Progress(ion) in Multiple Sclerosis
(and what can we learn from the field of multiple sclerosis to optimize data-driven care in Alzheimer’s disease)
It is that time of the year again, ECTRIMS-time, when world-leading experts, neurologists, industry partners, nurses, people with Multiple Sclerosis (MS), and other enthusiasts gather at the largest conference on MS research. Each year, I’m so excited to learn about the latest research in this field, to experience the progress being made toward precision medicine, and to reunite with colleagues, collaborators, and friends.
We’re living in an extraordinary time for neuroscience, with the first disease-modifying treatments (DMTs) being approved in the field of Alzheimer’s disease (AD). As icometrix is at the forefront of digital health and MRI-based artificial intelligence (AI) solutions in the field of AD, we have been intensively aligning with policymakers, physicians, pharmaceutical companies, and patient organizations. Technology and innovation are very much needed to standardize care pathways and aim for data-driven (early) diagnosis, treatment decision-making, and (safety) monitoring in this new era of AD care and management.
When discussing the need to organize and optimize our healthcare systems for people with AD and their loved ones, the example of MS is often brought forward. There are many parallels to be made indeed: both are chronic neurodegenerative disorders, early diagnosis and treatment onset are extremely important, brain MRI scans play a central role, and with the availability of DMTs, treatment and safety monitoring will become part of the care pathway in AD, as is already the case in MS for many decades.
So where are we actually on that journey towards precision medicine in MS?
Data-driven decision-making in multiple sclerosis
There is accumulating evidence in MS that it isn’t only crucial to ensure timely treatment switches during the MS journey, but that long-term disability and outcomes are also strongly impacted by an early diagnosis followed by getting the first treatment right (Saposnik & Montalban, 2018, Chalmer et al., 2018; Spelman et al., 2021; Strijbis et al., 2021). Recent literature indeed highlights the complexities clinicians face when having to decide on initiating or switching DMTs, leading to a delay in implementing the most optimal strategy and potential accumulation of disease progression (Gustavo & Montalban, 2018; Saposnik et al., 2017, Alsmusalam et al., 2019).
In the diagnostic process of AD, multiple biomarkers and tests are needed, including amyloid confirmation by PET and/or lumbar puncture, brain MRI scans, plasma measures, cognitive tests, and clinical exams. In comparison, the data needed for the diagnosis as well as for the assessment of disease activity are relatively well defined in MS. Depending on the treatment strategy, clinical measures such as relapses and the EDSS disability scale (and possibly cognitive measures, the 9-hole peg test, the 25-foot walk test, etc) and MRI-based measures of new/enlarging lesions and brain atrophy are evaluated.
At icometrix, we’ve been leading the transition towards more data-driven care in MS during the last decade, mainly through the icobrain ms MRI reports. These are regulatory cleared in most countries worldwide, and are now adopted clinically at a global scale, not only in academic centers, but also in private practices.
Based on our experience in analyzing 100s of thousands of brain MRI scans of people with MS and the strong clinical footprint, we have updated the icobrain ms report. This report allows us to even better support clinicians in monitoring disease worsening, as it was meticulously put together based on recent literature and clinician feedback. The report has been redesigned, wherein the most clinically relevant data is presented in an easier manner to be assessed by clinicians. Furthermore, this new version of the icobrain ms report now also includes the count of new FLAIR white matter hyperintensities (including a comparison with a large population), in addition to their volume as previously reported, as well as T1 hyperintensities.
The person with multiple sclerosis at the center of care
Placing the person with dementia at the center of care was a recurring theme at the Defeating Dementia meeting in The Hague on October 2nd. Providing each individual with the right information impacts prevention and improves the quality of care. In addition, easy-to-access regulatory-cleared phone apps or other medical devices can help people in their daily lives, for example through reminders, locating their home, preparing for doctor’s visits, etc.
In this context, a lot of work has been done in the field of MS, as multiple apps have been developed and introduced for research purposes and clinical care, for example, Floodlight, Konnectom, BelongMS, the app of the National MS Society, etc.
At icometrix, we developed the medical device app icompanion.ms together with hundreds of people living with MS, caregivers, nurses, and neurologists. The app is already helping more than 6000 people in their daily lives. icompanion allows people to track their symptoms and measure cognition, fatigue, disability etc. in between visits to the neurologist. But more importantly, icompanion is a true companion, by assisting people with treatment reminders, preparation of doctor visits, curated educational information, etc.
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During the last few months, icompanion has undergone several major improvements based on many interactions with the users and several focus groups. The visit preparation module now takes a more prominent role in the app, allowing people with MS to feel even more prepared for their doctor visits and being able to discuss what truly matters during these visits. In addition, we have vastly expanded the knowledge base in icompanion, with up-to-date and tailored educational content about all aspects of MS, from relapses, physical exercise, symptom management, and complex topics such as MRI and why it is important to get a scan every year.
