Summary
Alemtuzumab is a monoclonal antibody that targets the surface molecule CD52 on white blood cells or leukocytes. It is given as two courses of intravenous infusions. The first course is five infusions, usually given over five consecutive days in year 1. The second course is three infusions over three consecutive days in year 2. Alemtuzumab works by depleting your white cells and then allowing them to recover over several months. It is an immune reconstitution therapy (IRT); hence, after your immune system returns to normal, hopefully without the cells that cause MS, it can fight infections, respond to vaccines and provide peripheral immune surveillance for tumours. Alemtuzumab is the most effective licensed MS DMT in network analyses comparing it to other DMTs. It promotes a high rate of ‘no evident disease activity’ and prevents or slows down disability worsening; many patients treated with alemtuzumab also notice a sustained improvement in disability. In addition, alemtuzumab effectively ‘normalises’ the accelerated brain volume loss that occurs in people with MS. Its effect on brain volume loss can be explained partially by the fact that alemtuzumab was used early and in relatively young patients with MS in the clinical trials.
The most common adverse effects are infusion reactions, infections and delayed secondary autoimmunity. The adverse event profile changes when alemtuzumab is used in older patients, particularly those with comorbidities. A minority of patients treated with alemtuzumab go into long-term remission with no evident inflammatory disease activity (NEIDA) and no evidence of ongoing end-organ damage. Whether these individuals are cured will require much longer follow-up. Alemtuzumab works similarly to AHSCT (autologous haemopoietic stem cell transplantation) but is a much safer treatment option.
Trade name
Lemtrada.
Mode of action
An immune reconstitution therapy (IRT) that works by rebooting the immune system.
Efficacy
Very high.
Class
IRT.
Immunosuppression
Yes, short-term, whilst the immune system is depleted.
Dosing
Two annual courses with up to two additional treatment courses later if needed.
- Year 1: five 12 mg doses given as five daily intravenous infusions (60 mg total).
- Year 2: three 12 mg doses given as three daily intravenous infusions (36 mg total).
Alemtuzumab can be administered successfully by the subcutaneous route in patients who cannot take steroids.
Pre-treatment and prophylaxis treatment
Our centre has a protocol of drugs we administer before alemtuzumab infusions to prevent inflammatory reactions, pain, infection and other common side effects. Guidance about listeriosis prevention is also important.
Main adverse events
- Infusion reactions: most infusion reactions are mild to moderate; severe infusion reactions are uncommon in patients pretreated with steroids.
- Infections, notably during the first 4 weeks after starting treatment. Common community-acquired infections (usually mild) can occur later; more serious, opportunistic infections occur in only 2 ̶ 3% of treated patients.
- Delayed secondary autoimmunity. The most common autoimmune diseases are Grave’s disease, immune thrombocytopenic purpura and Goodpasture’s syndrome. These autoimmune diseases are treatable, generally monophasic (occur just once) and reversible.
- Additional adverse events (e.g. cardiovascular and respiratory) have been seen in older people with more advanced MS and multiple comorbidities or risk factors.
Pharmacovigilance monitoring requirements
- Standard blood tests and comprehensive screening for infection, pregnancy and blood pressure are done at baseline.
- A full blood count and urine assessments are done monthly after starting alemtuzumab and up to 4 years after the last course.
- Unexplained clinical signs and/or symptoms must be detected early and treated promptly. Delayed secondary autoimmunity complications can be avoided with vigilance and monthly blood monitoring.
- A rebaseline MRI scan should be done 18 ̶ 24 months after starting treatment, including Gd-enhancement. A monitoring MRI is performed annually after that.
- Women of childbearing age require a negative urine pregnancy test before starting alemtuzumab. Breastfeeding is not advised.