Why is relapse rate high for someone with Multiple Sclerosis (MS)?

Why Relapse Rates Are High in Multiple Sclerosis

MS is fundamentally an autoimmune-mediated inflammatory disease that causes recurrent episodes of demyelination and axonal damage, with relapses occurring because the underlying immune dysregulation persists without effective disease-modifying therapy. 1

The Core Pathophysiology Driving Relapses

MS relapses occur due to ongoing inflammatory demyelination with axonal transection in the central nervous system. 1 The disease is characterized by:

• Autoimmune attacks where the immune system targets myelin and axons, creating focal inflammatory lesions that manifest as clinical relapses 1
• Continuous subclinical disease activity that often goes undetected between clinical relapses, with MRI showing new T2 lesions and gadolinium-enhancing lesions even when patients appear stable 2
• Progressive neurodegeneration that begins early in the disease course, occurring through both relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) 3

Why Relapses Continue Despite Treatment

The relapse rate remains elevated in many MS patients because:

• Inadequate disease control with moderate-efficacy therapies—current disease-modifying therapies reduce annualized relapse rates by only 29-68% compared to placebo, meaning substantial disease activity persists even on treatment 1
• Delayed treatment escalation using traditional step-therapy approaches, where patients start on lower-efficacy therapies and only escalate after breakthrough disease activity has already caused irreversible damage 2
• Silent progression occurring beneath the threshold of clinical detection, with neurological decline not captured by standard relapse and MRI monitoring 2

The Natural History Without Intervention

Untreated or inadequately treated MS demonstrates:

• Frequent inflammatory activity with mean relapse rates of 1.3 per year in clinical trial populations 4
• Rapid disability accumulation in placebo-treated patients, taking 8.95 years to progress from minimal disability (EDSS 1) to increased walking limitation (EDSS 4) 3
• Cumulative damage where each relapse increases the hazard of subsequent disability worsening by 31-48% in the following year 3

Factors That Increase Relapse Risk

Pre-existing disability and older age are the principal risk factors for incomplete relapse recovery and further disability accumulation. 3 Additional factors include:

• Younger age at onset (mean 20-30 years) when the immune system is most active 1
• Presence of gadolinium-enhancing lesions at baseline (40% of patients in clinical trials had active lesions) 4
• Inadequate treatment response to current therapy, with "hidden" indicators like cognitive impairment, brain atrophy, and fatigue not captured by routine monitoring 2

The Relationship Between Relapses and Long-Term Disability

Treatment differences in relapse reduction are positively and significantly related to differences in disease progression (p < 0.01), with lower treatment effects associated with higher rates of disability progression. 5 This means:

• Relapses directly contribute to disability accumulation, primarily early in MS 3
• Each relapse matters because patients who worsen exclusively due to relapse-associated worsening progress as quickly as those with PIRA events 3
• The fastest disability progression occurs in patients with both PIRA and superimposed relapses 3

Why Nutritional Interventions Don't Reduce Relapses

Vitamin D supplementation and nutritional interventions show no significant benefit for reducing relapses in MS. 6 Specifically:

• Omega-6 fatty acids (linoleic acid) showed no effect on relapse rate or disability in multiple small studies 7
• Omega-3 fatty acids (fish oil with EPA and DHA) demonstrated no significant differences in relapse frequency, duration, or severity in a large 292-patient trial 7
• Vitamin D supplementation at various doses (20,000 IU weekly to 40,000 IU daily) failed to reduce annualized relapse rates in multiple randomized controlled trials 7

Common Pitfalls in Understanding MS Relapse Rates

Clinicians must recognize that:

• Apparent disease stability may mask ongoing subclinical activity, with silent progression occurring despite no clinical relapses 2
• MRI lesion activity alone underestimates true disease burden, as brain atrophy and cognitive decline occur independently of visible lesions 2
• Delayed treatment intensification allows irreversible neurological damage to accumulate before switching to high-efficacy therapies 2