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Merck: Driving new understanding to help unravel the impact of smouldering inflammation for people with multiple sclerosis

min read

At Merck we’re incredibly proud of our ongoing partnership with the multiple sclerosis (MS) community. This partnership has enabled us to truly understand MS from the inside out, and we have a 25+ year history of pushing the boundaries of knowledge within this disease. An important outcome of our dedication has been the successful introduction of innovative new treatment options for MS, which over the years have helped to change aspirations around effective therapies.

Whilst it’s important to celebrate the positive strides that have been made so far towards transforming outcomes, we know there is still a significant amount that can be done to improve the lives of individuals with MS and support the clinical teams and caregivers that look after them. Today, we are as committed as ever to developing transformative treatment solutions that can create the closest thing to normalcy for individuals living with neurological and immune-mediated conditions, such as MS.

This drive to achieve more is what propels our ongoing work, and in this spirit, we’re excited to join the >9,000 colleagues and peers that are expected to attend the 9th Joint ECTRIMS-ACTRIMS Meeting in Milan, to exchange knowledge and gather new insights from across the MS community. With its dedicated focus on MS, MSMilan2023 offers us a vital touchpoint to come together and explore the latest clinical data from both new and existing therapies for MS, as well as probing some of the most pressing issues facing the MS community today.

Progression independent of relapse activity (PIRA), has been highlighted within one of 10 ‘hot topics’ by the organisers of MSMilan2023, and is also a central focus of our latest research and development work at Merck. Conducted in close partnership with HCPs, we are driving forward the recognition of this critical unmet need by increasing our understanding of the pathophysiology of smouldering MS.

Smouldering MS refers to the pathological central nervous system (CNS) process that may manifest clinically as the meaningful worsening of neurological deficits, even in the absence of relapses or new MRI lesions.[1] While the presence of smouldering MS may not be as immediately noticeable as a relapse, the impact it has on a patient’s daily life can be significant.[2] For people living with smouldering MS, the damage created can result in a worsening of their day-to-day physical and cognitive functioning and abilities.[1],[3],[4],[5],[6] This can include symptoms such as “brain fog”, fatigue, diminished fine motor skills, incontinence and impacts on their ability to walk.[2],[7],[8],[9] As this loss of function continues and disability accumulates, individuals with MS that are affected by smouldering MS will require more care and suffer reduced quality of life.

Recent evidence suggests that the accumulating disability caused by smouldering MS is common and can be present at the very earliest stages of the disease.[10],[11],[12] As many as six out of ten people recently diagnosed with MS have experienced progression independent of relapse activity, even when on treatment.[10],[11],[12] Given that current treatment approaches to MS primarily target peripheral sources of inflammation, approaches that can target the pathology of smouldering MS are still needed to improve outcomes for people living with MS.[1],[3],[4]

In response to this unmet need, Merck is undertaking research to better understand the role of biological pathways that drive neuroinflammation and neurodegeneration, and how they contribute to smouldering MS. One pathway that we are currently investigating is the Bruton’s Tyrosine Kinase (BTK) pathway, which we believe may play a key role in these underlying processes.

BTK is a protein that is essential for the development and maturation of B cells and is also involved in the activation of myeloid cells, such as macrophages and microglia, which may also be drivers of smouldering inflammation within the CNS.[3],[13],[14],[15],[16],[17] To optimally treat MS, both peripheral and central/smouldering sources of neuroinflammation must be addressed.[3],[18],[19] Therapies that target the activity of BTK may have the potential to act synergistically on several sources of inflammation (B cells & microglia) to help prevent disability accumulation and progression in relapsing forms of MS.[20]

At MSMilan2023 there will be several opportunities to hear more about what Merck is doing to advance the field of MS, including two Merck-hosted satellite symposia. Our first session in the Gold Room at 13.15pm CEST on Wednesday 11th October is titled ‘Addressing early smouldering inflammation and disease worsening in MS’ and will be co-chaired by Professor Massimo Filippi and Professor Xavier Montalban. The session will explore what advances have been made and what challenges remain in the treatment of MS, the role of imaging markers and novel pathways, and the use of personalised solutions to detect early MS disability.

A second Merck-hosted satellite symposium will consider the subject ‘How immune reconstitution therapy has transformed MS management: Lessons from real-world experience with cladribine tablets’. This session will also take place in the Gold Room at 8.45am CEST on Thursday 12th October and will be co-chaired by Professor Gavin Giovannoni and Professor Christoph Kleinschnitz. Themes to be covered within this symposium include the importance of time in MS, what lessons have been learned regarding immune reconstitution treatment (IRT) and the use of cladribine tablets early in MS, long-term management of patients on IRTs, and finally putting those learnings in context for patients’ quality of life, such as targeting cognitive decline early. Both symposia will feature Q&As with our expert speakers.

A Merck-hosted product theatre session in the Exhibition Hall at 11.05am CEST on Thursday 12th October will offer delegates the opportunity to hear from Neurology Specialist Dr Jaqueline Nicholas, as she presents ‘A new pathway in MS’. Those visiting the Merck booth will also be able to join us for three exclusive ‘Meet the Expert’ presentations. The first will be presided over by Consultant Neurologist Dr Tarunya Arun, who will discuss the topic ‘Long-term management with cladribine tablets: What do the data say?’. The second presentation on the booth will be led by Neurologist Dr Regina Berkovich, who will provide insights on the subject of ‘Early treatment with cladribine tablets’. Our final ‘Meet the Expert’ presentation will be hosted by Professor of Neurology and Neurotherapeutics Dr Darin Okuda, who will discuss the topic ‘Uncovering smouldering inflammation’.

It’s set to be a busy meeting for our Merck team onsite at MSMilan2023, and we look forward to connecting with as many delegates as possible as we seek to further scientific discussion, gather new insights and foster understanding around the latest data advances in MS.


[1] Bittner S, Pape K, Klotz, et al. Implications of immunometabolism for smouldering MS pathology and therapy. Nat Rev Neurol. 19, 477–488 (2023).
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[3] Giovannoni G, Popescu V, et al. Smouldering multiple sclerosis: the ‘real MS’. Ther Adv Neurol Disord. 2022; 15: 1–18.
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[13] Cao T, Wang Z, Zhu X. The Immunomodulatory Functions of BTK Inhibition in the Central Nervous System. Journal of Inflammation Research 2022:15.
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GL-MAV-01070 | September 2023