American Academy of Neurology Guidelines for Multiple Sclerosis Disease-Modifying Therapy



2018 American Academy of Neurology Guidelines for Multiple Sclerosis Disease-Modifying Therapy

Alexander D. Rae-Grant

In April 2018, the American Academy of Neurology (AAN) published a systematic review and guidelines for disease-modifying therapy (DMT) for multiple sclerosis (MS) (1,2). The systematic review analyzed seven clinical questions related to DMT in patients with relapsing remitting, secondary and primary progressive MS, as well as those with clinically isolated syndromes. Twenty-three different medications were included in this systematic review, including Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved medicines and off label use of medicines with moderate-to-high-quality evidence. Recommendations were developed by an expert panel using an electronic modified Delphi process. Thirty recommendations were developed for starting, switching, and stopping MS DMT. The systematic review and recommendation process followed Institute of Medicine recommendations for guideline development (3).

Some key points to take away from these recommendations include the following:

1.    Proper diagnosis of MS is the gateway to treatment with DMT; avoiding misdiagnosis is as important as early diagnosis in MS care.

2.    Engaging the patient actively in a dialogue about the role of DMT, their readiness to initiate therapy, specific patient characteristics that may affect choice of medicine, and ongoing monitoring for adherence is key to success in the use of DMT.

3.    Clinicians should be ready to recommend switching DMTs when patients have ongoing disease activity as measured by relapses and/or new MRI lesions.

4.    Counselling about DMTs before pregnancy is important and consists of evaluating risks of medication in pregnancy, risks of certain medications for teratogenicity and infertility, and evaluating the ongoing risk of MS relapses in an individual patient.

5.    The decision of which medicine to use should include an evaluation of the disease activity in the patient; higher disease activity should prompt a higher efficacy medication earlier in the disease course.

6.    There may be a subgroup of patients with MS where disease activity is low enough, risk is high enough, and disability is large enough that further DMT treatment is not helpful. However, the committee was not able to come to consensus on a specific indicator for stopping DMT.

7.    The committee did not have enough evidence to decide whether a high-efficacy initial strategy was better or worse than a standard escalation (or stepped) approach, although studies are underway to evaluate this question. In addition, there was limited data to compare medications in most cases; further pragmatic clinical trials will be helpful in evaluating comparative efficacy in the clinic population.


Starting Recommendations

  1.  Level B: Clinicians should counsel people with newly diagnosed MS about specific treatment options with DMT at a dedicated treatment visit.

  2.  Level A: Clinicians must ascertain and incorporate/review preferences in terms of safety, route of administration, lifestyle, cost, efficacy, common adverse effects (AEs), and tolerability in the choice of DMT in people with MS being considered for DMT.
Level A: Clinicians must engage in an ongoing dialogue regarding treatment decisions throughout the disease course with people with MS.

  3.  Level B: Clinicians should counsel people with MS that DMTs are prescribed to reduce relapses and new MRI lesion activity. DMTs are not prescribed for symptom improvement in people with MS.
Level A: Clinicians must counsel people with MS on DMTs to notify the clinicians of new or worsening symptoms.

  4.  Level B: Clinicians should evaluate readiness or reluctance to initiate DMT and counsel on its importance in people with MS who are candidates to initiate DMT.

  5.  Level B: Clinicians should counsel about comorbid disease, adverse health behaviors, and potential interactions of the DMT with concomitant medications when people with MS initiate DMTs.

  6.  Level B: Clinicians should evaluate barriers to adherence to DMT in people with MS.
Level B: Clinicians should counsel on the importance of adherence to DMT when people with MS initiate DMTs.


  7.  Level B: Clinicians should discuss the benefits and risks of DMTs for people with a single clinical demyelinating event with two or more brain lesions that have imaging characteristics consistent with MS.
Level B: After discussing the risks and benefits, clinicians should prescribe DMT to people with a single clinical demyelinating event and two or more brain lesions characteristic of MS who decide they want this therapy.

