[Note: This blog post reflects ongoing research. The SAW Index is currently in development, and all findings are preliminary.]
At Sanofi, while we continue developing treatments for multiple sclerosis (MS), we’re pioneering a broader approach to disability progression. We’re working alongside people living with MS, patient advocacy groups and clinicians to develop new ways to characterize and measure disability progression beyond conventional measures.
Multiple sclerosis (MS) is a complex neurological condition driven by two distinct biological processes. Standard treatments and measurement tools have traditionally focused on relapses and obvious motor skills caused by acute neuroinflammation driven by B and T cells of the peripheral nervous system. However, chronic “smoldering” neuroinflammation – driven primarily by disease-associated microglia found in the central nervous system (CNS) – manifests clinically as progression independent of relapse activity (PIRA), impacting cognitive and physical changes, often in a subtle manner. These changes can be small at first but add up over time and impact multiple clinical domains – known as smoldering-associated worsening (SAW). SAW refers to the subtle, ongoing disability progression that occurs in MS patients even in the absence of relapses or new lesions visible on MRI scans.
Recent research has highlighted a critical gap in how we assess and treat disability progression. Current clinical metrics, including imaging techniques and the Expanded Disability Status Scale, primarily reflect damage that has already occurred rather than the ongoing neurodegenerative processes.
Addressing this gap is particularly important because early identification of progression could lead to better treatment decisions, avoid the possibility of missing important changes and more accurately reflect the realities of living with MS, which is precisely what the SAW Index aims to address.
What is the SAW Index?
The SAW Index Study is a groundbreaking study working to revolutionize our understanding of MS progression and potentially improve patient care, led by Dr. Jeremy Hobart, a practicing neurologist at Plymouth Hospitals National Health Service Trust, UK and a professor of clinical neurology and health measurement at Plymouth University Peninsula Schools of Medicine and Dentistry in Plymouth, England. This research aims to create an evidence-based framework to identify, assess, and measure SAW in people living with MS, potentially transforming the current landscape of MS measurement. The research is also being conducted in close consultation with the SAW Index Steering Committee – a group of consisting of internationally renowned MS experts, people living with MS and representatives from patient advocacy groups. Both the study and the steering committee are funded by Sanofi.
Dr. Hobart and colleagues have conducted over 150 hours of structured, qualitative interviews with people living with MS across six countries. This approach enabled the identification of 15 domains beyond physical symptoms—such as walking ability, cognition, and fatigue—alongside less commonly assessed aspects like taste and swallowing.
The structured and iterative nature of the interviews, allows for a deep understanding of what truly matters to people living with MS. The large volume of statements (around 1,600) derived from those interviews, is instrumental in shaping item responses of the SAW Index. This moves away from abstract research language – terms like mild, moderate, or severe – toward patient-centered expressions that reflect actual functional impact. Because the results are based on multiple interviews across several timepoints, this ensures the metrics developed truly reflect patients’ experiences and identify what domains truly matter to them. The ultimate goal is to explain the disconnect between what patients experience (gradual worsening) and what current clinical measures might show (stability).
Addressing the concerns of the MS community
The European Multiple Sclerosis Platform recently released findings from the Impact of Multiple Sclerosis Symptoms Survey (IMSS), gathering insights from over 17,000 people living with MS across Europe. The survey revealed that people with MS face not only delays in diagnosis and treatment access barriers but also struggle with invisible symptoms that are often overlooked despite being among the most debilitating. People with MS typically experience an average of 13 symptoms simultaneously – including fatigue, sleep disturbance, balance problems, mood changes, pain, and various functional issues—many resulting from SAW.
As Dr. Hobart explains, “As clinicians, these findings challenge us to look beyond traditional measures like EDSS and pay more attention to what our patients are saying. The quality of the index depends on what we ask, how we ask, and what response options we provide. By interviewing the same people multiple times, we build a clearer understanding of what is worsening for them and in what way.”
He illustrates this with an example about walking assessment: “If you ask a person living with MS how walking is going, they typically receive vague options like ‘good, fine, not great.’ This approach misses crucial factors like tripping, stumbling, rest periods, walking surfaces, and multitasking while walking. These seemingly minor details actually have significant impact not only on how someone responds but can tell us about how their disease might be progressing or worsening.”
The large volume of statements derived from the interviews is crucial in shaping the item responses and categories. It allows us to move away from abstract “research speak”, using terms like mild, moderate, or severe as response items, toward “people speak”, where responses reflect the actual functional impact as experienced by individuals.”
Looking Ahead
The SAW Index study is ongoing with plans for extension and real-world data collection. As this research progresses, it has the potential to significantly impact how MS is understood, monitored and treated, potentially leading to earlier interventions and better outcomes.
The SAW Index is also designed with a life cycle perspective in mind. Initially, it will serve to identify SAW but over time, as the evidence base grows, the SAW Index holds promise to measure and assess SAW more precisely, potentially offering predictive value. It’s an evolving tool grounded in real patient experience.
For the MS community, the SAW Index represents hope – for better understanding and more accurate assessments. By shining a light on the subtle but impactful changes that occur when disability accumulates in MS, this research is paving the way for more personalized and effective care strategies.
As we await further results from this groundbreaking study, our goal remains clear: to develop solutions that address the visible and invisible challenges of MS, ultimately making a meaningful difference in the lives of those affected by this complex disease.
Sanofi at ECTRIMS 2025
At ECTRIMS 2025, we’re excited to showcase our cutting-edge research, while highlighting recent clinical advancements from across our neurology portfolio. Through ongoing collaboration with the MS community around the world, we’re working towards helping people live for the moment and not the disease.
You can visit us at the Sanofi exhibition booth (A10) to learn more about how we are unlocking the science of neuroimmunology with the goal of revolutionizing MS care. Our medical symposium will be on Thursday, September 25 at 13:15 PM CEST in Room 7/8 featuring MS experts Amit Bar-Or, Celia Oreja-Guevara and Martina Absinta who will discuss Navigating the New Era of Therapeutic Strategies for MS Disability Accumulation.