Multiple Sclerosis Treatment — Cost, Top Hospitals & Success Rates | MyMedicPlus

Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disease of the central nervous system (CNS). In MS, autoreactive T-cells and B-cells breach the blood-brain barrier, causing focal inflammation with demyelination and axonal damage in the brain, spinal cord, and optic nerves. Over time, accumulation of neurological disability reflects both relapsing inflammatory damage and progressive neurodegenerative mechanisms (including progressive axonal loss, mitochondrial dysfunction, and microglial activation) that operate independently of acute inflammation.

Epidemiology

Approximately 2.8 million people worldwide are living with MS. Prevalence is highest in Northern Europe (UK: 200–280 per 100,000), North America (~350,000–400,000 individuals), Australia, and New Zealand. The disease is 2–3 times more common in women than men. Onset is typically between ages 20–40 years. Risk factors include genetic susceptibility (HLA-DRB1*15:01 allele), vitamin D deficiency, Epstein-Barr virus (EBV) exposure (landmark Bjornevik et al., Science 2022 study showing EBV infection precedes MS in virtually all cases), smoking, and obesity in adolescence.

McDonald 2017 Diagnostic Criteria

The McDonald 2017 criteria (Lancet Neurology 2018; Thompson et al.) define MS diagnosis based on demonstration of:

• Dissemination in Space (DIS) — lesions in ≥2 of 4 characteristic MS locations: periventricular, cortical/juxtacortical, infratentorial, and spinal cord; or a new T2 lesion on follow-up MRI; or clinical second attack involving different CNS region
• Dissemination in Time (DIT) — simultaneous presence of gadolinium-enhancing and non-enhancing T2 lesions on a single MRI scan; or new T2 or Gd-enhancing lesion on follow-up MRI; or a second clinical attack

Key 2017 updates: CSF-specific oligoclonal bands (OCBs) can substitute for DIT in clinically isolated syndrome (CIS); symptomatic lesions are now counted toward DIS; cortical lesions are formally included as an MS-characteristic location.

MS Subtypes

• Relapsing-Remitting MS (RRMS) — 85% of patients at diagnosis; characterised by discrete attacks (relapses) with full or partial recovery; treated with disease-modifying therapies (DMTs)
• Secondary Progressive MS (SPMS) — evolves from RRMS in ~65% of untreated patients over 15–25 years; steady neurological worsening with or without superimposed relapses; siponimod and ofatumumab are approved for active SPMS
• Primary Progressive MS (PPMS) — ~15% at diagnosis; progressive neurological worsening from onset without distinct relapses; ocrelizumab is the only approved DMT (ORATORIO trial)
• Clinically Isolated Syndrome (CIS) — first demyelinating attack not yet meeting full McDonald criteria for MS; early DMT initiation after CIS reduces time to second attack and MS diagnosis

MRI in MS

Brain and spinal cord MRI is essential for diagnosis and monitoring. Key MS MRI features include ovoid periventricular T2 lesions (Dawson's fingers), juxtacortical lesions, infratentorial lesions, optic nerve signal change (STIR/fat-suppressed sequences), and acute gadolinium-enhancing lesions indicating active inflammation. Standardised MRI protocols (MAGNIMS/CMSC 2021 guidelines) specify field strength (≥1.5T, preferably 3T), sequences, and slice thickness for consistent monitoring.

Acute Relapse Treatment

An MS relapse (attack, exacerbation) is defined as new or worsening neurological symptoms lasting >24 hours, in the absence of fever/infection, representing a new inflammatory CNS lesion or reactivation of a prior lesion. Severity determines need for treatment:

• Mild relapse (e.g., sensory symptoms, mild fatigue without functional impact) — observation; time-limited steroid treatment does not affect long-term outcomes and may be withheld
• Moderate-severe relapse (e.g., motor weakness, severe visual impairment, cerebellar symptoms affecting function) — IV methylprednisolone 1 g/day × 3–5 days (RRMS relapse ACTRIMS/ECTRIMS guidelines); accelerates recovery but does not change final neurological outcome or disability accumulation
• Steroid-refractory relapse — plasma exchange (7 exchanges over 14 days) is beneficial in approximately 42% of steroid-refractory attacks (Mayo RCT; Weinshenker NEJM 1999)

