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neuro.ms-rrms.v1PRODUCTION
neuro.ms-rrms.v1

Relapsing-Remitting Multiple Sclerosis (chronic DMT)

neurologychronicadultpediatricpregnancy
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Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Confirm RRMS per McDonald 2017 (DIS + DIT) with active or stable disease; distinguish from SPMS (progression independent of relapses) and PPMS (steady accumulation from onset) (PMID 29275977)

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Advance rule
Set
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RRMS subtype confirmed and active/non-active status assigned

Patient inputs (17)

HBV reactivation risk on anti-CD20 — screen pre-DMT (AAN 2024)

VZV-naive → vaccinate before S1P modulator or anti-CD20 (AAN 2024)

Latent TB screen before DMT, especially anti-CD20 + S1P (AAN 2024)

Younger patients have higher relapse rate; pregnancy alters DMT eligibility (AAN 2024)

Anchor for relapse counting + DIT per McDonald 2017 (PMID 29275977)

Active disease = new T2 / gad+ lesion since prior MRI; NEDA-3 target on DMT (AAN 2024)

Lymphopenia surveillance on DMF / cladribine / siponimod / fingolimod (AAN 2024)

DMT hepatotoxicity surveillance (DMF, teriflunomide, ocrelizumab) (AAN 2024)

ARR drives high vs moderate efficacy decision (ECTRIMS 2024) — schema-blocked, captured in required_assessments

Pregnancy excludes most DMTs; planning required for washout (cladribine 6 mo, teriflunomide cholestyramine washout) (AAN 2024)

Required before DMT initiation in reproductive-age females (AAN 2024)

AV block, bradycardia, recent MI/stroke contraindicate fingolimod/siponimod first-dose (AAN 2024)

Cervical cord lesions strong disability predictor; baseline + annual (AAN 2024)

Hypogammaglobulinemia on anti-CD20 (ocre/ofa/ublitux) — infection risk (AAN 2024)

EDSS pre-DMT anchors NEDA-3 + progression-independent-of-relapse (PIRA) tracking — schema-blocked

JCV-Ab index gates natalizumab eligibility; recheck q6 mo on natalizumab (PML risk) (AAN 2024)

CYP2C9 *3/*3 contraindicates siponimod (genotype-driven dose) (AAN 2024)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (8)

8 need judgement
  • informationallife_threateningpml_risk_natalizumab_jcv_positive
    JCV-Ab positivity on natalizumab (especially >2 y therapy + prior IS) → PML risk → switch to anti-CD20 (AAN 2024)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverehighly_active_rrms_escalation_indicated
    Highly active RRMS — ≥2 relapses in past 12 mo OR ≥3 gad+ lesions OR rapid EDSS progression — aggressive escalation (ECTRIMS 2024)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverebreakthrough_on_dmt_escalation_indicated
    Breakthrough relapse OR new MRI activity despite ≥6 mo on adequate-dose DMT → escalate to higher efficacy tier (ECTRIMS 2024)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateactive_rrms_relapse_eligible
    Active RRMS — relapse in past 12 mo OR new T2/gad+ lesion on surveillance MRI (AAN 2024)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateclinically_isolated_syndrome_cis
    CIS — first demyelinating event + MRI lesions meeting DIS/DIT risk → start DMT per McDonald 2017 (PMID 29275977)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatepregnancy_rrms_dmt_washout
    Active pregnancy or near-term plan → DMT washout / switch to pregnancy-compatible (glatiramer, IFN OK; teriflunomide cholestyramine washout; cladribine 6 mo washout) (AAN 2024)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatepediatric_rrms
    Pediatric-onset MS (<18 y) — different PK; PARADIGMS fingolimod FDA-approved ≥10 y (PMID 30207920 NEEDS_SOURCE_REVIEW)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildclassic_rrms_modest_activity
    Classic RRMS — modest activity (ARR ≤1) + EDSS ≤3 + patient prefers oral/SC — moderate efficacy first-line (AAN 2024)
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

