AAN Practice Guideline: Disease-Modifying Therapies for Adults with Multiple Sclerosis (2018, Reaffirmed 2024) with Post-Guideline Evidence
Current AAN practice guideline on starting, switching, and stopping MS disease-modifying therapy (reaffirmed October 2024). Read together with post-guideline evidence — including HERCULES (tolebrutinib for non-relapsing SPMS, 2025) and DISCOMS (DMT discontinuation in older stable patients, 2023) — that informs shared decision-making.
What changed in this edition
- 30 recommendations: 17 on starting DMTs, 10 on switching with breakthrough disease, 3 on stopping.
- Early initiation of DMT recommended for patients with a diagnosis of relapsing MS.
- Counseling and shared decision-making emphasized across adherence, comorbidities, family planning, and adverse-effect monitoring.
- JCV antibody status drives natalizumab decision-making given progressive multifocal leukoencephalopathy risk.
- Post-guideline evidence: HERCULES (2025) shows tolebrutinib reduces confirmed disability progression in non-relapsing SPMS; not yet in the AAN guideline but available for shared decision-making.
- Post-guideline evidence: DISCOMS (2023) informs DMT discontinuation discussions in older patients (≥55) with prolonged disease stability.
- Guideline reaffirmed by the AAN on October 19, 2024.
Clinical takeaways
Early initiation
AAN guideline recommends offering DMT to patients with newly diagnosed relapsing MS after shared decision-making. Post-guideline evidence and practice trends favor higher-efficacy agents (anti-CD20, S1P modulators, natalizumab in JCV-negative patients, cladribine) earlier in disease.
Progressive MS
Ocrelizumab remains the only FDA-approved DMT for PPMS. The 2025 HERCULES trial shows tolebrutinib reduces 6-month confirmed disability progression in non-relapsing SPMS; tolebrutinib is not yet in the AAN guideline but can inform shared decision-making where disability is accruing without new MRI activity.
Monitoring
Annual MRI on stable therapy, every 6 months during switches. JCV antibody every 6 months on natalizumab. CBC, IgG/IgM, and hepatitis screening on anti-CD20. Consider NfL for subclinical activity.
Pregnancy and breastfeeding
Anti-CD20 compatible with breastfeeding; timing of last dose pre-conception is flexible given low placental transfer of monoclonals early in pregnancy. Natalizumab can be continued through pregnancy in high-activity disease.
De-escalation
In patients ≥60 with ≥5 years of stable disease, discuss DMT discontinuation or transition to lower-intensity therapy, balancing infection risk and residual relapse risk.
Supporting trials
- OPERA I/IIPubMed 28002679
Ocrelizumab superior to interferon beta-1a for relapsing MS.
- ORATORIOPubMed 28002688
Ocrelizumab slowed disability progression in PPMS.
- HERCULESPubMed 40202696
Tolebrutinib reduced 6-month confirmed disability progression in non-relapsing SPMS (22.6% vs 30.7%; HR 0.69).
- ASCLEPIOS I/IIPubMed 32757523
Ofatumumab superior to teriflunomide with a subcutaneous, monthly regimen.
- DISCOMSPubMed 37353277
Among patients ≥55 with prolonged MS stability, discontinuation did not meet non-inferiority vs continuation; informs but does not preclude shared decision-making.