Key Monitoring Endpoints

• Annualised Relapse Rate (ARR) — number of confirmed relapses per year; primary endpoint of most RRMS phase III trials
• Disability progression (EDSS) — Expanded Disability Status Scale (0–10); sustained disability worsening confirmed at 12 or 24 weeks is the primary endpoint in progressive MS trials
• MRI endpoints — T2 lesion volume, new T2 lesions, Gd-enhancing lesions, brain atrophy rate (whole-brain volume loss ~0.5%/year in MS vs 0.3%/year normal ageing)
• NEDA (No Evidence of Disease Activity) — absence of all of: clinical relapses, disability progression, new T2 MRI lesions, and new Gd-enhancing lesions; NEDA-3 (clinical + MRI); NEDA-4 adds brain atrophy rate
• PIRA (Progression Independent of Relapse Activity) — disability worsening occurring outside of relapses; an emerging endpoint reflecting the degenerative component of MS that persists even with excellent anti-inflammatory treatment

Initial DMT Selection Framework

DMT selection is guided by four key factors:

• Disease activity and prognosis — high disease activity (multiple relapses, large lesion burden, rapid disability accumulation) justifies high-efficacy DMT from the outset; low activity may start with moderate-efficacy DMT
• Risk tolerance — natalizumab carries PML risk requiring anti-JC virus antibody testing; alemtuzumab causes secondary autoimmunity in 30–40% of patients; patient risk appetite guides choice
• Comorbidities — lymphopaenia (baseline) affects safety of DMF, cladribine, siponimod; cardiac conduction abnormalities affect fingolimod, siponimod, ozanimod (S1P modulators require first-dose cardiac monitoring); pre-existing liver disease affects several DMTs
• Family planning — most high-efficacy DMTs are contraindicated in pregnancy; glatiramer acetate and natalizumab have relatively better pregnancy data; alemtuzumab requires 4-year washout before conception; teriflunomide requires accelerated elimination

Special Situations

• Pregnancy and MS — disease activity typically reduces during pregnancy (especially third trimester) then rebounds postpartum; glatiramer acetate considered relatively safe in pregnancy; natalizumab continued through 30 weeks gestation at some centres to protect from postpartum rebound; careful interdisciplinary counselling required
• CIS (Clinically Isolated Syndrome) — all approved DMTs reduce risk of second attack and delay formal MS diagnosis; high-risk CIS (large lesion burden, infratentorial lesions, OCBs) may justify early high-efficacy DMT
• Paediatric MS — ~5% of MS patients are paediatric (<18 years); interferon-beta, fingolimod (FDA-approved for paediatric RRMS 2018), dimethyl fumarate, and natalizumab are used; alemtuzumab is under investigation

Low-Efficacy Tier (Platform Therapies)

These first-generation DMTs reduce relapse rate by ~30% vs placebo and have decades of safety data.

• Interferon-beta products — IFN-beta-1a (Avonex IM weekly, Rebif SC 3×/week), IFN-beta-1b (Betaseron/Extavia SC alternate days), pegylated IFN-beta-1a (Plegridy SC every 2 weeks). ARR reduction ~30%; injection site reactions, flu-like symptoms, transient liver enzyme elevation, lymphopaenia. Neutralising antibodies reduce efficacy in 5–30% depending on preparation.
• Glatiramer acetate (Copaxone, Glatopa) — daily or 3×/week SC injection; ARR reduction ~30%; mechanism involves shift from Th1 to Th2 immune response; no systemic immunosuppression; safest profile in pregnancy; injection site reactions common.

Moderate-Efficacy Tier

These oral and infusion agents achieve 50–60% ARR reduction vs placebo with more nuanced safety profiles.

• Dimethyl fumarate / DMF (Tecfidera, Vumerity [diroximel fumarate]) — oral twice daily; ARR reduction ~49–53% vs placebo (DEFINE, CONFIRM trials); mechanism: Nrf2 antioxidant pathway activation + lymphocyte modulation; flushing and GI side effects (improved with Vumerity); lymphopaenia monitoring mandatory (risk of PML in severe lymphopaenia <0.5 × 10⁹/L, though much lower than natalizumab).
• Teriflunomide (Aubagio) — oral once daily; ARR reduction ~31–36% vs placebo (TEMSO, TOWER trials); mechanism: inhibits dihydroorotate dehydrogenase (DHODH), reducing rapidly proliferating lymphocytes; liver enzyme monitoring required; teratogenic — accelerated elimination protocol (cholestyramine) mandatory before pregnancy; hair thinning common.
• Siponimod (Mayzent) — oral once daily; selective S1P1/5 receptor modulator; approved for active SPMS and RRMS; EXPAND trial (SPMS): 21% reduction in 3-month confirmed disability progression vs placebo; cardiac monitoring required at first dose; macular oedema screening in diabetics; requires CYP2C9 genotyping (poor metabolisers receive lower dose).
• Ozanimod (Zeposia) — oral once daily; selective S1P1/5 modulator; SUNBEAM and RADIANCE trials (RRMS): ARR reduction 48–51% vs IFN-beta-1a; cardiac monitoring at first dose; no first-dose observation required in current labelling if titrated per protocol.
• Ponesimod (Ponvory) — oral once daily; selective S1P1 modulator; OPTIMUM trial vs teriflunomide: ARR reduction 30.5%; fatigue endpoint also showed benefit.

