MRI Activity Drives Early High-Efficacy Treatment Choices in Multiple Sclerosis

A French expert panel reached consensus that magnetic resonance imaging findings were the strongest drivers of early treatment with monoclonal high-efficacy therapies for people with newly diagnosed relapsing-remitting multiple sclerosis. In the two-round Delphi study, 31 neurologists evaluated eight fictional cases and 108 statements, with all experts responding in both rounds. Consensus was achieved for 82.4% of statements, and the factors that most consistently prompted a recommendation included more than 20 brain lesions, at least two spinal cord lesions, at least three gadolinium-enhancing lesions and at least three infratentorial lesions. These were findings from an expert-consensus exercise, not a clinical trial, and the researchers cautioned that they do not establish that any particular treatment improves outcomes in these groups.

The results address a growing change in multiple sclerosis care. Treatment strategies have traditionally included beginning with moderate-efficacy therapy and escalating if inflammatory activity persists, but an early-intensive approach has also become more common. High-efficacy therapies include monoclonal antibodies directed against CD20 and α4-integrin, as well as non-monoclonal agents such as cladribine and sphingosine-1-phosphate receptor modulators. The study focused only on the two monoclonal classes, because available comparative evidence suggested greater efficacy than with the other high-efficacy classes. Their use nevertheless requires balancing disease control against potential harms, including progressive multifocal leukoencephalopathy, hypogammaglobulinemia and infection.

To identify the features that mattered most, the researchers first presented eight fictional patients with combinations of demographic, clinical and MRI characteristics. The cases covered sex, age, ethnicity, comorbidities, cognitive impairment, severity of the initial neurological attack, motor impairment or ataxia, previous attacks, brain lesion load and the number and location of lesions. Participants then rated 108 modified scenarios in which one characteristic at a time was changed while the rest of the case remained constant. Recommendations were recorded on a five-point scale, with scores of 4 or 5 grouped as an indication for treatment, 3 as indecision and 1 or 2 as no indication.

After the first round, 27 of the 31 panelists attended a national online workshop to examine scenarios that had not produced consensus. The panel then completed a second round containing the unresolved statements, with all 31 again responding. Consensus for recommending treatment required a median score of at least 4 and at least 80% of ratings in the 4–5 range; consensus against treatment required a median of no more than 2 and at least 80% of ratings in the 1–2 range. Strong consensus required at least 90% agreement within the relevant rating range. This process produced 70 statements with strong consensus in favour, 18 with moderate consensus in favour, one with strong consensus against and 19 without consensus.

The strongest and most consistent influence was radiological evidence of high inflammatory or structural activity. A high brain lesion load, defined in the questionnaire as more than 20 lesions, systematically led the panel to recommend monoclonal high-efficacy therapy. The same pattern occurred with two or more spinal cord lesions, three or more gadolinium-enhancing lesions and three or more infratentorial lesions. Factors classified as intermediate because they prompted treatment recommendations in most, but not all, cases included a moderate brain lesion load of 10–20 lesions, clinically concerning symptoms during the initial attack, a previous attack within the preceding 12 months, cognitive impairment, one or two infratentorial lesions and a single spinal cord lesion.

The spinal cord finding was notable because one lesion carried more apparent weight than several other intermediate factors. Although a single spinal cord lesion did not always produce agreement on its own, its presence in combination with other concerning characteristics systematically moved the panel toward recommending monoclonal therapy. The researchers proposed that a patient with any strong factor should be considered for early monoclonal treatment, while a single spinal cord lesion would support that decision when accompanied by one or more intermediate factors. If neither category was present, they proposed discussing the choice in light of demographic and clinical-history information. This is a proposed framework reflecting expert judgment, not a validated clinical guideline.

The imaging emphasis is consistent with previous observational evidence cited by the study. A cohort of 178 people initially diagnosed with clinically isolated syndrome found that spinal cord lesions and active inflammation on MRI were associated with poorer long-term outcomes. A separate Dutch longitudinal study reported that baseline spinal cord lesions strongly predicted disability for up to 11 years, while infratentorial lesions also predicted disability. In another prospective cohort, a greater number of brain T2 lesions was associated with earlier irreversible disability. Such findings provide prognostic context for the panelists’ choices, but they do not demonstrate that choosing therapy on the basis of the Delphi thresholds will itself prevent disability.

The panel’s conclusions may also reflect the contemporary treatment environment. The study notes that the use of high-efficacy therapy has increased alongside evidence of benefit and tools for monitoring certain risks. For example, the anti-JC virus antibody index can help assess risk of progressive multifocal leukoencephalopathy in patients receiving anti-α4-integrin antibodies, and real-world data have linked its introduction with fewer such events. However, important determinants of safety and feasibility—including infection history, immunoglobulin levels, vaccination status, pregnancy plans and patient preference—were outside the Delphi exercise. The findings therefore describe what this group of neurologists would recommend in fictional cases, not what every patient should receive.

Several limitations constrain how the consensus can be interpreted. The scenarios were hypothetical, their combinations were not a representative sample of routine patients, and changing one factor at a time may exaggerate its apparent importance or miss interactions among clinical and imaging characteristics. The study also omitted recovery after the initial attack and emerging biomarkers such as serum neurofilament light chains, cerebrospinal-fluid measures, cortical or paramagnetic-rim lesions, atrophy and optical-coherence tomography findings. The second workshop round also allowed panelists to reconsider ratings after discussing evidence, illustrating the dynamic nature of consensus. Most importantly, the proposed framework has not been validated against patient outcomes, and the ongoing TREAT-MS and DELIVER-MS randomised trials have not yet reported whether early high-efficacy treatment improves long-term clinical results. The consensus offers a structured map of current expert reasoning, but its thresholds remain exploratory until tested in empirical studies.

Subject of Research: Expert consensus on MRI and clinical factors guiding early monoclonal high-efficacy therapy for relapsing-remitting multiple sclerosis

Article Title: DELPHI expert consensus-derived factors influencing the early use of monoclonal high-efficacy therapies in treatment-naïve patients with relapsing-remitting multiple sclerosis

Article References: Bourre, B., Guerrier, O., Ayrignac, X., Suchet, L., de Seze, J., Masmoudi, I., Ricigliano, V. A. G., Vermersch, P., Ciron, J., & the CAReSEP working group (2026). DELPHI expert consensus-derived factors influencing the early use of monoclonal high-efficacy therapies in treatment-naïve patients with relapsing-remitting multiple sclerosis. Journal of Neurology, 273(11), 679. https://doi.org/10.1007/s00415-026-14167-4

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14167-4

Keywords: multiple sclerosis, relapsing-remitting MS, monoclonal antibodies, high-efficacy therapy, MRI biomarkers, Delphi consensus, anti-CD20 antibodies, anti-α4-integrin antibodies, treatment-naïve patients, French neurologists, DELPHI, expert