Switching

Switching-2-alemtuzumab

Last updated on November 28th, 2024 at 01:38 pm

Possible reasons to switch

  • Alemtuzumab is the most effective licensed MS DMT in network analyses that compare it to other DMTs.
  • It promotes a high rate of ‘no evident disease activity’.
  • Many patients treated with alemtuzumab notice a sustained improvement in disability.
  • Alemtuzumab effectively ‘normalises’ the accelerated brain volume loss that occurs in people with MS.

Reasons for caution

  • Infusion reactions, infections and delayed secondary autoimmunity are the most common adverse effects of alemtuzumab.
    • Most infusion reactions are mild to moderate.
    • Infection risk is greatest during the first 4 weeks after starting course 1 of alemtuzumab, but infections (sometimes serious) can occur after this time.
    • Patients considering alemtuzumab treatment must be prepared for monthly blood and urine monitoring and the significant risk of developing a secondary autoimmune disorder.
  • The risk:benefit ratio of alemtuzumab changes dramatically in older patients with more advanced MS, particularly those with comorbidities.
  • It is not advisable for women receiving alemtuzumab to fall pregnant or breastfeed whilst significantly immunosuppressed.

Interferon and glatiramer acetate

Generally, alemtuzumab can be started immediately after discontinuing interferon or glatiramer acetate. Before starting alemtuzumab, all the recommended baseline screening tests and vaccination reviews must be done.

Natalizumab

A prolonged wash-out period is not recommended due to the risk of rebound activity on stopping natalizumab. Most often, the reason for switching from natalizumab to alemtuzumab or another DMT is to reduce the risk of carry-over PML (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 would typically initiate alemtuzumab immediately after the last natalizumab infusion. We offer a 6 ̶ 12-month bridge on fingolimod to patients at very high risk of carry-over PML. This bridge on fingolimod, which is reversible, means we can exclude carry-over PML that typically declares itself within 6 months. Before starting alemtuzumab, all the recommended baseline screening tests and vaccination reviews must be done.

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. Before starting alemtuzumab, all the recommended baseline screening tests and vaccination reviews must be done. 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 alemtuzumab.

Fumarates

All the recommended baseline screening tests and vaccination reviews must be done before starting alemtuzumab. 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 alemtuzumab. 

Teriflunomide

All the recommended baseline screening tests and vaccination reviews must be done before starting alemtuzumab. I recommend waiting for the total peripheral lymphocyte counts to exceed 800/mm3 before starting alemtuzumab. We don’t routinely do an accelerated washout of teriflunomide before starting alemtuzumab. 

Anti-CD20 therapies (selective cell depleting DMTs)

All the recommended baseline screening tests and vaccination reviews must be done before starting alemtuzumab. If patients are switching for safety concerns, it is advisable to wait for B-cell counts to recover before starting alemtuzumab. Some neurologists prefer starting alemtuzumab before B-cell recovery as a potential strategy to prevent secondary autoimmunity. If patients are switching for loss of efficacy on an anti-CD20, there is no need to wait for B-cell recovery. 

Cladribine (selective cell depleting DMT)

All the recommended baseline screening tests and vaccination reviews must be done before starting alemtuzumab. I recommend waiting for the total peripheral lymphocyte counts to exceed 800/mm3.

Mitoxantrone

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

HSCT

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