High-Efficacy Tier

These agents achieve 60–70%+ ARR reduction and are preferred for patients with highly active MS at diagnosis or those who fail moderate-efficacy DMTs.

• Natalizumab (Tysabri) — IV infusion every 4 weeks (SC formulation Kesimpta is ofatumumab, not natalizumab); anti-alpha-4 integrin antibody preventing lymphocyte trafficking into CNS; AFFIRM trial: ARR reduction 68%, MRI lesion reduction 83%; critical safety concern: Progressive Multifocal Leukoencephalopathy (PML) caused by JC virus reactivation.
  STRATIFY programme — anti-JC virus antibody testing (JC index); JC-negative patients: very low PML risk (~1/10,000); JC-positive patients: risk stratified by index value and prior immunosuppressant use — up to 1/50 at very high index >1.5 with prior immunosuppressant and >24 months natalizumab; extended interval dosing (every 6 weeks) reduces PML risk in JC-positive patients (NOVA study). Brain MRI surveillance every 3–6 months in JC-positive patients. Plasma exchange for suspected PML to accelerate natalizumab removal.
• Alemtuzumab (Lemtrada) — IV infusion: 5 consecutive days at year 1, then 3 consecutive days at year 2; anti-CD52 antibody causing profound and prolonged lymphocyte depletion with immune reconstitution; CARE-MS I (treatment-naive) and CARE-MS II (active RRMS after prior DMT) trials: ARR reduction 49–55% vs IFN-beta-1a; 42–65% of patients remain free of sustained disability accumulation at 6 years. Secondary autoimmunity: thyroid (38%), ITP (2%), anti-GBM nephropathy (0.3%) — monthly thyroid function, CBC, and renal monitoring for 48 months post-treatment. Alemtuzumab has EMA restriction to highly active RRMS only (since 2019 cardiovascular safety warning: stroke, arterial dissection in rare cases).
• Ocrelizumab (Ocrevus) — IV infusion 600 mg every 6 months (SC formulation approved in USA 2024); humanised anti-CD20 B-cell depleting monoclonal antibody; FDA-approved for both RRMS and PPMS:
  - OPERA I and OPERA II (RRMS): ARR reduction 46–47% vs IFN-beta-1a; 40–43% fewer T1 gadolinium lesions; the only anti-CD20 to show superiority vs an active comparator (IFN-beta-1a)
  - ORATORIO (PPMS): 24% reduction in 12-week confirmed disability progression vs placebo; 10-year open-label extension (PPMS) showed continued slowing of progression
  Safety: infusion-related reactions (premedicate with methylprednisolone, antihistamine); upper respiratory tract infections; hepatitis B reactivation screening mandatory; moderate increase in malignancy risk with very long-term use (monitoring programme); hypogammaglobulinaemia with prolonged use — monitor IgG and consider IVIG supplementation.
• Cladribine (Mavenclad) — oral short-course tablets given over 4 days in month 1 and 4 days in month 2, for 2 years only; subsequently treatment-free; purine analogue causing selective lymphocyte depletion with prolonged reconstitution; CLARITY trial: ARR reduction 55–58% vs placebo; 87% reduction in new T2 lesions; 4-year data show durable remission post-treatment in many patients. Lymphopaenia is expected and required for efficacy (grade 3–4 lymphopaenia in ~25%); reactivation risk — VZV prophylaxis mandatory; teratogenic — effective contraception required during treatment and 6 months after last dose.
• Ofatumumab (Kesimpta) — subcutaneous self-injection monthly (after initial weekly doses for 3 weeks); fully human anti-CD20 B-cell depleting antibody; ASCLEPIOS I and II trials (vs teriflunomide): ARR reduction 50.5–58.5%; also approved for active SPMS. SC administration allows self-injection, avoiding infusion centre visits — major convenience advantage over IV ocrelizumab for eligible patients.

