Evidence map›Paper›PMID 36307225›Full record

SynthesisNeurology2023

Risk of Multiple Sclerosis Among Users of Antitumor Necrosis Factor α in 4 Canadian Provinces: A Population-Based Study.

Lingyi Li, J Antonio Aviña-Zubieta, Charles N Bernstein, Gilaad G Kaplan, Helen Tremlett, Hui Xie, Juan-Nicolás Peña-Sánchez, Ruth Ann Marrie, Mahyar Etminan

Open access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 7% 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

15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Article
  6. Observational
  7. Central nervous system demyelination associated with biological agents used in the treatment of rheumatologic diseases: a retrospective cohort study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Article
  8. High-risk populations should be screened for MS: Yes.Multiple sclerosis (Houndmills, Basingstoke, England) · 2025
    Article
  9. Article
  10. Review
  11. Article
  12. Ex-VivoJournal of proteome research · 2024
    Article
  13. Review
  14. Review
  15. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 1 country.

Lingyi LiFrom the Experimental Medicine Program (L.L., J.A.A.-Z., M.E.), Division of Rheumatology (J.A.A.-Z.), Department of Medicine, Division of Neurology (H.T.), Faculty of Medicine, and Departments of Ophthalmology and Visual Sciences (M.E.), Medicine and Pharmacology, University of British Columbia, Vancouver; Arthritis Research Canada (L.L., J.A.A.-Z., H.X.), Vancouver, British Columbia; Departments of Internal Medicine (C.N.B., R.A.M.) and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; Departments of Medicine and Community Health Sciences (G.G.K.), University of Calgary, Alberta; The Djavad Mowafaghian Centre for Brain Health (H.T.), Vancouver, British Columbia; Faculty of Health Sciences (H.X.), Simon Fraser University, Burnaby, British Columbia; and Department of Community Health and Epidemiology (J.-N.P.-S.), College of Medicine, University of Saskatchewan, Saskatoon, Canada.
J Antonio Aviña-ZubietaFrom the Experimental Medicine Program (L.L., J.A.A.-Z., M.E.), Division of Rheumatology (J.A.A.-Z.), Department of Medicine, Division of Neurology (H.T.), Faculty of Medicine, and Departments of Ophthalmology and Visual Sciences (M.E.), Medicine and Pharmacology, University of British Columbia, Vancouver; Arthritis Research Canada (L.L., J.A.A.-Z., H.X.), Vancouver, British Columbia; Departments of Internal Medicine (C.N.B., R.A.M.) and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; Departments of Medicine and Community Health Sciences (G.G.K.), University of Calgary, Alberta; The Djavad Mowafaghian Centre for Brain Health (H.T.), Vancouver, British Columbia; Faculty of Health Sciences (H.X.), Simon Fraser University, Burnaby, British Columbia; and Department of Community Health and Epidemiology (J.-N.P.-S.), College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Charles N BernsteinFrom the Experimental Medicine Program (L.L., J.A.A.-Z., M.E.), Division of Rheumatology (J.A.A.-Z.), Department of Medicine, Division of Neurology (H.T.), Faculty of Medicine, and Departments of Ophthalmology and Visual Sciences (M.E.), Medicine and Pharmacology, University of British Columbia, Vancouver; Arthritis Research Canada (L.L., J.A.A.-Z., H.X.), Vancouver, British Columbia; Departments of Internal Medicine (C.N.B., R.A.M.) and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; Departments of Medicine and Community Health Sciences (G.G.K.), University of Calgary, Alberta; The Djavad Mowafaghian Centre for Brain Health (H.T.), Vancouver, British Columbia; Faculty of Health Sciences (H.X.), Simon Fraser University, Burnaby, British Columbia; and Department of Community Health and Epidemiology (J.-N.P.-S.), College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Gilaad G KaplanFrom the Experimental Medicine Program (L.L., J.A.A.-Z., M.E.), Division of Rheumatology (J.A.A.-Z.), Department of Medicine, Division of Neurology (H.T.), Faculty of Medicine, and Departments of Ophthalmology and Visual Sciences (M.E.), Medicine and Pharmacology, University of British Columbia, Vancouver; Arthritis Research Canada (L.L., J.A.A.-Z., H.X.), Vancouver, British Columbia; Departments of Internal Medicine (C.N.B., R.A.M.) and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; Departments of Medicine and Community Health Sciences (G.G.K.), University of Calgary, Alberta; The Djavad Mowafaghian Centre for Brain Health (H.T.), Vancouver, British Columbia; Faculty of Health Sciences (H.X.), Simon Fraser University, Burnaby, British Columbia; and Department of Community Health and Epidemiology (J.-N.P.-S.), College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Helen TremlettFrom the Experimental Medicine Program (L.L., J.A.A.-Z., M.E.), Division of Rheumatology (J.A.A.-Z.), Department of Medicine, Division of Neurology (H.T.), Faculty of Medicine, and Departments of Ophthalmology and Visual Sciences (M.E.), Medicine and Pharmacology, University of British Columbia, Vancouver; Arthritis Research Canada (L.L., J.A.A.