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Background <p>Platform therapies, such as dimethylfumarate, teriflunomide, and interferons beta, are insufficient to control relapsing–remitting multiple sclerosis in many patients. Having biomarkers available to stratify patients as good or poor responders before starting treatment would represent a considerable advance.</p> Methods <p>We tested serum and cerebrospinal fluid (CSF) levels of chitinase 3-like 1 (c and s-CHI3L1), soluble trigger receptor expressed on myeloid cells (sTREM2) and neuronal pentraxin 2 (NPTX2), and CSF levels of neurofilament light chains and of interleukin-6 (c-IL6) collected before treatment start in 70 patients in Eastern France. We explored associations with the status responder or non-responder after 12&#xa0;months of efficient treatment. Non-responders were defined as patients with sign of activity, or confirmed increase of disability, or treatment cessation due to «&#xa0;inefficacy» according to the treating physician.</p> Results <p>39 patients were non-responders (55.7%). c-CHI3L1 taken as a binary variable (under or above 164.6&#xa0;ng/mL) and c-IL6 either as a binary variable (detectable or not) were associated with being non-responders. The positive predictive value of being non-responder in case of c-CHI3L1 higher than 164.6&#xa0;ng/mL was 0.63 (95 confidence interval 95CI 0.43–0.82). No responder patients had detectable c-IL6, 12 non-responders (46.2%) had detectable c-IL6. Having high values of c-CHI3L1 and/or detectable c-IL6 was associated with an 8.33 higher risk of being non-responder after 1&#xa0;year of effective platform treatment (95CI 1.44–33.33; <i>p</i> = 0.001).</p> Conclusions <p>CHI3L1 and IL6 in CSF could predict the first-year response to platform therapies.</p>

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Cerebrospinal fluid levels of chitinase 3-like 1 and interleukin-6 can predict response to platform therapies in relapsing multiple sclerosis

  • 期刊论文

  • 发表日期：

    2025年8月25日

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  • Guillaume Mathey,
  • Jonathan Epstein,
  • Tom Alix,
  • Melissa Julien,
  • Estelle Nisse,
  • Sophie Pittion-Vouyovitch,
  • Chloé Prunis,
  • Catherine Malaplate

摘要

Background

Platform therapies, such as dimethylfumarate, teriflunomide, and interferons beta, are insufficient to control relapsing–remitting multiple sclerosis in many patients. Having biomarkers available to stratify patients as good or poor responders before starting treatment would represent a considerable advance.

Methods

We tested serum and cerebrospinal fluid (CSF) levels of chitinase 3-like 1 (c and s-CHI3L1), soluble trigger receptor expressed on myeloid cells (sTREM2) and neuronal pentraxin 2 (NPTX2), and CSF levels of neurofilament light chains and of interleukin-6 (c-IL6) collected before treatment start in 70 patients in Eastern France. We explored associations with the status responder or non-responder after 12 months of efficient treatment. Non-responders were defined as patients with sign of activity, or confirmed increase of disability, or treatment cessation due to « inefficacy» according to the treating physician.

Results

39 patients were non-responders (55.7%). c-CHI3L1 taken as a binary variable (under or above 164.6 ng/mL) and c-IL6 either as a binary variable (detectable or not) were associated with being non-responders. The positive predictive value of being non-responder in case of c-CHI3L1 higher than 164.6 ng/mL was 0.63 (95 confidence interval 95CI 0.43–0.82). No responder patients had detectable c-IL6, 12 non-responders (46.2%) had detectable c-IL6. Having high values of c-CHI3L1 and/or detectable c-IL6 was associated with an 8.33 higher risk of being non-responder after 1 year of effective platform treatment (95CI 1.44–33.33; p = 0.001).

Conclusions

CHI3L1 and IL6 in CSF could predict the first-year response to platform therapies.