The future of multiple sclerosis care: Progression focused therapies and real world evidence
Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system (CNS) and can lead to significant disability over time. It remains the most common inflammatory neurological condition worldwide and in the United States alone, approximately one million people are living with MS.
Decades of drug development has yielded substantial advancements in suppressing inflammatory relapses, particularly for patients with relapsing–remitting MS (RRMS). However, focus has increasingly shifted towards slowing or preventing disability progression, especially in progressive forms of MS. This transition has important implications for pharmaceutical innovation, clinical development strategies, and health economics modelling—areas now increasingly shaped by real‑world data (RWD).
Demographics of newly diagnosed multiple sclerosis patients
Real‑world claims data highlight patients newly diagnosed with MS across age, sex, and ethnicity.
MS is most frequently diagnosed between the ages of 30 and 59, with peak incidence observed in individuals aged 40–59.
Females represent nearly three‑quarters of newly diagnosed MS patients, reinforcing the well‑established sex disparity observed in MS epidemiology.
While the majority of newly diagnosed patients are Caucasian, MS affects individuals across all racial and ethnic groups, underscoring the importance of inclusive research and treatment access.
Multiple sclerosis disease forms and clinical courses
MS is a heterogeneous disease characterised by clinical courses that are defined by how and when neurological damage accumulates.
- Clinically Isolated Syndrome (CIS): CIS represents the first clinical episode suggestive of MS, lasting at least 24 hours and driven by CNS inflammation and demyelination. Early diagnosis can help delay or prevent subsequent disease activity.
- Relapsing Remitting MS (RRMS): RRMS is marked by acute recurring relapses followed by periods of recovery and accounts for approximately 85% of initial MS diagnoses.
- Secondary Progressive MS (SPMS): SPMS develops following an initial relapsing course, with gradual disability progression occurring with or without relapses. Without treatment, around half of RRMS patients transition to SPMS within 10–20 years.
- Primary Progressive MS (PPMS): PPMS is characterised by a steady and gradual worsening of disability from disease onset and represents 10–15% of MS cases.
ICD-10 subtype codes and a new era of real-world data precision
Historically, claims data lacked the granularity to differentiate MS disease forms, as all patients were coded under a single ICD‑10 code (G35). From 1 October 2025, new ICD‑10 codes enable clear identification of RRMS, PPMS, and SPMS subtypes, including active and non‑active disease states.
Although adoption will take time, these codes mark a pivotal step forward for real‑world evidence generation, allowing more accurate assessment of treatment patterns, outcomes, and safety signals across distinct MS forms.
The evolution of MS treatments: From relapse-focused to progression-directed strategies
Early Therapeutic Landscape: Relapse Suppression as the Initial Priority
Given the predominance of RRMS at diagnosis, early MS drug development focused on reducing relapse rates and MRI activity of new or enlarging lesions, reflecting CNS inflammation. This led to the development of multiple disease‑modifying treatments, including:
- Platform injectable therapies (e.g. interferons, glatiramer acetate)
- Oral therapies (e.g. fumarates, S1P receptor modulators)
- Biologics (e.g. anti‑CD20 monoclonal antibodies)
Despite these advances, treatment options for progressive MS remained limited, as disability progression often occurs independently of relapse activity.
Breakthrough approvals in progressive multiple sclerosis
Ocrelizumab (Ocrevus®) became the first therapy approved for PPMS in 2017, representing a major milestone for this underserved population. A subcutaneous formulation, approved in 2024, has further improved treatment flexibility.
Some RRMS therapies have since expanded into active SPMS; however, treatment options for progressive disease remain constrained, particularly for non‑active progression, reinforcing the need for novel therapeutic mechanisms.
Emergence of Bruton’s Tyrosine Kinase Inhibitors (BTKi)
Bruton’s Tyrosine Kinase Inhibitors (BTKi) represent a promising shift toward therapies capable of targeting compartmentalised CNS inflammation, including microglial activation, which is a suspected driver of progression beyond relapses. As oral agents, BTKis may also improve patient adherence, reduce infusion burden, and expand treatment accessibility. There is currently a race for which BTKi will be the first approved for MS.
- Fenebrutinib is a CNS-penetrant BTKi being studied for the treatment of PPMS and RRMS. Results of a phase III trial were released in February 2026, where fenebrutinib demonstrated non-inferiority to ocrelizumab and reduced disability progression risk by 12%, with differences showing up at 24 weeks.
- Orelabrutinib is another BTKi being developed for PPMS and SPMS. Early results showed strong phase II efficacy in RRMS, demonstrating significant reductions in new brain lesions. Orelabrutinib is now progressing into global phase III trials for PPMS and SPMS.
- Tolebrutinib initially showed wide applicability across RRMS, SPMS, and PPMS; however, regulatory setbacks have been faced due to liver safety concerns and the lack of an established favourable benefit-risk profile. Tolebrutinib as Cenrifki® was provisionally approved in July 2025 in the United Arab Emirates for the treatment of SPMS.
Real World Data (RWD) insights: Treatment initiation trends
Analysis of open claims data from 2021 to 2025 reveals a clear shift in first‑line treatment patterns among newly diagnosed MS patients.
Biologics have become increasingly dominant, driven largely by anti‑CD20 antibodies. By 2025, nearly two‑thirds of newly diagnosed patients initiated treatment with a biologic, while use of oral therapies and platform injectables steadily declined.
Notably, anti‑CD20 therapies accounted for 49% of all first‑line treatments across modalities.
Looking ahead: Progression, precision and real-world evidence
The MS treatment landscape has evolved from a primary focus on inflammatory relapse suppression towards addressing disability progression in SPMS and PPMS. Anti‑CD20 biologics remain foundational, while emerging oral therapies have the potential to reshape clinical practice, patient preferences, and payer dynamics.
The introduction of MS‑specific ICD‑10 subtype codes in October 2025 represents a transformative moment for real‑world evidence, enabling more precise, form-specific insights. Together, therapeutic innovation and improved data granularity position the field for a new era of understanding, with the ultimate goal of improving long‑term outcomes for people living with MS.
With new MS subtype codes and an evolving treatment paradigm, the demand for precise, real‑world insight has never been greater. Symphony Health, an ICON plc company, provides industry‑leading data, analytics, and expertise to help life sciences teams understand treatment patterns, patient journeys, and outcomes at scale. Discover how real‑world evidence can power the next generation of MS innovation.
To learn more about how Symphony Health can support your RWD strategy, connect with us today.