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Blood biomarkers at disease onset may help predict relapse-associated worsening and progression independent of relapse activity (PIRA) in multiple sclerosis (MS), an observational study suggested.

Serum levels of neurofilament light (NfL), a marker of axonal injury, predicted both relapse-associated worsening and PIRA, reported Enric Monreal, MD, PhD, of the Hospital Universitario Ramón y Cajal in Madrid, who presented the findings at the annual European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting in Copenhagen.

Moreover, serum levels of glial fibrillary acidic protein (GFAP), an intermediate filament of astrocytes, correlated with PIRA in patients who had low NfL levels, Monreal said.

NfL has gained traction as an MS biomarker in recent years. In March, a consensus panel of experts for the Consortium of Multiple Sclerosis Centers as a cerebrospinal fluid and blood biomarker in MS management. GFAP may be more strongly than NfL, according to earlier research.

In this study, Monreal and co-authors analyzed blood samples that were collected within 12 months of disease onset from 725 MS patients across 13 hospitals in Spain and Italy. Most participants (70.2%) were women, and the median baseline age was 34.2.

"The time from first relapse to analysis was a little bit more than 3 months," Monreal pointed out. "Nearly a third of patients were treated with monoclonal antibodies and the median follow-up time was more than 6 years." Monoclonal antibodies were considered high-efficacy disease-modifying treatments (DMTs).

The researchers used a single-molecule array to assess the prognostic value of serum NfL and GFAP levels. Multivariable Cox regression analysis showed:

• Higher serum NfL z-score levels were associated with a 45% higher risk of relapse-associated worsening (HR 1.45, 95% CI 1.19-1.76, P<0.001) and a 43% higher risk of PIRA (HR 1.43, 95% 1.13-1.81, P=0.003)
• Higher serum GFAP values were linked with an increased risk of PIRA (HR 1.86, 95% CI 1.01-3.45, P=0.047), but only in patients with low levels of serum NfL

"We saw that neurofilament levels were affecting the ability of GFAP to predict the risk of PIRA," Monreal said.

The researchers further grouped patients into three categories: those with low levels of serum NfL and GFAP (31.3% of participants), those with high levels of NfL (55.3% of participants), and those with low levels of NfL and high levels of GFAP (13.4% of participants).

Compared with the low NfL-GFAP group, patients in the high NfL group showed a higher risk of relapse-associated worsening and PIRA if they were not treated or using injectable or oral treatments.

All participants had a similar risk of relapse-associated worsening or PIRA if treated with high-efficacy DMTs.

Identifying serum NfL and GFAP as predictive biomarkers could help tailor treatment strategies for MS patients, Monreal observed.

"Patients with low levels of both biomarkers had a good prognosis and could be treated with injectable or oral DMTs," he suggested. High NfL levels indicate a need for high-efficacy DMTs to prevent disability worsening, while patients with high serum GFAP levels and low values of serum NfL may require new therapeutic approaches, Monreal noted.

"By measuring both serum NfL and serum GFAP levels at disease onset, we gain valuable insights into the progression pathways of MS, enabling clinicians to identify the optimal patients for specific DMTs," he said. "This approach aims to prevent disability while avoiding unnecessary treatment-related risks for those at lower risk."

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