MULTIPLE SCLEROSIS SCIENCE

Why First-Line DMTs
Often Fail in MS

Your MS is driven by specific neuroinflammatory pathways. Understanding whether you're Th1, Th17, or B-cell dominant helps you start with the right high-efficacy DMT from day one.

The First-Line Therapy Problem

Standard MS treatment follows an escalation approach: start with first-line DMTs like Copaxone or Avonex, wait 12-18 months to see if they work, then escalate to high-efficacy therapies if they fail. Meanwhile, new lesions form and disability accumulates.

What This Means for Patients:

  • 18+ months on first-line therapy with modest efficacy (~30% reduction in relapses)
  • New lesions and brain volume loss during this "trial period"
  • Neurological damage that cannot be reversed
  • Delayed access to the DMT that would have worked from the start

The question is: If you're going to need Ocrevus, Tysabri, or Mavenclad anyway, why waste 18 months on therapies that won't control YOUR disease? The answer lies in understanding your neuroinflammatory pathways.

The Three Main MS Pathways

Understanding which pathway is driving YOUR neuroinflammation

PATHWAY 1 ~30-40% of Patients

Th1 Pathway (IFN-γ Dominant)

What's happening: Your immune system's Th1 cells release interferon-gamma (IFN-γ), which activates macrophages to attack your myelin. This pathway creates inflammation that damages the protective coating around your nerves.

Think of it like this: Your immune system has activated a "seek and destroy" program against myelin. Th1 cells are sending signals that recruit damage-causing cells to your brain and spinal cord.

What we test:

IFN-γ, IL-2, TNF-α, IL-12

If this is YOUR pathway, consider these DMTs:

Tysabri (natalizumab), Gilenya (fingolimod), Mavenclad (cladribine)

PATHWAY 2 ~25-35% of Patients

Th17 Pathway (IL-17 Dominant)

What's happening: Th17 cells produce IL-17, which breaks down the blood-brain barrier and allows inflammatory cells to flood into your central nervous system. This pathway is associated with more aggressive, relapsing MS.

Think of it like this: IL-17 is like breaking down the security gates around your brain, allowing damaging immune cells to rush in. The more IL-17, the more breaches in your defenses.

What we test:

IL-17A, IL-17F, IL-23, IL-6, IL-21

If this is YOUR pathway, consider these DMTs:

Mavenclad (cladribine), Kesimpta (ofatumumab), Tysabri (natalizumab)

PATHWAY 3 ~30-40% of Patients

B-Cell Pathway (CD20+ Dominant)

What's happening: B-cells (not just antibodies) play a major role in MS by presenting antigens, producing inflammatory cytokines, and organizing inflammatory responses in your CNS. They're actively driving your disease progression.

Think of it like this: B-cells are like project managers coordinating the attack on your myelin. Remove the project managers (B-cells), and the attack becomes disorganized and less effective.

What we test:

CD19+ B-cells, memory B-cells, BAFF/BLyS, CXCL13, oligoclonal bands

If this is YOUR pathway, these DMTs target it:

Ocrevus (ocrelizumab), Kesimpta (ofatumumab), Briumvi (ublituximab) - B-cell depletion therapies

Why Start with High-Efficacy DMTs?

🎯

Prevent Irreversible Damage

Every new lesion and every bit of brain volume loss is permanent. High-efficacy DMTs reduce annual relapse rates by 70-90% vs 30% for first-line therapies.

📊

Better Long-Term Outcomes

Studies show patients who start with high-efficacy DMTs have better disability outcomes 5-10 years later compared to those who escalate gradually.

Your Window is Now

Early, aggressive treatment preserves brain volume and function. The inflammatory phase of MS is when you have the most opportunity to change the disease course.

The Evidence for Pathway Testing

Research shows that immune profiling can predict DMT response. Patients with high B-cell activity respond better to B-cell depleting therapies. Those with Th17 dominance benefit from therapies targeting IL-17 pathways. It's not a crystal ball, but it's far better than guessing.

Additional Testing We Include

Neurofilament Light Chain (NfL)

A marker of active neurological damage. Elevated NfL means your disease is currently destroying neurons. This helps determine if your current DMT is working or if you need to switch.

JC Virus Antibodies

Determines your risk of PML (progressive multifocal leukoencephalopathy) if considering Tysabri. JC-negative patients have extremely low PML risk, while JC-positive patients need careful monitoring.

MOG & AQP4 Antibodies

Rules out MOG-antibody disease and Neuromyelitis Optica Spectrum Disorder (NMOSD), which look like MS but require completely different treatments. Critical for accurate diagnosis.

Understand Your MS Pathways

Don't waste 18 months on first-line therapies. Start with the DMT most likely to work for YOUR disease.

See MS Testing Options →