Multiple Sclerosis Guidelines: AAN’s Recommendations for Initiating, Switching, Stopping Disease-Modifying Therapy

The following article is part of conference coverage from the 2018 American Academy of Neurology Annual Meeting in Los Angeles, California. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AAN 2018.

LOS ANGELES – Starting treatment with disease-modifying therapy (DMT) for multiple sclerosis (MS) as early as possible allows for the greatest chance to alter disease course, according to new MS guidelines published by the American Academy of Neurology (AAN).

The guidelines, which have been endorsed by the National Multiple Sclerosis Society and the Multiple Sclerosis Association of America, were announced at the 2018 AAN Annual Meeting, April 21-27 in Los Angeles.

A systematic review was conducted by the Guidelines Development, Dissemination, and Implementation Subcommittee of the AAN in which 20 Cochrane reviews and 73 full-text articles were selected for data review. As the last AAN MS guidelines were published in 2002, the committee sought to review the most current evidence on starting, switching, and stopping DMT in clinically isolated syndrome, relapsing-remitting MS (RRMS), and progressive forms of MS.

“The treatment landscape for people with MS has changed dramatically in the last decade, and we now have many [DMTs] from which to choose,” said guideline author Alexander Rae-Grant, MD, FRCP, FAAN. “We now have 17 or so FDA-approved medicines [for MS], with several other medicines used off-label, so it’s a dramatically different landscape of choices that clinicians have to make. In addition, there’s more choices in terms of side effects, route of administration, some pills, some infusions, so the landscape for clinicians is very complicated and makes it hard to make decisions.”

Overall, the authors found high-quality evidence suggesting that in patients with RRMS, many DMTs are superior to placebo for the reduction of annualized relapse rates and new disease activity as measured by new MRI T2 lesion burden and disease progression. Patients with primary progressive MS may benefit from treatment with ocrelizumab vs placebo for reducing disease progression, and treatment with glatiramer acetate and interferon beta-1a vs placebo is more likely to reduce the risk for conversion to MS in patients with clinically isolated syndrome.

“We now know that treating earlier is better in reducing the number of new relapses and reducing the chance of having more injury to the brain,” Dr Rae-Grant said.

The panel made recommendations in the following areas: patient engagement; individualization of treatment; monitoring of treatment adherence; assessment of disease comorbidities; identifying which patients should begin DMT treatment; switching DMTs after a disease breakthrough event; and counseling on risks associated with DMTs. The recommendations were categorized based on level of obligation: Level A (must), Level B (should), and Level C (may).

When starting DMTs:

• Clinicians should counsel patients with newly diagnosed MS on treatment options during a dedicated treatment visit, as many patients who receive major diagnoses often do not recall information given to them at the time of diagnosis. (Level B)
• Clinicians should take into account patient preferences regarding DMT safety, route of administration, lifestyle, cost, efficacy, adverse effects, and tolerability when choosing a DMT and should revisit this choice throughout the MS disease course. (Level A)
• Clinicians should counsel patients on realistic expectations of DMTs, advising patients that DMTs do not address MS symptoms, which may require additional treatment. (Level A/B)
• Clinicians should be aware of a patient’s readiness or reluctance to initiate DMT use and appropriately counsel patients with comorbid disease and concomitant medications that may create barriers to adherence to DMT. (Level B)
• Patients who present with a single demyelinating event and 2 or more brain lesions characteristic of MS should be counseled on the risks and benefits of DMTs; therapy should be initiated in patients who decide that they want this therapy. (Level B)
• Clinicians should actively monitor patients taking DMTs for treatment adherence, adverse events, tolerability, and safety, and should follow up annually or according to treatment-specific risk evaluation and mitigation strategy recommendations. (Level B)
• Clinicians should account for reproductive plans for male and female patients taking DMTs and counsel patients accordingly on risks for male infertility and safety of DMT use for fetal development. (Level B)
• Clinicians should not prescribe mitoxantrone unless potential benefits greatly outweigh risks, as postapproval evidence has shown a high risk of serious adverse effects. (Level B)
• Patients with highly active MS should be prescribed alemtuzumab, fingolimod, or natalizumab vs interferon beta therapy pending consideration of the risks and benefits for individual patients. (Level B)

“There is a specific recommendation within the guidelines for people who may not have access for financial reasons to some of the therapies, for clinicians to consider off-label use of a couple of medications, specifically azathioprine and cladribine,” said guidelines co-author Ruth Ann Marrie, MD, PhD, FRCP. “The guideline also points clinicians to think about some of the sources where patients might be able to get financial assistance with medication, recognizing that this is a substantial concern for many individuals with MS.”