Alemtuzumab is the active ingredient of the MS drug Lemtrada®. It is used in adult individuals with relapsing-remitting multiple sclerosis to reduce the number of relapses. Alemtuzumab (Lemtrada®) is used in patients with high disease activity, an immunosuppressive drug. Alemtuzumab (Lemtrada®) is administered by infusion under medical supervision in an intensive care environment.

What is Alemtuzumab (Lemtrada®)?

Alemtuzumab is a medication used for relapsing MS with high inflammatory activity (RMS). It is often said that alemtuzumab is immunotherapy, but what does this mean?

Immunotherapies are drugs that treat diseases of the immune system. This type of therapy uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. However, the exact mechanism of action of immunosuppressive drugs in MS is not yet fully understood. However, it is known that further flares are reduced and the inflammatory activity in the central nervous system decreases because of the medication.

It is presumed that Alemtuzumab binds to CD52, a cell surface antigen (a toxin or foreign substance that induces an immune response) present on T and B lymphocytes, and on natural killer cells, monocytes, and macrophages. Following the binding it depletes T and B cells which cause MS inflammation.

Who is Alemtuzumab (Lemtrada®) treatment available for?

Only people with RMS who still have measurable disease activity under two or more drugs indicated for MS treatment may be treated with alemtuzumab (Lemtrada®). They must also be between 18 and 60 years old and must not have any cardiovascular disease, bleeding disorders, or other autoimmune diseases aside from multiple sclerosis.

Elderly

In the clinical trials for the approval of the drug, no patients were older than 61 years. It is therefore not known how this group of people will respond to the drug.. In such cases, doctors usually advice against treatment.

Children and young people

There is also no data on the effect of Alemtuzumab (Lemtrada®) on children and adolescents under the age of 18 years.

Pregnant and breastfeeding women

There is not much experience with the application of (Lemtrada®) during pregnancy. Therefore, during treatment, it must always be considered whether the risk to the fetus is lower than the success of treatment. Alemtuzumab is able to pass through the placental barrier, which protects the child. However, the extent to which this could lead to damage is not known.

However, therapy with Alemtuzumab can have an effect on the thyroid gland (side effect). It is known that in the case of thyroid disease during pregnancy, it can lead to impairment of fetal development or possibly miscarriage.

Alemtuzumab (Lemtrada®) is also transferred to breast milk and a possible risk for the child to be breastfed cannot be excluded. Therefore, it is strongly recommended not to breastfeed the child during the treatment phase and at least four months after the last infusion.

What are the side effects of Alemtuzumab (Lemtrada®)?

For treatment with Alemtuzumab (Lemtrada®), a strict safety follow-up by your doctor is provided, which lasts for more than 48 months (after your last infusion). This is to observe the patient's response to the therapeutic agent and monitor side effects. For a complete list of possible side effects, see the package leaflet. At the beginning of the treatment, your doctor will also inform you about the possible risks of using alemtuzumab (Lemtrada®).