Treat-to-Target: NEDA and PIRA

No Evidence of Disease Activity (NEDA) is the contemporary treatment target in RRMS. NEDA-3 (no relapses + no new MRI lesions + no disability worsening) guides DMT escalation decisions. Failure to achieve NEDA-3 on a platform/moderate-efficacy DMT is an indication to switch to high-efficacy therapy.

PIRA (Progression Independent of Relapse Activity) is increasingly recognised as the dominant mechanism of long-term disability accumulation in MS, occurring even in the absence of clinical relapses. PIRA is not fully suppressed by current anti-inflammatory DMTs; this is the rationale for ongoing neuroprotective and remyelination research programmes. Induction strategies (alemtuzumab, HSCT) applied early may be better at limiting PIRA than maintenance strategies applied later.

Haematopoietic Stem Cell Transplantation (HSCT) for MS

Autologous HSCT involves: myeloablative or non-myeloablative conditioning chemotherapy (most commonly BEAM: carmustine + etoposide + cytarabine + melphalan; or cyclophosphamide-based) to ablate the autoreactive immune system, followed by rescue with autologous haematopoietic stem cells. The reconstituted immune system lacks the autoreactive clones driving MS.

MIST trial (NEJM 2019) — the definitive RCT: 110 patients with active RRMS despite 1 DMT, randomised to HSCT vs mitoxantrone or natalizumab. At 5 years: treatment failure rate 6% (HSCT) vs 60% (DMT; p <0.0001). Median time to treatment failure not reached in HSCT group vs 24 months in DMT group. NEDA at 5 years: 63% HSCT vs 2% DMT.

Current ECTRIMS/EAN 2024 recommendations: HSCT may be considered for highly active RRMS refractory to ≥2 DMTs, in young patients with EDSS 3.0–5.5, at experienced HSCT centres. Non-myeloablative protocols (BEAM or cyclophosphamide alone) have reduced transplant-related mortality to ~0.3% at experienced centres. HSCT is not appropriate for progressive MS without active inflammation.

Comparative Efficacy (Annualised Relapse Rate Reduction vs Placebo)

Progressive MS — Evidence for DMTs

• Ocrelizumab (PPMS) — ORATORIO trial: 24% relative risk reduction in 12-week confirmed disability progression vs placebo; first and only FDA/EMA-approved therapy for PPMS (2017)
• Siponimod (active SPMS) — EXPAND trial: 21% relative reduction in 3-month CDP; approved for active SPMS (with recent relapses or active MRI); the S1P modulator mechanism has both anti-inflammatory and potential neuroprotective effects
• Ofatumumab (active SPMS) — approved by EMA 2021 based on pooled ASCLEPIOS data for active SPMS
• Cladribine — approved for highly active RRMS/CIS with active inflammation; not for inactive progressive MS

PML Risk with Natalizumab

Progressive Multifocal Leukoencephalopathy (PML) is caused by reactivation of JC polyomavirus in the setting of natalizumab-induced CNS immunosuppression. Risk stratification via the STRATIFY programme:

• JC antibody negative (tested every 6 months): risk ~1/10,000; natalizumab can be continued with reassurance
• JC antibody positive, index <0.9: risk ~1/2,000; continue with regular MRI surveillance
• JC antibody positive, index 0.9–1.5, ≤24 months: risk ~1/1,000
• JC antibody positive, index >1.5, >24 months, prior immunosuppressant: risk up to ~1/50 — most neurologists recommend switching to alternative DMT at this risk level

Extended interval dosing (every 6 weeks vs 4 weeks) reduces PML incidence by ~94% in JC-positive patients (NOVA study) while maintaining reasonable efficacy. Brain MRI every 3–6 months in JC-positive patients allows detection of asymptomatic radiologically isolated PML (radPML) before symptoms, enabling plasma exchange to remove natalizumab and improve outcomes.

Alemtuzumab Secondary Autoimmunity

The immune reconstitution following alemtuzumab-induced lymphocyte depletion can generate new autoimmune conditions in up to 50% of patients over 5+ years:

• Thyroid disease (38%) — most commonly Graves hyperthyroidism or Hashimoto thyroiditis; monitored by monthly TSH/T4 for 48 months
• Immune thrombocytopenic purpura (ITP) (2–3%) — potentially life-threatening; monthly CBC for 48 months; patients educated about bruising/petechiae and instructed to seek immediate evaluation
• Goodpasture syndrome / anti-GBM nephropathy (<0.5%) — monthly serum creatinine and urinalysis for 48 months; rarely fatal with early detection and treatment (plasma exchange + cyclophosphamide)
• Rare: autoimmune hepatitis, haemolytic anaemia, neutropenia

