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. 2025 Feb 14;15(2):69.
doi: 10.3390/jpm15020069.

Attitudes of Neurologists Toward Serum Neurofilament Light-Chain Testing in the Management of Relapsing-Remitting Multiple Sclerosis with Cognitive Impairment

José M García-Domínguez  1 , Jorge Maurino  2 , José E Meca-Lallana  3 , Lamberto Landete  4 , Virginia Meca-Lallana  5 , Elena García-Arcelay  2 , Eduardo Agüera-Morales  6 , Ana B Caminero  7 , Sergio Martínez-Yélamos  8 , Luis Querol  9 , Nicolas Medrano  2 , Rocío Gómez-Ballesteros  2 , Luisa M Villar  10 , Enric Monreal  11 , Gustavo Saposnik  12
Affiliations

Attitudes of Neurologists Toward Serum Neurofilament Light-Chain Testing in the Management of Relapsing-Remitting Multiple Sclerosis with Cognitive Impairment

José M García-Domínguez et al. J Pers Med. .

Abstract

Background: Cognitive impairment has an impact upon the function and quality of life of patients with multiple sclerosis (MS). High-serum neurofilament light-chain (sNfL) levels predict disease progression and are also associated with impaired cognitive performance. This study aimed to assess the attitudes of neurologists toward sNfL testing as regards making therapeutic decisions in clinically and radiologically stable patients experiencing cognitive decline. Methods: A web-based observational study was conducted among neurologists caring for patients with MS. The role of sNfL in therapeutic decisions was assessed through a simulated case scenario describing a 31-year-old woman with relapsing-remitting MS for four years on glatiramer acetate. Her partner reported increased distractibility and difficulties in organizing daily activities over the past 18 months. There was no history of new relapses, and a follow-up brain MRI scan showed no new lesions. Her performance in the Symbol Digit Modalities Test decreased by 8 points from the previous year, with 46 correct answers. The patient had an sNfL level of 21 pg/mL, with no other identified factors that could have altered this value. The participants were tasked with deciding to either escalate treatment or to continue the current treatment and schedule the patient for reassessment in 6-12 months (defined as decisions misaligned with emerging evidence [DMEE]). Multivariate regression analysis was conducted to determine factors associated with DMEE. Results: One hundred and sixteen neurologists participated in the study. Almost 50% of the participants (n = 57) opted not to escalate treatment despite high sNfL levels. This was more common among neurologists not fully dedicated to MS care (60.5% vs. 43.6%). The multivariate analysis showed that being a neurologist not fully dedicated to MS (odds ratio [OR] = 2.35, 95% confidence interval [CI] 1.01-5.50; p = 0.04) and having a poor perception of sNfL benefits (OR = 1.02, 95% CI 1.00-1.04; p = 0.01) were associated with DMEE. Conclusions: Neurologists' lack of full dedication to MS care and limited perception of sNfL's clinical utility were key factors associated with suboptimal therapeutic decisions in a simulated case of cognitive decline with elevated sNfL. These findings underscore the need for increased education on the role of sNfL to improve evidence-based decision-making in MS management.

Keywords: cognition; decision-making; multiple sclerosis; neurofilament light chain; personalized medicine.

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Conflict of interest statement

J.M.G.-D. has received honoraria as a speaker, advisor, and researcher from Almirall, Bristol Myers Squibb, Biogen, Janssen, Merck, Novartis, Roche, Teva, and Sanofi. G.S. has provided consultancy services for Roche Farma Spain and is a recipient of the University of Toronto Scientific Merit Award. J.E.M.-L. has been compensated for roles as a consultant, chairman, and lecturer in various meetings and has participated in clinical trials and research projects supported by Alexion, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, and Sanofi. E.M. has received research grants, travel support, and honoraria for speaking engagements from Almirall, Merck, Roche, Sanofi, Bristol Myers Squibb, Biogen, Janssen, and Novartis. L.L. has earned honoraria for participating in advisory boards and contributing to scientific and educational activities with Almirall, Bayer, Biogen, Bristol Myers Squibb, Sanofi, Merck, Novartis, UCB, Roche, and Teva. V.M.-L. has received consulting and speaking fees from Almirall, Biogen, Genzyme, Janssen, Merck, Novartis, Roche, Terumo, Sanofi, Teva, and Bristol Myers Squibb. L.Q. has been compensated for speaking engagements by Merck, Sanofi, Roche, Biogen, Grifols, and CSL Behring; provided expert testimony for Grifols, Johnson & Johnson, Annexon Pharmaceuticals, Sanofi, Novartis, Takeda, and CSL Behring; and received research funding from Roche, UCB, and Grifols. E.A. has received honoraria for speaking engagements from Roche, Novartis, Merck, Sanofi, and Biogen. The institution where S.M-Y. works has received in the last 3 years and destined exclusively to support the research of the Unit, fees for advisory council, collaborations, donations, and advice from Almirall, Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Horizon/Amgen, Janssen, Kern Pharma, Lilly, Merck, Neuraxpharm, Novartis, Roche, Sandoz, and Sanofi. S.M.-Y. has received support for attendance at congress in the last 3 years from Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, and Sandoz. L.M.V. has received research grants and personal fees from Merck, Roche, Sanofi, Bristol Myers Squibb, Biogen, and Novartis. A.B.C. has received compensation for her roles as a speaker, meeting moderator, and symposium organizer from Alter, Almirall, Bayer, Bial, Biogen, Bristol Myers Squibb, Lilly, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, Teva, and UCB, as well as support to attend scientific meetings from Biogen, Bial, Merck-Serono, Novartis, Roche, Sanofi, and Teva. R.G.-B., E.G.-A., N.M., and J.M. are employees of Roche Farma Spain. Data were partially presented as an e-poster (P1532) at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held from 18 to 20 September 2024, in Copenhagen, Denmark.

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