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Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy.
J Neurol Neurosurg Psychiatry. 2015 Feb; 86(2):208-15.JN

Abstract

OBJECTIVES

Alemtuzumab is a newly licensed treatment of active relapsing-remitting multiple sclerosis (RRMS) in Europe, which in phase II and III studies demonstrated superior efficacy over β-interferon in reducing disability progression over 2-3 years. In this observational cohort study, we sought to describe our longer-term experience of the efficacy and safety of alemtuzumab in active RRMS.

METHODS

Clinical and laboratory data including serial Expanded Disability Status Scale (EDSS) assessments, from all 87 patients treated with alemtuzumab on investigator-led studies in Cambridge, UK, from 1999 to 2012, were collected. The occurrence of adverse events including secondary autoimmunity, malignancy and death, and pregnancy outcomes was recorded. Baseline variables including age, disease duration and relapse rate were compared in univariate and logistic regression analyses between groups with different disability outcomes.

RESULTS

Over a median 7-year follow-up (range 33-144 months), most patients (52%) required just two cycles of alemtuzumab. In the remaining patients, relapses triggered re-treatment to a total of three cycles (36%), four cycles (8%) or five cycles (1%). Using a 6-month sustained accumulation of disability definition, 59/87 (67.8%) of patients had an improved or unchanged disability compared with baseline. By an area under the curve analysis, 52/87 (59.8%) patients had an overall improvement or stabilisation of disability. Higher baseline relapse rate was associated with worse long-term disability outcomes, with trends for longer disease duration and older age at first treatment. Secondary autoimmunity was the most frequent adverse event occurring in 41/86 (47.7%) patients, most commonly involving the thyroid gland.

CONCLUSIONS

Alemtuzumab is associated with disease stabilisation in the majority of patients with highly active RRMS over an average seven-year follow-up. No new safety concerns arose over this extended follow-up.

Authors+Show Affiliations

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.Department of Neurology, Beaumont Hospital, Dublin, Ireland.Sydney Institute of Emerging Infectious Diseases and Biosecurity, University of Sydney, Sydney, Australia.Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.Institute of Psychological Medicine and Clinical Neuroscience, Cardiff University, Cardiff, Wales, UK.Institute of Psychological Medicine and Clinical Neuroscience, Cardiff University, Cardiff, Wales, UK.Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.Biostatistics Unit, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Pub Type(s)

Clinical Trial
Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24849515

Citation

Tuohy, Orla, et al. "Alemtuzumab Treatment of Multiple Sclerosis: Long-term Safety and Efficacy." Journal of Neurology, Neurosurgery, and Psychiatry, vol. 86, no. 2, 2015, pp. 208-15.
Tuohy O, Costelloe L, Hill-Cawthorne G, et al. Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy. J Neurol Neurosurg Psychiatry. 2015;86(2):208-15.
Tuohy, O., Costelloe, L., Hill-Cawthorne, G., Bjornson, I., Harding, K., Robertson, N., May, K., Button, T., Azzopardi, L., Kousin-Ezewu, O., Fahey, M. T., Jones, J., Compston, D. A., & Coles, A. (2015). Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy. Journal of Neurology, Neurosurgery, and Psychiatry, 86(2), 208-15. https://doi.org/10.1136/jnnp-2014-307721
Tuohy O, et al. Alemtuzumab Treatment of Multiple Sclerosis: Long-term Safety and Efficacy. J Neurol Neurosurg Psychiatry. 2015;86(2):208-15. PubMed PMID: 24849515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy. AU - Tuohy,Orla, AU - Costelloe,Lisa, AU - Hill-Cawthorne,Grant, AU - Bjornson,Ingunn, AU - Harding,Katharine, AU - Robertson,Neil, AU - May,Karen, AU - Button,Tom, AU - Azzopardi,Laura, AU - Kousin-Ezewu,Onajite, AU - Fahey,Michael T, AU - Jones,Joanne, AU - Compston,D Alastair S, AU - Coles,Alasdair, Y1 - 2014/05/21/ PY - 2014/5/23/entrez PY - 2014/5/23/pubmed PY - 2015/4/2/medline KW - Immunology KW - Multiple Sclerosis SP - 208 EP - 15 JF - Journal of neurology, neurosurgery, and psychiatry JO - J Neurol Neurosurg Psychiatry VL - 86 IS - 2 N2 - OBJECTIVES: Alemtuzumab is a newly licensed treatment of active relapsing-remitting multiple sclerosis (RRMS) in Europe, which in phase II and III studies demonstrated superior efficacy over β-interferon in reducing disability progression over 2-3 years. In this observational cohort study, we sought to describe our longer-term experience of the efficacy and safety of alemtuzumab in active RRMS. METHODS: Clinical and laboratory data including serial Expanded Disability Status Scale (EDSS) assessments, from all 87 patients treated with alemtuzumab on investigator-led studies in Cambridge, UK, from 1999 to 2012, were collected. The occurrence of adverse events including secondary autoimmunity, malignancy and death, and pregnancy outcomes was recorded. Baseline variables including age, disease duration and relapse rate were compared in univariate and logistic regression analyses between groups with different disability outcomes. RESULTS: Over a median 7-year follow-up (range 33-144 months), most patients (52%) required just two cycles of alemtuzumab. In the remaining patients, relapses triggered re-treatment to a total of three cycles (36%), four cycles (8%) or five cycles (1%). Using a 6-month sustained accumulation of disability definition, 59/87 (67.8%) of patients had an improved or unchanged disability compared with baseline. By an area under the curve analysis, 52/87 (59.8%) patients had an overall improvement or stabilisation of disability. Higher baseline relapse rate was associated with worse long-term disability outcomes, with trends for longer disease duration and older age at first treatment. Secondary autoimmunity was the most frequent adverse event occurring in 41/86 (47.7%) patients, most commonly involving the thyroid gland. CONCLUSIONS: Alemtuzumab is associated with disease stabilisation in the majority of patients with highly active RRMS over an average seven-year follow-up. No new safety concerns arose over this extended follow-up. SN - 1468-330X UR - https://www.unboundmedicine.com/medline/citation/24849515/Alemtuzumab_treatment_of_multiple_sclerosis:_long_term_safety_and_efficacy_ L2 - https://jnnp.bmj.com/lookup/pmidlookup?view=long&pmid=24849515 DB - PRIME DP - Unbound Medicine ER -