EMA restricts indications for Alemtuzumab while safety review is ongoing
The European Medicines Agency (EMA) has temporarily restricted the use of alemtuzumab. It should only be started in patients with relapsing-remitting multiple sclerosis that is highly active despite treatment with at least two disease modifying therapies, or where other disease-modifying therapies cannot be used. [81] The restriction follows new reports, some fatal, of cardiovascular adverse effects that occur within 1-3 days of receiving alemtuzumab, and immune-mediated adverse effects:
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Bleeding in the lungs, myocardial infarction, stroke, cervicocephalic arterial dissection
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Autoimmune hepatitis (with damage to the liver) and haemophagocytic lymphohistiocytosis
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Severe neutropenia.
Healthcare professionals should consider stopping alemtuzumab in patients who develop signs of these conditions. Existing patients who benefit from alemtuzumab therapy may continue treatment in consultation with their doctor. Patients should be informed of the signs and symptoms of these conditions, and advised to seek immediate medical attention should they occur. [81]
Restrictions to alemtuzumab indications are a temporary measure while the EMA safety review is ongoing. At the conclusion of the review, the EMA will consider whether additional measures and changes to the authorised use of alemtuzumab are required.
Alemtuzumab, a monoclonal antibody directed against the CD52 antigen, is approved for use in adult patients with relapsing-remitting multiple sclerosis. It acts through antibody-dependent cellular cytolysis and complement-mediated lysis following cell surface binding to T and B lymphocytes.
See Management: approach See Management: treatment algorithmSummary
Definition
History and exam
Other diagnostic factors
- female
- age 20 to 40 years
- foot dragging or slapping
- leg cramping
- fatigue
- urinary frequency
- bowel dysfunction
- spasticity/increased muscle tone
- increased deep tendon reflexes
- imbalance/incoordination
- pale optic disc or non-correctable visual loss
- incorrect responses to Ishihara colour blindness test plates
- abnormal eye movements
Risk factors
- female sex
- genetic factors
- northern latitude
- smoking
- vitamin D deficiency
- autoimmune disease
- Epstein-Barr virus (EBV)
Diagnostic investigations
1st investigations to order
- MRI - brain
- MRI - spinal cord
- FBC
- comprehensive metabolic panel
- thyroid-stimulating hormone
- vitamin B12
Investigations to consider
- anti-neuromyelitis optica antibody
- cerebrospinal fluid evaluation
- evoked potentials
Treatment algorithm
Contributors
Authors VIEW ALL
Staff Neurologist
Mellen Center for MS Treatment and Research
Neurological Institute
Cleveland Clinic Foundation
Cleveland
OH
Disclosures
MAW has received payment for participating on the speakers' bureaus of Biogen, Genzyme, and Novartis. MAW also serves on the editorial board for the International Journal of MS Care.
Dr Mary Alissa Willis would like to gratefully acknowledge Dr Lael A. Stone, a previous contributor to this topic. LAS declares that she has no competing interests.
Peer reviewers VIEW ALL
Project Leader for Neurology
Neurological Institute
Cleveland Clinic
Cleveland
OH
Disclosures
ARG declares that he has no competing interests.
Associate Professor of Neurology
Department of Clinical Neurological Sciences
London Health Sciences Centre
University Hospital
Ontario
Canada
Disclosures
SAM declares that she has no competing interests.
Director
The London Multiple Sclerosis Clinic
Associate Professor
Schulich School of Medicine
University of Western Ontario
Neurologist
Clinical Neurological Sciences Department
University Hospital
London Health Sciences Centre
Ontario
Canada
Disclosures
MK declares that he has no competing interests.
Consultant Neurologist
Department of Neurology
Queen’s Hospital
Romford
UK
Disclosures
AC declares that he has no competing interests.
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