When switching DMTs:
- Clinicians should actively monitor disease activity for accumulation of new lesions and recognize that new lesions or relapses may occur after DMT initiation before the treatment becomes fully effective. Switching DMTs should be considered after patients have been using DMTs long enough with good adherence and they experience 1 or more relapses, 2 or more new brain lesions, or increased disability over a 1-year DMT treatment period. (Level B)
- When considering switching DMTs, clinicians should consider DMTs with different mechanisms or efficacy profiles, as this may be beneficial (Level B); clinicians should also consider changing to noninjectable or less-frequent injectable DMTs in patients who report injection fatigue or related pain, which may contribute to poor DMT adherence. (Level B)
- Clinicians should monitor laboratory abnormalities and should consider switching DMT or reducing dosage or frequency in patients with these abnormalities. (Level B)
- Clinicians should counsel patients considering treatment with natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate about the risk of progressive multifocal leukoencephalopathy and should consider switching to a DMT with a lower risk profile for patients taking natalizumab or those who become JCV-antibody positive. (Level B)
- Clinicians should counsel patients taking newer DMTs without long-term study data that an undefined risk for malignancy and infection exists and should consider switching DMTs in patients who develop a malignancy or serious DMT-related infection during treatment. (Level B)
- Patients taking natalizumab should be made aware of the increased risk for MS relapse or disease activity within 6 months of natalizumab discontinuation; those switching from natalizumab to fingolimod should do so within 8 to 12 weeks after discontinuation to reduce the risk for increased disease activity. (Level A/B)
- Prior to planned pregnancy, clinicians should advise patients to stop DMTs unless risk for MS activity outweighs the risks associated with DMT use during pregnancy; DMTs should be discontinued if accidental exposure during pregnancy occurs, and DMTs should not be initiated during pregnancy unless the risk of MS activity outweighs the risk associated with DMT use during pregnancy. (Level B)
When stopping DMTs:
- Patients with stable RRMS who want to discontinue DMT use should be counseled on the need for ongoing follow-up and re-evaluation, and should be advised that continued DMT use is recommended unless both patient and clinician feel that an off-therapy trial is warranted. (Level B)
- Patients with secondary progressive MS who wish to discontinue DMT use should be assessed for likelihood for future relapse based on patient age, disease duration, relapse history, and MRI activity; clinicians can advise discontinuation in patients who do not have ongoing relapses and who have not been ambulatory for at least 2 years. (Level B/C)
- In patients with clinically isolated syndrome who have not been diagnosed with MS, clinicians should review risks of continuing vs discontinuing DMTs. (Level B)
Based on gaps in current knowledge and evidence, the committee suggested that future research consider the following:
- Evidence regarding the effects of DMTs on MS outcomes deemed important to clinicians and patients beyond standard trial outcomes;
- Comparative efficacy studies between different DMTs in MS subpopulations;
- Benefits of DMTs in nonambulatory patients with secondary progressive MS;
- Trials examining long-term outcomes of high-potency therapy vs step-up DMTs early in the disease course;
- Comparisons of highly active DMTs vs different DMTs for patients with clinically isolated syndrome;
- Trials examining whether switching vs continuing DMTs following disease breakthrough results in improved long-term outcomes;
- Studies to identify biomarkers for DMT efficacy in MS patient subpopulations;
- More evidence to inform decisions regarding DMT discontinuation and the risks and benefits of doing so;
- More research on the minimization of risk to pregnant women and fetal health, and the long-term effects of DMT discontinuation throughout the pre- and postpregnancy periods.
Disclosures: Several guideline authors report relevant disclosures. Please see the published guidelines for a full list of author disclosures.
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Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline: disease-modifying therapies for adults with multiple sclerosis. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Presented at: 2018 American Academy of Neurology Annual Meeting. April 21-27, 2018; Los Angeles, CA.