Use of fluid biomarkers in ongoing Clinical Trials on Multiple Sclerosis (MS)

Background and aims: The present study aimed to describe the state of art of fluid biomarkers use in ongoing MS clinical trials. Methods: A review of 600 ongoing protocols in the clinicaltrials.gov database was performed. The trials enrolled subjects with a diagnosis of RRMS, SPMS and/or PPMS according to Revised McDonald Criteria 2017 or RMS according to Lublin et al. 2014. The presence of CSF (c) or blood (b), either plasma (p) or serum (s), biomarkers among the primary and/or secondary study outcomes was assessed. Results: Overall, 5% of ongoing studies on MS adopted CSF or blood biomarkers. They were mostly adopted as secondary outcomes in phase 3–4 clinical trials to support the potential disease modifying properties of the intervention. Most studies evaluated sNfL, some considered pNfL or cNfL. A small number considered novel biomarkers of neuroinflammation and neurodegeneration as sGFAP/ cGFAP, bIL-6, sChi3L1, and/or inflammatory biomarkers: sVCAM, sMAdCAM, sCXCL13. Conclusions: Considering the numerous ongoing clinical trials in MS, still a small number considers fluid biomarkers as outcome measures, thus testifying the distance from clinical practice. Fluid biomarkers were prevalently considered in studies evaluating the effectiveness of approved second line therapies. Almost all clinical trials evaluating new drugs, particularly BTK-inhibitors considered fluid biomarkers, suggesting a future clinical utility in assessing the effectiveness of these treatments. Nevertheless, the cost-effectiveness in the “real word” remains to be clarified. NfLs have been also used to monitor disease progression after natalizumab suspension in stable patients, cladribine efficacy after anti-CD20 discontinuation, and the efficacy of AHSCT compared to medical treatment. Disclosure: Nothing to disclose