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October 29, 2019; 93 (18) Views & Reviews

Head-to-head drug comparisons in multiple sclerosis

Urgent action needed

View ORCID ProfileCarmen Tur, View ORCID ProfileTomas Kalincik, Jiwon Oh, Maria P. Sormani, Mar Tintoré, Helmut Butzkueven, Xavier Montalban
First published October 7, 2019, DOI: https://doi.org/10.1212/WNL.0000000000008319
Carmen Tur
From the Department of Neuroinflammation (C.T.), Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, University College London, UK; Neurology/Neuroimmunology Department (C.T., M.T., X.M.), Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain; Department of Medicine (T.K.), CORe, University of Melbourne, Australia; Department of Neurology (T.K.), Royal Melbourne Hospital, Australia; Division of Neurology (J.O., X.M.), University of Toronto, St Michael's Hospital, Canada; Department of Health Sciences (DISSAL) (M.P.S.), University of Genoa, Italy; and Central Clinical School (H.B.), Alfred Centre, Monash University, Melbourne, Australia.
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Tomas Kalincik
From the Department of Neuroinflammation (C.T.), Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, University College London, UK; Neurology/Neuroimmunology Department (C.T., M.T., X.M.), Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain; Department of Medicine (T.K.), CORe, University of Melbourne, Australia; Department of Neurology (T.K.), Royal Melbourne Hospital, Australia; Division of Neurology (J.O., X.M.), University of Toronto, St Michael's Hospital, Canada; Department of Health Sciences (DISSAL) (M.P.S.), University of Genoa, Italy; and Central Clinical School (H.B.), Alfred Centre, Monash University, Melbourne, Australia.
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Jiwon Oh
From the Department of Neuroinflammation (C.T.), Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, University College London, UK; Neurology/Neuroimmunology Department (C.T., M.T., X.M.), Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain; Department of Medicine (T.K.), CORe, University of Melbourne, Australia; Department of Neurology (T.K.), Royal Melbourne Hospital, Australia; Division of Neurology (J.O., X.M.), University of Toronto, St Michael's Hospital, Canada; Department of Health Sciences (DISSAL) (M.P.S.), University of Genoa, Italy; and Central Clinical School (H.B.), Alfred Centre, Monash University, Melbourne, Australia.
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Maria P. Sormani
From the Department of Neuroinflammation (C.T.), Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, University College London, UK; Neurology/Neuroimmunology Department (C.T., M.T., X.M.), Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain; Department of Medicine (T.K.), CORe, University of Melbourne, Australia; Department of Neurology (T.K.), Royal Melbourne Hospital, Australia; Division of Neurology (J.O., X.M.), University of Toronto, St Michael's Hospital, Canada; Department of Health Sciences (DISSAL) (M.P.S.), University of Genoa, Italy; and Central Clinical School (H.B.), Alfred Centre, Monash University, Melbourne, Australia.
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Mar Tintoré
From the Department of Neuroinflammation (C.T.), Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, University College London, UK; Neurology/Neuroimmunology Department (C.T., M.T., X.M.), Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain; Department of Medicine (T.K.), CORe, University of Melbourne, Australia; Department of Neurology (T.K.), Royal Melbourne Hospital, Australia; Division of Neurology (J.O., X.M.), University of Toronto, St Michael's Hospital, Canada; Department of Health Sciences (DISSAL) (M.P.S.), University of Genoa, Italy; and Central Clinical School (H.B.), Alfred Centre, Monash University, Melbourne, Australia.
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Helmut Butzkueven
From the Department of Neuroinflammation (C.T.), Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, University College London, UK; Neurology/Neuroimmunology Department (C.T., M.T., X.M.), Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain; Department of Medicine (T.K.), CORe, University of Melbourne, Australia; Department of Neurology (T.K.), Royal Melbourne Hospital, Australia; Division of Neurology (J.O., X.M.), University of Toronto, St Michael's Hospital, Canada; Department of Health Sciences (DISSAL) (M.P.S.), University of Genoa, Italy; and Central Clinical School (H.B.), Alfred Centre, Monash University, Melbourne, Australia.
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Xavier Montalban
From the Department of Neuroinflammation (C.T.), Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, University College London, UK; Neurology/Neuroimmunology Department (C.T., M.T., X.M.), Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain; Department of Medicine (T.K.), CORe, University of Melbourne, Australia; Department of Neurology (T.K.), Royal Melbourne Hospital, Australia; Division of Neurology (J.O., X.M.), University of Toronto, St Michael's Hospital, Canada; Department of Health Sciences (DISSAL) (M.P.S.), University of Genoa, Italy; and Central Clinical School (H.B.), Alfred Centre, Monash University, Melbourne, Australia.
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Full PDF
Citation
Head-to-head drug comparisons in multiple sclerosis
Urgent action needed
Carmen Tur, Tomas Kalincik, Jiwon Oh, Maria P. Sormani, Mar Tintoré, Helmut Butzkueven, Xavier Montalban
Neurology Oct 2019, 93 (18) 793-809; DOI: 10.1212/WNL.0000000000008319

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Abstract

Disease-modifying drugs are changing the natural history of multiple sclerosis (MS). However, currently available clinical trial data are insufficient to develop accurate personalized treatment algorithms to assign the best possible treatment to each person with MS according to disease features, treatment history, and comorbidities. Such accurate algorithms would require the presence of numerous head-to-head trials of long duration, which is virtually impossible, given the economic costs, required time, and difficulties with attrition. Thus, efforts are being made to compare relative treatment efficacy through observational designs, using large multicenter prospective cohorts or “big MS data,” and network meta-analyses. Although such studies can yield useful information, they are liable to biases and their results should be confirmed in other study populations, including smaller, single-center cohorts, where some of these biases can be minimized. In this View article, we analyze the potential benefits and biases of all these strategies alternative to head-to-head trials in MS. Finally, we propose the combination of all these types of studies to obtain reliable head-to-head drug comparisons in the absence of randomized designs.

Glossary

CIS=
clinically isolated syndrome;
DMD=
disease-modifying drug;
MS=
multiple sclerosis;
PANGAEA=
Post-Authorization Non-interventional German Safety of Gilenya;
PPMS=
primary progressive multiple sclerosis;
RRMS=
relapsing-remitting MS;
TOP=
Tysabri Observational Program

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received October 12, 2018.
  • Accepted in final form August 8, 2019.
  • © 2019 American Academy of Neurology
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  • Article
    • Abstract
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    • Network meta-analyses, their benefits, and potential biases
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