• Acne, skin damage (skin lesion), skin inflammation
• Acute severe allergic reaction affecting several or all body areas (anaphylaxis)
• Increase in aspartate aminotransferase (ASAT) concentration in the blood, increase in aminotransferase (ALAT) concentration in the blood
• Autoimmune disease of the thyroid gland (Basedow disease), hyperthyroidism (hyperthyroidism), hypothyroidism (hypothyroidism), thyroid enlargement, detection of thyroid antibodies in the blood
• Accelerated pulse (tachycardia)
• Conjunctivitis, thyroid disease with protruding eyeballs, blurred vision
• Bleeding of the pulmonary vesicles (alveoli)
• Inflammation of the liver caused by the immune system (autoimmune hepatitis), strong inflammatory reaction of the immune system (haematophagic histiocytosis)
• Inflammation of the oral mucosa (stomatitis)
• Inflammation of the ear
• Epstein-Barr viral infection, Epstein-Barr hepatitis
• Increased protein excretion in urine (proteinuria), excretion of blood with urine (hematuria)
• Fever, flu, fatigue, chills
• Spot-like skin haemorrhage (ecchymosis)
• Vasoconstriction of the heart
• Shingles (herpes zoster infection), infection of the lower respiratory tract, infectious inflammation of the gastrointestinal tract
• Hair loss with baldness (alopecia)
• Hashimoto
• Skin redness due to increased blood circulation (erythema)
• Yeast fungal infection (candidasis) of the oral mucosa, vaginal gland (yeast fungal infection of the vagina and labia)
• Cerebral haemorrhage
• Cough, nosebleeds, hiccups, sore throat, stomach pain, vomiting, diarrhea, indigestion
• Immune disorders with small skin or mucous membrane bleeding (Werlhof’s disease)
• Infection of the upper respiratory tract (URTI) or urinary tract, a herpes virus infection
• Infection in the tooth area
• Headaches, migraines
• Shortness of breath (dyspnea), bronchial asthma
• Slow pulse (bradycardia), palpitations, low blood pressure (hypotension)
• Pneumonia due to infection (pneumonia)
• Moderately acute thyroid inflammation (subacute thyroiditis)
• Muscle pain, muscle weakness, joint pain, back pain, limb pain, muscle cramps, neck pain, pain in the posture and musculoskeletal system
• Detection of thyroid antibodies in the blood
• Hives (urticaria), rash, itching (pruritus)
• Vaginal infection
• Thyroid enlargement
• Insomnia, anxiety, depression
• Dizziness, numbness, sensations, tremors
• Sweating (hyperhidrosis)
• Disturbance of taste
• Nausea
• Hypersensitivity
• Enlargement of the lymph nodes
• Prolonged monthly bleeding, irregular monthly bleeding
• Reduced number of platelets (thrombocytopenia), anemia (anemia), reduction of blood cells, blood formation disorder with more white blood cells in the blood (leukocytosis)
• Reduced white blood cell count (lymphocytopenia, leukopenia, neutropenia)
• Warmth
• Wart bulge (papilloma) of the skin
• Cytokine release syndrome

Note: MS patients receive the infusion with alemtuzumab (Lemtrada®) in-patient (so you can be monitored by a healthcare professional). Nevertheless, it should be noted that the ability to react is impaired by the treatment with the drug. Keep this in mind in order to avoid injuries caused by the operation of machines - in road traffic, household etc (especially shortly after you are discharged from medical care).

What effects does Alemtuzumab (Lemtrada®) have on the thyroid gland?

By using alemtuzumab (Lemtrada®), patients can develop a disease of the thyroid gland. The thyroid gland is located below the larynx. From there, it produces hormones that enter the bloodstream and become part of metabolic processes in the body.

Possible thyroid diseases include:

Hashimoto: The thyroid gland can either increase in size and its function is impaired or the tissue of the thyroid gland is destroyed.

Graves disease(also known as Basedow's): Antibodies trigger inflammation through autoimmune reactions, which can affect the eyes, lower legs, feet or hands. In addition, Basedow's disease can be a trigger for hyperthyroidism.

Hypothyroidism: A term describing an underactive thyroid occurs when the thyroid gland doesn't make enough thyroid hormones to meet the body's needs. This slows down metabolic processes in the body and reduces your performance.

Hyperthyroidism: An overactive thyroid happens when the thyroid gland makes more thyroid hormones than the body needs. People with hyperthyroidism are often restless and nervous. This often leads to significant weight loss despite hunger and a fast heartbeat.

Was alemtuzumab (Lemtrada®) once used as chemotherapy for cancer?

Yes, Alemtuzumab was a chemotherapy drug and was marketed under the trade name MabCampath®. In August 2012, the manufacturer voluntarily requested the withdrawal of the EMA approval of alemtuzumab for commercial reasons. It was previously used to treat chronic lymphocytic leukemia.

In September 2013, alemtuzumab was re-approved by the EMA under the trade name Lemtrada® but as a multiple sclerosis drug.

When should treatment with alemtuzumab (Lemtrada®) not take place?

If the following diseases or health conditions are present, the medicine may not be used. Please note that if you have any questions, you should always contact your doctor or health care professional, as this is general information, not patient specific.

• Immunodeficiency due to viral infection (HIV infection)
• Splitting (dissection) of the cervicocephalic vessel walls of a blood vessel (artery)
• Coagulation disorder (coagulopathy)
• Hypertension without medical supervision (uncontrolled hypertension)
• Chest narrowness (angina pectoris)
• Other disease (not MS) by the immune system (autoimmune disease)
• Heart attacks
• Strokes
• Severe active infection (until complete decay)
• Hypersensitivity to the ingredients

Women of childbearing age are recommended to use effective contraceptives during and after treatment, as the effects of the drug may have developmental consequences for the fetus or pregnancy.

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