Summary
Cladribine is an immune reconstitution therapy (IRT) that works by depleting your lymphocytes and allowing them to recover over several months. It is selective, mainly targeting B lymphocytes. After your immune system recovers, hopefully without the cells that cause MS, it can fight infections, respond to vaccines and provide peripheral immune surveillance for tumours. Cladribine is given as two courses of oral tablets, each of 2 treatment weeks, during which a patient receives 10 or 20 mg daily for 4 or 5 days.
Cladribine’s mode of action triggers a process called programmed cell death or apoptosis. This means that lymphocytes don’t release their contents via cell lysis but are gradually taken up by cells of the immune system by phagocytosis. As a result, lymphocyte cell death occurs slowly after cladribine administration, and there is no cell lysis syndrome. Therefore, cladribine-treated patients with MS don’t get infusion-type reactions, nor do they need steroids and antihistamines to prevent such reactions.
Cladribine is a highly effective disease-modifying therapy (DMT) with a high rate of no evident inflammatory disease activity (NEIDA), and it slows down disability worsening. It is very well tolerated, with very few side effects. The most common adverse effects are infections, usually mild. A minority of patients may experience a non-specific headache post-cladribine. No delayed secondary autoimmunity is seen, differentiating cladribine from other IRTs used to treat MS.
Cladribine is unlikely to be associated with an increased risk of secondary malignancies, but it is contraindicated in MS patients with active malignancies. Many patients treated with cladribine go into long-term remission. Whether these individuals are cured or not will require much longer follow-up. Cladribine works similarly to alemtuzumab (Lemtrada) or AHSCT (autologous haemopoietic stem cell transplantation) but is a much safer treatment option.
Trade name
Mavenclad.
Mode of action
As an IRT, cladribine aims to kill the cells that cause MS and then reboot the immune system to reset the regulatory mechanisms that keep autoreactive cells under control. It works similarly to alemtuzumab and AHSCT but does not cause infusion-type reactions.
Efficacy
High, with a positive impact on annual relapse rate, 3-month disability progression and rates of no evident disease activity (NEDA).
Class
Selective immune reconstitution therapy (IRT).
Immunosuppression
Yes, short-term, whilst the immune system is depleted.
Dosing
Two courses of oral tablets over 2 years, with a recommended cumulative dose of 1.75 mg/kg per year.
- Year 1: month 1, week 1, days 1 ̶ 5; month 2, week 1, days 1 ̶ 5. Each treatment week consists of 4 or 5 days on which a patient receives 10 or 20 mg daily.
- Year 2: as in year 1 but starting the first dosing week any time up to month 6.
No further cladribine treatment is required in subsequent years unless there is a recurrence of disease activity. No anti-inflammatory pretreatments or prophylactic antivirals and/or antibiotics are required to prevent infusion reactions or infections with cladribine. For fuller details, please refer to Dosing section of cladribine full details summary.
Main adverse events
- Herpes zoster due to reactivation of the varicella-zoster virus (VZV).
- Increased likelihood of infections.
Pharmacovigilance monitoring requirements
- Full range of tests and infection screening at baseline, plus negative urine pregnancy test.
- Cladribine is contraindicated in MS patients with active malignancies.
- Full blood count and liver function tests 2 and 6 months after the start of treatment in each treatment year.
- Be vigilant for unexplained bleeding, bruising, nausea, vomiting, abdominal pain, fatigue, loss of appetite, jaundice and/or dark urine and any symptoms of an infection.
- A rebaseline MRI is recommended 18 ̶ 24 months after starting treatment, including Gd-enhancement. A monitoring MRI annually thereafter.