-Z., H.X.), Vancouver, British Columbia; Departments of Internal Medicine (C.N.B., R.A.M.) and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; Departments of Medicine and Community Health Sciences (G.G.K.), University of Calgary, Alberta; The Djavad Mowafaghian Centre for Brain Health (H.T.), Vancouver, British Columbia; Faculty of Health Sciences (H.X.), Simon Fraser University, Burnaby, British Columbia; and Department of Community Health and Epidemiology (J.-N.P.-S.), College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Hui XieFrom the Experimental Medicine Program (L.L., J.A.A.-Z., M.E.), Division of Rheumatology (J.A.A.-Z.), Department of Medicine, Division of Neurology (H.T.), Faculty of Medicine, and Departments of Ophthalmology and Visual Sciences (M.E.), Medicine and Pharmacology, University of British Columbia, Vancouver; Arthritis Research Canada (L.L., J.A.A.-Z., H.X.), Vancouver, British Columbia; Departments of Internal Medicine (C.N.B., R.A.M.) and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; Departments of Medicine and Community Health Sciences (G.G.K.), University of Calgary, Alberta; The Djavad Mowafaghian Centre for Brain Health (H.T.), Vancouver, British Columbia; Faculty of Health Sciences (H.X.), Simon Fraser University, Burnaby, British Columbia; and Department of Community Health and Epidemiology (J.-N.P.-S.), College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Juan-Nicolás Peña-SánchezFrom the Experimental Medicine Program (L.L., J.A.A.-Z., M.E.), Division of Rheumatology (J.A.A.-Z.), Department of Medicine, Division of Neurology (H.T.), Faculty of Medicine, and Departments of Ophthalmology and Visual Sciences (M.E.), Medicine and Pharmacology, University of British Columbia, Vancouver; Arthritis Research Canada (L.L., J.A.A.-Z., H.X.), Vancouver, British Columbia; Departments of Internal Medicine (C.N.B., R.A.M.) and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; Departments of Medicine and Community Health Sciences (G.G.K.), University of Calgary, Alberta; The Djavad Mowafaghian Centre for Brain Health (H.T.), Vancouver, British Columbia; Faculty of Health Sciences (H.X.), Simon Fraser University, Burnaby, British Columbia; and Department of Community Health and Epidemiology (J.-N.P.-S.), College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Ruth Ann MarrieFrom the Experimental Medicine Program (L.L., J.A.A.-Z., M.E.), Division of Rheumatology (J.A.A.-Z.), Department of Medicine, Division of Neurology (H.T.), Faculty of Medicine, and Departments of Ophthalmology and Visual Sciences (M.E.), Medicine and Pharmacology, University of British Columbia, Vancouver; Arthritis Research Canada (L.L., J.A.A.-Z., H.X.), Vancouver, British Columbia; Departments of Internal Medicine (C.N.B., R.A.M.) and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; Departments of Medicine and Community Health Sciences (G.G.K.), University of Calgary, Alberta; The Djavad Mowafaghian Centre for Brain Health (H.T.), Vancouver, British Columbia; Faculty of Health Sciences (H.X.), Simon Fraser University, Burnaby, British Columbia; and Department of Community Health and Epidemiology (J.-N.P.-S.), College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Mahyar EtminanFrom the Experimental Medicine Program (L.L., J.A.A.-Z., M.E.), Division of Rheumatology (J.A.A.-Z.), Department of Medicine, Division of Neurology (H.T.), Faculty of Medicine, and Departments of Ophthalmology and Visual Sciences (M.E.), Medicine and Pharmacology, University of British Columbia, Vancouver; Arthritis Research Canada (L.L., J.A.A.-Z., H.X.), Vancouver, British Columbia; Departments of Internal Medicine (C.N.B., R.A.M.) and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; Departments of Medicine and Community Health Sciences (G.G.K.), University of Calgary, Alberta; The Djavad Mowafaghian Centre for Brain Health (H.T.), Vancouver, British Columbia; Faculty of Health Sciences (H.X.), Simon Fraser University, Burnaby, British Columbia; and Department of Community Health and Epidemiology (J.-N.P.-S.), College of Medicine, University of Saskatchewan, Saskatoon, Canada. etminanm@mail.ubc.ca.
Research Canada · CAUniversity of Manitoba · CASimon Fraser University · CAUniversity of Calgary · CAVancouver Coastal Health · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesAntitumor necrosis factor α (TNFα) agents are a class of biologic drugs used for the treatment of several immune-mediated conditions. An increased risk of multiple sclerosis (MS) with their use has been suggested, but studies have been limited. Relevant population-based epidemiologic data linking anti-TNFα to MS are scarce. The objective was to compare the risk of MS in anti-TNFα users with nonusers among patients with rheumatic disease (RD) or inflammatory bowel disease (IBD).

