Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis
Copyright © 2022. Published by Elsevier B.V..
BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), early disease control reduces the risk of permanent disability. The blood-brain barrier (BBB) is compromised in MS, and its permeability is a potential biomarker.
OBJECTIVE: To investigate BBB permeability measured by MRI as a marker of alemtuzumab efficacy.
METHODS: Patients with RRMS initiating alemtuzumab treatment were recruited prospectively. BBB permeability was assessed as the Patlak-derived influx constant (Ki) by dynamic contrast-enhanced MRI before and 6, 12, and 18 months after the first course of alemtuzumab. No Evidence of Disease Activity-3 (NEDA-3) status was ascertained two years after treatment initiation.
RESULTS: Patients who maintained NEDA-3 status at two years (n = 7) had a larger decrease in Ki between baseline and six months (-0.029 ml/100 g/min [CI -0.005 - -0.053]) and between baseline and 12 months in normal appearing white matter (0.043 [CI 0.022 - -0.065]), than those who experienced disease activity (n = 8). ROC curve analysis of the Ki change between baseline and 12 months in NAWM predicted a loss of NEDA status at 2 years with 86% sensitivity and 86% specificity (AUC 0.98, p = 0.002).
CONCLUSION: BBB permeability predicted alemtuzumab efficacy at two years, indicating that BBB permeability is a biomarker of treatment response in RRMS.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:63 |
|---|---|
| Enthalten in: |
Multiple sclerosis and related disorders - 63(2022) vom: 02. Juli, Seite 103891 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Knudsen, Maria Højberg [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
3A189DH42V |
|---|
| Anmerkungen: |
Date Completed 28.06.2022 Date Revised 28.06.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.msard.2022.103891 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM341834556 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM341834556 | ||
| 003 | DE-627 | ||
| 005 | 20231226012704.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.msard.2022.103891 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1139.xml |
| 035 | |a (DE-627)NLM341834556 | ||
| 035 | |a (NLM)35661562 | ||
| 035 | |a (PII)S2211-0348(22)00393-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Knudsen, Maria Højberg |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 28.06.2022 | ||
| 500 | |a Date Revised 28.06.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022. Published by Elsevier B.V. | ||
| 520 | |a BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), early disease control reduces the risk of permanent disability. The blood-brain barrier (BBB) is compromised in MS, and its permeability is a potential biomarker | ||
| 520 | |a OBJECTIVE: To investigate BBB permeability measured by MRI as a marker of alemtuzumab efficacy | ||
| 520 | |a METHODS: Patients with RRMS initiating alemtuzumab treatment were recruited prospectively. BBB permeability was assessed as the Patlak-derived influx constant (Ki) by dynamic contrast-enhanced MRI before and 6, 12, and 18 months after the first course of alemtuzumab. No Evidence of Disease Activity-3 (NEDA-3) status was ascertained two years after treatment initiation | ||
| 520 | |a RESULTS: Patients who maintained NEDA-3 status at two years (n = 7) had a larger decrease in Ki between baseline and six months (-0.029 ml/100 g/min [CI -0.005 - -0.053]) and between baseline and 12 months in normal appearing white matter (0.043 [CI 0.022 - -0.065]), than those who experienced disease activity (n = 8). ROC curve analysis of the Ki change between baseline and 12 months in NAWM predicted a loss of NEDA status at 2 years with 86% sensitivity and 86% specificity (AUC 0.98, p = 0.002) | ||
| 520 | |a CONCLUSION: BBB permeability predicted alemtuzumab efficacy at two years, indicating that BBB permeability is a biomarker of treatment response in RRMS | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Alemtuzumab | |
| 650 | 4 | |a Biomarker | |
| 650 | 4 | |a MRI | |
| 650 | 4 | |a Neuroimaging | |
| 650 | 4 | |a Relapsing-remitting multiple sclerosis | |
| 650 | 7 | |a Alemtuzumab |2 NLM | |
| 650 | 7 | |a 3A189DH42V |2 NLM | |
| 700 | 1 | |a Lindberg, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Frederiksen, Jette Lautrup |e verfasserin |4 aut | |
| 700 | 1 | |a Vestergaard, Mark Bitsch |e verfasserin |4 aut | |
| 700 | 1 | |a Simonsen, Helle Juhl |e verfasserin |4 aut | |
| 700 | 1 | |a Varatharaj, Aravinthan |e verfasserin |4 aut | |
| 700 | 1 | |a Galea, Ian |e verfasserin |4 aut | |
| 700 | 1 | |a Blinkenberg, Morten |e verfasserin |4 aut | |
| 700 | 1 | |a Sellebjerg, Finn |e verfasserin |4 aut | |
| 700 | 1 | |a Larsson, Henrik Bo Wiberg |e verfasserin |4 aut | |
| 700 | 1 | |a Cramer, Stig Præstekjær |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Multiple sclerosis and related disorders |d 2012 |g 63(2022) vom: 02. Juli, Seite 103891 |w (DE-627)NLM219118388 |x 2211-0356 |7 nnns |
| 773 | 1 | 8 | |g volume:63 |g year:2022 |g day:02 |g month:07 |g pages:103891 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.msard.2022.103891 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 63 |j 2022 |b 02 |c 07 |h 103891 | ||