Updated MS Guidelines Advocate Earlier, More Aggressive Treatment


Updated European guidelines on the treatment of patients with multiple sclerosis (MS) have been announced, and include a recommendation for siponimod (Mayzent) in progressive MS, as well as a general emphasis toward earlier and more aggressive treatment.

The updated guidelines were presented at last week’s European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, and the result of a collaboration between ECTRIMS and the European Academy of Neurology (EAN).

Maria Pia Amato, MD, ECTRIMS president and co-chair of the guidelines steering committee, noted that the European MS treatment guidelines were last published in 2018. “Since then more trials have been published and we felt this was a good time to incorporate the new evidence into updated guidelines,” she said.

“As before, the updated guidelines contain a number of core questions that address the efficacy of disease-modifying therapies, early treatment decisions, disease/treatment response monitoring and treatment modifications, treatment suspension and disease reactivation, and pregnancy and breastfeeding,” Amato told Medscape Medical News.

New features of the updated guidelines include a recommendation for siponimod for secondary progressive MS with evidence of disease inflammatory activity; in addition, there is more emphasis on starting  treatment early, with greater consideration of higher efficacy drugs, depending on the characteristics of the disease and the patient, Amato commented.

“We also provided more detailed information on disease-modifying therapy use in pregnancy and breastfeeding, and also for women with high disease activity who desire to become pregnant,” she added.

Other new features include the introduction of clinical questions dealing with treatment safety and monitoring (eg, for natalizumab) and also considering the current COVID-19 pandemic scenario; switching strategies with more detailed practical indications on timing; and long lasting effects of drugs such as alemtuzumab and cladribine, Amato said.

The updated guidelines include the following recommendations:

  • The entire spectrum of disease-modifying drugs should be prescribed by a neurologist with expertise in MS and ready access to adequate infrastructure to provide proper monitoring of patents, comprehensive assessment, early detection of side effects, and the capacity to address those side effects promptly.

  • Offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) highly suggestive of MS and an abnormal MRI with lesions suggestive of MS who do not fulfil criteria for MS.

  • For patients with relapsing-remitting MS, the choice between a wide range of available drugs (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, fingolimod, ozanimod, ponesimod, natalizumab, alemtuzumab, ocrelizumab, rituximab, or ofatumumab), from modestly to highly effective, will depend on factors including: underlying disability progression, disease severity/clinical or radiological activity, patient characteristics and morbidity, drug safety profile, family planning, and patient preferences.

Progressive MS

  • For patients with secondary progressive MS with evidence of inflammatory activity (relapses and/or MRI activity) offer treatment with siponimod.  Treatment with other therapies use for relapsing remitting MS may also be considered.

  • For secondary progressive MS without evidence of inflammatory activity, particularly in young patients and those in whom progression has started recently, consider treatment with siponimod or anti-CD20 monoclonal antibodies, taking into account that there is scarce evidence to support their use in this setting.  

  • For patients with active secondary progressive MS when there is no other therapy available, consider treatment with mitoxantrone, taking into account the safety concerns and tolerability issues of this agent. 

  • Consider ocrelizumab for patients with primary progressive MS, particularly early and active (clinically and/or radiologically) disease.

Emphasis Toward Higher-Efficacy Drugs

  • Consider choosing a higher-efficacy disease-modifying drug early on, according to disease activity (either clinically or on MRI).

  • Offer a more efficacious drug to patients who show evidence of disease activity with their current treatment.

  • When treatment with a high-efficacy drug is stopped, whether because of inefficacy or risk of adverse effects, consider starting another high-efficacy drug, taking into account clinical and MRI disease activity before and during treatment, pharmacokinetics and biological activity of the previous drug, and the potential for resumed disease activity or even rebound syndrome (particularly with natalizumab and S1P modulators).

  • In the stable patient (clinically and on MRI) who shows no safety or tolerability issues, consider continuing treatment with disease-modifying therapy taking into account patient characteristics and comorbidities, drug safety profile, family planning, and patient preferences.

Recommendations for Pregnancy and Breastfeeding

Recommendations for pregnant women and mothers who choose to breastfeed include:

  • Advise women who wish to become pregnant to plan their pregnancy beforehand.

  • Advise women of childbearing potential that MS disease-modifying therapies are not licensed during pregnancy, with the exception of interferons and glatiramer acetate.

  • For women planning a pregnancy, offer interferons and glatiramer acetate and consider continuing these agents during pregnancy after assessment of risk and benefits. Consider using dimethyl fumarate until pregnancy is confirmed and stopping during pregnancy after assessment of the risks and benefits. 

  • For women with highly active disease who wish to become pregnant, there are a number of therapeutic options:

    1)  treatment with long lasting effects such as alemtuzumab or cladribine provided that at least 4 or 6 months respectively have elapsed between the last dose and conception
    2)  treatment with anti-CD20 drugs before pregnancy with advice to wait for 2-6 months after the last infusion before becoming pregnant and to avoid further infusions during pregnancy, or
    3) for patients treated with natalizumab, consider continuing treatment during pregnancy using a 6-week extended dosage regimen until the end of the second trimester or up until week 34, and resuming after delivery (in newborns exposed to natalizumab check for hematological abnormalities and liver function)

  • Only interferons and ofatumumab are currently approved during breastfeeding.   

Treatment Safety/Monitoring

  • When treating patients with natalizumab and after a period of stability, consider switching to a 6-week interval regimen in order to minimize the risk of progressive multifocal leukoencephalopathy (PML).

  • Consider treatment with high-efficacy drugs including natalizumab in patients with high disease activity, in whom a quick therapeutic effect is required,  taking into account the risk of PML in John Cunningham virus (JCV)-positive patients, as well as the therapeutic lag of the different disease-modifying drugs.

  • Ideally, prioritize vaccination against COVID-19 before starting immunosuppressive disease-modifying treatments to achieve the highest protection rate possible.

Long-Lasting Treatments

  • When using long-lasting treatments (alemtuzumab or cladribine) in patients who experience disease activity before the treatment is completed (between the first and second cycles), consider waiting until completion of the therapeutic regimen before switching to other drugs.

  • Consider offering additional courses of alemtuzumab after the first two cycles at least 1 year apart from each other when disease activity has not remitted completely or reappears after a period of stability, taking into account the balance between the potential benefits and side effects.

European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress. Presented October 15, 2021.

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