Serum neurofilament light chain and glial fibrillary acidic protein for predicting response to apheresis in steroid-refractory multiple sclerosis relapses.
MS relapse
clinical trial
immunoadsorption
multiple sclerosis
plasma exchange
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
03 May 2024
03 May 2024
Historique:
revised:
11
04
2024
received:
29
02
2024
accepted:
12
04
2024
medline:
3
5
2024
pubmed:
3
5
2024
entrez:
3
5
2024
Statut:
aheadofprint
Résumé
The predictive value of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) for apheresis outcome in steroid-refractory multiple sclerosis (MS) relapse has not yet been evaluated. We used pre- and postapheresis serum samples from 38 participants of the IAPEMS trial (clinicaltrials.gov: NCT02671682), which investigated the use of immunoadsorption versus plasma exchange for the treatment of steroid-refractory MS attacks. Response to apheresis was classified based on improvement on (i) the Expanded Disability Status Scale (EDSS), (ii) the affected functional system scores (FSS) of the EDSS, or (iii) the visual acuity for patients with optic neuritis, 4 weeks postapheresis. sNFL and sGFAP were measured by single molecule arrays. Preprocedural sGFAP levels could discriminate between responders and nonresponders, determined by FSS improvement (p = 0.017). In multivariate logistic regression analysis, younger age (odds ratio [OR] = 0.781, 95% confidence interval [CI] = 0.635-0.962, p = 0.020) and lower sGFAP levels (OR = 0.948, 95% CI = 0.903-0.995, p = 0.031) could predict response to apheresis in the overall cohort. We could observe a trend towards a favourable apheresis outcome with higher sNfL levels (OR = 1.413, 95% CI = 0.965-2.069, p = 0.076). Analysis of the sNfL-to-sGFAP ratio showed an OR of 1.924 (95% CI = 1.073-3.451, p = 0.028) for predicting apheresis response. The ratio showed a better predictive value than the individual parameters. Neither biomarker was affected by the number of steroid cycles preapheresis. Lower sGFAP levels, a higher sNfL-to-sGFAP ratio, and younger age are associated with a favourable apheresis outcome.
Sections du résumé
BACKGROUND AND PURPOSE
OBJECTIVE
The predictive value of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) for apheresis outcome in steroid-refractory multiple sclerosis (MS) relapse has not yet been evaluated.
METHODS
METHODS
We used pre- and postapheresis serum samples from 38 participants of the IAPEMS trial (clinicaltrials.gov: NCT02671682), which investigated the use of immunoadsorption versus plasma exchange for the treatment of steroid-refractory MS attacks. Response to apheresis was classified based on improvement on (i) the Expanded Disability Status Scale (EDSS), (ii) the affected functional system scores (FSS) of the EDSS, or (iii) the visual acuity for patients with optic neuritis, 4 weeks postapheresis. sNFL and sGFAP were measured by single molecule arrays.
RESULTS
RESULTS
Preprocedural sGFAP levels could discriminate between responders and nonresponders, determined by FSS improvement (p = 0.017). In multivariate logistic regression analysis, younger age (odds ratio [OR] = 0.781, 95% confidence interval [CI] = 0.635-0.962, p = 0.020) and lower sGFAP levels (OR = 0.948, 95% CI = 0.903-0.995, p = 0.031) could predict response to apheresis in the overall cohort. We could observe a trend towards a favourable apheresis outcome with higher sNfL levels (OR = 1.413, 95% CI = 0.965-2.069, p = 0.076). Analysis of the sNfL-to-sGFAP ratio showed an OR of 1.924 (95% CI = 1.073-3.451, p = 0.028) for predicting apheresis response. The ratio showed a better predictive value than the individual parameters. Neither biomarker was affected by the number of steroid cycles preapheresis.
CONCLUSIONS
CONCLUSIONS
Lower sGFAP levels, a higher sNfL-to-sGFAP ratio, and younger age are associated with a favourable apheresis outcome.
Banques de données
ClinicalTrials.gov
['NCT02671682']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16323Informations de copyright
© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
Références
Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O. Multiple sclerosis. Lancet. 2018;391:1622‐1636.
Sotiropoulos MG, Lokhande H, Healy BC, et al. Relapse recovery in multiple sclerosis: effect of treatment and contribution to long‐term disability. Mult Scler J Exp Transl Clin. 2021;7:20552173211015503.
Kantarci OH, Zeydan B, Atkinson EJ, Conway BL, Castrillo‐Viguera C, Rodriguez M. Relapse recovery: the forgotten variable in multiple sclerosis clinical trials. Neurol Neuroimmunol Neuroinflamm. 2019;7:e653.
Lublin FD, Häring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disability. Brain. 2022;145:3147‐3161.
