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Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement.

ABSTRACT: 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:To assess the safety of intrathecal (IT) rituximab in progressive MS (PMS) and to assess its effects on LME and CSF biomarkers. 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: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:IT rituximab was well tolerated in PMS patients and had transient effects on CSF biomarkers but did not change LME.

SUBMITTER: Bhargava P

PROVIDER: S-EPMC7325522 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement.

Bhargava Pavan P Wicken Cassie C Smith Matthew D MD Strowd Roy E RE Cortese Irene I Reich Daniel S DS Calabresi Peter A PA Mowry Ellen M EM

Multiple sclerosis and related disorders 20190211

<h4>Background</h4>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).<h4>Objective</h4>To assess the safety of intrathecal (IT) rituximab in progressive MS (PMS) and to assess its effects on LME and CSF biomarkers.<h4>Methods</h4>PMS patients had a screening MRI to detect LME. Participants satisfying eligibility criteria underwent t ...[more]

PMID: 30771580

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Project description:BackgroundThe lack of systematic evidence on leptomeningeal enhancement (LME) on MRI in neurological diseases, including multiple sclerosis (MS), hampers its interpretation in clinical routine and research settings.PurposeTo perform a systematic review and meta-analysis of MRI LME in MS and other neurological diseases.Materials and methodsIn a comprehensive literature search in Medline, Scopus, and Embase, out of 2292 publications, 459 records assessing LME in neurological diseases were eligible for qualitative synthesis. Of these, 135 were included in a random-effects model meta-analysis with subgroup analyses for MS.ResultsOf eligible publications, 161 investigated LME in neoplastic neurological (n = 2392), 91 in neuroinfectious (n = 1890), and 75 in primary neuroinflammatory diseases (n = 4038). The LME-proportions for these disease classes were 0.47 [95%-CI: 0.37-0.57], 0.59 [95%-CI: 0.47-0.69], and 0.26 [95%-CI: 0.20-0.35], respectively. In a subgroup analysis comprising 1605 MS cases, LME proportion was 0.30 [95%-CI 0.21-0.42] with lower proportions in relapsing-remitting (0.19 [95%-CI 0.13-0.27]) compared to progressive MS (0.39 [95%-CI 0.30-0.49], p = 0.002) and higher proportions in studies imaging at 7 T (0.79 [95%-CI 0.64-0.89]) compared to lower field strengths (0.21 [95%-CI 0.15-0.29], p < 0.001). LME in MS was associated with longer disease duration (mean difference 2.2 years [95%-CI 0.2-4.2], p = 0.03), higher Expanded Disability Status Scale (mean difference 0.6 points [95%-CI 0.2-1.0], p = 0.006), higher T1 (mean difference 1.6 ml [95%-CI 0.1-3.0], p = 0.04) and T2 lesion load (mean difference 5.9 ml [95%-CI 3.2-8.6], p < 0.001), and lower cortical volume (mean difference -21.3 ml [95%-CI -34.7--7.9], p = 0.002).ConclusionsOur study provides high-grade evidence for the substantial presence of LME in MS and a comprehensive panel of other neurological diseases. Our data could facilitate differential diagnosis of LME in clinical settings. Additionally, our meta-analysis corroborates that LME is associated with key clinical and imaging features of MS. PROSPERO No: CRD42021235026.

Dataset Information

Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement.

Publications

Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement.

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