TY - JOUR
T1 - Serum contactin-1 as a biomarker of long-term disease progression in natalizumab-treated multiple sclerosis
AU - van Lierop, Zoë Y. GJ
AU - Wieske, Luuk
AU - Koel-Simmelink, Marleen J. A.
AU - Chatterjee, Madhurima
AU - Dekker, Iris
AU - Leurs, Cyra E.
AU - Willemse, Eline A. J.
AU - Moraal, Bastiaan
AU - Barkhof, Frederik
AU - Eftimov, Filip
AU - Uitdehaag, Bernhard M. J.
AU - Killestein, Joep
AU - Teunissen, Charlotte E.
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The MS Center Amsterdam was supported by a program grant (grant number 18-358f) from the Dutch MS Research Foundation. This study was supported by an Amsterdam UMC Neuroscience Alliance grant. F.B. is supported by the NIHR Biomedical Research Centre at UCLH.
Funding Information:
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Z.Y.G.J.v.L., M.J.A.K.-S., M.C., I.D., C.L., E.A.J.W., and B.M. report no disclosures. L.W. and F.E. report to have received research grants from Grifols and the GBS|CIDP Foundation for the study of disease activity biomarkers in CIDP. F.B. acts as a consultant to Biogen Idec, Janssen Alzheimer Immunotherapy, Bayer Schering, Merck Serono, Roche, Novartis, Genzyme, and Sanofi-Aventis; has received sponsorship from EU-H2020, NWO, SMSR, EU-FP7, TEVA, Novartis, and Toshiba; and is on the editorial board of Radiology, Brain, Neuroradiology, Multiple Sclerosis Journal and Neurology. B.M.J.U. reports receiving personal fees from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, and Teva. C.E.T. has served on advisory boards for Roche, has received nonfinancial support in the form of research consumables from ADx NeuroSciences and Euroimmun, and has performed contract research or received grants from Probiodrug, Biogen, Esai, Toyama, Janssen Prevention Center, Boehringer, Axon Neuroscience, EIP Pharma, PeopleBio, and Roche. J.K. reports having accepted speaker fees from Merck, Biogen, TEVA, Sanofi, Genzyme, Roche, and Novartis.
Publisher Copyright:
© The Author(s), 2021.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2022/1
Y1 - 2022/1
N2 - Background: Natalizumab treatment provides a model for non-inflammation-induced disease progression in multiple sclerosis (MS). Objective: To study serum contactin-1 (sCNTN1) as a novel biomarker for disease progression in natalizumab-treated relapsing-remitting MS (RRMS) patients. Methods: Eighty-nine natalizumab-treated RRMS patients with minimum follow-up of 3 years were included. sCNTN1 was analyzed at baseline (before natalizumab initiation), 3, 12, 24 months (M) and last follow-up (median 5.2 years) and compared to 222 healthy controls (HC) and 15 primary progressive MS patients (PPMS). Results were compared between patients with progressive, stable, or improved disability according to EDSS-plus criteria. Results: Median sCNTN1 levels (ng/mL,) in RRMS (baseline: 10.7, 3M: 9.7, 12M: 10.4, 24M: 10.8; last follow-up: 9.7) were significantly lower compared to HC (12.5; p ⩽ 0.001). It was observed that 48% of patients showed progression during follow-up, 11% improved, and 40% remained stable. sCNTN1 levels were significantly lower in progressors both at baseline and at 12M compared to non-progressors. A 1 ng/mL decrease in baseline sCNTN1 was consistent with an odds ratio of 1.23 (95% confidence interval 1.04–1.45) (p = 0.017) for progression during follow-up. Conclusion: Lower baseline sCNTN1 concentrations were associated with long-term disability progression during natalizumab treatment, making it a possible blood-based prognostic biomarker for RRMS.
AB - Background: Natalizumab treatment provides a model for non-inflammation-induced disease progression in multiple sclerosis (MS). Objective: To study serum contactin-1 (sCNTN1) as a novel biomarker for disease progression in natalizumab-treated relapsing-remitting MS (RRMS) patients. Methods: Eighty-nine natalizumab-treated RRMS patients with minimum follow-up of 3 years were included. sCNTN1 was analyzed at baseline (before natalizumab initiation), 3, 12, 24 months (M) and last follow-up (median 5.2 years) and compared to 222 healthy controls (HC) and 15 primary progressive MS patients (PPMS). Results were compared between patients with progressive, stable, or improved disability according to EDSS-plus criteria. Results: Median sCNTN1 levels (ng/mL,) in RRMS (baseline: 10.7, 3M: 9.7, 12M: 10.4, 24M: 10.8; last follow-up: 9.7) were significantly lower compared to HC (12.5; p ⩽ 0.001). It was observed that 48% of patients showed progression during follow-up, 11% improved, and 40% remained stable. sCNTN1 levels were significantly lower in progressors both at baseline and at 12M compared to non-progressors. A 1 ng/mL decrease in baseline sCNTN1 was consistent with an odds ratio of 1.23 (95% confidence interval 1.04–1.45) (p = 0.017) for progression during follow-up. Conclusion: Lower baseline sCNTN1 concentrations were associated with long-term disability progression during natalizumab treatment, making it a possible blood-based prognostic biomarker for RRMS.
KW - Multiple sclerosis
KW - contactin 1
KW - disease activity
KW - disease progression
KW - natalizumab
KW - prediction
UR - http://www.scopus.com/inward/record.url?scp=85104865515&partnerID=8YFLogxK
U2 - 10.1177/13524585211010097
DO - 10.1177/13524585211010097
M3 - Article
C2 - 33890520
SN - 1352-4585
VL - 28
SP - 102
EP - 110
JO - Multiple Sclerosis
JF - Multiple Sclerosis
IS - 1
ER -