Evidence map›Paper›PMID 34165694›Full record

ArticleNeurology and therapy2021

Confirmed 6-Month Disability Improvement and Worsening Correlate with Long-term Disability Outcomes in Alemtuzumab-Treated Patients with Multiple Sclerosis: Post Hoc Analysis of the CARE-MS Studies.

Samuel F Hunter, Rany A Aburashed, Raed Alroughani, Andrew Chan, Dominique Dive, Sara Eichau, Daniel Kantor, Ho Jin Kim, Jan Lycke, Richard A L Macdonell and 9 more

4 registry-linked trialsAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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.

NCT00530348 phase3completednot on this map

A Phase 3 Randomized, Rater-Blinded Study Comparing Two Annual Cycles of Intravenous Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta-1a (Rebif®) in Treatment-Naïve Patients With Relapsing-Remitting Multiple Sclerosis

TypeinterventionalSponsorGenzyme, a Sanofi CompanyRan2007 to 2011Enrolled581ConditionsMultiple Sclerosis, Relapsing-RemittingArmsAlemtuzumab, Interferon beta-1a
NCT00548405 phase3completednot on this map

A Phase 3, Randomized, Rater- and Dose-Blinded Study Comparing Two Annual Cycles of Intravenous Low- and High-Dose Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta 1a (Rebif®) in Patients With Relapsing Remitting Multiple Sclerosis Who Have Relapsed On Therapy

TypeinterventionalSponsorGenzyme, a Sanofi CompanyRan2007 to 2011Enrolled840ConditionsMultiple Sclerosis, Relapsing-RemittingArmsAlemtuzumab 12 mg, Alemtuzumab 24 mg, Interferon beta-1a
NCT00930553 phase3completednot on this map

An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab

TypeinterventionalSponsorGenzyme, a Sanofi CompanyRan2009 to 2016Enrolled1,314ConditionsMultiple Sclerosis, Relapsing-RemittingArmsalemtuzumab
NCT02255656 phase4completednot on this map

A Long-term Follow-up Study for Multiple Sclerosis Patients Who Have Completed the Alemtuzumab Extension Study (CAMMS03409)

TypeinterventionalSponsorGenzyme, a Sanofi CompanyRan2015 to 2020Enrolled1,062ConditionsRelapsing Remitting Multiple SclerosisArmsalemtuzumab GZ402673
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

19 authors.

Samuel F HunterAdvanced Neurosciences Institute, 101 Forrest Crossing Blvd., Franklin, TN, 37064, USA. sfhunter@neurosci.us.ORCID http://orcid.org/0000-0002-0542-1176
Rany A AburashedInstitute for Neurosciences and Multiple Sclerosis, Owosso, MI, USA.
Raed AlroughaniDivision of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait.
Andrew ChanDepartment of Neurology, Inselspital Bern, Bern University Hospital, University of Bern, Bern, Switzerland.
Dominique DiveUniversity Hospital Centre of Liège, Liège, Belgium.
Sara EichauHospital Universitario Virgen Macarena, Seville, Spain.
Daniel KantorFlorida Atlantic University, Boca Raton, FL, USA.
Ho Jin KimResearch Institute and Hospital of National Cancer Center, Goyang, Korea.
Jan LyckeDepartment of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Richard A L MacdonellAustin Health and Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
Carlo PozzilliDepartment of Human Neuroscience, Sapienza University, Rome, Italy.
Thomas ScottAllegheny General Hospital, Drexel University College of Medicine, Pittsburgh, PA, USA.
Basil SharrackSheffield NIHR Neuroscience BRC and Sheffield Teaching Hospitals, Sheffield, UK.
Heinz WiendlUniversity of Münster, Münster, Germany.
Luke ChungSanofi, Cambridge, MA, USA.
Nadia DaizadehSanofi, Cambridge, MA, USA.
Darren P BakerSanofi, Cambridge, MA, USA.
Patrick VermerschUniv. Lille, INSERM U1172 LilNCog, CHU Lille, FHU Precise, Lille, France.
CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ Investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionIn the 2-year CARE-MS trials (NCT00530348; NCT00548405) in patients with relapsing-remitting multiple sclerosis, alemtuzumab showed superior efficacy versus subcutaneous interferon beta-1a. Efficacy was maintained in two consecutive extensions (NCT00930553; NCT02255656). This post hoc analysis compared disability outcomes over 9 years among alemtuzumab-treated patients according to whether they experienced confirmed disability improvement (CDI) or worsening (CDW) or neither CDI nor CDW.

methodsCARE-MS patients were randomized to receive two alemtuzumab courses (12 mg/day; 5 days at baseline; 3 days at 12 months), with additional as-needed 3-day courses in the extensions. CDI or CDW were defined as ≥ 1.0-point decrease or increase, respectively, in Expanded Disability Status Scale (EDSS) score from core study baseline confirmed over 6 months, assessed in patients with baseline EDSS score ≥ 2.0. Improved or stable EDSS scores were defined as ≥ 1-point decrease or ≤ 0.5-point change (either direction), respectively, from core study baseline. Functional systems (FS) scores were also assessed.

resultsOf 511 eligible patients, 43% experienced CDI and 34% experienced CDW at any time through year 9 (patients experiencing both CDI and CDW were counted in each individual group); 29% experienced neither CDI nor CDW. At year 9, patients with CDI had a -0.58-point mean EDSS score change from baseline; 88% had stable or improved EDSS scores. Improvements occurred across all FS, primarily in sensory, pyramidal, and cerebellar domains. Patients with CDW had a +1.71-point mean EDSS score change; 16% had stable or improved EDSS scores. Patients with neither CDI nor CDW had a -0.10-point mean EDSS score change; 98% had stable or improved EDSS scores.

conclusionCDI achievement at any point during the CARE-MS studies was associated with improved disability at year 9, highlighting the potential of alemtuzumab to change the multiple sclerosis course. Conversely, CDW at any point was associated with worsened disability at year 9.

Indexed as

AlemtuzumabConfirmed disability improvementConfirmed disability worseningDisease-modifying therapyExpanded Disability Status ScaleFunctional systemsMultiple sclerosis

Identifiers

PMID34165694
PMCPMC8571457

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Registered trials

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.