@article{8a102dca77ba4d99ba0133f5479627dc,
title = "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.",
keywords = "Clinical trial, Intrathecal rituximab, Leptomeningeal inflammation, Progressive multiple sclerosis",
author = "Pavan Bhargava and Cassie Wicken and Smith, {Matthew D.} and Strowd, {Roy E.} and Irene Cortese and Reich, {Daniel Salo} and Calabresi, {Peter A.} and Mowry, {Ellen M.}",
note = "Funding Information: Dr. Reich reports personal fees and non-financial support from At the Limits, personal fees from Leventhal and Puga, LLC, outside the submitted work; In addition, Dr. Reich has a patent System and method of automatically detecting tissue abnormalities (US Patent 9607392) issued, and a patent Method of analyzing multi-sequence MRI data for analyzing brain abnormalities in a subject (US20150045651A1) pending.Dr. Calabresi reports grants from Progressive MS Alliance, grants from Race to Erase MS, during the conduct of the study; personal fees from Biogen, grants from Novartis, grants from Annexon, grants from MedImmune, grants from Sanofi, personal fees from Disarm, outside the submitted work.Dr. Mowry reports grants from Biogen, other from Teva Neuroscience, grants from Genzyme, grants from Sun Pharma, personal fees from UpToDate outside the submitted work.This study was supported by a pilot award from the Race to Erase MS and a grant from the International Progressive MS Alliance to PAC. P.B. was supported by a Career Transition Award from the National MS Society, the John F Kurtzke Clinician Scientist development award from the American Academy of Neurology and a Young Investigator Award from the Race to Erase MS. D.S.R. and I.C. are supported by the Intramural Research Program of NINDS. Funding Information: This study was supported by a pilot award from the Race to Erase MS and a grant from the International Progressive MS Alliance to PAC . P.B. was supported by a Career Transition Award from the National MS Society , the John F Kurtzke Clinician Scientist development award from the American Academy of Neurology and a Young Investigator Award from the Race to Erase MS . D.S.R. and I.C. are supported by the Intramural Research Program of NINDS . Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",
year = "2019",
month = may,
doi = "10.1016/j.msard.2019.02.013",
language = "English (US)",
volume = "30",
pages = "136--140",
journal = "Multiple Sclerosis and Related Disorders",
issn = "2211-0348",
publisher = "Elsevier",
}