Table 3.

Potential advantages and disadvantages comparing continuous immunosuppression and pulsed immunosuppression.

	Continuous immunosuppression (e.g. dimethyl fumarate, teriflunomide, fingolimod, natalizumab)	Pulsed immunosuppression (e.g. alemtuzumab, cladribine)
Clinical efficacy duration	Only during active treatment	Extends beyond period of active treatment
Infections: • PML • Reactivation of latent infections, e.g. tuberculosis • Herpes zoster	Risk of PML with some treatments Low risk of reactivation Low to moderate risk	Low risk of PML Higher risk of reactivation Higher risk during lymphopenia
Live vaccines	Contraindicated	May not be contraindicated after immune reconstitution
Risk of cancer	Long-term immunosuppression may increase risk of cancer	No indication of increased risk of cancer
Pregnancy	Not recommended*	Pregnancy safe after drug elimination (4 months after alemtuzumab and 6 months after cladribine administration)
Lactation	Not recommended	Lactation safe after drug elimination (see above)
Treatment escalation in case of suboptimal treatment response	Well-documented and generally well tolerated using risk-mitigation strategies	Only limited experience
Risk of adverse effects after discontinuation of treatment	Short-term risk only	Long-term risk even after immune reconstitution
Long-term tolerability	Well-known and generally good. Serious infections occur, and PML has been reported for natalizumab and in rare cases for fingolimod and dimethyl fumarate	Uncertain

^*The general rule is that pregnancy is not recommended. However, for some drugs, such as natalizumab, use during pregnancy should be based on a benefit–risk evaluation taking into account the patient’s clinical condition and the possible return of disease activity after stopping the medicinal product.

PML: progressive multifocal leukoencephalopathy.