New guidelines for starting MS treatment early and switching issued at AAN 2018

New guidelines on the use of MS DMTs were issued at AAN and published online on April 23^rd 2018. These guidelines were meant for the patients with MS and aimed at providing guidance around starting, switching, and stopping treatment in MS. The guidelines advocated starting treatment early in MS disease course for effective treatment of the patients.

A multidisciplinary panel developed DMT recommendations, integrating findings from a systematic review; followed an Institute of Medicine–compliant process to ensure transparency and patient engagement; and developed modified Delphi consensus–based recommendations concerning starting, switching, and stopping DMTs pertinent to people with relapsing-remitting MS, secondary progressive MS, primary progressive MS, and clinically isolated syndromes of demyelination. Recommendations were supported by structured rationales, integrating evidence from one or more sources: systematic review, related evidence (evidence not from the systematic review), principles of care, and inference from evidence.

Thirty recommendations were developed: 17 on starting DMTs, including recommendations on who should start them; 10 on switching DMTs if breakthrough disease develops; and 3 on stopping DMTs. Recommendations encompassed patient engagement strategies and individualization of treatment, including adherence monitoring and disease comorbidity assessment. The panel also discussed DMT risks, including counselling about progressive multifocal leukoencephalopathy risk in people with MS using natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate; and made suggestions for future research to evaluate relative merits of early treatment with higher potency DMTs vs standard stepped-care protocols, DMT comparative effectiveness, optimal switching strategies, long-term effects of DMT use, definitions of highly active MS, and effects of treatment on patient-specified priority outcomes. This guideline reflects the complexity of decision-making for starting, switching, or stopping MS DMTs.

Starting DMT: Recommendations

Starting: Recommendation 1

• Clinicians should counsel people with newly diagnosed MS about specific treatment options with DMT at a dedicated treatment visit.

Starting: Recommendation 2

• 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.
• Clinicians must engage in an ongoing dialogue regarding treatment decisions throughout the disease course with people with MS.

Starting: Recommendation 3

• 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.
• Clinicians must counsel people with MS on DMTs to notify the clinicians of new or worsening symptoms.

Starting: Recommendation 4

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

Starting: Recommendation 5

• Clinicians should counsel about comorbid disease, adverse health behaviours, and potential interactions of the DMT with concomitant medications when people with MS initiate DMTs.

Starting: Recommendation 6

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

Starting: Recommendation 7

• Clinicians should discuss the benefits and risks of DMTs for people with a single clinical demyelinating event with 2 or more brain lesions that have imaging characteristics consistent with MS.
• After discussing the risks and benefits, clinicians should prescribe DMT to people with a single clinical demyelinating event and 2 or more brain lesions characteristic of MS who decide they want this therapy.

Starting: Recommendation 8

• Clinicians may recommend serial imaging at least annually for the first 5 years and close follow-up rather than initiating DMT in people with 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.

Starting: Recommendation 9

• Clinicians should offer DMTs to people with relapsing forms of MS with recent clinical relapses or MRI activity.

Starting: Recommendation 10

• Clinicians should monitor for medication adherence, AEs, tolerability, safety, and effectiveness of the therapy in people with MS on DMTs.
• Clinicians should follow up either annually or according to medication-specific REMS in people with MS on DMTs.

Starting: Recommendation 11

• 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.

Starting: Recommendation 12

• Clinicians should counsel men with MS on their reproductive plans regarding treatment implications before initiating treatment with teriflunomide or cyclophosphamide.

Starting: Recommendation 13

• 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.

Starting: Recommendation 14

• Clinicians should prescribe alemtuzumab, fingolimod, or natalizumab for people with MS with highly active MS.

Starting: Recommendation 15

• Clinicians may direct people with MS who are candidates for DMTs to support programs.
• Clinicians may recommend azathioprine or cladribine for people with relapsing forms of MS who do not have access to approved DMTs.

Starting: Recommendation 16

• 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 PML.

Starting: Recommendation 17

• Clinicians should offer ocrelizumab to people with PPMS who are likely to benefit from this therapy unless there are risks of treatment that outweigh the benefits.

Switching DMT: Recommendations

Switching: Recommendation 1

• 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.
• 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.
• 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 1 or more relapses, 2 or more unequivocally new MRI-detected lesions, or increased disability on examination, over a 1-year period of using a DMT

Switching: Recommendation 2

• 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.

Switching: Recommendation 3

• 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.

Switching: Recommendation 4

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

Switching: Recommendation 5

• 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.
• 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.

Switching: Recommendation 6

• Clinicians should counsel people with MS considering natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate about the PML risk associated with these agents.
• 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.

Switching: Recommendation 7

• Clinicians should counsel that new DMTs without long-term safety data have an undefined risk of malignancy and infection for people with MS starting or using new DMTs.
• If a patient with MS develops a malignancy while using a DMT, clinicians should promptly discuss switching to an alternate DMT, especially for people with MS using azathioprine, methotrexate, mycophenolate, cyclophosphamide, fingolimod, teriflunomide, alemtuzumab, or dimethyl fumarate.
• People with MS with serious infections potentially linked to their DMT should switch DMTs (does not pertain to PML management in people with MS using DMT).

Switching: Recommendation 8

• Clinicians should check for natalizumab antibodies in people with MS who have infusion reactions before subsequent infusions, or in people with MS who experience breakthrough disease activity with natalizumab use.
• Clinicians should switch DMTs in people with MS who have persistent natalizumab antibodies.

Switching: Recommendation 9

• Physicians must counsel people with MS considering natalizumab discontinuation that there is an increased risk of MS relapse or MRI-detected disease activity within 6 months of discontinuation.
• Physicians and people with MS choosing to switch from natalizumab to fingolimod should initiate treatment within 8–12 weeks after natalizumab discontinuation (for reasons other than pregnancy or pregnancy planning) to diminish the return of disease activity.

Switching: Recommendation 10

• Clinicians should counsel women to stop their DMT before conception for planned pregnancies unless the risk of MS activity during pregnancy outweighs the risk associated with the specific DMT during pregnancy.
• Clinicians should discontinue DMTs during pregnancy if accidental exposure occurs, unless the risk of MS activity during pregnancy outweighs the risk associated with the specific DMT during pregnancy.
• Clinicians should not initiate DMTs during pregnancy unless the risk of MS activity during pregnancy outweighs the risk associated with the specific DMT during pregnancy.

Stopping DMT: Recommendations

Stopping: Recommendation 1

• In people with RRMS who are stable on DMT and want to discontinue therapy, clinicians should counsel people regarding the need for ongoing follow-up and periodic reevaluation of the decision to discontinue DMT.
• Clinicians should advocate that people with MS who are stable (that is, no relapses, no disability progression, stable imaging) on DMT should continue their current DMT unless the patient and physician decide a trial off therapy is warranted.

Stopping: Recommendation 2

• Clinicians should assess the likelihood of future relapse in individuals with SPMS by assessing patient age, disease duration, relapse history, and MRI-detected activity (e.g., frequency, severity, time since most recent relapse or gadolinium-enhanced lesion).
• Clinicians may advise discontinuation of DMT in people with SPMS who do not have ongoing relapses (or gadolinium-enhanced lesions on MRI activity) and have not been ambulatory (EDSS 7 or greater) for at least 2 years.

Stopping: Recommendation 3

• Clinicians should review the associated risks of continuing DMTs vs those of stopping DMTs in people with CIS using DMTs who have not been diagnosed with MS.

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News Source: AAN 2018 websites

Image Source: https://mitochondrialdiseasenews.com/2017/07/31/mitochondria-medicine-society-updates-patient-care-guidelines/