Abstract: 102
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Serum neurofilament light (NfL) is a candidate marker of disease severity in multiple sclerosis (MS). Current NfL observations are mostly based on cross-sectional or short-term studies. Evolution of serum NfL as a biomarker for clinical decision-making will require information on NfL levels variability over time in individual patients.
Objectives: To evaluate temporal variability profile of serum NfL levels in patients with MS.
Methods: Serum NfL was measured at baseline and week 48 in 272 patients from the phase III study of peginterferon beta-1a (PEG-IFN; ADVANCE); 116 received PEG-IFN and 156 received placebo in year 1, all switched to PEG-IFN at the start of year 2. In 40 patients from the placebo group, comprising 20 patients with no evidence of disease activity (NEDA; no relapses, no Gd+ and no new T2 lesions over 2 years), and 20 patients with evident disease activity (EDA; ≥1 relapse, ≥1 Gd+ and/or new T2 lesions at year 1 and year 2) serum NfL was measured every 3 months using a sensitive Single Molecule Array (SIMOA) assay. Statistical analyses included Spearman correlation, ANOVA, chi-squared test, and multivariate logistic regression.
Results: Serum NfL levels at baseline were significantly associated with number of Gd+ lesions (p< 0.00001) and T2 lesion volume (p< 0.0001) at baseline, number of new T2 lesions at year 2 (p< 0.00001), and percent brain volume change over 2 years (p< 0.0001). In patients with elevated baseline NfL (>10 pg/mL), NfL levels decreased significantly in the PEG-IFN compared to the placebo group (mean 55%, n=87 vs 26%, n=70, p< 0.05). In the longitudinal subgroup, patients with NEDA revealed consistently low and stable NfL levels, similar to those in healthy individuals (mean 7.9 pg/mL, mean within-subject coefficient of variation (CV=21%). In patients with EDA, serum NfL levels were significantly higher at each time-point (mean 28.9 pg/mL p< 0.0001) and more variable (CV=31%, p< 0.01) compared to those in the NEDA group, with highest variability in those with highest baseline NfL. Both NfL levels and intra-patient variability in the EDA group decreased on PEG-IFN treatment.
Conclusions: In patients with NEDA, NfL levels remained consistently low; in patients with EDA NfL levels appeared consistently elevated and more variable, while decreasing on PEG-IFN treatment. These findings support the view that serum NfL is a promising candidate marker for disease and treatment monitoring in MS.
Disclosure: Study was sponsored by Biogen.
PAC reports consulting fees from Biogen, and grants from Biogen, MedImmune, Annexon, Teva, Genzyme, and Novartis.
DLA reports an equity interest in NeuroRx during the conduct of the study and consulting activities with Biogen, Celgene, Genentech, Genzyme, Hoffman-La Roche, MedImmune, Mitsubishi, Novartis, Receptos, Acorda, Sanofi-Aventis, as well as grants from Biogen and Novartis.
DS, CMS, CDM, BE, AD, EF, BCK, RAR and TP 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.
Abstract: 102
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Serum neurofilament light (NfL) is a candidate marker of disease severity in multiple sclerosis (MS). Current NfL observations are mostly based on cross-sectional or short-term studies. Evolution of serum NfL as a biomarker for clinical decision-making will require information on NfL levels variability over time in individual patients.
Objectives: To evaluate temporal variability profile of serum NfL levels in patients with MS.
Methods: Serum NfL was measured at baseline and week 48 in 272 patients from the phase III study of peginterferon beta-1a (PEG-IFN; ADVANCE); 116 received PEG-IFN and 156 received placebo in year 1, all switched to PEG-IFN at the start of year 2. In 40 patients from the placebo group, comprising 20 patients with no evidence of disease activity (NEDA; no relapses, no Gd+ and no new T2 lesions over 2 years), and 20 patients with evident disease activity (EDA; ≥1 relapse, ≥1 Gd+ and/or new T2 lesions at year 1 and year 2) serum NfL was measured every 3 months using a sensitive Single Molecule Array (SIMOA) assay. Statistical analyses included Spearman correlation, ANOVA, chi-squared test, and multivariate logistic regression.
Results: Serum NfL levels at baseline were significantly associated with number of Gd+ lesions (p< 0.00001) and T2 lesion volume (p< 0.0001) at baseline, number of new T2 lesions at year 2 (p< 0.00001), and percent brain volume change over 2 years (p< 0.0001). In patients with elevated baseline NfL (>10 pg/mL), NfL levels decreased significantly in the PEG-IFN compared to the placebo group (mean 55%, n=87 vs 26%, n=70, p< 0.05). In the longitudinal subgroup, patients with NEDA revealed consistently low and stable NfL levels, similar to those in healthy individuals (mean 7.9 pg/mL, mean within-subject coefficient of variation (CV=21%). In patients with EDA, serum NfL levels were significantly higher at each time-point (mean 28.9 pg/mL p< 0.0001) and more variable (CV=31%, p< 0.01) compared to those in the NEDA group, with highest variability in those with highest baseline NfL. Both NfL levels and intra-patient variability in the EDA group decreased on PEG-IFN treatment.
Conclusions: In patients with NEDA, NfL levels remained consistently low; in patients with EDA NfL levels appeared consistently elevated and more variable, while decreasing on PEG-IFN treatment. These findings support the view that serum NfL is a promising candidate marker for disease and treatment monitoring in MS.
Disclosure: Study was sponsored by Biogen.
PAC reports consulting fees from Biogen, and grants from Biogen, MedImmune, Annexon, Teva, Genzyme, and Novartis.
DLA reports an equity interest in NeuroRx during the conduct of the study and consulting activities with Biogen, Celgene, Genentech, Genzyme, Hoffman-La Roche, MedImmune, Mitsubishi, Novartis, Receptos, Acorda, Sanofi-Aventis, as well as grants from Biogen and Novartis.
DS, CMS, CDM, BE, AD, EF, BCK, RAR and TP 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.