Koch‐Henriksen N, Thygesen LC, Sørensen PS, Magyari M. Worsening of disability caused by relapses in multiple sclerosis: a different approach. Mult Scler Relat Disord. 2019;32:1‐8.
Hemmer B et al. Diagnose und Therapie der Multiplen Sklerose, Neuromyelitis‐Optica‐Spektrum‐Erkrankungen und MOG‐IgG‐Assoziierten Erkrankungen, S2k‐Leitlinie, 2023. Deutsche Gesellschaft für Neurologie, Leitlinien für Diagnostik und Therapie in der Neurologie. Accessed February 1, 2024. www.dgn.org/leitlinien
Sellebjerg F, Barnes D, Filippini G, et al. EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses. Eur J Neurol. 2005;12:939‐946.
Leone MA, Bonissoni S, Collimedaglia L, et al. Factors predicting incomplete recovery from relapses in multiple sclerosis: a prospective study. Mult Scler. 2008;14:485‐493.
West T, Wyatt M, High A, Bostrom A, Waubant E. Are initial demyelinating event recovery and time to second event under differential control? Neurology. 2006;67:809‐813.
Novotna M, Paz Soldán MM, Abou Zeid N, et al. Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis. Neurology. 2015;85:722‐729. Erratum in: Neurology. 2015; 85: 1355.
Scalfari A, Neuhaus A, Daumer M, Muraro PA, Ebers GC. Onset of secondary progressive phase and long‐term evolution of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2014;85:67‐75.
Schimrigk S, Faiss J, Kohler W, et al. Escalation therapy of steroid refractory multiple sclerosis relapse with tryptophan immunoadsorption – observational multicenter study with 147 patients. Eur Neurol. 2016;75:300‐306.
Blechinger S, Ehler J, Bsteh G, et al. Therapeutic plasma exchange in steroid‐refractory multiple sclerosis relapses. A retrospective two‐center study. Ther Adv Neurol Disord. 2021;14:1756286420975642.
Lipphardt M, Wallbach M, Koziolek MJ. Plasma exchange or immunoadsorption in demyelinating diseases: a meta‐analysis. J Clin Med. 2020;9:1597.
Dorst J, Fangerau T, Taranu D, et al. Safety and efficacy of immunoadsorption versus plasma exchange in steroid‐refractory relapse of multiple sclerosis and clinically isolated syndrome: a randomised, parallel‐group, controlled trial. EClinicalMedicine. 2019;16:98‐106.
Pfeuffer S, Rolfes L, Wirth T, et al. Immunoadsorption versus double‐dose methylprednisolone in refractory multiple sclerosis relapses. J Neuroinflammation. 2022;19:220.
Bramlage CP, Schroder K, Bramlage P, et al. Predictors of complications in therapeutic plasma exchange. J Clin Apher. 2009;24:225‐231.
Dorst J, Fillies F, Dreyhaupt J, Senel M, Tumani H. Safety and tolerability of plasma exchange and immunoadsorption in neuroinflammatory diseases. J Clin Med. 2020;9:2874.
Lipphardt M, Muhlhausen J, Kitze B, et al. Immunoadsorption or plasma exchange in steroid‐refractory multiple sclerosis and neuromyelitis optica. J Clin Apher. 2019;34:381‐391.
Boedecker SC, Luessi F, Engel S, et al. Immunoadsorption and plasma exchange‐efficient treatment options for neurological autoimmune diseases. J Clin Apher. 2022;37:70‐81.
Bittner S, Oh J, Havrdová EK, Tintoré M, Zipp F. The potential of serum neurofilament as biomarker for multiple sclerosis. Brain. 2021;144:2954‐2963.
Barro C, Benkert P, Disanto G, et al. Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis. Brain. 2018;141:2382‐2391.
Abdelhak A, Huss A, Kassubek J, Tumani H, Otto M. Serum GFAP as a biomarker for disease severity in multiple sclerosis. Sci Rep. 2018;8:14798. Erratum in: Sci Rep 2019; 9: 8433.
Högel H, Rissanen E, Barro C, et al. Serum glial fibrillary acidicic protein correlates with multiple sclerosis disease severity. Mult Scler. 2020;26:210‐219.
Conway BL, Zeydan B, Uygunoğlu U, et al. Age is a critical determinant in recovery from multiple sclerosis relapses. Mult Scler. 2019;25:1754‐1763.
Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17:162‐173.
Stoppe M, Busch M, Krizek L, Then BF. Outcome of MS relapses in the era of disease‐modifying therapy. BMC Neurol. 2017;17:151.
Ramo‐Tello C, Blanco Y, Brieva L, et al. Recommendations for the diagnosis and treatment of multiple sclerosis relapses. J Pers Med. 2021;12:6.