Contributions
Abstract: P1747
Type: Poster Sessions
Abstract Category: N/A
Background: Blood neurofilament light chain levels are promising biomarkers of neuro-axonal damage and may serve as indicators of response to DMT. In CARE-MS I (NCT00530348), alemtuzumab significantly improved clinical/MRI outcomes, including brain volume loss (BVL), vs SC IFNB-1a over 2 years in treatment-naive patients with RRMS. Efficacy was maintained over 8 years total follow-up during 2 consecutive extension studies (CARE-MS extension [NCT00930553] and TOPAZ [NCT02255656]).
Goal: To investigate the effects of alemtuzumab on serum neurofilament light chain (sNfL) levels over 2 years in CARE-MS I patients, and determine the relationship between sNfL and clinical and MRI measures at baseline (BL) and post-BL.
Methods: Patients received 2 annual courses of alemtuzumab 12 mg/day (BL: 5 days; 1 year later: 3 days), and could receive additional alemtuzumab as needed in the extension studies, or another DMT. A single molecule array assay was used to determine sNfL levels at BL, 6, 12, 18 and 24 months post alemtuzumab. P values evaluating sNfL change from BL were derived using a likelihood-based repeated measures model with BL sNfL level, age, gender, BL EDSS, visit, and relapse within 60 days prior to treatment as fixed effects, and assuming unstructured variance-covariance structure. BVL over 8 years was measured by change in brain parenchymal fraction.
Results: >1500 samples from 329 alemtuzumab-treated patients were analyzed. Patients had active disease at BL; 48% had gadolinium (Gd)-enhancing lesions. Higher BL sNfL levels were associated with higher BL Gd-enhancing lesion count (Spearman correlation coefficient: 0.482; P< 0.0001). Median sNfL level was 31.6 pg/mL at BL, decreased significantly at 6 months post-alemtuzumab (median 17.2 pg/mL, P< 0.0001), and remained significantly below BL through Month 24 (median 13.0-13.9 pg/mL, P< 0.0001 for all comparisons to BL). 92% of patients had reduced sNfL post-alemtuzumab; of those, 78% had a reduction of ≥50%. BL NfL correlated with future BVL but robust reductions in BVL over 8 years were observed in patients across BL sNfL levels. Over 7000 samples through 7 years are being analyzed and additional results in relation to clinical and imaging endpoints will be presented.
Conclusion: Initiation of alemtuzumab was associated with a significant sNfL reduction that was maintained over 2 years, consistent with alemtuzumab's previously reported effects on reduction in MRI activity and preservation of brain volume.
Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure: JK: Dr. Kuhle's institution (University Hospital Basel) received and used exclusively for research support: consulting fees from Biogen, Novartis, Protagen AG, Roche, Teva; speaker fees from the Swiss MS Society, Biogen, Novartis, Roche, Genzyme; travel expenses from Merck Serono, Novartis, Roche; grants from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221), Bayer AG, Biogen, Genzyme, Merck, Novartis, Roche. CB: Dr. Barro has received travel support from Teva and Novartis. ZM: Nothing to disclose. LK: Ludwig Kappos' Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, Sanofi-Aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations. AJ, CK, EH, JG, LC, ND, NR, SS, TS: Employees of Sanofi.
Abstract: P1747
Type: Poster Sessions
Abstract Category: N/A
Background: Blood neurofilament light chain levels are promising biomarkers of neuro-axonal damage and may serve as indicators of response to DMT. In CARE-MS I (NCT00530348), alemtuzumab significantly improved clinical/MRI outcomes, including brain volume loss (BVL), vs SC IFNB-1a over 2 years in treatment-naive patients with RRMS. Efficacy was maintained over 8 years total follow-up during 2 consecutive extension studies (CARE-MS extension [NCT00930553] and TOPAZ [NCT02255656]).
Goal: To investigate the effects of alemtuzumab on serum neurofilament light chain (sNfL) levels over 2 years in CARE-MS I patients, and determine the relationship between sNfL and clinical and MRI measures at baseline (BL) and post-BL.
Methods: Patients received 2 annual courses of alemtuzumab 12 mg/day (BL: 5 days; 1 year later: 3 days), and could receive additional alemtuzumab as needed in the extension studies, or another DMT. A single molecule array assay was used to determine sNfL levels at BL, 6, 12, 18 and 24 months post alemtuzumab. P values evaluating sNfL change from BL were derived using a likelihood-based repeated measures model with BL sNfL level, age, gender, BL EDSS, visit, and relapse within 60 days prior to treatment as fixed effects, and assuming unstructured variance-covariance structure. BVL over 8 years was measured by change in brain parenchymal fraction.
Results: >1500 samples from 329 alemtuzumab-treated patients were analyzed. Patients had active disease at BL; 48% had gadolinium (Gd)-enhancing lesions. Higher BL sNfL levels were associated with higher BL Gd-enhancing lesion count (Spearman correlation coefficient: 0.482; P< 0.0001). Median sNfL level was 31.6 pg/mL at BL, decreased significantly at 6 months post-alemtuzumab (median 17.2 pg/mL, P< 0.0001), and remained significantly below BL through Month 24 (median 13.0-13.9 pg/mL, P< 0.0001 for all comparisons to BL). 92% of patients had reduced sNfL post-alemtuzumab; of those, 78% had a reduction of ≥50%. BL NfL correlated with future BVL but robust reductions in BVL over 8 years were observed in patients across BL sNfL levels. Over 7000 samples through 7 years are being analyzed and additional results in relation to clinical and imaging endpoints will be presented.
Conclusion: Initiation of alemtuzumab was associated with a significant sNfL reduction that was maintained over 2 years, consistent with alemtuzumab's previously reported effects on reduction in MRI activity and preservation of brain volume.
Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure: JK: Dr. Kuhle's institution (University Hospital Basel) received and used exclusively for research support: consulting fees from Biogen, Novartis, Protagen AG, Roche, Teva; speaker fees from the Swiss MS Society, Biogen, Novartis, Roche, Genzyme; travel expenses from Merck Serono, Novartis, Roche; grants from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221), Bayer AG, Biogen, Genzyme, Merck, Novartis, Roche. CB: Dr. Barro has received travel support from Teva and Novartis. ZM: Nothing to disclose. LK: Ludwig Kappos' Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, Sanofi-Aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations. AJ, CK, EH, JG, LC, ND, NR, SS, TS: Employees of Sanofi.