BACKGROUND: Neurofilament light chain is a promising biomarker of disease activity and treatment response in relapsing-remitting multiple sclerosis (MS). Its role in progressive MS is less clear. AIM: The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept NEDA-3 (No Evident Disease Activity), and brain volumetry, in a cohort of patients with the progressive disease form (PMS). METHODS: Levels of pNfL (SIMOA technology) were examined in 52 PMS patients and analysed in relationship to NEDA-3 status and annual brain volume loss (BVL) during the last 12 months. The statistical model was developed using logistic regression analysis, including demographic, clinical and magnetic resonance imaging (MRI) data as independent variables. Dependent variables were NEDA-3 status and BVL. RESULTS: The mean age of the study participants (n=52, 50% females) was 45.85 (SD, 9.82) and the median disability score was 5.0 (IQR: 5.0-5.5). ROC analysis showed that pNfL predicts NEDA-3 (the sensitivity and specificity of the model were 77.8% and 87.6%, respectively, P<0.001) and abnormal BVL (the sensitivity and specificity were 96.6% and 68.2%, respectively, P<0.001). CONCLUSIONS: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA-3 status, including brain MRI-volumetry, in patients with the progressive form of MS.

• Keywords
• brain volume loss, multiple sclerosis, neurofilament light chain, no evident disease activity, progressive MS,
• MeSH
• Atrophy MeSH
• Biomarkers MeSH
• Intermediate Filaments MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Brain diagnostic imaging   pathology   MeSH
• Central Nervous System Diseases * MeSH
• Disease Progression MeSH
• Multiple Sclerosis, Relapsing-Remitting * diagnostic imaging   drug therapy   pathology   MeSH
• Multiple Sclerosis * diagnostic imaging   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH

BACKGROUND: No evidence of disease activity (NEDA; defined as no 12-week confirmed disability progression, no protocol-defined relapses, no new/enlarging T2 lesions and no T1 gadolinium-enhancing lesions) using a fixed-study entry baseline is commonly used as a treatment outcome in multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to assess the effect of ocrelizumab on NEDA using re-baselining analysis, and the predictive value of NEDA status. METHODS: NEDA was assessed in a modified intent-to-treat population (n = 1520) from the pooled OPERA I and OPERA II studies over various epochs in patients with relapsing MS receiving ocrelizumab (600 mg) or interferon beta-1a (IFN β-1a; 44 μg). RESULTS: NEDA was increased with ocrelizumab vs IFN β-1a over 96 weeks by 75% (p < 0.001), from Week 0‒24 by 33% (p < 0.001) and from Week 24‒96 by 72% (p < 0.001). Among patients with disease activity during Weeks 0‒24, 66.4% vs 24.3% achieved NEDA during Weeks 24‒96 in the ocrelizumab and IFN β-1a groups (relative increase: 177%; p < 0.001). CONCLUSION: Superior efficacy with ocrelizumab compared with IFN β-1a was consistently seen in maintaining NEDA status in all epochs evaluated. By contrast with IFN β-1a, the majority of patients with disease activity early in the study subsequently attained NEDA status with ocrelizumab.

• Keywords
• MRI activity, NEDA, disability progression, disease activity, relapse,
• Publication type
• Journal Article MeSH

Using combined endpoints to define no evident disease activity (NEDA) is becoming increasingly common when setting targets for treatment outcomes in multiple sclerosis (MS). Historically, NEDA has taken account of the occurrence of relapses, brain magnetic resonance imaging (MRI) lesions and disability worsening, but this approach places emphasis on inflammatory activity in the brain and mostly overlooks ongoing neurodegenerative damage. Combined assessments of NEDA which take account of changes in brain volume or neuropsychological outcomes such as cognitive function may begin to address this imbalance, and such assessments may also consider blood or spinal-fluid neurofilament levels or patient-reported outcomes and quality of life measures. If a combined NEDA assessment can be validated in prospective studies as indicative of long-term disease remission at the individual patient level, treating to achieve NEDA could become the goal of clinical practice and achieving NEDA may become the "new normal" state of disease control for patients with MS.

• Keywords
• Brain volume loss, NEDA-4, cognition, combined assessments, no evident disease activity, treatment algorithms,
• MeSH
• Outcome Assessment, Health Care methods   standards   MeSH
• Humans MeSH
• Multiple Sclerosis diagnosis   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH