Pavan Bhargava1, Cassie Wicken2, Matthew D Smith2, Roy E Strowd2, Irene Cortese3, Daniel S Reich3, Peter A Calabresi2, Ellen M Mowry2. 1. Department of Neurology, Johns Hopkins University School of Medicine, 600 N Wolfe St, Pathology 627, Baltimore, MD 21287, USA. Electronic address: pbharga2@jhmi.edu. 2. Department of Neurology, Johns Hopkins University School of Medicine, 600 N Wolfe St, Pathology 627, Baltimore, MD 21287, USA. 3. Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
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.
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.
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