Multiple Sclerosis: Assessing and Monitoring Treatment Responses

Multiple sclerosis (MS) is a highly heterogeneous disease, both in its clinical course and treatment response. The latest discussions in the field underscore the importance of refining our understanding of heterogeneous treatment effects (HTEs), treatment response across relapsing and progressive MS, and considerations for special populations. These topics represent critical challenges and opportunities for improving patient care. This issue of Practical Neurology reviews some of these key considerations and offers neurologists a high-level, yet practical, overview of how they can integrate these contemporary topics into the evaluation, management, and counseling of their patients and care partners.

Drs. Aboseif, Orme, Chitnis, and Hersh open this issue with an article on “Utilizing Heterogeneous Treatment Effects in Pursuit of Personalized Multiple Sclerosis Care” in which the authors discuss how HTEs have been a longstanding yet underappreciated concept in the care of people with MS (pwMS). Emerging evidence highlights the variability in response to disease-modifying therapies (DMTs) due to factors such as demographics, baseline disease characteristics, patient preferences, immunobiologic differences, genetic variations, environmental factors, health behaviors, comorbidities, and social determinants of health. These variabilities emphasize the necessity of personalizing treatment beyond the use of average treatment effects from pivotal clinical trials that may not appropriately evaluate therapeutic responses in underrepresented populations.

The issue then transitions to a summary of treatment response assessment in relapsing and progressive MS. William Kim and Drs. Mahmoudi, McCarthy, Ortega, Gonzalez, Baldwin, Rammohan, Nelson review “Treatment Response Assessment Tools for Relapsing Multiple Sclerosis” and Dr. Pardo summarizes “Progressive Multiple Sclerosis: Functional, Anatomic, and Biologic Tools to Assess Disability Progression and Improve Patient Outcomes.” These articles highlight the utilization of clinical, radiographic, and biomarker data in addition to patient reported outcomes and technology for evaluating treatment effectiveness in relapsing and progressive MS. The authors examine the integration of standard metrics for macroinflammatory disease and progression (eg, relapses, new T2 and/or gadolinium-enhancing lesions, and clinical markers of disability such as components of the Multiple Sclerosis Functional Composite and Expanded Disability Status Scale) with newer approaches that provide more nuanced understanding of treatment response. In addition, they discuss the role of chronic active lesions as correlates of slow clinical worsening in progressive MS.

Special populations with MS, including pediatric, pregnant, and older patients and pwMS from underrepresented demographic groups experience unique complications in measuring treatment responses due to a dearth of data. Drs. Valizadeh, Khosravi, and Freeman close the issue with the article “Monitoring Disease Course and Treatment Response in Special Populations with Multiple Sclerosis.” They summarize the challenges inherent in these populations. Disparities in MS diagnosis, treatment access, and outcomes among underserved, underrepresented, and minority populations demand urgent attention. These groups are not only underrepresented in research and clinical trials but also face risks of greater MS disease burden early in the disease course. Efforts to increase trial diversity, conduct population-specific analyses, and improve access to care are critical for addressing these gaps.

As we refine our understanding of the complexities associated with MS treatment responses, the promise of personalized treatment strategies and how we measure treatment response becomes increasingly attainable, offering hope for improved outcomes across the diverse MS community.

Many thanks to the authors for their excellent contributions on monitoring and assessing treatment responses.