Evidence map›Paper›PMID 36224046›Full record

SynthesisNeurology(R) neuroimmunology & neuroinflammation2022

Association of NEDA-4 With No Long-term Disability Progression in Multiple Sclerosis and Comparison With NEDA-3: A Systematic Review and Meta-analysis.

Dalia Rotstein, Jacqueline M Solomon, Maria Pia Sormani, Xavier Montalban, Xiang Y Ye, Dina Dababneh, Alexandra Muccilli, Georges Saab, Prakesh Shah

Open access · goldAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Neurology(R) neuroimmunology & neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Refining predictors of long-term NEDA-3 status in relapsing-remitting multiple sclerosis: insights from real-world data.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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  7. Observational
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  9. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 4 countries.

Dalia RotsteinFrom the Department of Medicine, (D.R., A.M., G.S.), University of Toronto, Ontario, Canada; St. Michael's Hospital (D.R., A.M., G.S.), Toronto, Ontario, Canada; Department of Medicine, (J.M.S.), McMaster University, Hamilton, Ontario, Canada; Department of Health Sciences (M.P.S.), Section of Biostatistics, University of Genova, Italy; IRCCS Ospedale Policlinico San Martino (M.P.S.), Genova, Italy; Department of Neurology and Cemcat (X.M.), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona; Department of Pediatrics (X.Y.Y., P.S.), Mount Sinai Hospital, Toronto, Canada; Columbia University Irving Medical Center (D.D.), Department of Neurology, New York City; York Presbyterian Hospital (NYP) (D.D.), New York City; and Institute of Health (P.S.), Policy, Management and Evaluation, University of Toronto, Canada. dalia.rotstein@unityhealth.to.
Jacqueline M SolomonFrom the Department of Medicine, (D.R., A.M., G.S.), University of Toronto, Ontario, Canada; St. Michael's Hospital (D.R., A.M., G.S.), Toronto, Ontario, Canada; Department of Medicine, (J.M.S.), McMaster University, Hamilton, Ontario, Canada; Department of Health Sciences (M.P.S.), Section of Biostatistics, University of Genova, Italy; IRCCS Ospedale Policlinico San Martino (M.P.S.), Genova, Italy; Department of Neurology and Cemcat (X.M.), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona; Department of Pediatrics (X.Y.Y., P.S.), Mount Sinai Hospital, Toronto, Canada; Columbia University Irving Medical Center (D.D.), Department of Neurology, New York City; York Presbyterian Hospital (NYP) (D.D.), New York City; and Institute of Health (P.S.), Policy, Management and Evaluation, University of Toronto, Canada.
Maria Pia SormaniFrom the Department of Medicine, (D.R., A.M., G.S.), University of Toronto, Ontario, Canada; St. Michael's Hospital (D.R., A.M., G.S.), Toronto, Ontario, Canada; Department of Medicine, (J.M.S.), McMaster University, Hamilton, Ontario, Canada; Department of Health Sciences (M.P.S.), Section of Biostatistics, University of Genova, Italy; IRCCS Ospedale Policlinico San Martino (M.P.S.), Genova, Italy; Department of Neurology and Cemcat (X.M.), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona; Department of Pediatrics (X.Y.Y., P.S.), Mount Sinai Hospital, Toronto, Canada; Columbia University Irving Medical Center (D.D.), Department of Neurology, New York City; York Presbyterian Hospital (NYP) (D.D.), New York City; and Institute of Health (P.S.), Policy, Management and Evaluation, University of Toronto, Canada.
Xavier MontalbanFrom the Department of Medicine, (D.R., A.M., G.S.), University of Toronto, Ontario, Canada; St. Michael's Hospital (D.R., A.M., G.S.), Toronto, Ontario, Canada; Department of Medicine, (J.M.S.), McMaster University, Hamilton, Ontario, Canada; Department of Health Sciences (M.P.S.), Section of Biostatistics, University of Genova, Italy; IRCCS Ospedale Policlinico San Martino (M.P.S.), Genova, Italy; Department of Neurology and Cemcat (X.M.), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona; Department of Pediatrics (X.Y.Y., P.S.), Mount Sinai Hospital, Toronto, Canada; Columbia University Irving Medical Center (D.D.), Department of Neurology, New York City; York Presbyterian Hospital (NYP) (D.D.), New York City; and Institute of Health (P.S.), Policy, Management and Evaluation, University of Toronto, Canada.
Xiang Y YeFrom the Department of Medicine, (D.R., A.M., G.S.), University of Toronto, Ontario, Canada; St. Michael's Hospital (D.R., A.M., G.S.), Toronto, Ontario, Canada; Department of Medicine, (J.M.S.), McMaster University, Hamilton, Ontario, Canada; Department of Health Sciences (M.P.S.), Section of Biostatistics, University of Genova, Italy; IRCCS Ospedale Policlinico San Martino (M.P.S.), Genova, Italy; Department of Neurology and Cemcat (X.M.), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona; Department of Pediatrics (X.Y.Y., P.S.), Mount Sinai Hospital, Toronto, Canada; Columbia University Irving Medical Center (D.D.), Department of Neurology, New York City; York Presbyterian Hospital (NYP) (D.D.), New York City; and Institute of Health (P.S.), Policy, Management and Evaluation, University of Toronto, Canada.
Dina DababnehFrom the Department of Medicine, (D.R., A.M., G.S.), University of Toronto, Ontario, Canada; St. Michael's Hospital (D.R., A.M., G.S.), Toronto, Ontario, Canada; Department of Medicine, (J.M.S.), McMaster University, Hamilton, Ontario, Canada; Department of Health Sciences (M.P.S.), Section of Biostatistics, University of Genova, Italy; IRCCS Ospedale Policlinico San Martino (M.P.S.), Genova, Italy; Department of Neurology and Cemcat (X.M.), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona; Department of Pediatrics (X.Y.Y., P.S.), Mount Sinai Hospital, Toronto, Canada; Columbia University Irving Medical Center (D.D.), Department of Neurology, New York City; York Presbyterian Hospital (NYP) (D.D.), New York City; and Institute of Health (P.S.), Policy, Management and Evaluation, University of Toronto, Canada.
Alexandra MuccilliFrom the Department of Medicine, (D.R., A.M., G.S.), University of Toronto, Ontario, Canada; St. Michael's Hospital (D.R., A.M., G.S.), Toronto, Ontario, Canada; Department of Medicine, (J.M.S.), McMaster University, Hamilton, Ontario, Canada; Department of Health Sciences (M.P.S.), Section of Biostatistics, University of Genova, Italy; IRCCS Ospedale Policlinico San Martino (M.P.S.), Genova, Italy; Department of Neurology and Cemcat (X.M.), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona; Department of Pediatrics (X.Y.Y., P.S.), Mount Sinai Hospital, Toronto, Canada; Columbia University Irving Medical Center (D.D.), Department of Neurology, New York City; York Presbyterian Hospital (NYP) (D.D.), New York City; and Institute of Health (P.S.), Policy, Management and Evaluation, University of Toronto, Canada.
Georges SaabFrom the Department of Medicine, (D.R., A.M., G.S.), University of Toronto, Ontario, Canada; St. Michael's Hospital (D.R., A.M., G.S.), Toronto, Ontario, Canada; Department of Medicine, (J.M.S.), McMaster University, Hamilton, Ontario, Canada; Department of Health Sciences (M.P.S.), Section of Biostatistics, University of Genova, Italy; IRCCS Ospedale Policlinico San Martino (M.P.S.), Genova, Italy; Department of Neurology and Cemcat (X.M.), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona; Department of Pediatrics (X.Y.Y., P.S.), Mount Sinai Hospital, Toronto, Canada; Columbia University Irving Medical Center (D.D.), Department of Neurology, New York City; York Presbyterian Hospital (NYP) (D.D.), New York City; and Institute of Health (P.S.), Policy, Management and Evaluation, University of Toronto, Canada.
Prakesh ShahFrom the Department of Medicine, (D.R., A.M., G.S.), University of Toronto, Ontario, Canada; St. Michael's Hospital (D.R., A.M., G.S.), Toronto, Ontario, Canada; Department of Medicine, (J.M.S.), McMaster University, Hamilton, Ontario, Canada; Department of Health Sciences (M.P.S.), Section of Biostatistics, University of Genova, Italy; IRCCS Ospedale Policlinico San Martino (M.P.S.), Genova, Italy; Department of Neurology and Cemcat (X.M.), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona; Department of Pediatrics (X.Y.Y., P.S.), Mount Sinai Hospital, Toronto, Canada; Columbia University Irving Medical Center (D.D.), Department of Neurology, New York City; York Presbyterian Hospital (NYP) (D.D.), New York City; and Institute of Health (P.S.), Policy, Management and Evaluation, University of Toronto, Canada.
Universitat Autònoma de Barcelona · ESNewYork–Presbyterian Hospital · USOspedale Policlinico San Martino · ITMcMaster University · CASt. Michael's Hospital · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesNo evidence of disease activity (NEDA)-4 has been suggested as a treatment target for disease-modifying therapy (DMT) in relapsing-remitting multiple sclerosis (RRMS). However, the ability of NEDA-4 to discriminate long-term outcomes in MS and how its performance compares with NEDA-3 remain uncertain. We conducted a systematic review and meta-analysis to evaluate (1) the association between NEDA-4 and no long-term disability progression in MS and (2) the comparative performance of NEDA-3 and NEDA-4 in predicting no long-term disability progression.

