PSI perspectives on the world’s largest MS congress
The European Committee for Treatment and Research in MS (ECTRIMS) held its 2025 annual meeting between 24– and 26 September in Barcelona, Spain. PSI’s MS Therapeutic Area Lead Julia Smolina and Senior Director of Business Development Steven De Hertefelt were there and provide their key takeaways below.
ECTRIMS 2025 had the theme of “a new era of precision”. This means a focus on precision medicine, and on earlier and more precise detection and stratification of MS (including progressive types, and pre-symptomatic stages). More attention is finally being paid to progressive MS, and early data suggests treatment benefit in primary progressive forms.
"The move from focusing on reactive to proactive, preventative treatment of MS impacts our work as a CRO. Our input into studies is needed at an earlier stage of protocol design, and we are developing new strategies to aid in patient identification and recruitment.”
Refining the McDonald Criteria
One of the major topics discussed at ECTRIMS was the 2024 updates to the McDonald Criteria [1], which were also recently published in The Lancet Neurology [2]. These changes can be summarized as:
- The optic nerve can now serve as a fifth anatomical location within the CNS for diagnosis
- Use of more biomarkers (imaging and fluid) to increase sensitivity/specificity
- Patients with atypical presentation are also better captured – e.g., those with symptoms not fitting classic patterns, or radiologically isolated syndrome (RIS)/asymptomatic individuals
- Dissemination in time is no longer a required diagnostic criterion in some circumstances
- Improved global applicability (through the use of new biomarkers), which will help pragmatism in resource-limited settings
What this means for the industry is that more patients can receive an MS diagnosis and at an earlier point in time, and therefore, more patients are likely to become available to enroll in trials.
This is based on a formal analysis:
- One study compared suspected MS patients using 2017 vs 2024 criteria: Compared with the 2017 criteria, under the 2024 revisions, 43% more patients would have received an MS diagnosis
- In the same study, diagnosis was approximately 6 months earlier using the 2024 revised criteria versus the 2017 criteria
Cognition
Despite up to 65% of patients with MS experiencing cognitive impairment [3], there has been a lack of research on cognitive function deterioration. So, while current therapies can decrease or even eliminate relapses, the impact of cognitive function decline on patients and the effect of a new treatment is so far undervalued.
Key domains affected:
- Processing speed (most common, and usually earliest)
- Attention and working memory
- Executive function
- Learning and memory
Cognitive issues directly impact QoL, employment, and independence, and are under-assessed in clinics. Regular cognition monitoring should become SoC, and so we expect to see cognition making an impact on trial endpoints in the future.
For CROs, this means qualifying vendors for cognitive assessments and also working with CRAs to ensure they have the skills needed to handle these often subjective tests.
PIRA
For non-relapse progression (PIRA, progression independent of relapse activity), invisible symptoms and smoldering disease are a growing concern. PIRA is now recognized as a major driver of long-term disability [4], and researchers are working on identifying biomarkers that might signal early PIRA.
Due to its burden on the healthcare system, new strategies to treat PIRA and new trials are expected soon.
Biomarkers
- Traditional biomarkers
- Certain cerebrospinal fluid (CSF) proteins may predict early PIRA risk
- Imaging biomarkers
- Paramagnetic rim lesions (PRLs), seen with newer MRI techniques, are becoming diagnostic biomarkers
- Thalamic and cortical atrophy are strongly linked with cognitive decline, becoming potential MRI biomarkers
- Blood-based biomarkers
- Neurofilament light chain (NfL)
- Digital biomarkers
- Instead of relying only on MRI scans or lab tests, digital and functional biomarkers capture real-world patient function using:
- Smartphone apps (voice, dexterity, cognition tests)
- Wearables (accelerometers, smartwatches, pressure sensors)
- Remote monitoring platforms (home-based cognitive or motor testing)
Detecting subtle changes in mobility, cognition, or daily activity before they become clinically obvious is especially useful for monitoring PIRA and also increases the potential number of patients with MS available to participate in clinical trials. Being able to capture additional data through digital biomarkers will result in an impact on data management: Larger databases and more data may mean the growth of AI systems to aid in accurate reporting and monitoring.
"The MS market is poised to grow to around $25 billion by 2034, according to GlobalData. We anticipate the launch of many late-stage products over the next few years – and we are at the forefront of running the clinical trials for them. We have the industry knowledge and experience needed."
Hot topic: Anti-CD20 mAbs vs. CAR-T
Cell trafficking and CNS immune cell targeting are hot topics in MS — and the therapies showing the most promise for this at the moment are CAR-T cell therapy and new monoclonal antibodies (particularly anti-CD20). Anti-CD20 mAbs are a proven, widely used, highly effective class for controlling inflammatory MS [5]; however, their long-term effects on the immune system and impact on PIRA are questionable. CAR-T cell therapy is feasible in MS, even in more advanced or progressive disease [6]. Achieving CNS penetration, modulating CSF biomarkers (OCBs, kappa light chains), and producing functional/disability improvements. They have the potential to “reset the immune system”.CAR-T cell therapy manufacture is particularly laborious, as are the logistics surrounding storage and transportation, so seeing more CAR-T trials outside of the field of oncology is a promising development. Widening the scope of their application results in advancements in development and reductions in cost. Breakthroughs with CAR-T therapies are expected in MS, especially as there are multiple Phase 1 trials and a large Phase 2 trial running at present; longer trials are required to define efficacy, safety, and the right patient population.
