Trial reportNeurology2015
No association of multiple sclerosis activity and progression with EBV or tobacco use in BENEFIT.
Open access · greenAbstract readRandomized Controlled Trial
In one paragraph
Trial report in Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
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.
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.
Who cites it
24 citing papers in PubMed, 63 citations in OpenAlex.
- Vitamin D, smoking, EBV, and long-term cognitive performance in MS: 11-year follow-up of BENEFIT.Neurology · 2020Trial
- Exploring the effect of vitamin DMultiple sclerosis (Houndmills, Basingstoke, England) · 2018Trial
- Article
- Antinuclear antibodies in early multiple sclerosis reflect systemic lupus erythematosus shared risk factors.Scientific reports · 2025Article
- The Effect of Smoking and Passive Exposure on Multiple Sclerosis and Correlation with IL17 & IL23 Levels.Noro psikiyatri arsivi · 2025Article
- Impact of tobacco smoking on disease-specific outcomes in common neurological disorders: A scoping review.Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia · 2024Article
- Environmental Influences on Risk and Disease Course in Pediatric Multiple Sclerosis.Seminars in pediatric neurology · 2023Article
- Markers of Epstein-Barr Virus Infection in Patients with Multiple Sclerosis.Microorganisms · 2023Review
- Epstein-Barr virus as a leading cause of multiple sclerosis: mechanisms and implications.Nature reviews. Neurology · 2023Review
- The Effect of Smoking on Long-term Gray Matter Atrophy and Clinical Disability in Patients with Relapsing-Remitting Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2022Article
- Body mass index as a predictor of MS activity and progression among participants in BENEFIT.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Article
- Evaluation of IL-1β and IL-6 Expression following EBNA-1 and BRLF-1 Peptide Treatment in Epstein-Barr Virus-Positive Multiple Sclerosis Patients.Intervirology · 2022Article
- Associations between smoking and walking, fatigue, depression, and health-related quality of life in persons with multiple sclerosis.Acta neurologica Belgica · 2021Article
- Evolution of antibody titres against Epstein-Barr virus and human herpesvirus 6A/B and expression of multiple sclerosis-associated retrovirus in the serum of pregnant multiple sclerosis patients.Scientific reports · 2021Article
- The role of Epstein-Barr virus in multiple sclerosis: from molecular pathophysiology toNeural regeneration research · 2019Review
- Emerging small-molecule treatments for multiple sclerosis: focus on B cells.F1000Research · 2019Review
- Metabolic Dysfunction and Peroxisome Proliferator-Activated Receptors (PPAR) in Multiple Sclerosis.International journal of molecular sciences · 2018Review
- Smoking at time of CIS increases the risk of clinically definite multiple sclerosis.Journal of neurology · 2018Article
- Diet, Gut Microbiota, and Vitamins D + A in Multiple Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Review
- Age-related small vessel disease: a potential contributor to neurodegeneration in multiple sclerosis.Brain pathology (Zurich, Switzerland) · 2017Review
Corrections and comments
- Commented on by
Authors and funding
14 authors at 1 institution in 1 country.
Kassandra L MungerFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany. kgorham@hsph.harvard.edu.
Kathryn C FitzgeraldFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
Mark S FreedmanFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
Hans-Peter HartungFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
David H MillerFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
Xavier MontalbánFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
Gilles EdanFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
Frederik BarkhofFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
Gustavo SuarezFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
Ernst-Wilhelm RadueFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
Rupert SandbrinkFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
Ludwig KapposFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
Christoph PohlFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
Alberto AscherioFrom the Departments of Nutrition (K.L.M., K.C.F., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Ottawa Hospital Research Institute (M.S.F.), Canada; Heinrich-Heine Universität (H.-P.H., R.S.), Düsseldorf, Germany; UCL Institute of Neurology (D.H.M.), London, UK; Hospital Universitari Vall d'Hebron (X.M.), Barcelona, Spain; CHU-Hôpital Pontchaillou (G.E.), Rennes, France; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Bayer HealthCare Pharmaceuticals (G.S.), Montville, NJ; Medical Image Analysis Center (E.-W.R.), and Neurology, Departments of Medicine, Clinical Research and Biomedicine (L.K., C.P.), University Hospital Basel, Switzerland; Bayer HealthCare (R.S.), Berlin; and Department of Neurology (C.P.), University Hospital of Bonn, Germany.
CIC Rennes · FR
Funding
Vitamin D, cigarette smoking, EBV infection and risk of MS progressionR01NS071082 · NINDS · HARVARD SCHOOL OF PUBLIC HEALTH · PI ASCHERIO, ALBERTO · 2010 to 2014
$695kNINDS NIH HHS NS071082
Abstract
objectiveTo evaluate whether Epstein-Barr virus (EBV) immunoglobulin G (IgG) antibody levels or tobacco use were associated with conversion to multiple sclerosis (MS) or MS progression/activity in patients presenting with clinically isolated syndrome (CIS).
methodsIn this prospective, longitudinal study, we measured EBV IgG antibody and cotinine (biomarker of tobacco use) levels at up to 4 time points (baseline, months 6, 12, and 24) among 468 participants with CIS enrolled in the BENEFIT (Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment) clinical trial. Outcomes included time to conversion to clinically definite or McDonald MS, number of relapses, Expanded Disability Status Scale (EDSS) changes, brain and T2 lesion volume changes, and number of new active lesions over 5 years. Analyses were adjusted for age, sex, treatment allocation, baseline serum 25-hydroxyvitamin D level, number of T2 lesions, body mass index, EDSS, steroid treatment, and CIS onset type.
resultsWe found no associations between any EBV IgG antibody or cotinine levels with conversion from CIS to MS or MS progression as measured by EDSS or activity clinically or on MRI. The relative risk of conversion from CIS to clinically definite MS was 1.14 (95% confidence interval 0.76-1.72) for the highest vs the lowest quintile of EBNA-1 IgG levels, and 0.96 (95% confidence interval 0.71-1.31) for cotinine levels >25 ng/mL vs <10.
conclusionsNeither increased levels of EBV IgG antibodies, including against EBNA-1, nor elevated cotinine levels indicative of tobacco use, were associated with an increased risk of CIS conversion to MS, or MS activity or progression over a 5-year follow-up.
Indexed as
Disease ProgressionAdultBiomarkersCotinineFemaleFollow-Up StudiesHerpesvirus 4, HumanHumansImmunoglobulin GLongitudinal StudiesMaleMultiple SclerosisProspective StudiesTobacco UseYoung AdultBiomarkersCotinineImmunoglobulin G
Identifiers
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.