Summary

AAN 2018 guideline on disease-modifying therapy (DMT) for adults with multiple sclerosis, replacing the 2002 AAN DMT guideline. Thirty consensus recommendations address starting (17), switching (10), and stopping (3) DMTs across RRMS, SPMS, PPMS, and clinically isolated syndrome (CIS), emphasizing shared decision-making, adherence, comorbidity management, and PML risk counseling. Ocrelizumab is endorsed for ambulatory PPMS, and specific guidance is given for natalizumab JCV-antibody risk stratification and pregnancy-related DMT decisions.

Key Recommendations

Counsel newly diagnosed MS patients about DMT options at a dedicated treatment visit, separate from the diagnosis visit (Level B).
Incorporate patient preferences regarding safety, route, lifestyle, cost, efficacy, AEs, and tolerability when selecting a DMT (Level A).
Counsel patients that DMTs reduce relapses and new MRI lesions but do not treat symptoms, and instruct them to report new/worsening symptoms (Level A/B).
Assess and address comorbidities (depression, anxiety, vascular risk factors), adverse health behaviors, adherence barriers, and drug interactions before starting DMT (Level B).
Offer DMT to patients with CIS (single demyelinating event) plus ≥2 brain lesions characteristic of MS who elect therapy (Level B).
Offer ocrelizumab to ambulatory patients with primary progressive MS unless risks outweigh benefits (Level B).
Discuss switching DMT when, after adequate time on therapy with good adherence, a patient has ≥1 relapse, ≥2 unequivocally new MRI lesions, or increased disability over 1 year (Level B).
Counsel about PML risk with natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate; consider switching JCV-positive natalizumab patients (especially index >0.9) to a lower-PML-risk DMT (Level B).
When switching from natalizumab to fingolimod, initiate fingolimod 8–12 weeks after natalizumab discontinuation to reduce relapse and MRI activity.
Counsel women to stop DMT before conception for planned pregnancies, and do not start or continue DMT during pregnancy unless MS disease activity risk outweighs fetal risk (Level B).
Counsel men on reproductive implications before starting teriflunomide or cyclophosphamide (Level B).
May discontinue DMT in SPMS patients without ongoing relapses or gadolinium-enhancing lesions who have been nonambulatory (EDSS ≥7) for at least 2 years (Level C).
Monitor adherence, AEs, safety labs, and effectiveness at least annually or per medication-specific REMS (Level B); consider serial MRI at least annually for 5 years in untreated CIS/relapsing MS without recent activity (Level C).

Thresholds & Doses

CIS with ≥2 brain lesions characteristic of MS → offer DMT; highest conversion risk within 5 years of initial event.
Switching trigger: ≥1 relapse, ≥2 new MRI lesions, or increased disability over 1 year on adequate DMT with good adherence.
Natalizumab PML risk (25–36 months, no prior immunosuppression): 0.2/1,000 if JCV index ≤0.9; 0.3/1,000 if index 0.9–1.5; 3/1,000 if index >1.5.
Overall natalizumab PML risk ~4/1,000.
Natalizumab → fingolimod switch: start fingolimod 8–12 weeks (not 16 weeks) after natalizumab discontinuation.
Natalizumab discontinuation: increased relapse/MRI activity within 6 months (rebound risk).
Stopping DMT in SPMS: may discontinue if no relapses/Gd-enhancing lesions and nonambulatory (EDSS ≥7) for ≥2 years.
Untreated CIS/relapsing MS without relapses in preceding 2 years and no new MRI activity: serial MRI at least annually for first 5 years (Level C).
DMT follow-up: at least annually or per medication-specific REMS.
Teriflunomide: potential teratogenic risk from male sperm up to 2 years after cessation without accelerated elimination.
Obtain new baseline MRI 3–6 months after starting a DMT to allow treatment effect.

Citations

Starting Recommendations 1–6 — patient counseling, preference incorporation, adherence, and comorbidity assessment at DMT initiation.
Starting Recommendation 7 — DMT for CIS with ≥2 characteristic brain lesions.
Starting Recommendation 8 — serial imaging vs DMT in stable CIS/relapsing MS without recent activity.
Starting Recommendation 16 — natalizumab and JCV antibody index-based PML risk stratification.
Starting Recommendation 17 — ocrelizumab for ambulatory PPMS.
Switching Recommendations 1c, 6, 9 — defining breakthrough disease, PML counseling, and natalizumab-to-fingolimod transition timing.
Switching Recommendation 10 — DMT management around pregnancy.
Stopping Recommendations 1–3 — discontinuation considerations in RRMS, SPMS (EDSS ≥7 for ≥2 years), and CIS.