methodsA nested case-control study was conducted. Population-based health care-linked databases from 4 Canadian provinces were used. All patients with RD or IBD residing within a participating province between January 2000 and March 2018 were identified by validated case definitions. Any anti-TNFα dispensation in the 2 years before the index date (MS onset) was identified. Incident onset MS cases were ascertained using a validated algorithm. Up to 5 controls were matched to each MS case based on birth year ±3 years, disease duration, and health authority (based on region of residence). Conditional logistic regressions were used to calculate the incidence rate ratio (IRR) after adjusting for potential confounders. A meta-analysis was conducted to provide pooled estimates across provinces using random-effects models.

resultsAmong 296,918 patients with RD patients, 462 MS cases (80.1% female, mean [SD] age, 47.4 [14.6] years) were matched with 2,296 controls (59.5% female, mean [SD] age, 47.4 [14.5] years). Exposure to anti-TNFα occurred in 18 MS cases and 42 controls. After adjusting for matching variables, sex, and the Charlson Comorbidity Index, the pooled IRR was 2.05 (95% CI, 1.13-3.72). Among 84,458 patients with IBD, 190 MS cases (69.5% female, mean [SD] age, 44.3 [12.3] years) were matched with 943 controls (54.1% female, mean [SD] age, 44.2 [12.2] years). Exposure to anti-TNFα occurred in 23 MS cases and 98 controls. The pooled adjusted IRR was 1.35 (95% CI, 0.70-2.59). DISCUSSION: The use of anti-TNFα was associated with an increased risk of MS compared with nonusers, especially among patients with RD. These findings could help clinicians and patients with RD to make more informed treatment decisions. Further studies are needed to validate these results for patients with IBD.

Indexed as

Inflammatory Bowel DiseasesMultiple SclerosisTumor Necrosis Factor InhibitorsAdultCanadaCase-Control StudiesFemaleHumansMaleMiddle AgedNecrosisTumor Necrosis Factor Inhibitors

Identifiers

PMID36307225
PMCPMC9946189
OpenAlexW4307584930

What OpenQuestion holds

Textmetadata
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.