Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial

Introduction: Several studies have described prognostic value of serum neurofilament light chain (sNfL) at the group level in relapsing multiple sclerosis (RMS) patients. Here, we aimed to explore the temporal association between sNfL and development of subclinical disease activity as assessed by ma...

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Autores: Bar-Or, Amit|||0000-0001-7179-0335, Montalban, Xavier|||0000-0002-0098-9918, Hu, Xixi, Kropshofer, Harald, Kukkaro, Petra, Coello, Neva, Ludwig, Inga|||0000-0002-2963-5179, Willi, Roman|||0000-0001-9612-9877, Zalesak, Martin, Ramanathan, Krishnan, Kieseier, Bernd C., Häring, Dieter A., Bagger, Morten, Fox, Edward J
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:275799
Acceso en línea:https://ddd.uab.cat/record/275799
https://dx.doi.org/urn:doi:10.1007/s40120-022-00427-8
Access Level:acceso abierto
Palabra clave:Biomarker
Ofatumumab
Relapsing multiple sclerosis
Serum neurofilament light chain
Subclinical disease activity
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spelling Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS TrialBar-Or, Amit|||0000-0001-7179-0335Montalban, Xavier|||0000-0002-0098-9918Hu, XixiKropshofer, HaraldKukkaro, PetraCoello, NevaLudwig, Inga|||0000-0002-2963-5179Willi, Roman|||0000-0001-9612-9877Zalesak, MartinRamanathan, KrishnanKieseier, Bernd C.Häring, Dieter A.Bagger, MortenFox, Edward JBiomarkerOfatumumabRelapsing multiple sclerosisSerum neurofilament light chainSubclinical disease activityIntroduction: Several studies have described prognostic value of serum neurofilament light chain (sNfL) at the group level in relapsing multiple sclerosis (RMS) patients. Here, we aimed to explore the temporal association between sNfL and development of subclinical disease activity as assessed by magnetic resonance imaging (MRI) at the group level and evaluate the potential of sNfL as a biomarker for capturing subclinical disease activity in individual RMS patients. Methods: In the 12-week APLIOS study, patients (N = 284) received subcutaneous ofatumumab 20 mg. Frequent sNfL sampling (14 time points over 12 weeks) and monthly MRI scans enabled key analyses including assessment of the group-level temporal relationship of sNfL levels with on-study subclinical development of gadolinium-enhancing (Gd +)T1 lesions. Prognostic value of baseline sNfL ("high" vs. "low") level for subsequent on-study clinical relapse or Gd + T1 activity was assessed. Individual patient-level development of on-study Gd + T1 lesions wascompared across three predictors: baseline Gd + T1 lesion number, baseline sNfL ("high" vs. "low"), and time-matched sNfL. Results: In patients developing Gd + T1 lesions at week 4 (absent at baseline), sNfL levels increased during the month preceding the week-4 MRI scan and then gradually decreased back to baseline. High versus low baseline sNfL conferred increased risk of subsequent on-study clinical relapse or Gd + T1 activity (HR, 2.81; p < 0.0001) in the overall population and, notably, also in the patients without baseline Gd + T1 lesions (HR, 2.48; p = 0.0213). Individual patient trajectories revealed a marked difference in Gd + T1 lesions between patients with the ten highest vs. lowest baseline sNfL levels (119 vs. 19 lesions). Prognostic value of baseline or time-matched sNfL for on-study Gd + T1 lesions was comparable to that of the number of baseline MRI Gd + T1 lesions. Conclusions: sNfL measurement may have utility in capturing and monitoring subclinical disease activity in RMS patients. sNfL assessments could complement regular MRI scans and may provide an alternative when MRI assessment is not feasible. ClinicalTrials.gov: NCT03560739. Classification of Evidence: This study provides class I evidence that serum neurofilament light may be used as a biomarker for monitoring subclinical disease activity in relapsing multiple sclerosis patients, as shown by its elevation in the weeks preceding the development of new gadolinium-enhancing T1 lesion activity.Universitat Autònoma de Barcelona 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/275799https://dx.doi.org/urn:doi:10.1007/s40120-022-00427-8reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2757992026-06-06T12:50:31Z
dc.title.none.fl_str_mv Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial
title Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial
spellingShingle Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial
Bar-Or, Amit|||0000-0001-7179-0335
Biomarker
Ofatumumab
Relapsing multiple sclerosis
Serum neurofilament light chain
Subclinical disease activity
title_short Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial
title_full Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial
title_fullStr Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial
title_full_unstemmed Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial
title_sort Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial
dc.creator.none.fl_str_mv Bar-Or, Amit|||0000-0001-7179-0335
Montalban, Xavier|||0000-0002-0098-9918
Hu, Xixi
Kropshofer, Harald
Kukkaro, Petra
Coello, Neva
Ludwig, Inga|||0000-0002-2963-5179
Willi, Roman|||0000-0001-9612-9877
Zalesak, Martin
Ramanathan, Krishnan
Kieseier, Bernd C.
