Alemtuzumab for multiple sclerosis
Information
- DOI:
- https://doi.org/10.1002/14651858.CD011203.pub3Copy DOI
- Database:
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- Cochrane Database of Systematic Reviews
- Version published:
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- 05 June 2023see what's new
- Type:
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- Intervention
- Stage:
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- Review
- Cochrane Editorial Group:
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Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group
- Copyright:
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- Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Authors
Contributions of authors
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ALM was the contact person who coordinated the contributions from coauthors and was responsible for the final draft of the review update.
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RR, RLP, and ALM worked on study selection, data extraction, risk‐of‐bias assessment, and GRADE assessment.
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RR and RLP performed data analyses.
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RR, RLP, ALM, and MRT wrote the review update.
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RR, RLP, ALM, and MRT responded to the clinical comments of the referees.
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RR, RLP, ALM, and MRT answered the methodologic and statistical questions of the referees.
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RR, RLP, ALM, and MRT will be in charge of further updating.
Sources of support
Internal sources
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New Source of support, Other
None.
External sources
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New Source of support, Other
None.
Declarations of interest
ALM: none known.
MRT: none known.
RLP: none known.
RR: none known.
Acknowledgements
For this update, the authors would like to thank:
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Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System, especially Ben Ridley (Managing Editor) for all the support along the updating process.
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Maria Domeica Camerlingo (Information Specialist) for her kind help in running searches.
Editorial and peer‐reviewer contributions
The following people conducted the editorial process for this review update.
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Sign‐off Editor (final editorial decision): Robert Boyle, Imperial College London.
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Managing Editor (provided editorial guidance to authors, edited the article): Joey Kwong, Cochrane Central Editorial Service.
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Editorial Assistant (conducted editorial policy checks, selected peer reviewers, collated peer‐reviewer comments, supported editorial team): Sara Hales‐Brittain, Cochrane Central Editorial Service.
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Copy Editor (copy editing and production): Anne Lawson, Central Production Service, Cochrane.
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Peer‐reviewers (provided comments and recommended an editorial decision): Dennis Bourdette, Department of Neurology, Oregon Health & Science University (clinical/content review); Hans‐Peter Hartung, Department of Neurology, Heinrich‐Heine‐University Düsseldorf, Germany; Brain and Mind Center, University of Sydney, Australia; Department of Neurology, Palacky University Olomouc, Czech Republic (clinical/content review); Ivan Perez‐Neri, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez (consumer review), Nuala Livingstone, Cochrane Evidence Production and Methods Directorate (methods review). An additional peer reviewer provided search peer review, but chose not to be publicly acknowledged.
Version history
| Published | Title | Stage | Authors | Version |
| 2023 Jun 05 | Alemtuzumab for multiple sclerosis | Review | Rachel Riera, Maria Regina Torloni, Ana Luiza C Martimbianco, Rafael L Pacheco | |
| 2016 Apr 15 | Alemtuzumab for multiple sclerosis | Review | Rachel Riera, Gustavo JM Porfírio, Maria R Torloni | |
| 2014 Jul 08 | Alemtuzumab for multiple sclerosis | Protocol | Rachel Riera, Gustavo Porfirio, Cristine R Migliorini, Maria R Torloni | |
Differences between protocol and review
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One of the coauthors of the protocol, for unforeseen reasons, could no longer collaborate on the review and asked to be excluded from authoring.
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At the protocol stage, we planned the following subgroup analyses for disease type (relapsing–remitting, primary‐progressive, secondary‐progressive or progressive‐relapsing) and disability at baseline (EDSS scores 5.0 or less or 5.5 or greater), but due to lack of sufficient data these additional analyses were not conducted.
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At the protocol stage, we planned to conduct subgroup analyses for different doses and regimens of alemtuzumab (12 mg or 24 mg). However, it would not be clinically reasonable to pool such different schemes as main analyses. So, we maintained separated main analyses for different doses or regimens, rather than as subgroup analyses.
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We did not plan the subgroup analysis taking into account previous treatment (treatment naive versus previously treated participants) at the protocol stage but as it seemed to be clinically relevant, we performed it when there were sufficient data.
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In the protocol, we proposed to assess 'number of participants without relapse' and 'number of progression‐free participants' as primary outcomes. However, we found available data only for 'relapse‐free survival' and 'sustained disease progression‐free survival'. We decided to use both measures in the final review, since they are the opposite of the same measurement and this change would not influence neither the effect of the intervention nor its interpretation.
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In the protocol, we proposed to assess the 'Changes in the number of MRI T2‐ and T1‐weighted lesions after treatment'. However, we discussed among the review authors and peer reviewers whether 'Patients with new or enlarging T2‐hyperintense lesions' could be more relevant for decision‐making, since it comprises the total area of all MS lesions. Moreover, since this is a dichotomous measure, it could be easier for physicians and consumers to interpret. We considered this outcome sufficiently relevant (even though it is a secondary outcome) to warrant a change in its presentation regardless of the tool/measurement used to assess it. Therefore, we decided to change the way it was measured, leading to the presentation of the existing results.
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We planned the following outcomes for the summary of findings tables at the protocol stage, but we did not include them due to lack of data: 1‐point EDSS increase confirmed at three months' follow‐up and quality of life. We included the outcome dropout rate in the summary of findings tables.
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In the protocol, we did not predefine the use of the hazard ratio to estimate the effect size of time‐to‐event outcomes. We added this information in the final version of the review because we used this measure for the outcomes of relapse‐free survival and sustained disease progression.
Differences between original review and current update
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The search for this update did not retrieve any new studies, and we included the same three RCTs from the first version of the review. Any changes we performed were related to methodologic advances and new recommendations in Cochrane guidance.
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In this updated version, we added a second summary of findings table with results from the comparison alemtuzumab 24 mg compared to interferon beta‐1a. We also added the follow‐up 36 months to the original summary of findings table.
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We revised the certainty of evidence appraisal for the comparison alemtuzumab 12 mg compared to interferon beta‐1a at 24 months, which led to it being further downgraded for some outcomes. We judged a need to better reflect uncertainties related to the risk of bias and inconsistency in the outcome results. The updated assessment followed the most recent GRADE guidelines, and Chapter 14 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021).
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The new GRADE assessment resulted in a downgrade of the certainty of evidence from moderate to low for the outcomes relapse‐free survival, sustained disease progression‐free survival, and number of participants with at least one adverse event (following further considerations of risk of bias). We downgraded the outcome number of participants with new or enlarging T2‐hyperintense lesions from moderate to very low (following further considerations of risk of bias and inconsistency).
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We reworded the certainty of evidence presentation and estimates of results following the most recent guidance from Chapter 15 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021).
