Lemtrada: Deleterious unwanted effects in some multiple sclerosis patients
Alemtuzumab (Lemtrada) is used in the treatment of multiple sclerosis (MS). Moreover, Alemtuzumab, under the Tradenames of Campt, MabCampath and Campt-1H is on the markets for the treatment of chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma (CTCL), and T-cell lymphoma. It is also used as an anti-rejection agent in some conditioning regimens for bone marrow transplantation, kidney transplantation and islet cell transplantation.
Alemtuzumab is a monoclonal antibody that binds to CD52, a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes are derived. After treatment with Alemtuzumab, these CD52-bearing lymphocytes are targeted for destruction. In 2008 early tests at Cambridge University in the UK suggested that Alemtuzumab was useful in treating and even reversing the effects of multiple sclerosis, although the exact mode of action was not lined out. Promising results were reported later, in 2011, from a phase III trial comparing Aletuzumab with Interferon beta 1a in multiple sclerosis patients.
In September 2013, Alemtuzumab (Lemtrada) was approved for first-line use in the European Union (EU) by the European Medicines Agency (EMA). In contrast, in November 2013, the American Food and Drug Administration (FDA) issued a comprehensive briefing on Alemtuzumab (Lemtrada) for an agency review meeting. The document highlighted numerous very serious safety aspects, including substantial doubts about the adequacy of relevant clinical trials. Consequently, in December 2013, the FDA indicated that the Alemtuzumab (Lemtrada) application was not ready for approval, due to lack of evidence from “adequate and well-controlled studies” that demonstrated that the benefits of the drug outweigh the considerable health risks associated. Only in November 2014, Alemtuzumab (Lemtrada) was finally approved by the FDA for the indication multiple sclerosis.
Ever since, multiple sclerosis patients have been plagued by the considerable spectrum of serious, sometimes even fatal unwanted effects of Alemtuzumab (Lemtrada). There are very common adverse reactions associated with Alemtuzumab (Lemtrada) infusion in MS patients which include upper respiratory tract and urinary tract infections, herpes virus infections, lymphopenia, leucopenia, changes in thyroid function, tachycardia, skin rashes, pruritus, pyrexia, and fatigue as well as serious opportunistic nocardial infections and cytomegalovirus syndrome.
On a much more serious note, in November 2018, the FDA issued a Safety Announcement warning about rare but serious instances of stroke and blood vessel wall tears in multiple sclerosis patients who have received Alemtuzumab (Lemtrada), mostly occurring within 1 day of initiating treatment and leading in some cases to permanent disability and even death. In addition to the 13 cases to which the FDA Safety Announcement refers, a further 5 cases of spontaneous intracranial haemorrhage have been retrospectively identified from four US multiple sclerosis centres until February 2019. Similarly, in April 2019, the Pharmacovigilance Risk Assessment Committee (PRAC) of the EMA reported that it has started a review of the multiple sclerosis medicine Alemtuzumab (Lemtrada) following new reports of immune-mediated conditions and of problems with the heart and blood vessels with this medicine, including fatal cases. PRAC advised that while the review is ongoing, Alemtuzumab (Lemtrada) should only be started in adults with relapsing-remitting multiple sclerosis that is highly active despite treatment with at least two disease-modifying therapies (a type of multiple sclerosis medicine) or where other disease-modifying therapies cannot be used. PRAC further advised that patients being treated with Alemtuzumab (Lemtrada) who are benefitting from it may continue treatment in consultation with their doctor.
Apart from that, Alemtuzumab (Lemtrada) is contraindicated in patients who have active systemic infections, underlying immunodeficiency (e.g., seropositive for HIV), or known Type I hypersensitivity or anaphylactic reactions to the substance. In addition, Alemtuzumab (Lemtrada) can also precipitate secondary autoimmune diseases through the suppression of suppressor T cell populations and/or the emergence of autoreactive B-cells. Cases of mutiple sclerosis reactivation/relapse have also been reported. Moreover, in some patients, hemophagocytic lymphohistiocytosis (HLH) emerged following Alemtuzumab (Lemtrada) treatment. HLH in itself is a life-threatening condition of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages, characterised by proliferation of morphologically benign lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. It is classified as one of the cytokine storm syndromes.
In any case, patients or their caregivers should seek emergency treatment as soon as possible if the patient experiences signs or symptoms of a stroke or tears in the lining of the head and neck arteries, called arterial dissection, which can include:
- Sudden numbness or weakness in the face, arms, or legs, especially if it occurs on only one side of the body
- Sudden confusion, trouble speaking, or difficulty understanding speech
- Sudden trouble seeing in one or both eyes
- Sudden trouble with walking, dizziness, or loss of balance or coordination
- Sudden severe headache or neck pain!
See here a patient with hemophagocytic lymphohistiocytosis (HLH):