of Neurology (B.H.), Klinikum Rechts der Isar, Technical University of Munich; Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Infectious Diseases Division (B.J.W.), Research Institute of the McGill University Health Centre, Montreal, Canada; Novartis Pharmaceuticals Corporation (V.M.D.), East Hanover, NJ; and Novartis Pharma AG (M.M.), Basel, Switzerland.
The University of Texas Southwestern Medical Center · USKlinikum rechts der Isar · DEMcGill University Health Centre · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveWe describe the characteristics of the 15 patients with fingolimod-associated progressive multifocal leukoencephalopathy (PML) identified from the Novartis data safety base and provide risk estimates for the disorder.

methodsThe Novartis safety database was searched for PML cases with a data lock point of August 31, 2017. PML classification was based on previously published criteria. The risk and incidence were estimated using the 15 patients with confirmed PML and the overall population of patients treated with fingolimod.

resultsAs of August 31, 2017, 15 fingolimod-treated patients had developed PML in the absence of natalizumab treatment in the preceding 6 months. Eleven (73%) were women and the mean age was 53 years (median: 53 years). Fourteen of the 15 patients were treated with fingolimod for >2 years. Two patients had confounding medical conditions. Two patients had natalizumab treatment. This included one patient whose last dose of natalizumab was 3 years and 9 months before the diagnosis of PML. The second patient was receiving fingolimod for 4 years and 6 months, which was discontinued to start natalizumab and was diagnosed with PML 3 months after starting natalizumab. Absolute lymphocyte counts were available for 14 of the 15 patients and none exhibited a sustained grade 4 lymphopenia (≤200 cells/μL).

conclusionsThe risk of PML with fingolimod in the absence of prior natalizumab treatment is low. The estimated risk was 0.069 per 1,000 patients (95% confidence interval: 0.039-0.114), and the estimated incidence rate was 3.12 per 100,000 patient-years (95% confidence interval: 1.75-5.15). Neither clinical manifestations nor radiographic features suggested any unique features of fingolimod-associated PML.

Indexed as

Treatment OutcomeAgedBrainDisability EvaluationFemaleFingolimod HydrochlorideFollow-Up StudiesHumansImmunosuppressive AgentsLeukoencephalopathy, Progressive MultifocalMagnetic Resonance ImagingMaleMiddle AgedFingolimod HydrochlorideImmunosuppressive Agents

Identifiers

PMID29669908
PMCPMC5957303
OpenAlexW2802030355

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.