An Open Label Add-On Trial of Cetirizine for Neuromyelitis Optica (P4.003)

Abstract

OBJECTIVE To determine the efficacy and tolerability of cetirizine as an add-on to current therapy for neuromyelitis optica (NMO) BACKGROUND NMO is a severe inflammatory disease affecting the CNS with the potential to cause serious neurological disability and in some cases, death. Currently available treatments have significant failure rates, necessitating ongoing research regarding novel therapies. Granulocyte infiltration with subsequent neutrophil and eosinophil degranulation are critical to the ultimate destruction of astrocytes, demyelination, and neuronal/axonal loss. This trial will examine the efficacy and tolerability of cetirizine, an eosinophil-stabilizer approved for allergy treatment, as an add-on to currently-available therapies for NMO. DESIGN/METHODS Eligible patients meet Wingerchuk 2006 NMO criteria or have optic neuritis or longitudinally-extensive transverse myelitis with positive NMO IgG, and have been stable on current NMO therapy for 3 months. Subjects are followed clinically and with serum/CSF analysis for cytokines/chemokines associated with eosinophil priming (IL-3, IL-5, Il-13, GM-CSF, TNF-alpha), chemotaxis (eotaxins, RANTES, IL-8), degranulation (ECP and EDN), and expression of markers of activation and degranulation (CXCR2, CXCR4, CD63,CD69, ICAM-1) by flow cytometry at multiple time points over 1 year. Endpoints include relapse rates and relapse severity before and after cetirizine, tolerability, and changes in immunological parameters. Enrollment goal is 15-20. RESULTS 13 patients were enrolled between April and October 2014, including 3 in the CSF sub-study. Mean age was 37.5. Mean disease duration was 6.5 years. Median EDSS was 1.5. Six patients were being treated with rituximab, 6 with mycophenolate, and 1 with azathioprine. As of October 2014, no relapses have occurred and no patient has discontinued study participation due to adverse effects from cetirizine. CONCLUSIONS Eosinophil-stabilizing properties and favorable safety profile make cetirizine an attractive add-on therapy for NMO. Thus far it has been well-tolerated in our patient population, with incoming data about efficacy expected over the coming months.

Disclosure: Dr. Katz Sand has nothing to disclose. Dr. Fabian has nothing to disclose. Dr. Cook has nothing to disclose. Dr. Chehade has nothing to disclose. Dr. Masilamani has nothing to disclose. Dr. Kraus has nothing to disclose. Dr. Farrell has nothing to disclose. Dr. Phelps has nothing to disclose. Dr. Riffle has nothing to disclose. Dr. Rose has received research support from Biogen Idec, AbbieVie, Teva Neuroscience, Cumming Foundation, National Multiple Sclerosis Society, Veterans Affairs, and the National Institutes of Health. Dr. Moran has nothing to disclose. Acorda Therapeutics, Inc.; Biogen Idec; Novartis Pharmaceuticals Corp; Teva Neuroscience, Inc.; Genzyme; Sanofi; Celgene; NIH; NMSS