S1P Modulator Safety (Fingolimod, Siponimod, Ozanimod)

• Bradycardia / AV block — first-dose effect from S1P1 cardiac agonism; 6-hour first-dose cardiac monitoring in cardiology setting required; patients with existing cardiac conduction disease are higher risk
• Macular oedema — 0.5–1% incidence; ophthalmological examination before treatment, and at 3–4 months; annual thereafter; contraindicated in patients with diabetic maculopathy
• Lymphopaenia — dose-dependent reduction in circulating lymphocytes; increases risk of VZV, cryptococcal and other opportunistic infections; VZV vaccination ≥4 weeks before initiating S1P modulators
• Rebound MS activity — severe rebound relapses on discontinuation of S1P modulators (especially fingolimod and siponimod); must bridge with another DMT; do not stop abruptly

DMF/Vumerity Safety

• GI adverse effects (flushing, diarrhoea, nausea) in 30–40% at treatment initiation; significantly reduced by taking with food and gradual dose titration; Vumerity (diroximel fumarate) has lower GI side effects than Tecfidera
• Lymphopaenia — monitor absolute lymphocyte count every 6 months; hold or discontinue if ALC <500/µL for >6 months (PML risk with prolonged severe lymphopaenia)

Structured MS Monitoring Programme

All patients on DMTs require regular neurological review integrating:

• Clinical assessment — EDSS scoring, relapse frequency, symptom review, functional assessment (walking speed, hand function, cognition)
• MRI monitoring — annual brain MRI (with gadolinium at baseline and when new activity suspected); spinal cord MRI at baseline and as clinically indicated; standardised MAGNIMS/CMSC protocol maintained consistently at the same scanner where possible
• Laboratory monitoring — varies by DMT: CBC every 6 months (DMF, cladribine, alemtuzumab); LFTs (teriflunomide, DMF); renal function (alemtuzumab post-treatment); thyroid function (alemtuzumab, amiodarone in cardiac monitoring); JC antibody index (natalizumab every 6 months)

DMT Switching and Escalation

Escalation from lower- to higher-efficacy DMT is indicated when:

• ≥1 confirmed relapse on platform therapy
• New or enlarging T2 lesions or new Gd-enhancing lesion on annual MRI
• Sustained disability accumulation (3-month confirmed worsening on EDSS)
• Failure to achieve NEDA-3 at 6–12 months

The escalation vs induction treatment strategy debate continues. Emerging evidence from large observational studies (MSBase registry, Swedish MS registry) suggests that earlier use of high-efficacy therapies achieves better long-term disability outcomes and may be cost-effective by preventing disability-related costs over decades. The 'induction' approach (starting with high-efficacy DMT immediately in active RRMS) is increasingly advocated at specialist MS centres.

Symptom Management in MS

DMTs address the inflammatory disease process but do not reverse existing deficits. Symptom management is a critical parallel component of MS care:

• Fatigue — most common and disabling symptom (~80% of patients); assess for contributory factors (depression, sleep disorder, anaemia, thyroid disease); non-pharmacological: energy conservation, graded exercise (NICE-recommended: aerobic + resistance); pharmacological: amantadine, modafinil, methylphenidate (limited evidence; not licensed for MS fatigue)
• Spasticity — baclofen oral (first-line); tizanidine; physiotherapy; intrathecal baclofen pump for severe spasticity; cannabinoids (Sativex oromucosal spray — licensed in UK and EU for MS spasticity); botulinum toxin for focal spasticity
• Bladder dysfunction — overactive bladder: anticholinergics (oxybutynin, tolterodine) or mirabegron (beta-3 agonist); detrusor underactivity/incomplete emptying: clean intermittent self-catheterisation (CISC); UTI prevention critical; urodynamics assessment in complex cases
• Neuropathic pain — pregabalin, gabapentin (first-line); amitriptyline; duloxetine; carbamazepine for trigeminal neuralgia
• Depression — prevalent in 50% of MS patients over disease course; SSRIs and SNRIs; cognitive behavioural therapy (CBT); mindfulness-based stress reduction; exercise; psychological support from MS specialist nurse
• Cognition — cognitive impairment affects 40–60% of MS patients; neuropsychological assessment; cognitive rehabilitation; aerobic exercise has the strongest evidence-base for MS-related cognitive fatigue
• Gait and mobility — fampridine (4-aminopyridine; Fampyra/Ampyra) — licensed for walking speed improvement in MS patients who respond (50% of treated patients show ≥20% improvement in 25-foot walk); requires trial period to establish response