To further enhance the clinical impact and evidence of icompanion, the icometrix team, together with leading scientists, has worked hard on developing and validating phone-based cognitive and fine motor skill tests, which can be done reliably at home. It was demonstrated that these phone-based tests at home correlate strongly with the established digital versions of the Symbol Digit Modalities Test (SDMT) and the Nine-hole peg test, which are often conducted in the clinic (Denissen et al. 2023).
The inclusion of these more advanced measures of cognition and fine motor skills in icompanion, in addition to the icobrain MRI measures and the existing assessment of fatigue, symptoms, disability, etc, provides neurologists even more data and tools to truly implement a personalized precision medicine approach clinically. An example of the healthcare professional portal can be seen below (new version to be released soon). This cockpit view, including all relevant data and insights of the individual sitting in front of the doctor and is also seamlessly integrated into the EMR system.
The therapy-biomarker combination
Biomarkers, digital health solutions, AI, and new innovations are only relevant when impacting clinical decisions on diagnosis, treatment planning, or (safety) monitoring. Hence, they are tightly connected to the availability of treatment options. This is why such a revolution is needed (and happening) in Alzheimer’s disease, as care pathways, biomarker integrations, and education of individuals living with AD and their caregivers, are adapting to the new reality of DMTs becoming available. For example, the current amyloid treatments can lead to safety events, known as amyloid-related imaging abnormalities (ARIA), resulting in the need for at least 3 monitoring brain MRI scans during the first year of treatment. It is clear that AI technology is needed to assist with the reading of these MRI scans to detect and assess the severity of ARIA (Hampel et al. 2023).
In MS, there is an increasing emphasis on moving towards assessment of progression independent of relapse activity (PIRA). In response to the needs of the field, Bruton’s tyrosine kinase inhibitors (BTKis) are being developed and currently evaluated in several clinical studies. BTKis form a new drug class in MS, which has shown promise in halting disease progression due to its effect on inflammation. In particular, BTK-positive inflammatory cells have been seen to be increased in the rim of MS lesions (Kramer et al., 2023), and inhibition of BTK works through suppressing these inflammatory cells in people with MS. In addition, further evidence to highlight the association between spinal cord atrophy and MS severity has been accumulating (Bischof et al., 2021; Krieger, 2022), making it an interesting biomarker for researchers to target, and one that is starting to enter clinical practice. Recent work has also uncovered understudied markers of disease progression, such as atrophy of the cerebellum (Cocozza et al., 2017; Meijboom et al,. 2023) and thalamus (Azevedo et al., 2018; Cagol et al., 2022).
As these new BTKIs are expected to become available clinically over the coming years, neurologists will have even more options to treat people with MS. However, with more treatment options, the need for precision medicine approaches only increases. And with new drug classes entering the arena, new biomarkers should be available to assess in each individual person, which treatment option is most optimal.
In preparation for the clinical availability of the BTKIs, and as icometrix already collaborates with many pharmaceutical companies and leading research institutes, a new icobrain ms+ report was developed (currently only available for research purposes). This report aims to capture more advanced brain MRI related information. For example, it includes the volume and count of paramagnetic rim lesions, enabling the identification of early signs of more progressive MS. The report also includes cervical spinal cord measures, which are associated with disease severity (Eden et al., 2019; Laitman et al., 2018). Finally, also included are volumes of several brain structures that have been shown in the literature to be associated with MS severity and progression (white matter, cortical gray matter, hippocampus, cerebellum, and thalamus).
So where are we actually on that journey towards precision medicine in MS?
When looking back a decade, or even only 5 or 3 years, so much has changed in the field of multiple sclerosis. Precision medicine in MS is becoming a reality. Neurologists have several treatment strategy options, validated (digital health) biomarkers are clinically accessible, and many neurologists are now using a more data-driven and personalized approach in MS care.
The new CPT III code in the US, for advanced and quantitative assessment of longitudinal lesion changes on brain MRI scans, will only help in adopting these precision medicine measures further. For people living outside the US, we are working hard in many countries towards a reimbursement for these much-needed MRI measures.
We keep pushing ourselves hard to impact the lives of people with MS. And we are more than ready to do the same for people with dementia and other neurological conditions.
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Data scientist 🦄 - Entrepreneur 🐸 - Idealist 🦋 Passionate about using my talents to make the world a better place
1yLooking forward to seeing you there!!! Lets connect in Milan.
CEO & Founder @eSteps | Relentless Mindset | Building the Best Life Companion for mobility longevity and MS
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Director The Alzheimer Society of Ireland and Member The National Research Ethics Committee NREC-CT-B
1yThe Alzheimer Society of Ireland