Lack of efficacy (repeat course of mitoxantrone): As mitoxantrone is an Immune Reconstitution Therapy (IRT), breakthrough activity may trigger the need for additional courses to be given, provided the total lifetime dose of mitoxantrone does not exceed 140 mg/m² and that cardiac monitoring (ECG and echo/MUGA) do not show signs of an underlying cardiomyopathy.
Other DMTs: Provided the baseline screening tests are okay and there are no specific contraindications I see no reason why mitoxantrone can't be used after any of the licensed DMTs.
Interferon-beta and glatiramer acetate: There are no specific cautions.
Fingolimod: The development of mitoxantrone-related cardiomyopathy and/or cardiac arrhythmia is a contraindication for using fingolimod after mitoxantrone. It is important to be extra-vigilant when doing the routine baseline cardiac checks post-mitoxantrone. If it has been some time since the last dose of mitoxantrone I would recommend having a cardiac ejection fraction checked with echocardiography or a MUGA scan.
Non-selective cell depleting DMTs (alemtuzumab & HSCT): a persistently low peripheral white cell count post alemtuzumab or HSCT, i.e. a neutrophil count < 1000/mm³ or a total lymphocyte count <800/mm³ is a relative contraindication to using mitoxantrone. Another hit on the bone marrow and primary and secondary lymphoid organs may worsen their leukopaenia and render them more immunosuppressed. The decision to use mitoxantrone in this situation has to be based on the potential benefits versus the risks of these treatments and the risks of untreated active MS.
Selective cell depleting DMTs (cladribine): a persistently low peripheral lymphocyte cell count post cladribine, i.e. a total lymphocyte count <800/mm³ is a relative contraindication to using mitoxantrone. The effect of mitoxantrone on primary and secondary lymphoid organs may worsen the lymphopaenia and is a risk factor for developing grade 3 or grade 4 lymphopaenia, i.e. <500/mm³ or <200/mm³, respectively. However, the decision to use mitoxantrone in this situation has to be based on the potential benefits of the treatment versus the risks of lymphopaenia and the risks of untreated active MS.
Selective cell depleting DMTs (ocrelizumab): as ocrelizumab is a selective B-cell depleting agent mitoxantrone is theoretically much safer than the other less selective and non-selective agents post ocrelizumab.
Natalizumab: As mitoxantrone is an IRT that can't be rapidly reversed it is critical to make sure that there is no asymptomatic PML. Carry-over PML from natalizumab to mitoxantrone is potentially fatal. It is therefore essential that a baseline MRI scan and possibly a CSF examination is done to exclude the possibility of PML.
Dimethyl fumarate: DMF reduces the lymphocyte count by approximately 30% and in some MSers by more than this. Therefore, MSers who have lymphopaenia on DMF may be more susceptible to developing clinically significant prolonged lymphopaenia post-mitoxantrone.
Teriflunomide: Because teriflunomide is an antiproliferative agent it may delay or prevent the recovery of the peripheral white cell count post mitoxantrone. One option is to do an accelerated teriflunomide washout to prevent this potential problem. Interestingly, rheumatologists who use leflunomide, a prodrug that is converted to teriflunomide, don't use an accelerated washout when using antiproliferative agents post-leflunomide.
Special circumstances: The presence of other specific comorbidities and adverse events may make it difficult to start mitoxantrone after other DMTs.