| Topic | Anti-CD20 monoclonal antibodies | CAR-T cell therapy |
| Mechanism | Humanized/fully human antibodies bind CD20 on B cells → Fc-mediated depletion (ADCC, CDC, phagocytosis). | Autologous T cells engineered with a chimeric antigen receptor to recognize a chosen B-lineage or plasma-cell antigen (MHC-independent) and kill target cells. |
| Typical targets | CD20 (ocrelizumab, ofatumumab, rituximab). | CD19, BCMA, (experimental constructs may target other B/plasma cell antigens). |
| Administration | Repeated dosing (IV infusion every months or subcutaneous monthly). | Single (or limited) cell infusion after leukapheresis and lymphodepletion chemo. |
| Durability of effect | B-cell depletion lasts weeks–months; requires ongoing dosing to maintain effect. | Potentially long-lasting or durable immune reset after single treatment; duration under active study. |
| CNS penetration | Large antibodies have limited direct CNS entry; effect mainly via peripheral B-cell depletion and downstream CNS effects. | Living T cells can traffic into tissues and have been observed to enter CSF/CNS compartments in early studies — may achieve deeper compartmental depletion. |
| Evidence in MS | Large randomized trials show robust reduction in relapses, MRI activity, and impact on disability (for relapsing MS); established standard of care. | Very early-phase data (small cohorts, Phase 1) — promising signals (safety, biomarker changes, some functional gains) but not yet proven in large trials. |
| Onset of action | Rapid reduction in MRI activity and relapse risk within weeks–months. | May act quickly after infusion; kinetics depend on expansion/persistence of CAR-T cells. |
| Efficacy (current view) | High level of evidence for relapse and MRI control; some benefit on disability in certain settings. | Unknown at scale — initial reports suggest possible functional improvement in progressive MS but need larger/longer trials. |
| Key risks / toxicities | Infusion reactions, increased infection risk (esp. hypogammaglobulinemia long-term), rare progressive multifocal leukoencephalopathy (PML) reported with some B-cell therapies. | Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) (seen in oncology), prolonged cytopenias, hypogammaglobulinemia; long-term safety still being defined. |
| Monitoring required | Periodic blood counts, immunoglobulins, infection surveillance, vaccination status. | Intensive short-term monitoring for CRS/ICANS, long-term immune monitoring (B-cell recovery, IgG), infection surveillance, specialized follow-up. |
| Reversibility / control | Effects wane after stopping; B cells eventually reconstitute. | CAR-T persistence can be long and less easily reversed; potential use of suicide switches or anti-CD20 rescue strategies is experimental. |
| Logistics & access | Widely available in many countries; standardized manufacturing & delivery; lower one-time cost but ongoing drug cost. | Complex manufacturing (autologous), specialized centers, high upfront cost, supply/logistics challenges; scalability is currently limited. |
| Best suited / potential niche | Relapsing MS and some early progressive cases to reduce inflammatory activity. | Being explored for refractory disease and progressive MS where compartmentalized CNS inflammation (plasma cells/B-cell niches) may be driver; may suit patients who need durable immune reset. |
| Open questions | Optimal timing vs other therapies, long-term infection/immune consequences, effect on progression independent of relapse activity. | Durability vs safety balance, ideal antigen target (CD19 vs BCMA etc.), optimal lymphodepletion, patient selection, long-term outcomes, comparative benefit vs HSCT/anti-CD20. |
"The anti-CD20 versus CAR-T debate will likely be at the forefront of our discussions for some time. Determining the patients most likely to respond to a particular treatment is of great importance, and designing trials smartly around the right patient populations is crucial.”
Artificial intelligence
A number of presentations focused on how AI is becoming central to MS research and care:
- Digital biomarkers: Smartphone-based tools showed that digital assessments of motor and cognitive function, such as cognitive processing speed and dexterity tasks, can reliably distinguish MS patients from healthy controls and correlate with quality of life
- Personalized medicine: AI models are being developed to predict which patients will respond best to specific therapies, supporting precision treatment approaches
- Imaging and disease monitoring: Machine learning is improving lesion detection, brain and tissue segmentation, and prediction of new lesions or progression using MRI combined with clinical data
- Clinical research optimization: AI is helping refine clinical trial design by identifying patients most likely to show measurable disease activity or respond to therapies, making trials more efficient
In summary
ECTRIMS 2025 showcased significant progress in precision medicine, early diagnosis, and innovative treatment approaches for MS, including advancements in biomarkers, digital tools, and AI-driven research. As the field continues to evolve, collaboration and adaptability will be key to optimizing patient outcomes and advancing clinical research.
Contact PSI for help and insights on your MS trial today.
References
[1] ECTRIMS, 2024 Revisions to McDonald Diagnostic Criteria for Multiple Sclerosis Published. 2025.
[2] Montalban, X., et al., Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol, 2025. 24(10): p. 850–865.
[3] European Commission. Data protection aspects of clinical trials. 01 October 2025; Available from: https://health.ec.europa.eu/document/download/f7be57c2-f40b-45cd-b0e9-b9d00f1234f9_en.
[4] Progression Independent of Relapse Activity in Multiple Sclerosis: Closer to Solving the Pathologic Puzzle. Neurology, 2024. 102(1): p. e207936.
[5] de Sèze, J., et al., Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic. Front Immunol, 2023. 14: p. 1004795.
[6] Chinas, N.A. and H. Alexopoulos, CAR T-cells meet autoimmune neurological diseases: a new dawn for therapy. Front Immunol, 2025. 16: p. 1604174.
