Reader Response: Blood Neurofilament Light in Progressive Multiple Sclerosis: Post Hoc Analysis of 2 Randomized Controlled Trials
ChristianBarro, Research Fellow, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Submitted April 21, 2022
The study of Leppert et al. presents interesting findings on neurofilament light chain (NfL) but raises methodological concerns.1 First, it was not stated if the NfL quantification in EXPAND and INFORMS was performed with the same batches of reagents; a batch-to-batch variability of 20-50% is a common concern. Second, a fixed NfL threshold was used, which may lead to inaccurate conclusions.
The authors should describe if the batch-to-batch variability was addressed. Otherwise, the comparison between the NfL values of secondary progressive multiple sclerosis (EXPAND) and primary progressive MS (INFORMS) may be inadequate. Fixed thresholds lead to false classification of patients as “high NfL” because of their age. The correct classification of high/low NfL requires the use of age adjusted thresholds.2 The results from Leppert et al. are based on a fixed threshold and are therefore showing that older patients are at higher risk of disability progression. Age is a known risk factor for disability progression.
To provide convincing evidence, the authors should address the batch-to-batch variability and age adjusted thresholds, or NfL as a continuous variable should be used when exploring the prognostic value of NfL. Until then, a prognostic ability of NfL for disability progression cannot be ascertained.3,4
Disclosure
The author reports no relevant disclosures. Contact journal@neurology.org for full disclosures.
References
Leppert D, Kropshofer H, Häring DAA, et al. Blood Neurofilament Light in Progressive Multiple Sclerosis: Post Hoc Analysis of 2 Randomized Controlled Trials [published online ahead of print, 2022 Apr 4]. Neurology. 2022;10.1212/WNL.0000000000200258.
Benkert P, Meier S, Schaedelin S, et al. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study. Lancet Neurol. 2022;21(3):246-257. doi:10.1016/S1474-4422(22)00009-6
Bridel C, Leurs CE, van Lierop ZYGJ, et al. Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis. Neurology. 2021;97(19):e1898-e1905.
Gafson AR, Jiang X, Shen C, et al. Serum Neurofilament Light and Multiple Sclerosis Progression Independent of Acute Inflammation. JAMA Netw Open. 2022;5(2):e2147588. Published 2022 Feb 1. doi:10.1001/jamanetworkopen.2021.47588
The study of Leppert et al. presents interesting findings on neurofilament light chain (NfL) but raises methodological concerns.1 First, it was not stated if the NfL quantification in EXPAND and INFORMS was performed with the same batches of reagents; a batch-to-batch variability of 20-50% is a common concern. Second, a fixed NfL threshold was used, which may lead to inaccurate conclusions.
The authors should describe if the batch-to-batch variability was addressed. Otherwise, the comparison between the NfL values of secondary progressive multiple sclerosis (EXPAND) and primary progressive MS (INFORMS) may be inadequate. Fixed thresholds lead to false classification of patients as “high NfL” because of their age. The correct classification of high/low NfL requires the use of age adjusted thresholds.2 The results from Leppert et al. are based on a fixed threshold and are therefore showing that older patients are at higher risk of disability progression. Age is a known risk factor for disability progression.
To provide convincing evidence, the authors should address the batch-to-batch variability and age adjusted thresholds, or NfL as a continuous variable should be used when exploring the prognostic value of NfL. Until then, a prognostic ability of NfL for disability progression cannot be ascertained.3,4
Disclosure
The author reports no relevant disclosures. Contact journal@neurology.org for full disclosures.
References