Author Topic: (ECTRIMS) Lemtrada more effective than competing MS treatments  (Read 98 times)

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Offline agate

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(ECTRIMS) Lemtrada more effective than competing MS treatments
« on: September 25, 2016, 04:19:09 pm »
From MedPage Today, September 19, 2016:

Quote
Meeting Coverage

Registry Data: Lemtrada More Effective than Competing MS Tx

Better than fingolimod or interferon; comparable to natalizumab

by John Gever
Managing Editor, MedPage Today


LONDON -- Data from a large multiple sclerosis patient registry suggest that alemtuzumab (Lemtrada) is more effective in key efficacy measures than two other common drugs for MS and similar in efficacy to a third, a researcher said here.

In an analysis covering some 4,500 patients who had recently started alemtuzumab, fingolimod (Gilenya), interferon-beta-1a (Rebif, Avonex), or natalizumab (Tysabri), alemtuzumab was better than fingolimod and interferon for at least one of the following outcome measures: relapse risk, disability progression, or functional improvement, and was not less effective on any efficacy measure, reported Tomas Kalincik, MD, PhD, of the University of Melbourne in Australia.

And alemtuzumab and natalizumab were in a virtual dead heat for relapse prevention and reducing disability progression, Kalincik told attendees at an oral late-breaker session during the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.

There was only one outcome analyzed in the entire study for which alemtuzumab was inferior to another drug: natalizumab was more likely to produce an improvement in functional ability during the first year of treatment, though not in subsequent years.

However, the study, which was not specifically supported by any one drugmaker, had important limitations: it did not address safety at all, and the efficacy outcomes analyzed did not include effects on MRI-detected brain lesions.

Nevertheless, Robert Fox, MD, of the Cleveland Clinic, who was not involved with the analysis, said the data were important for informing clinicians about the real-world experience with these agents.

This type of analysis, he told MedPage Today, "allows us to compare drugs head-to-head that weren't compared in head to head trials, and probably won't be."

No major surprises were evident in the results, Fox said. Still, the data provide "more confidence about the emerging picture of alemtuzumab," which only gained approval less than 2 years ago.

He also pointed to a significant strength of the analysis: its use of propensity matching to make the observational study more of an "apples to apples" comparison, as he put it.

For the study Kalincik and colleagues drew on the MSbase database that currently includes some 41,000 MS patients in 35 countries treated for a cumulative 210,000 patient-years. Out of those, the researchers focused on 189 patients treated with alemtuzumab, 2,155 receiving interferon-beta-1a, 828 treated with fingolimod, and 1,160 treated with natalizumab.

To be included, patients had to meet the following criteria:

~Definite MS by standard diagnostic criteria
~New treatment with one of the four agents
~Baseline scores on the Expanded Disability Status Scale of no more than 5.5
~Age ≤65
~MS duration of <10 years
~At least one relapse in the past year
~At least 12 months of data prior to starting the drug, and at least 6 months of post-initiation follow-up
~Minimum of two post-baseline visits at least 6 months apart

Patients were also selected so that they could be matched with others with different treatment types according to clinical and demographic data (propensity matching).

Highlights of the comparisons cited by Kalincik were:

~Alemtuzumab vs interferon: superior for mitigating relapse activity and, in patients with highly active disease, disability progression; and improving functional ability
~Alemtuzumab vs fingolimod: superior for preventing relapses, otherwise comparable
~Alemtuzumab vs natalizumab: comparable for relapse activity and disability progression, natalizumab superior for early regression of disability

Kalincik said his group also performed numerous sensitivity analyses in which various parameters, such as definitions of pre-baseline disease activity, or specifying a different minimum follow-up interval, were altered. There was no important change in the overall results, he said.

_______________________
Kalincik disclosed relevant relationships with Roche, Genzyme, Novartis, Merck KGaA, Biogen, WebMD Global, Sanofi-Genzyme, Teva, and BioCSL. Co-authors disclosed multiple relevant relationships with industry.

http://www.medpagetoday.com/MeetingCoverage/ECTRIMS/60301?xid=nl_mpt_DHE_2016-09-19&eun=g345846d0r&pos=2
MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.

Offline agate

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Abstract for an article about this study (appearing in The Lancet), from PubMed, February 19, 2017:

Quote
Lancet Neurol. 2017 Feb 10.

Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study


Kalincik T1, Brown JW2, Robertson N3, Willis M3, Scolding N4, Rice CM4, Wilkins A4, Pearson O5, Ziemssen T6, Hutchinson M7, McGuigan C7, Jokubaitis V8, Spelman T8, Horakova D9, Havrdova E9, Trojano M10, Izquierdo G11, Lugaresi A12, Prat A13, Girard M13, Duquette P13, Grammond P14, Alroughani R15, Pucci E16, Sola P17, Hupperts R18, Lechner-Scott J19, Terzi M20, Van Pesch V21, Rozsa C22, Grand'Maison F23, Boz C24, Granella F25, Slee M26, Spitaleri D27, Olascoaga J28, Bergamaschi R29, Verheul F30, Vucic S31, McCombe P32, Hodgkinson S33, Sanchez-Menoyo JL34, Ampapa R35, Simo M36, Csepany T37, Ramo C38, Cristiano E39, Barnett M40, Butzkueven H41, Coles A42; MSBase Study Group.

