Evidence map›Paper›PMID 32554770›Full record

Trial reportNeurology2020

Comorbidity is associated with disease activity in MS: Findings from the CombiRx trial.

Amber Salter, Kaarina Kowalec, Kathryn C Fitzgerald, Gary Cutter, Ruth Ann Marrie

Open access · greenAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Review
  6. Comorbidity and modifiable risk factors in multiple sclerosis.Therapeutic advances in neurological disorders · 2026
    Review
  7. Observational
  8. Article
  9. Observational
  10. Article
  11. Linking Pathogenesis to Fall Risk in Multiple Sclerosis.Archives of internal medicine research · 2025
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Correlates and trajectories of relapses in relapsing-remitting multiple sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
    Article
  18. Article
  19. Review
  20. The Barancik lecture: Comorbidity in multiple sclerosis-Looking backward, looking forward.Multiple sclerosis (Houndmills, Basingstoke, England) · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 3 countries.

Amber SalterFrom the Department of Biostatistics (A.S.), Washington University in St. Louis, MO; College of Pharmacy (K.K.), and Departments of Internal Medicine and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institutet, Solna, Sweden; Department of Neurology (K.C.F.), Johns Hopkins School of Medicine, Baltimore, MD; and Department of Biostatistics (G.C.), University of Alabama in Birmingham School of Public Health. amber@wustl.edu.ORCID 0000-0002-1088-110X
Kaarina KowalecFrom the Department of Biostatistics (A.S.), Washington University in St. Louis, MO; College of Pharmacy (K.K.), and Departments of Internal Medicine and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institutet, Solna, Sweden; Department of Neurology (K.C.F.), Johns Hopkins School of Medicine, Baltimore, MD; and Department of Biostatistics (G.C.), University of Alabama in Birmingham School of Public Health.
Kathryn C FitzgeraldFrom the Department of Biostatistics (A.S.), Washington University in St. Louis, MO; College of Pharmacy (K.K.), and Departments of Internal Medicine and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institutet, Solna, Sweden; Department of Neurology (K.C.F.), Johns Hopkins School of Medicine, Baltimore, MD; and Department of Biostatistics (G.C.), University of Alabama in Birmingham School of Public Health.
Gary CutterFrom the Department of Biostatistics (A.S.), Washington University in St. Louis, MO; College of Pharmacy (K.K.), and Departments of Internal Medicine and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institutet, Solna, Sweden; Department of Neurology (K.C.F.), Johns Hopkins School of Medicine, Baltimore, MD; and Department of Biostatistics (G.C.), University of Alabama in Birmingham School of Public Health.
Ruth Ann MarrieFrom the Department of Biostatistics (A.S.), Washington University in St. Louis, MO; College of Pharmacy (K.K.), and Departments of Internal Medicine and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institutet, Solna, Sweden; Department of Neurology (K.C.F.), Johns Hopkins School of Medicine, Baltimore, MD; and Department of Biostatistics (G.C.), University of Alabama in Birmingham School of Public Health.
Johns Hopkins University · US

Funding

Circadian Rhythms and Sleep, Structural Neuroimaging and Depression in People with Multiple SclerosisK01MH121582 · NIMH · JOHNS HOPKINS UNIVERSITY · PI FITZGERALD, KATHRYN C. · 2019 to 2022
$675k
6 · The paper itself

Abstract

objectiveTo determine whether comorbidity is associated with clinical (relapses, disability worsening) and MRI outcomes in multiple sclerosis (MS) by conducting a secondary analysis of the CombiRx clinical trial.

methodsCombiRx compared interferon beta-1a, glatiramer acetate, and the combination of these agents. For participants eligible for evaluation of 6-month confirmed disability worsening, we used medical history, concomitant medications, and adverse events to ascertain comorbidity status. Comorbid conditions evaluated included hypertension, dyslipidemia, diabetes mellitus, depression, anxiety disorders, and migraine. Clinical outcomes included disease activity consisting of protocol-defined relapses, disability worsening, and MRI activity. We summarized the prevalence of these comorbid conditions and their association with disease activity and its components using multivariable Cox regression.

resultsOf the 1,008 participants randomized, 959 (95.1%) were eligible for assessment of 6-month disability worsening; for this subgroup, the median length of follow-up was 3.4 years (range 0.5-6.9 years). Overall, 55.1% of participants had ≥1 comorbidity at enrollment. After adjustment, anxiety (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.01-1.55) and dyslipidemia (HR 1.32, 95% CI 1.01-1.72) were associated with an increased hazard of any disease activity, while migraine (HR 0.80, 95% CI 0.67-0.97) was associated with a decreased hazard.

conclusionsIn this large trial population with rigorously obtained outcomes, comorbid conditions were common among participants and influenced disease outcomes, including relapses. The comorbidity burden of clinical trial participants with MS may be an important factor in the outcome of clinical trials. Additional investigations of the impact of comorbidity on clinical trial outcomes and response to disease-modifying therapies are warranted.

Indexed as

Treatment OutcomeAdultDepressionDiabetes MellitusDisease ProgressionDouble-Blind MethodFemaleGlatiramer AcetateHumansHyperlipidemiasHypertensionImmunosuppressive AgentsInterferon beta-1aMaleMiddle AgedMigraine DisordersGlatiramer AcetateImmunosuppressive AgentsInterferon beta-1a

Identifiers

PMID32554770
PMCPMC9629214
OpenAlexW3036820413

What Socratic 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 Socratic graph.