Treatment costs for Multiple Sclerosis Treatment vary significantly by procedure complexity, healthcare system, and geographic location. In India — the leading global medical tourism destination — major procedures cost 60–85% less than comparable treatment in the USA or UK while maintaining equivalent or superior clinical outcomes at NABH- or JCI-accredited facilities. Consultation and diagnostic workup: $30–200 India vs $500–3,000 USA. Inpatient procedures: $1,000–10,000 India vs $10,000–80,000 USA. Medications and ongoing management: generic drugs available in India at 80–95% lower cost than branded equivalents in the USA. Follow-up imaging and laboratory monitoring: 70–85% cost savings in India. Medical tourism packages (including treatment, accommodation, and local logistics support) are offered by major Indian hospital groups (Apollo, Fortis, Medanta, Narayana Health, Manipal Hospitals). For patients from high-income countries, medical tourism to India, Thailand, or Turkey for elective procedures can achieve savings of $10,000–200,000 per episode while accessing care from internationally trained specialists.

Remyelination Therapies

Current DMTs reduce inflammation but do not repair existing myelin damage. Remyelination therapies targeting oligodendrocyte precursor cells (OPCs) are in active clinical development:

• Opicinumab (anti-LINGO-1) — BIIB033; phase II SYNERGY trial results (2018) mixed; subgroup analyses suggest remyelination benefit in certain patients
• Bexarotene — retinoid X receptor agonist promoting OPC differentiation; positive signal in CCMR-1 trial (Cambridge); phase II ongoing
• Clemastine fumarate — antihistamine with MUSCARINIC receptor antagonism promoting remyelination; ReBUILD trial showed significant improvement in visual evoked potential latency, a biomarker of remyelination
• Olesoxime, liothyronine (T3), benztropine — additional OPC-promoting agents in early trials

Neuroprotective Strategies

• Simvastatin — MS-STAT2 phase III trial (UK) for SPMS: evaluating neuroprotection via anti-inflammatory and direct neuroprotective mechanisms; results awaited
• Ibudilast — non-selective phosphodiesterase inhibitor with neuroprotective effects; SPRINT-MS trial (NEJM 2018): reduced brain atrophy rate in progressive MS (0.71 vs 1.15% over 96 weeks); not yet licensed for MS
• Biotin (MD1003) — high-dose pharmaceutical-grade biotin; SPI2 trial results negative in PPMS and SPMS after initial positive phase II signal

BTK Inhibitors

Bruton's tyrosine kinase (BTK) inhibitors that penetrate the CNS (fenebrutinib, tolebrutinib, evobrutinib, remibrutinib) are in phase III trials for progressive MS. These agents target both B-cells and microglia within the CNS, potentially addressing the compartmentalised CNS inflammation that drives progression independent of peripheral inflammation — the mechanism not targeted by current DMTs. HERCULES (tolebrutinib, SPMS) and FENWAY/DAYBREAK (fenebrutinib) trials are ongoing; tolebrutinib phase III showed significant reduction in confirmed disability progression in SPMS in October 2024 (first positive progressive MS trial result for an agent addressing both peripheral and CNS inflammation).

Biomarker-Guided Treatment

Serum neurofilament light chain (sNfL) — a biomarker of neuroaxonal damage released into blood from damaged neurons — is increasingly used in MS research and moving toward clinical application. Elevated sNfL predicts future disability accumulation, detects subclinical MS activity, and shows normalisation with effective treatment. sNfL may become a complement to MRI for treatment monitoring and escalation decisions in routine clinical care within the next 5 years.

Dietary and Lifestyle Interventions

While no diet is proven to modify MS disease course in RCTs, observational evidence supports:

• Aerobic exercise — strong evidence (multiple RCTs) for improving fatigue, depression, mobility, and cognitive function in MS; recommended 150 minutes/week moderate-intensity
• Vitamin D supplementation — observational studies link vitamin D deficiency to MS risk and activity; supplementation is widely recommended to maintain serum 25-OH-D >75 nmol/L; high-dose vitamin D (Coimbra protocol) lacks robust RCT evidence
• Mediterranean diet — anti-inflammatory dietary pattern associated with lower fatigue and better quality of life in observational MS cohorts
• Smoking cessation — active smoking associated with faster progression to SPMS and is a modifiable risk factor; all MS patients should be supported to quit