Whether her MS presents as relapsing or progressive

Let’s shine a light on the CNS and peripheral immune drivers of disease.1

Recognizing that relapsing and progressive disease biologies coexist from the start opens up new possibilities to target immune drivers of damage on both sides of the blood-brain barrier.2-4

Explore the role of BTK

BTK=Bruton’s tyrosine kinase; CNS=central nervous system; MS=multiple sclerosis.

Contemporary views on MS

Watch the expert clinical exchange series on how MS damage can be hidden early—and what can help reveal it in clinical practice.

PART 1

Moving toward a biologic view of MS2,4

Both relapsing and progressive disease mechanisms drive underlying damage in MS 
from the start, even before clinically apparent.

PART 2

Redefining what we measure in MS—and how5

Explore more sensitive ways to assess for early signs of disability progression.

PART 3

Modifying disease trajectory via brain health behaviors6-9

How brain health strategies can support CNS reserve and help change the trajectory of MS.

Quotation iconThe understanding in the field has evolved toward the view of MS as one disease—which is important because the more we continue to split the clinical descriptors, the more confusing it becomes.Quotation icon

—Scott Newsome, DO, MSCS, FAAN, FANA

Toward a biologic view of MS

MS is one disease continuum driven by both relapsing and progressive disease biologies that coexist and interconnect from the start.1

Quotation iconClinically, there isn’t some magic point where a patient transitions to a progressive course of MS. Progressive biology is concurrent with relapsing biology and occurs throughout the disease course, driving the accrual of disability.Quotation icon

—Jiwon Oh, MD, PhD, FRCPC, FAAN

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Practical steps to proactively address progression in your practice.

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Both CNS and peripheral immune mechanisms drive damage in MS

MS is a chronic, immune-mediated disease with central and peripheral immune drivers that act together to incite and amplify acute and chronic neuroinflammation from the start. These processes involve key cells that operate on both sides of the blood-brain barrier to contribute to MS damage.1,2,4

Multiple immune pathways contribute to neuroinflammation in MS3,10

Bruton’s tyrosine kinase (BTK): A signaling mediator in both the adaptive and innate immune systems

BTK is present in B cells and myeloid cells and therefore acts as a central mediator of both relapsing and progressive disease biologies.

  • Relapsing disease biology: BTK activates B cells and macrophages to infiltrate the CNS, driving acute inflammation.
  • Progressive disease biology: BTK amplifies proinflammatory B cells and myeloid cells (ie, macrophages and microglia) within the CNS, sustaining chronic inflammation.

By activating key cells on both sides of the blood-brain barrier, BTK acts as a central mediator of both acute and chronic neuroinflammatory damage in MS.

BTK is a promising target because it mediates inflammatory processes on both sides of the blood-brain barrier.

What is the unmet need in MS?3

Despite therapeutic advancements in MS, disability progression continues to accrue insidiously for many people living with MS. Damage in MS is driven by an interplay between immune processes on both sides of the blood-brain barrier.

An important unmet need in MS is the ability to directly target the CNS and peripheral immune mechanisms that concurrently drive the relapsing and progressive disease biologies responsible for the accumulation of disability.3

Disrupting the MS dichotomy

MS has traditionally been thought of as a two-staged disease, with progression occurring later in the disease course. A contemporary view is that MS is one disease continuum with both relapsing and progressive biologic mechanisms contributing to the accrual of disability from the start.11-14

Disability can accumulate in 2 ways2,11-13,15

Multiple studies have demonstrated that, among patients who experience confirmed disability events, a substantial amount of disability is due to PIRA.11,12,15

Disability can occur across many functional domains, and recognizing it early can be challenging. Thus, more sensitive tools and probing in clinical conversations can help reveal early changes in function2:

Changing the trajectory of MS may entail targeting the dual immune drivers of disease

Measuring what matters: Clinical performance tools and novel biomarkers

Performance measures5,16

Upper extremity function testing (eg, 9-hole peg test [9HPT]) and walking and endurance tests (eg, timed 25-foot walk test [T25FWT]; 2-minute walking test [2MWT])

Digital17,18

Wearable gait sensors, smartphone cognitive apps

Advanced imaging measures2

Paramagnetic rim lesions (PRLs), slowly expanding lesions (SELs)

Fluid biomarkers2

Serum neurofilament light chain (sNfL), glial fibrillary acidic protein (GFAP)

Quotation iconRather than focusing on phenotypic descriptors, we should focus on the factors that lead to disease progression.Quotation icon

—Carrie M. Hersch, DO, MSc, FAAN

What can be done today?

There are actions clinicians and care teams can take now to help protect function—by addressing modifiable threats to disease trajectory and supporting positive health-related behaviors.

Identify and reduce modifiable threats2,19-21

Comorbidities, negative health-related behaviors (eg, smoking), and social determinants of health can negatively influence outcomes—often through delayed diagnosis, barriers to care, and differences in access and clinical continuity.

  • Screen for comorbidities; coordinate with primary care
  • Ask about barriers to care (transportation, insurance, time off work, caregiver support)
  • Connect patients to support services when available

Preserve reserve: Support “brain health” behaviors6-9

Brain reserve is influenced by fixed and modifiable factors. Positive health behaviors and rehabilitation strategies can support function.

  • Encourage appropriate physical activity and rehabilitation support
  • Discuss sleep, stress, nutrition, and cognitive strategies
  • Engage multidisciplinary care to coordinate individualized goals

Quotation iconCompensatory CNS reserve may mask early damage and can be modulated via brain health behaviors.Quotation icon

—Augusto Miravelle, MD, FAAN

Download your action plan

Practical steps to proactively address progression in your practice.

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