Häring, Dieter A.
Bagger, Morten
Fox, Edward J
author Bar-Or, Amit|||0000-0001-7179-0335
author_facet Bar-Or, Amit|||0000-0001-7179-0335
Montalban, Xavier|||0000-0002-0098-9918
Hu, Xixi
Kropshofer, Harald
Kukkaro, Petra
Coello, Neva
Ludwig, Inga|||0000-0002-2963-5179
Willi, Roman|||0000-0001-9612-9877
Zalesak, Martin
Ramanathan, Krishnan
Kieseier, Bernd C.
Häring, Dieter A.
Bagger, Morten
Fox, Edward J
author_role author
author2 Montalban, Xavier|||0000-0002-0098-9918
Hu, Xixi
Kropshofer, Harald
Kukkaro, Petra
Coello, Neva
Ludwig, Inga|||0000-0002-2963-5179
Willi, Roman|||0000-0001-9612-9877
Zalesak, Martin
Ramanathan, Krishnan
Kieseier, Bernd C.
Häring, Dieter A.
Bagger, Morten
Fox, Edward J
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Biomarker
Ofatumumab
Relapsing multiple sclerosis
Serum neurofilament light chain
Subclinical disease activity
topic Biomarker
Ofatumumab
Relapsing multiple sclerosis
Serum neurofilament light chain
Subclinical disease activity
description Introduction: Several studies have described prognostic value of serum neurofilament light chain (sNfL) at the group level in relapsing multiple sclerosis (RMS) patients. Here, we aimed to explore the temporal association between sNfL and development of subclinical disease activity as assessed by magnetic resonance imaging (MRI) at the group level and evaluate the potential of sNfL as a biomarker for capturing subclinical disease activity in individual RMS patients. Methods: In the 12-week APLIOS study, patients (N = 284) received subcutaneous ofatumumab 20 mg. Frequent sNfL sampling (14 time points over 12 weeks) and monthly MRI scans enabled key analyses including assessment of the group-level temporal relationship of sNfL levels with on-study subclinical development of gadolinium-enhancing (Gd +)T1 lesions. Prognostic value of baseline sNfL ("high" vs. "low") level for subsequent on-study clinical relapse or Gd + T1 activity was assessed. Individual patient-level development of on-study Gd + T1 lesions wascompared across three predictors: baseline Gd + T1 lesion number, baseline sNfL ("high" vs. "low"), and time-matched sNfL. Results: In patients developing Gd + T1 lesions at week 4 (absent at baseline), sNfL levels increased during the month preceding the week-4 MRI scan and then gradually decreased back to baseline. High versus low baseline sNfL conferred increased risk of subsequent on-study clinical relapse or Gd + T1 activity (HR, 2.81; p < 0.0001) in the overall population and, notably, also in the patients without baseline Gd + T1 lesions (HR, 2.48; p = 0.0213). Individual patient trajectories revealed a marked difference in Gd + T1 lesions between patients with the ten highest vs. lowest baseline sNfL levels (119 vs. 19 lesions). Prognostic value of baseline or time-matched sNfL for on-study Gd + T1 lesions was comparable to that of the number of baseline MRI Gd + T1 lesions. Conclusions: sNfL measurement may have utility in capturing and monitoring subclinical disease activity in RMS patients. sNfL assessments could complement regular MRI scans and may provide an alternative when MRI assessment is not feasible. ClinicalTrials.gov: NCT03560739. Classification of Evidence: This study provides class I evidence that serum neurofilament light may be used as a biomarker for monitoring subclinical disease activity in relapsing multiple sclerosis patients, as shown by its elevation in the weeks preceding the development of new gadolinium-enhancing T1 lesion activity.
publishDate 2023
dc.date.none.fl_str_mv 2
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/275799
https://dx.doi.org/urn:doi:10.1007/s40120-022-00427-8
url https://ddd.uab.cat/record/275799
https://dx.doi.org/urn:doi:10.1007/s40120-022-00427-8
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
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