Contributions
Abstract: P629
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: There is an unmet need for prognostic biomarkers to facilitate treatment decision- making in multiple sclerosis (MS) patients. Recently, increased levels of neurofilament light (NfL) in CSF and serum of MS patients were shown to be associated with higher levels of disease severity and a worse long-term clinical and paraclinical outcome. However, the long-term prognostic value of serum NfL at first MS presentation remains largely unknown.
Objectives: To evaluate serum NfL as a prognostic biomarker for long-term clinical and radiological disease outcome measures in patients with clinically isolated syndrome (CIS).
Methods: Serum NfL levels were measured using a sensitive Single Molecule Array (SIMOA) assay in 319 patients (308 at baseline, 139 at year 2) originally recruited in the CHAMPS study, a 36-month randomized placebo-controlled trial of intramuscular interferon beta-1a in CIS patients. The 5- and 10-year open-label extension of this study, CHAMPIONS, comprises data on conversion to clinically definite MS (CDMS), number of relapses, EDSS milestones and various MRI measures, including brain parenchymal fraction (BPF). Statistical analyses were performed using Spearman correlation, ANOVA, chi-squared tests, and multivariate logistic regression.
Results: Serum NfL levels at CHAMPS baseline were significantly associated with number and volume of Gd+ lesions (p< 0.00001) and T2 lesion volume (p< 0.00001) at the time of sampling. Serum NfL levels at baseline were also associated with the number of new T2 lesions and T2 lesion volume at 5 years (p< 0.00001 for both) and 10 years (p< 0.01 and p< 0.000001, respectively), BPF change over 5 years (p< 0.00001), number of relapses over 10 years (p< 0.05), and time to CDMS over 10 years (p< 0.05). Additionally, serum NfL levels at baseline were associated with the risk of reaching EDSS≥3.5 at 5 years (p< 0.05). Similar observations were noted for NfL serum levels assessed at year 2.
Conclusions: Serum NfL levels in CIS patients are significantly associated with various long-term clinical and paraclinical outcome measures up to 10 years of follow-up. Our findings support the view that serum NfL represents a promising candidate biomarker for disease stratification already in early MS. Additional studies are warranted to corroborate these observations.
Disclosure: Study was sponsored by Biogen.
TP, CMS, DS, CDM, BE, EF, AS, BCK, RAR are employees of Biogen and hold stock/stock options in the company.
JG was an employee of Biogen at the time of the study conduct.
RPK reports personal fees from Genzyme, a Sanofi Corp., from Biogen Idec, from Novartis, and grants from Accelerated Cure Project.
Abstract: P629
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: There is an unmet need for prognostic biomarkers to facilitate treatment decision- making in multiple sclerosis (MS) patients. Recently, increased levels of neurofilament light (NfL) in CSF and serum of MS patients were shown to be associated with higher levels of disease severity and a worse long-term clinical and paraclinical outcome. However, the long-term prognostic value of serum NfL at first MS presentation remains largely unknown.
Objectives: To evaluate serum NfL as a prognostic biomarker for long-term clinical and radiological disease outcome measures in patients with clinically isolated syndrome (CIS).
Methods: Serum NfL levels were measured using a sensitive Single Molecule Array (SIMOA) assay in 319 patients (308 at baseline, 139 at year 2) originally recruited in the CHAMPS study, a 36-month randomized placebo-controlled trial of intramuscular interferon beta-1a in CIS patients. The 5- and 10-year open-label extension of this study, CHAMPIONS, comprises data on conversion to clinically definite MS (CDMS), number of relapses, EDSS milestones and various MRI measures, including brain parenchymal fraction (BPF). Statistical analyses were performed using Spearman correlation, ANOVA, chi-squared tests, and multivariate logistic regression.
Results: Serum NfL levels at CHAMPS baseline were significantly associated with number and volume of Gd+ lesions (p< 0.00001) and T2 lesion volume (p< 0.00001) at the time of sampling. Serum NfL levels at baseline were also associated with the number of new T2 lesions and T2 lesion volume at 5 years (p< 0.00001 for both) and 10 years (p< 0.01 and p< 0.000001, respectively), BPF change over 5 years (p< 0.00001), number of relapses over 10 years (p< 0.05), and time to CDMS over 10 years (p< 0.05). Additionally, serum NfL levels at baseline were associated with the risk of reaching EDSS≥3.5 at 5 years (p< 0.05). Similar observations were noted for NfL serum levels assessed at year 2.
Conclusions: Serum NfL levels in CIS patients are significantly associated with various long-term clinical and paraclinical outcome measures up to 10 years of follow-up. Our findings support the view that serum NfL represents a promising candidate biomarker for disease stratification already in early MS. Additional studies are warranted to corroborate these observations.
Disclosure: Study was sponsored by Biogen.
TP, CMS, DS, CDM, BE, EF, AS, BCK, RAR are employees of Biogen and hold stock/stock options in the company.
JG was an employee of Biogen at the time of the study conduct.
RPK reports personal fees from Genzyme, a Sanofi Corp., from Biogen Idec, from Novartis, and grants from Accelerated Cure Project.