Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement.
Antigens, CD
/ cerebrospinal fluid
B-Lymphocytes
/ pathology
Cytokines
/ cerebrospinal fluid
Disability Evaluation
Female
Follow-Up Studies
Humans
Immunologic Factors
/ therapeutic use
Injections, Spinal
Magnetic Resonance Imaging
Male
Meninges
/ diagnostic imaging
Middle Aged
Multiple Sclerosis, Chronic Progressive
/ cerebrospinal fluid
Organic Chemicals
/ cerebrospinal fluid
Rituximab
/ therapeutic use
Statistics, Nonparametric
Treatment Outcome
Clinical trial
Intrathecal rituximab
Leptomeningeal inflammation
Progressive multiple sclerosis
Journal
Multiple sclerosis and related disorders
ISSN: 2211-0356
Titre abrégé: Mult Scler Relat Disord
Pays: Netherlands
ID NLM: 101580247
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
26
11
2018
revised:
01
02
2019
accepted:
09
02
2019
pubmed:
17
2
2019
medline:
10
8
2019
entrez:
17
2
2019
Statut:
ppublish
Résumé
Leptomeningeal inflammation is associated with increased cortical damage and worse clinical outcomes in MS. It may be detected on contrast-enhanced T2-FLAIR imaging as focal leptomeningeal contrast-enhancement (LME). To assess the safety of intrathecal (IT) rituximab in progressive MS (PMS) and to assess its effects on LME and CSF biomarkers. PMS patients had a screening MRI to detect LME. Participants satisfying eligibility criteria underwent two IT administrations of 25 mg rituximab 2 weeks apart. Follow-up lumbar puncture and MRI were performed at 8 and 24 weeks after the first treatment. Of 36 patients screened 15 had LME, 11 consented, and 8 received study treatment. Mean age was 56.7 years and number of LME lesions ranged from 1 to 3. No serious adverse effects occurred. We noted profound reductions in peripheral B cells from baseline to week 2 and 8 with some return at week 24. We also observed transient reductions in CSF B cells and CXCL-13 levels with an increase in BAFF levels. However, the number of LME did not change following treatment. IT rituximab was well tolerated in PMS patients and had transient effects on CSF biomarkers but did not change LME.
Sections du résumé
BACKGROUND
BACKGROUND
Leptomeningeal inflammation is associated with increased cortical damage and worse clinical outcomes in MS. It may be detected on contrast-enhanced T2-FLAIR imaging as focal leptomeningeal contrast-enhancement (LME).
OBJECTIVE
OBJECTIVE
To assess the safety of intrathecal (IT) rituximab in progressive MS (PMS) and to assess its effects on LME and CSF biomarkers.
METHODS
METHODS
PMS patients had a screening MRI to detect LME. Participants satisfying eligibility criteria underwent two IT administrations of 25 mg rituximab 2 weeks apart. Follow-up lumbar puncture and MRI were performed at 8 and 24 weeks after the first treatment.
RESULTS
RESULTS
Of 36 patients screened 15 had LME, 11 consented, and 8 received study treatment. Mean age was 56.7 years and number of LME lesions ranged from 1 to 3. No serious adverse effects occurred. We noted profound reductions in peripheral B cells from baseline to week 2 and 8 with some return at week 24. We also observed transient reductions in CSF B cells and CXCL-13 levels with an increase in BAFF levels. However, the number of LME did not change following treatment.
CONCLUSIONS
CONCLUSIONS
IT rituximab was well tolerated in PMS patients and had transient effects on CSF biomarkers but did not change LME.
Identifiants
pubmed: 30771580
pii: S2211-0348(19)30069-0
doi: 10.1016/j.msard.2019.02.013
pmc: PMC7325522
mid: NIHMS1596473
pii:
doi:
Substances chimiques
Antigens, CD
0
Cytokines
0
Immunologic Factors
0
Organic Chemicals
0
Rituximab
4F4X42SYQ6
kretazine
69866-39-3
Types de publication
Journal Article
Langues
eng
Pagination
136-140Subventions
Organisme : Intramural NIH HHS
ID : ZIA NS003119
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
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