CP-221 Clinical experience with intrathecal rituximab for treatment of progressive multiple sclerosis

• Published in: European journal of hospital pharmacy. Science and practice Vol. 24; no. Suppl 1; p. A99
• Main Authors: Robles, AA García, Albir, MJ Company, Vericat, JE Megías, Gascó, A Ferrada, Megía, MJ Fernández, Miralles, FC Pérez, Vicente, C Alcalá, Blasco, I Boscá, Andrés, JL Poveda, Estruch, B Casanova
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.03.2017
• Subjects: Immunotherapy; Lymphocytes; Monoclonal antibodies; Multiple sclerosis; Patients
• ISSN: 2047-9956; 2047-9964
• DOI: 10.1136/ejhpharm-2017-000640.219

BackgroundInaccessibility of inflammation compartmentalised to the CNS may underlie the lack of effectiveness of immunomodulatory treatments in progressive multiple sclerosis (PMS), turning its treatment into a challenge for researches. Intrathecal rituximab (IT-RTX) is a new treatment option which has shown promising results in clinical trials but clinical experience is limited.1 PurposeCase report of the use and outcomes in 3 patients with PMS treated with IT-RTX in a tertiary hospital.Material and methods3 cases of PMS are reported: patient A (man), patient B (man) and patient C (woman) aged 44, 48 and 42 years, respectively. All patients were treated with IT-RTX. Effectiveness and safety of IT-RTX were evaluated. Demographic and clinical data were collected from patients’ electronic medical records. All patients started IT-RTX treatment following a compassionate use clinical study protocol, after hospital approval and informed consent was obtained.ResultsAll patients received weekly 25 mg doses of IT-RTX, over a 3 week period. Patient B also received a fourth dose of 25 mg 8 months after the first dose. Flow cytometry was performed on peripheral blood (table), revealing a remarkable effect on peripheral B lymphocytes CD45 and CD19, with undetectable levels of CD19. Similar depletion was observed with peripheral B lymphocytes CD3, CD4, CD8 and CD16+CD56. This effect was maintained over time, rising again after several months without treatment.No changes in the Expanded Disability Status Scale (EDSS) were observed (table), except for patient B, who developed a slight improvement. The treatment was well tolerated, although patient B suffered a fever episode after the first dose and patient C died from massive pulmonary embolism, a rare RTX related complication, 5 months after finishing treatment.No ADM Patient A Patient B Patient C CD45 I1045II2285III111410141517*157911751901 CD19 I123II5III000*37841EDSS-pre8.56.56.5EDSS-post8.56.06.5*Post-treatment analysis: 5 months (patient A), 6 months (patient B), 2 months (patient C) after the last dose.ConclusionIn our patients, IT-RTX showed limited effectiveness, with disease stabilisation (similar EDSS) and depletion of peripheral B lymphocytes (especially CD19). Although the treatment was well tolerated, a rare and severe adverse event was reported.References and/or acknowledgements1. Svenningsson. Neurol Neuroimmunol Neuroinflamm2015;2:e79.No conflict of interest