RRMS DMT efficacy ladder — moderate vs high efficacy first-line (AAN 2024; ECTRIMS 2024)
axis: rrms_dmt_efficacy_ladderstep 1 - Step 1 — Moderate efficacy first-line (low-activity RRMS / patient preference)
Selected step "Step 1 — Moderate efficacy first-line (low-activity RRMS / patient preference)" — ARR ≤1 + ≤2 new T2 lesions/year + EDSS ≤3 + patient prefers oral/SC over IV; or pregnancy planning soon
  • glatiramer acetate
    first line
    immunomodulator
    20 mg SC daily OR 40 mg SC 3×/week • SC • daily / 3×/week
    triggers: pregnancy_planning, low_activity_RRMS
    Long safety track + pregnancy-compatible (Cat B); injection-site reaction common; PRISMS/COPAXONE pivotal
    rxcui 84375
  • interferon beta-1a
    first line
    interferon
    30 mcg IM weekly (Avonex) OR 44 mcg SC 3×/week (Rebif) • IM / SC • weekly / 3×/week
    triggers: pregnancy_compatible_preference
    PRISMS — moderate efficacy; flu-like ADRs; LFT + CBC monitoring
    rxcui 75917
  • dimethyl fumarate
    first line
    fumarate
    120 mg PO BID × 7 d then 240 mg PO BID • PO • BID
    triggers: oral_preference_low_activity
    DEFINE (Gold NEJM 2012 PMID 22992073) + CONFIRM — flush + GI ADRs; lymphopenia monitoring; PML rare in lymphopenic
    rxcui 1373478
  • teriflunomide
    first line
    pyrimidine_synthesis_inhibitor
    14 mg PO daily • PO • daily
    triggers: oral_preference, low_activity
    TEMSO/TOWER — modest efficacy; hepatotoxic; teratogenic (Cat X) — cholestyramine washout required before pregnancy
    rxcui 1310520

outpatient playbook — drug actions (10)

  1. 1. ocrelizumab
    600 mg IV q6 months • IV infusion • q6 mo
    trigger: Highly active RRMS first-line
    OPERA PMID 28002679
  2. 2. ofatumumab
    20 mg SC monthly • SC • monthly
    trigger: SC preference high efficacy
    ASCLEPIOS PMID 32757523
  3. 3. ublituximab
    450 mg IV q6 months • IV • q6 mo
    trigger: Rapid-infusion preference
    ULTIMATE PMID 36001711
  4. 4. natalizumab
    300 mg IV q4 weeks • IV • monthly
    trigger: Highly active JCV-negative
    AFFIRM; PML monitoring
  5. 5. cladribine
    3.5 mg/kg cumulative oral pulsed • PO • years 1+2
    trigger: Short-course induction
    CLARITY PMID 20089960
  6. 6. fingolimod
    0.5 mg PO daily • PO • daily
    trigger: Oral moderate-high efficacy
    FREEDOMS; first-dose cardiac monitor
  7. 7. glatiramer acetate
    20 mg SC daily • SC • daily
    trigger: Pregnancy planning
    Cat B safest
  8. 8. baclofen (spasticity)
    5-10 mg PO TID titrate • PO • TID
    trigger: Spasticity
    AAN 2024 symptomatic; max 80 mg/d; renal adjust
  9. 9. amantadine (fatigue)
    100 mg PO BID • PO • BID
    trigger: Fatigue
    AAN 2024 modest benefit; livedo + insomnia ADRs
  10. 10. oxybutynin (bladder)
    5 mg PO BID-TID • PO • BID-TID
    trigger: Neurogenic detrusor overactivity
    Anticholinergic — caution cognition

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Established RRMS per McDonald 2017 (Thompson Lancet Neurol PMID 29275977) — DIS + DIT confirmed; Clinically Isolated Syndrome (CIS) — first demyelinating event + MRI with risk → start DMT per McDonald 2017; New T2 lesion or gad+ enhancing lesion on surveillance MRI — disease activity (AAN 2024).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Relapsing-Remitting Multiple Sclerosis (chronic DMT)** (neuro.ms-rrms.v1).
Phenotype framing: Confirm RRMS vs CIS vs SPMS conversion (insidious progression ≥6 mo independent of relapse) vs PPMS vs NMOSD vs MOGAD vs ADEM (AAN 2024)
Scope: Confirm RRMS per McDonald 2017 (DIS + DIT) with active or stable disease; distinguish from SPMS (progression independent of relapses) and PPMS (steady accumulation from onset) (PMID 29275977)

No severity triggers fired against current inputs.