Author information

1Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, Royal Melbourne Hospital, 300 Grattan St, Melbourne, 3050, Australia. Electronic address: tomas.kalincik@unimelb.edu.au.
2NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London Institute of Neurology, London, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
3Department of Neurology, Institute of Psychological Medicine and Clinical Neuroscience, Cardiff University, University Hospital of Wales, Cardiff, UK.
4Department of Neurology, Southmead Hospital, Westbury-on-Trym, Bristol, UK; School of Clinical Sciences, University of Bristol, Bristol, UK.
5Abertawe Bro Morgannwg University Local Health Board, Swansea, UK.
6Center of Clinical Neuroscience, Department of Neurology, MS Center Dresden, Dresden, Germany; Center of Clinical Neuroscience, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
7School of Medicine and Medical Sciences, University College Dublin, St Vincent's University Hospital, Dublin, Ireland.
8Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, Royal Melbourne Hospital, 300 Grattan St, Melbourne, 3050, Australia.
9Department of Neurology and Center of Clinical Neuroscience, General University Hospital and Charles University, Prague, Czech Republic.
10Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy.
11Hospital Universitario Virgen Macarena, Sevilla, Spain.
12Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
13Hopital Notre Dame, Montreal, QC, Canada; Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada; Université de Montreal, Montreal, QC, Canada.
14Centres intégrés de santé et de services sociaux de Chaudičre-Appalache, Levis, QC, Canada.
15Amiri Hospital, Qurtoba, Kuwait City, Kuwait.
16Azienda Sanitaria Unica Regionale Marche AV3, Macerata, Italy.
17Nuovo Ospedale Civile Sant'Agostino-Estense, Modena, Italy.
18Zuyderland Ziekenhuis, Sittard, Netherlands.
19University of Newcastle, Newcastle, NSW, Australia.
20Medical Faculty, 19 Mayis University, Kurupelit, Samsun, Turkey.
21Cliniques Universitaires Saint-Luc, Brussels, Belgium.
22Jahn Ferenc Teaching Hospital, Budapest, Hungary.
23Neuro Rive-Sud, Greenfield Park, QC, Canada.
24KTÜ Medical Faculty Farabi Hospital, Karadeniz Technical University, Trabzon, Turkey.
25University of Parma, Parma, Italy.
26Flinders University, Adelaide, SA, Australia.
27Azienda Ospedaliera San Giuseppe Moscati di Avellino, Avellino, Italy.
28Hospital Universitario Donostia, San Sebastián, Spain.
29C Mondino National Neurological Institute, Pavia, Italy.
30Groene Hart Ziekenhuis, Gouda, Netherlands.
31Westmead Hospital, Sydney, NSW, Australia.
32Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
33Liverpool Hospital, Sydney, NSW, Australia.
34Hospital de Galdakao-Usansolo, Galdakao, Spain.
35Nemocnice Jihlava, Jihlava, Czech Republic.
36Semmelweis University Budapest, Budapest, Hungary.
37University of Debrecen, Faculty of Medicine, Department of Neurology, Debrecen, Hungary.
38Hospital Germans Trias i Pujol, Badalona, Spain.
39Hospital Italiano, Buenos Aires, Argentina.
40Brain and Mind Centre, Camperdown, NSW, Australia.
41Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, Royal Melbourne Hospital, 300 Grattan St, Melbourne, 3050, Australia; Department of Neurology, Box Hill Hospital, Monash University, Melbourne, VIC, Australia.
42Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.


BACKGROUND:


Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years.

METHODS:


In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6ˇ5 or lower, and no more than 10 years since the first multiple sclerosis symptom.

The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models.

FINDINGS:

Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0ˇ19 [95% CI 0ˇ14-0ˇ23] vs 0ˇ53 [0ˇ46-0ˇ61], p<0ˇ0001) and fingolimod (0ˇ15 [0ˇ10-0ˇ20] vs 0ˇ34 [0ˇ26-0ˇ41], p<0ˇ0001), and was associated with a similar annualised relapse rate as natalizumab (0ˇ20 [0ˇ14-0ˇ26] vs 0ˇ19 [0ˇ15-0ˇ23], p=0ˇ78). For the disability outcomes, alemtuzumab was associated with similar probabilities of disability accumulation as interferon beta (hazard ratio
0ˇ66 [95% CI 0ˇ36-1ˇ22], p=0ˇ37), fingolimod (1ˇ27 [0ˇ60-2ˇ70], p=0ˇ67), and natalizumab (0ˇ81 [0ˇ47-1ˇ39], p=0ˇ60). Alemtuzumab was associated with  probabilities of disability improvement [that were similar to] interferon beta (0ˇ98 [0ˇ65-1ˇ49], p=0ˇ93) and fingolimod (0ˇ50 [0ˇ25-1ˇ01], p=0ˇ18), and a lower probability of disability improvement than natalizumab (0ˇ35 [0ˇ20-0ˇ59], p=0ˇ0006).

INTERPRETATION:

Alemtuzumab and natalizumab seem to have similar effects on annualised relapse rates in relapsing-remitting multiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly effective and viable immunotherapies for multiple sclerosis. Treatment decisions between alemtuzumab and natalizumab should be primarily governed by their safety profiles.

________________
FUNDING:
National Health and Medical Research Council, and the University of Melbourne.

https://www.ncbi.nlm.nih.gov/pubmed/28209331
MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.

 

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