Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy
Open accessAbstract
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.
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Thyroid dysfunction frequently occurs as an autoimmune complication of immune reconstitution therapy, especially in individuals with multiple sclerosis treated with alemtuzumab.
“Thyroid dysfunction (TD) frequently occurs as an autoimmune complication of immune reconstitution therapy (IRT), especially in individuals with multiple sclerosis treated with alemtuzumab, a pan-lymphocyte depleting drug with subsequent recovery of immune cell numbers.”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [14]
In alemtuzumab-induced TD, autoantibodies against the thyrotropin receptor (TRAb) play a major role.
“In alemtuzumab-induced TD, the autoantibodies against the thyrotropin receptor (TRAb) play a major role”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [14]
Around one-third of patients with no previous history of thyroid disorders will develop TD following alemtuzumab.
“Around one-third of patients with no previous history of thyroid disorders will develop TD following alemtuzumab [12-14]”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [14]
Thyroid dysfunction onset after alemtuzumab for MS has been described at 16-23 months (range 2-107 months) after the last treatment.
“The TD onset has been described 32 months (average) or 16-23 months (range 2-107 months) after the first and last alemtuzumab treatment for MS, respectively [12-14]”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [14]
Thyroid dysfunction onset after alemtuzumab for MS has been described at an average of 32 months after the first treatment.
“The TD onset has been described 32 months (average) or 16-23 months (range 2-107 months) after the first and last alemtuzumab treatment for MS, respectively [12-14]”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [14]
In contrast, requirements for RAI or surgery were lower than expected in conventional Graves' disease in some reports; 14% and 27%.
“In contrast, requirements for RAI or surgery were lower than expected in conventional GD in some reports; 14% [14], 27% [77].”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [14]
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Alemtuzumab-Induced Thyroid Dysfunction Exhibits Distinctive Clinical and Immunological Features
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Self-citation
- Authors
- 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. S., & Coles, A.
- Affiliations
- University of Cambridge (GB)
- Beaumont Hospital (IE)
- The University of Sydney (AU)
- Cardiff University (GB)
- Monash University (AU)
- Corresponding author
- Tuohy, O.
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2014-05-21
- Volume
- 86
- Issue
- 2
- Pages
- 208-215
- ISSN
- 0022-3050 (ISSN-L)
- OpenAlex
- W2121127042
- Cited by
- 238
- References
- 21
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 10 · 2023: 13 · 2022: 9 · 2021: 25 · 2020: 23 · 2019: 28 · 2018: 37 · 2017: 22 · 2016: 27 · 2015: 28 · 2014: 5
- FWCI
- 20.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Funders
- Wellcome Trust (105924/Z/14/Z)
- National Institute for Health and Care Research (CL-2008-14-004, NF-SI-0508-10335)
- Medical Research Council (MR/L010305/1)
- NIHR Cambridge Biomedical Research Centre
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- alemtuzumab, relapsing-remitting multiple sclerosis, long-term safety, disability progression, secondary autoimmunity, thyroid autoimmunity, relapse rate, disease duration, adverse events, cancer, pregnancy outcomes
- MeSH terms
- Alemtuzumab, Adolescent, Adult, Anti-Inflammatory Agents, Non-Steroidal, Disability Evaluation, Female, Follow-Up Studies, Humans, Male, Middle Aged, Recurrence, Cohort Studies, Autoimmunity, Treatment Outcome, Multiple Sclerosis, Relapsing-Remitting, Young Adult, Antibodies, Monoclonal, Humanized
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