Lemtrada: Deleterious unwanted effects in some multiple sclerosis patients

19 April 2019 – 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.

Hemophagocytic lymphohistiocytosis

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. One 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 short sequence on hemophagocytic lymphohistiocytosis:

Print Friendly, PDF & Email

 

Tags: , , , , , , ,
About the Author
Joseph Gut - thasso Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

Your opinion

Comment

No comments yet

thasso: conditions

thasso: newest tweets

thasso: recent comments

View my Flipboard Magazine.

thasso: categories

thasso: archives

thasso: simple chat

You must be a registered user to participate in this chat.

  • Nurse practitioners play key role in opioid addiction treatment in very rural areas November 23, 2020
    Giving nurse practitioners the authority to prescribe buprenorphine has brought that gold standard treatment for opioid addiction to people who might not have had access to it before, according to a new study. Looking at prescription drug monitoring data in Oregon before and after 2017, when nurse practitioners and physician assistants gained the authority to […]
  • Identical evolution of isolated organisms November 23, 2020
    Palaeontologists at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and the University of Calgary in Canada have provided new proof of parallel evolution: conodonts, early vertebrates from the Permian period, adapted to new habitats in almost identical ways despite living in different geographical regions. The researchers were able to prove that this was the case using fossil teeth found […]
  • A chemist from RUDN University synthesized analogs of natural toxins November 23, 2020
    A chemist from RUDN University suggested a simple and accurate method for the synthesis of analogs of two natural toxins, antofine and septicine. This universal approach can also be used to obtain other biologically active substances for medicinal chemistry.
  • Researchers minimize quantum backaction in thermodynamic systems via entangled measurement November 23, 2020
    Researchers from University of Science and Technology of China theoretically proved that the backaction can be suppressed to zero in a two qubit system, and conducted the first experiment using entangled collective measurement for minimizing quantum measurement backaction based on photonic system.
  • Growing risks of STIs in over-45s November 23, 2020
    Sexually-active over-45s are at a high risk of contracting STIs because people do not want to talk about holder people having sex, a report has found.
Top