Plan

Regimen axis: **RRMS DMT efficacy ladder — moderate vs high efficacy first-line (AAN 2024; ECTRIMS 2024)** — step "Step 1 — Moderate efficacy first-line (low-activity RRMS / patient preference)".
1. glatiramer acetate 20 mg SC daily OR 40 mg SC 3×/week SC daily / 3×/week (immunomodulator, first line) — Long safety track + pregnancy-compatible (Cat B); injection-site reaction common; PRISMS/COPAXONE pivotal
2. interferon beta-1a 30 mcg IM weekly (Avonex) OR 44 mcg SC 3×/week (Rebif) IM / SC weekly / 3×/week (interferon, first line) — PRISMS — moderate efficacy; flu-like ADRs; LFT + CBC monitoring
3. dimethyl fumarate 120 mg PO BID × 7 d then 240 mg PO BID PO BID (fumarate, first line) — DEFINE (Gold NEJM 2012 PMID 22992073) + CONFIRM — flush + GI ADRs; lymphopenia monitoring; PML rare in lymphopenic
4. teriflunomide 14 mg PO daily PO daily (pyrimidine_synthesis_inhibitor, first line) — TEMSO/TOWER — modest efficacy; hepatotoxic; teratogenic (Cat X) — cholestyramine washout required before pregnancy

Setting playbook (outpatient) — Primary MS clinic — comprehensive RRMS management q3-6 mo: relapse + MRI + DMT + comorbidity + pregnancy + symptomatic care; NEDA-3 target (no relapse + no new MRI lesion + no EDSS progression) (AAN 2024; ECTRIMS 2024)
5. ocrelizumab 600 mg IV q6 months IV infusion q6 mo — Highly active RRMS first-line (OPERA PMID 28002679)
6. ofatumumab 20 mg SC monthly SC monthly — SC preference high efficacy (ASCLEPIOS PMID 32757523)
7. ublituximab 450 mg IV q6 months IV q6 mo — Rapid-infusion preference (ULTIMATE PMID 36001711)
8. natalizumab 300 mg IV q4 weeks IV monthly — Highly active JCV-negative (AFFIRM; PML monitoring)
9. cladribine 3.5 mg/kg cumulative oral pulsed PO years 1+2 — Short-course induction (CLARITY PMID 20089960)
10. fingolimod 0.5 mg PO daily PO daily — Oral moderate-high efficacy (FREEDOMS; first-dose cardiac monitor)
11. glatiramer acetate 20 mg SC daily SC daily — Pregnancy planning (Cat B safest)
12. baclofen (spasticity) 5-10 mg PO TID titrate PO TID — Spasticity (AAN 2024 symptomatic; max 80 mg/d; renal adjust)
13. amantadine (fatigue) 100 mg PO BID PO BID — Fatigue (AAN 2024 modest benefit; livedo + insomnia ADRs)
14. oxybutynin (bladder) 5 mg PO BID-TID PO BID-TID — Neurogenic detrusor overactivity (Anticholinergic — caution cognition)

Non-pharmacologic actions:
- PT/OT referral for gait + ADL
- Cognitive rehab if SDMT decline
- Mental health referral if PHQ-9 ≥10
- Vitamin D 2000-4000 IU/d
- Smoking cessation counseling
- Mediterranean diet
- Aerobic exercise 150 min/wk
- Pelvic floor PT for bladder
- Sleep hygiene + screen for RLS / sleep apnea
- Vocational rehab if work impact
- Driving safety review at progression
- Vaccination plan: live vaccines (MMR, VZV, yellow fever) pre-DMT; inactivated annually OK on most DMTs

AVOID / contraindication checks:
- JCV_index_check_before_and_q6mo_on_natalizumab (AAN 2024)
- VZV_vaccination_before_S1P_modulator (AAN 2024)
- HBV_screen_before_anti_CD20 (AAN 2024)
- TB_quantiferon_screen_before_DMT (AAN 2024)
- CYP2C9_genotype_for_siponimod (AAN 2024)
- Teriflunomide_pregnancy_X_cholestyramine_washout (AAN 2024)
- Cladribine_6mo_washout_before_conception (AAN 2024)
- Cardiac_monitoring_first_dose_fingolimod (AAN 2024)
- Alemtuzumab_secondary_autoimmunity_thyroid_ITP_GBM (CARE MS)
- Hypogammaglobulinemia_surveillance_on_anti_CD20 (AAN 2024)
- Vaccinations_4_to_6_wk_before_anti_CD20 (AAN 2024)