methodsEnglish-language abstracts and manuscripts were systematically searched in MEDLINE, Embase, and the Cochrane databases from January 2006 to November 2021 and reviewed independently by 2 investigators. We selected studies that assessed NEDA-4 at 1 or 2 years after DMT start and had at least 4 years of follow-up for determination of no confirmed disability progression. We conducted a meta-analysis using random-effects model to determine the pooled odds ratio (OR) for no disability progression with NEDA-4 vs EDA-4. For the comparative analysis, we selected studies that evaluated both NEDA-3 and NEDA-4 with at least 4 years of follow-up and examined the difference in the association of NEDA-3 and NEDA-4 with no disability progression.

resultsFive studies of 1,000 patients (3 interferon beta and 2 fingolimod) met inclusion criteria for both objectives. The median duration of follow-up was 6 years (interquartile range: 4-6 years). The prevalence of NEDA-4 ranged from 4.2% to 13.9% on interferon beta therapy and 24.9% to 25.1% on fingolimod therapy. The pooled OR for no long-term confirmed disability progression with NEDA-4 vs EDA-4 was 2.14 (95% confidence interval: 1.36-3.37; I DISCUSSION: In patients with RRMS, NEDA-4 at 1-2 years was associated with 2 times higher odds of no long-term disability progression, at 6 years compared with EDA-4, but offered no advantage over NEDA-3.

Indexed as

Multiple SclerosisMultiple Sclerosis, Relapsing-RemittingDisease ProgressionFingolimod HydrochlorideHumansInterferon-betaFingolimod HydrochlorideInterferon-beta

Identifiers

PMID36224046
PMCPMC9558627
OpenAlexW4304807432

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.