Possible reasons to switch

• Anti-CD20 therapies are highly effective DMTs with a high rate of no evident inflammatory disease activity.
• They have been shown to slow down disability worsening and brain volume loss; they reduce the annual relapse rate compared with interferon-beta and teriflunomide.
• Anti-CD20 therapies are generally available for use as ‘first-line’ treatment for DMT-naïve people with MS. This has transformed management of the disease by allowing the adoption of a strategy that starts with high-efficacy DMTs (‘flipping the pyramid’).
• In general, the anti-CD20 therapies are safe during breastfeeding because very little drug gets into the breast milk.
• Rituximab has recently been included on the WHO’s Essential Medicines List as a treatment for MS. (Being first approved for use in cancer and then in rheumatoid arthritis, it is now ‘off patent’.) It can therefore be accessed for off-label use in countries where other anti-CD20s are not available.

Reasons for caution

• Infusion-related reactions are relatively common and are experienced by about one in three subjects with the first and second infusions.
• Other common adverse effects include infections (particularly respiratory), low antibody levels in the blood, blunted vaccine responses and (rarely) delayed neutropenia.
• Anti-CD20s may be associated with anti-drug antibodies and neutralising antibodies (rates vary with the different formulations).
• A minority of people with MS treated with anti-CD20 therapies develop mild lymphopaenia or neutropaenia (often delayed), both of which may be associated with an increased rate of infections.

Interferon and glatiramer acetate

An anti-CD20 therapy can be started immediately after discontinuing interferon-beta or glatiramer acetate. All the recommended baseline screening tests and vaccination reviews must be done before starting one of the anti-CD20s.

Natalizumab

Owing to the risk of rebound activity on stopping natalizumab, a prolonged wash-out period is not recommended. Most often, switching from natalizumab to an anti-CD20 or another DMT is to reduce the risk of carry-over progressive multifocal leukoencephalopathy 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 typically initiate the anti-CD20 as soon as possible after the last natalizumab infusion. All the recommended baseline screening tests and vaccination reviews must be done before starting an anti-CD20.

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, before switching to another DMT; 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 lymphopaenia following S1P modulator administration. All the recommended baseline screening tests and vaccination reviews must be done before starting an anti-CD20. 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 an anti-CD20.

Fumarates

All the recommended baseline screening tests and vaccination reviews must be done before starting an anti-CD20. If lymphopaenia is the main reason for switching from fumarate, I recommend waiting for the total peripheral lymphocyte counts to exceed 800/mm³ before starting an anti-CD20. 

Teriflunomide

All the recommended baseline screening tests and vaccination reviews must be done before starting an anti-CD20. I recommend the total peripheral lymphocyte counts are above 800/mm³ before starting an anti-CD20. We don’t routinely do an accelerated washout of teriflunomide before starting an anti-CD20. 

Anti-CD20 therapies (selective cell depleting DMTs)

If patients switch between formulations of anti-CD20 therapies out of choice (patient preference), it can be done without safety concerns or needing to wait for B-cell counts to recover. If patients are switching for loss of efficacy, I suggest checking for antidrug antibodies and reviewing the diagnosis of MS to try and understand why the individual has not responded to the specific anti-CD20 and/or its formulation. 

Mitoxantrone/alemtuzumab/cladribine/AHSCT

Before starting an anti-CD20 therapy, I recommend waiting for the neutrophil and total peripheral lymphocyte counts to go above 1000/mm³ and 800/mm³, respectively. An exception to this would be the cases of severe rebound that are rarely seen after alemtuzumab. In these circumstances, the anti-CD20 therapy is given to treat very active, often pseudotumoral or tumefactive, MS. All the recommended baseline screening tests must be done before starting an anti-CD20 therapy.