Monitoring

Regimen monitoring:
- CBC lymphocyte count q3 to 6 mo (AAN 2024)
- LFT q3 to 6 mo (AAN 2024)
- JCV Ab q6 mo on natalizumab (AAN 2024)
- IgG annually on anti CD20 (AAN 2024)
- annual brain MRI with gad NEDA 3 target (AAN 2024)
- annual cervical cord MRI (AAN 2024)
- EDSS at each visit (schema-blocked — see depth bundle)
- ARR at each visit (schema-blocked — see depth bundle)

Setting (outpatient) monitoring:
- NEDA-3 (relapse + MRI + EDSS) annually
- CBC + LFT q3-6 mo
- JCV q6 mo on natalizumab
- IgG annually on anti-CD20
- Annual MRI brain + cord
- Pregnancy intent each visit

Follow-up plan: Rehab/PT/OT; symptomatic Rx (spasticity, fatigue, bladder); pregnancy planning + washout when applicable; vaccinations before next DMT cycle; annual MRI; cognitive screen (AAN 2024)
- Close-out criterion: Follow-up bundle scheduled

Monitoring phase: CBC + LFT q3-6 mo; annual brain MRI (NEDA-3 target); JCV-Ab q6 mo on natalizumab; IgG annually on anti-CD20; lymphocyte nadir on DMF/cladribine/siponimod; ARR + EDSS at each visit (AAN 2024)

Disposition

Current setting: outpatient — Primary MS clinic — comprehensive RRMS management q3-6 mo: relapse + MRI + DMT + comorbidity + pregnancy + symptomatic care; NEDA-3 target (no relapse + no new MRI lesion + no EDSS progression) (AAN 2024; ECTRIMS 2024)

Disposition criteria:
- Continue indefinite MS clinic q3-6 mo
- Transition to neuro.ms-spms.v1 if progression independent of relapse ≥6 mo (SPMS conversion)
- Hospice + palliative if severe disability + recurrent complications (rare in RRMS phase)

Escalation triggers (move to higher acuity):
- Breakthrough relapse on DMT → escalate efficacy tier
- PML suspicion on natalizumab → STAT MRI + neurology + d/c
- Severe lymphopenia (<500) on DMF → pause + workup
- Hepatotoxicity (LFT >3× ULN) on DMT → pause + workup
- IgG <500 + recurrent infection on anti-CD20 → IVIG / pause
- Severe ARI or COVID → consider hold DMT cycle

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] JCV-Ab positivity on natalizumab (especially >2 y therapy + prior IS) → PML risk → switch to anti-CD20 (AAN 2024)
- [SEVERE] Highly active RRMS — ≥2 relapses in past 12 mo OR ≥3 gad+ lesions OR rapid EDSS progression — aggressive escalation (ECTRIMS 2024)
- [SEVERE] Breakthrough relapse OR new MRI activity despite ≥6 mo on adequate-dose DMT → escalate to higher efficacy tier (ECTRIMS 2024)

Citations

- AAN 2024 MS DMT guideline + ECTRIMS 2024 + McDonald 2017 (Thompson Lancet Neurol PMID 29275977) [PMID:28002679](https://pubmed.ncbi.nlm.nih.gov/28002679/)
- Cited evidence (PMID 18272891) [PMID:18272891](https://pubmed.ncbi.nlm.nih.gov/18272891/)
- Cited evidence (PMID 22992073) [PMID:22992073](https://pubmed.ncbi.nlm.nih.gov/22992073/)
- Cited evidence (PMID 20089960) [PMID:20089960](https://pubmed.ncbi.nlm.nih.gov/20089960/)
- Cited evidence (PMID 32757523) [PMID:32757523](https://pubmed.ncbi.nlm.nih.gov/32757523/)

Last reconciled with current guidelines: 2026-05-22.
References