Alemtuzumab is indicated for:
Irrespective of gender only Adults (18 years old or older)
Alemtuzumab is indicated as a single disease modifying therapy in adults with highly active relapsing remitting multiple sclerosis (RRMS) for the following patient groups:
For this indication, the medical literature mentions below treatments (click for details):
Active ingredient Alemtuzumab is contraindicated in the following cases:
Alemtuzumab was detected in the milk and offspring of lactating female mice. It is unknown whether alemtuzumab is excreted in human milk. A risk to the suckling newborn/infant cannot be excluded. Therefore, breast-feeding should be discontinued during each course of treatment with alemtuzumab and for 4 months following the last infusion of each treatment course. However, benefits of conferred immunity through breast-milk may outweigh the risks of potential exposure to alemtuzumab for the suckling newborn/infant.
There is a limited amount of data from the use of alemtuzumab in pregnant women. alemtuzumab should be administered during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Human IgG is known to cross the placental barrier; alemtuzumab may cross the placental barrier as well and thus potentially pose a risk to the foetus. Animal studies have shown reproductive toxicity.
It is not known whether alemtuzumab can cause foetal harm when administered to pregnant women or whether it can affect reproductive capacity.
Thyroid disease poses special risks in women who are pregnant. Without treatment of hypothyroidism during pregnancy, there is an increased risk for miscarriage and foetal effects such as mental retardation and dwarfism. In mothers with Graves' disease, maternal thyroid stimulating hormone receptor antibodies can be transferred to a developing foetus and can cause transient neonatal Graves' disease.
Several of the patients reported were below 40 years of age and had no risk factors for ischemic heart disease. It was noted that in some of the patients, blood pressure and/or heart rate was temporarily abnormal during the infusion.
Several of the patient reported were below 50 years of age and had no history of hypertension, bleeding disorders or concomitant anticoagulants or platelet inhibitors. In some patients there was increased blood pressure from baseline before the haemorrhage.
Cases of cervicocephalic arterial dissections, including multiple dissections, have been reported both within the first days after the alemtuzumab infusion or later on within the first month after the infusion.
Patients with uncontrolled hypertension.
Alemtuzumab is contraindicated in severe active infection until resolution.
Infections occurred in 71% of patients treated with alemtuzumab 12 mg as compared to 53% of patients treated with subcutaneous interferon beta-1a [IFNB 1a](44mcg 3-times weekly) in controlled clinical trials in MS up to 2 years in duration and were predominantly mild to moderate in severity. Infections that occurred more often in alemtuzumab –treated patients than IFNB 1a patients included nasopharyngitis, urinary tract infection, upper respiratory tract infection, sinusitis, oral herpes, influenza, and bronchitis. Serious infections occurred in 2.7% of patients treated with alemtuzumab as compared to 1% of patients treated with IFNB-1a in controlled clinical trials in MS. Serious infections in the alemtuzumab group included: appendicitis, gastroenteritis, pneumonia, herpes zoster, and tooth infection. Infections were generally of typical duration and resolved following conventional medical treatment.
The cumulative annualised rate of infections was 0.99 through a median of 6.1 years (maximum 12 years) of follow-up from the first alemtuzumab exposure, as compared to 1.27 in controlled clinical trials.
Serious varicella zoster virus infections, including primary varicella and varicella zoster re-activation, have occurred more often in patients treated with alemtuzumab 12 mg (0.4%) in clinical trials as compared to IFNB-1a (0%). Cervical human papilloma virus (HPV) infection, including cervical dysplasia and anogenital warts, has also been reported in patients treated with alemtuzumab 12 mg (2%). It is recommended that HPV screening be completed annually for female patients.
Cytomegalovirus infections (CMV) including cases of CMV reactivation have been reported in alemtuzumab-treated patients. Most cases occurred within 2 months of alemtuzumab dosing. Before initiation of therapy, evaluation of immune serostatus could be considered according to local guidelines.
Epstein-Barr virus (EBV) reactivation, including severe EBV hepatitis cases, has been reported in alemtuzumab-treated patients.
Tuberculosis has been reported for patients treated with alemtuzumab and IFNB-1a in controlled clinical trials. Active and latent tuberculosis, including a few cases of disseminated tuberculosis, have been reported in 0.3% of the patients treated with alemtuzumab, most often in endemic regions. Before initiation of therapy, all patients must be evaluated for both active or inactive (“latent”) tuberculosis infection, according to local guidelines.
Listeriosis/Listeria meningitis has been reported in alemtuzumab treated patients, generally within one month of alemtuzumab infusion. To reduce the risk of infection, patients receiving alemtuzumab should avoid ingestion of uncooked or undercooked meats, soft cheeses and unpasteurized dairy products two weeks prior to, during, and for at least one month after alemtuzumab infusion.
Superficial fungal infections, especially oral and vaginal candidiasis, occurred more commonly in alemtuzumab–treated patients (12%) than in patients treated with IFNB-1a (3%) in controlled clinical trials in MS.
Pneumonitis has been reported in patients who received alemtuzumab infusions. Most cases occurred within the first month after treatment with alemtuzumab. Patients should be advised to report symptoms of pneumonitis, which may include shortness of breath, cough, wheezing, chest pain or tightness and hemoptysis.
Initiation of treatment with alemtuzumab should be delayed in patients with severe active infection until resolution. Patients receiving alemtuzumab should be instructed to report symptoms of infections to a physician.
Prophylaxis with an oral anti-herpes agent should be initiated starting on the first day of alemtuzumab treatment and continuing for a minimum of 1 month following each course of treatment. In clinical trials patients were administered cyclovir 200 mg twice a day or equivalent.
Alemtuzumab has not been administered for treatment of MS concomitantly with or following antineoplastic or immunosuppressive therapies. As with other immunomodulating therapies, potential combined effects on the patient’s immune system should be taken into account when considering administration of alemtuzumab. Concomitant use of alemtuzumab with any of these therapies could increase the risk of immunosuppression.
No data are available on the association of alemtuzumab with Hepatitis B virus (HBV) or Hepatitis C virus (HCV) reactivation as patients with evidence of active or chronic infections were excluded from clinical trials. Screening patients at high risk of HBV and/or HCV infection before initiation of alemtuzumab should be considered and caution should be exercised in prescribing alemtuzumab to patients identified as carriers of HBV and/or HCV as these patients may be at risk of irreversible liver damage relative to a potential virus reactivation as a consequence of their pre-existing status.
Patients with known coagulopathy, on anti-platelet or anti-coagulant therapy.
Patients with other concomitant autoimmune diseases (besides MS).
Alemtuzumab is contraindicated in HIV.