Last reviewed: August 2019
Last updated: August  2019
18 Apr 2019

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. [82]  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:

  • Bleeding in the lungs, myocardial infarction, stroke, cervicocephalic arterial dissection

  • Autoimmune hepatitis (with damage to the liver) and haemophagocytic lymphohistiocytosis

  • 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. [82]

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 algorithm

Original source of update



History and exam

Key diagnostic factors

  • visual disturbance in one eye
  • peculiar sensory phenomena

Other diagnostic factors

  • female sex
  • age 20-40 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
  • northern latitude
  • genetic factors
  • 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
Full details

Investigations to consider

  • anti-neuromyelitis optica antibody
  • cerebrospinal fluid evaluation
  • evoked potentials
Full details

Treatment algorithm


Authors VIEW ALL

Associate Professor and Chair

Department of Neurology

University of Mississippi Medical Center




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




ARG declares that he has no competing interests.

Associate Professor of Neurology

Department of Clinical Neurological Sciences

London Health Sciences Centre

University Hospital




SAM declares that she has no competing interests.


The London Multiple Sclerosis Clinic

Associate Professor

Schulich School of Medicine

University of Western Ontario


Clinical Neurological Sciences Department

University Hospital

London Health Sciences Centre




MK declares that he has no competing interests.

Consultant Neurologist

Department of Neurology

Queen’s Hospital




AC declares that he has no competing interests.

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