  8.  Level C: Clinicians may recommend serial imaging at least annually for the first 5 years and close follow-up rather than initiating DMT in people with clinically isolated syndrome (CIS) or relapsing forms of MS who are not on DMT, have not had relapses in the preceding 2 years, and do not have active new MRI lesion activity on recent imaging.

  9.  Level B: Clinicians should offer DMTs to people with relapsing forms of MS with recent clinical relapses or MRI activity.

10.  Level B: Clinicians should monitor for medication adherence, AEs, tolerability, safety, and effectiveness of the therapy in people with MS on DMTs.
Level B: Clinicians should follow up either annually or according to medication-specific risk evaluation and mitigation strategies (REMS) in people with MS on DMTs.

11.  Level B: Clinicians should monitor the reproductive plans of women with MS and counsel regarding reproductive risks and use of birth control during DMT use in women of childbearing potential who have MS.

12.  Level B: Clinicians should counsel men with MS on their reproductive plans regarding treatment implications before initiating treatment with teriflunomide or cyclophosphamide.

13.  Level B: Because of the high frequency of severe AEs, clinicians should not prescribe mitoxantrone to people with MS unless the potential therapeutic benefits greatly outweigh the risks.

14.  Level B: Clinicians should prescribe alemtuzumab, fingolimod, or natalizumab for people with MS with highly active MS.
Level C: Clinicians may direct people with MS who are candidates for DMTs to support programs.

15.  Level C: Clinicians may recommend azathioprine or cladribine for people with relapsing forms of MS who do not have access to approved DMTs.

16.  Level C: Clinicians may initiate natalizumab treatment in people with MS with positive anti-JCV antibody indexes above 0.9 only when there is a reasonable chance of benefit compared with the low but serious risk of progressive multifocal leukoencephalopathy (PML).

17.  Level B: Clinicians should offer ocrelizumab to people with primary progressive multiple sclerosis (PPMS) who are likely to benefit from this therapy unless there are risks of treatment that outweigh the benefits.

Switching Recommendations

  1.  Level B: Clinicians should monitor MRI disease activity from the clinical onset of disease to detect the accumulation of new lesions in order to inform treatment decisions in people with MS using DMTs.
Level B: Clinicians should recognize that relapses or new MRI-detected lesions may develop after initiation of a DMT and before the treatment becomes effective in people with MS who are using DMTs.
Level B: Clinicians should discuss switching from one DMT to another in people with MS who have been using a DMT long enough for the treatment to take full effect and are adherent to their therapy when they experience one or more relapses, two or more unequivocally new MRI-detected lesions, or increased disability on examination, over a 1-year period of using a DMT.

  2.  Level B: Clinicians should evaluate the degree of disease activity, adherence, AE profiles, and mechanism of action of DMTs when switching DMTs in people with MS with breakthrough disease activity during DMT use.

  3.  Level B: Clinicians should discuss a change to noninjectable or less frequently injectable DMTs in people with MS who report intolerable discomfort with the injections or in those who report “injection fatigue” on injectable DMTs.

  4.  Level B: Clinicians should inquire about medication AEs with people with MS who are taking a DMT and attempt to manage these AEs, as appropriate.
Level B: Clinicians should discuss a medication switch with people with MS for whom these AEs negatively influence adherence.

  5.  Level B: Clinicians should monitor laboratory abnormalities found on requisite laboratory surveillance (as outlined in the medication’s package insert) in people with MS who are using a DMT.
Level B: Clinicians should discuss switching DMT or reducing dosage or frequency (where there are data on different doses [e.g., interferons, teriflunomide, azathioprine]) when there are persistent laboratory abnormalities.

  6.  Level B: Clinicians should counsel people with MS considering natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate about the PML risk associated with these agents.
Level B: Clinicians should discuss switching to a DMT with a lower PML risk with people with MS taking natalizumab who are or become JCV antibody positive, especially with an index of above 0.9 while on therapy.


Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Jan 8, 2020 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on American Academy of Neurology Guidelines for Multiple Sclerosis Disease-Modifying Therapy

Full access? Get Clinical Tree

Get Clinical Tree app for offline access