The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have published new guidelines on the use of disease-modifying drugs (DMDs) for multiple sclerosis (Montalban et al. Mult Scler 2018; epublished January 1, 2018; free full text at http://journals.sagepub.com/doi/pdf/10.1177/1352458517751049). The groups identified 10 key questions, and issued a series of recommendations based on the level of evidence.
The following is a summary of the groups’ recommendations.
Therapeutic intervention
1- All DMDs should be prescribed only in centres with adequate infrastructure to provide proper patient monitoring, comprehensive assessment, detection of side effects and the capacity to address them promptly.
2- Clinically isolated syndrome: Offer an interferon or glatiramer acetate to patients with CIS and MRI lesions suggestive of MS (strong evidence).
3- Relapsing-remitting MS: Offer early treatment to patients with active RRMS (relapses and/or MRI activity).
4- The choice of DMD for active RRMS will depend on patient characteristics and comorbidities; disease severity/activity; drug safety profile; and accessibility of the drug.
5-7- Active secondary-progressive MS: Consider treatment with interferon-1a SC or IFN-1b SC (weak evidence); mitoxantrone (weak evidence); ocrelizumab or cladribine (weak).
8- Primary-progressive MS: Consider treatment with ocrelizumab.
9- Consult the Summary of Product Characteristics for dosage, special warnings and precautions for use, contraindications and monitoring of side effects and potential harms.
10- Consider combining MRI with clinical measures when evaluating disease evolution in treated patients (weak)
Clinical management
11- MRI: To assess treatment response, perform a standardized reference brain MRI (usually within 6 months of treatment onset), and compare the results with a brain MRI obtained typically 12 months after starting treatment. The timing of both MRIs should take into account the drug’s mechanism of action (i.e. time of onset), and disease activity.
12- MRI: The preferred measurement when monitoring treatment response is new/enlarging T2 lesions, supplemented by gadolinium-enhancing lesions.
13- MRI: When monitoring safety, obtain an MRI every year in patients at low risk of progressive multifocal leukoencephalopathy (PML). More frequent MRIs (every 3–6 months) are recommended for patients at high risk of PML (JCV Ab+, natalizumab treatment duration >18 months); and in patients at high risk of PML before switching to another DMD.
14-15- Inadequate response to an injectable: Offer a more efficacious drug to patients treated with interferon or glatiramer acetate who have evidence of ongoing disease activity. Consider the following when switching to another DMD: patient characteristics and comorbidities; drug safety profile; and disease severity/activity.
16-17- Switching high-efficacy therapies: After stopping a high-efficacy DMD due to lack of efficacy or safety concerns, consider starting another high-efficacy DMD. When starting a new DMD, consider disease activity, the half-life and biological activity of the previous drug, and the potential for increased disease activity or rebound.
18- Patients with long-term disease stability: Consider continuing a DMD if the patient is stable (clinically and radiologically) and there are no safety or tolerability issues (weak evidence)
19-21- Pregnancy: Advise all women of childbearing potential that DMDs (except glatiramer acetate) are not licensed during pregnancy. For women planning a pregnancy, consider using an interferon or glatiramer acetate until pregnancy is confirmed in women at high risk of disease reactivation. Continuing treatment with interferon or glatiramer acetate during pregnancy may be considered in some very specific active cases (weak evidence). Women with persistent high disease activity should generally be advised to delay pregnancy. If pregnancy occurs, consider treatment with natalizumab throughout pregnancy; alemtuzumab could be an alternative therapy provided that a four-month interval is strictly observed from the latest infusion until conception (weak evidence).