Last updated on November 28th, 2024 at 01:42 pm

Possible reasons to switch

• Cladribine is a highly effective DMT; follow-up of participants from clinical trials suggests it has a long-lasting treatment effect, especially when used early in the disease course.
• It has demonstrated improvements in annual relapse rate, disability progression and decreased brain volume loss compared to placebo.
• Cladribine-treated patients with MS don’t get infusion-type reactions, nor do they need steroids and antihistamines to prevent such reactions.
• Cladribine works similarly to alemtuzumab and AHSCT but is a much safer treatment option. It is very well tolerated, with very few side effects.

Reasons for caution

• Cladribine is an immunosuppressive therapy and may increase the likelihood of infections. Routine infection screening before starting treatment is essential, as is ongoing monitoring and prompt treatment if infection is detected.
• Herpes zoster is the most common clinically significant adverse event reported with cladribine.
• A lymphocyte count above 800/mm³ is recommended before starting course 2 of cladribine (in year 2) and before switching to cladribine from most other DMTs.
• Disease breakthrough after the second course of cladribine (before the end of year 2) is considered a treatment failure, particularly if associated with poor depletion of lymphocytes.
• Cladribine is contraindicated in MS patients with active malignancies. All cladribine-treated people with MS are advised to follow standard, country-specific cancer screening guidelines.
• Cladribine may cause birth defects. Patients are advised not to fall pregnant or father a child until at least 6 months after the last exposure to cladribine.
• Cladribine will cross over into the breast milk. We advise pregnant women to wait until 10 days after the last exposure to cladribine before breastfeeding.

Interferon and glatiramer acetate

In general, cladribine can be started immediately after discontinuation of interferon or glatiramer acetate. All the recommended baseline screening tests and vaccination reviews must be done before starting cladribine.

Natalizumab

Owing to the risk of rebound activity on stopping natalizumab, a prolonged wash-out period is not recommended. Most often, the reason for switching from natalizumab to cladribine, or another DMT, is to reduce the risk of carry-over PML from natalizumab. In our centre, we do an MRI and a lumbar puncture for cerebrospinal fluid analysis to exclude JC virus-DNA on polymerase chain reaction testing. Provided these two tests are clear, we would typically initiate cladribine as soon as possible after the last natalizumab infusion. All the recommended baseline screening tests and vaccination reviews must be done before starting cladribine.

S1P modulators (fingolimod, siponimod, ozanimod and ponesimod)

Because fingolimod has quite a long half-life, some neurologists recommend a short washout period, i.e. 4 ̶ 6 weeks; this may be appropriate, depending on the reason for switching. I recommend waiting for the total peripheral lymphocyte counts to exceed 800/mm³ to exclude the uncommon occurrence of persistent lymphopaenia following S1P modulator administration. All the recommended baseline screening tests and vaccination reviews must be done before starting cladribine. If you are switching because of abnormal liver function tests on an S1P modulator, you would ideally want the liver enzymes to normalise or at least drop to below three times the upper limit of normal before starting cladribine.

Fumarates

It is important that all the recommended baseline screening tests and vaccination reviews are done before starting cladribine. If lymphopaenia is the main reason for switching from a fumarate, I recommend waiting for the total peripheral lymphocyte counts to exceed 800/mm³ before starting cladribine.

Teriflunomide

It is important that all the recommended baseline screening tests and vaccination reviews are done before starting cladribine. I recommend that the total peripheral lymphocyte counts are above 800/mm³ before starting cladribine. We don’t routinely do an accelerated washout of teriflunomide before starting cladribine.

Anti-CD20 therapies (selective cell depleting DMTs)

It is important that all the recommended baseline screening tests and vaccination reviews are done before starting cladribine. If patients are switching for safety concerns, it would be advisable to wait for B cell counts to recover first. If patients are switching for lack or loss of efficacy on an anti-CD20, there is no need to wait for B-cell recovery.

Mitoxantrone/alemtuzumab/AHSCT

I recommend waiting for the neutrophil and total peripheral lymphocyte counts to go above 1,000/mm³ and 800/mm³, respectively. All the recommended baseline screening tests must be done before starting cladribine.