Contributions
Abstract: P625
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: NMO is a severe inflammatory disease affecting the CNS with the potential to cause serious neurological disability and in some cases, death. Granulocyte infiltration with subsequent neutrophil and eosinophil degranulation are critical to the ultimate destruction of astrocytes, demyelination, and neuronal/axonal loss. This trial was conducted to examine the efficacy and tolerability of cetirizine, an eosinophil-stabilizer approved for allergy treatment, as an add-on to currently-available therapies for NMO.
Methods: Eligible patients met Wingerchuk 2006 NMO criteria or had optic neuritis or longitudinally-extensive transverse myelitis with positive NMO IgG, and were stable on current NMO therapy for 3 months. Subjects were followed clinically and with serum/CSF analysis for cytokines/chemokines associated with eosinophil priming, chemotaxis, degranulation, and expression of markers of activation and degranulation by flow cytometry for 1 year. Planned endpoints included relapse rates and relapse severity before and after cetirizine, tolerability with particular attention to drowsiness, and changes in immunological parameters.
Results: 16 subjects were enrolled between April 2014 and February 2015, including 4 in the CSF sub-study. 15 were female, 7 were black, with median age 36.5. 13 were NMO IgG positive. 8 were on rituximab, 7 on mycophenolate, and 1 on azathioprine. 7 had previously experienced a total of 9 relapses while on the current treatment, 3 of which were in the year prior to study enrollment. There was 1 mild confirmed relapse during the study, characterized by eye pain with a small scotoma and red desaturation without decreased acuity. The pre and post study ARR differences were statistically significantly different from zero (p=0.047). Median EDSS was 3.0 at baseline and at study end. Mean Epworth Sleepiness Scale score was 6.5 ± 5.33 at baseline and 6.9 ± 4.50 at study end (p=0.74). There were no significant drug-related adverse events. Analysis of immunological profiling is in process.
Conclusions: Eosinophil-stabilizing properties and favorable safety profile make cetirizine an attractive add-on therapy for NMO. In our pilot study the drug was very well-tolerated with no significant increase in sleepiness. The very low pre-study relapse rates in our patient population preclude definitive conclusions related to cetirizine"s effect on relapse rates and severity, though results are promising and warrant further study.
Disclosure: This study was funded by a grant from the Guthy Jackson Charitable Foundation to Dr. Katz Sand, as well as by a philanthropic gift from the Muzio Family to Mount Sinai.
IK: has received research support from the Guthy Jackson Charitable Foundation, the National MS Society, and the US Department of Defense
FL:
Sources of Funding for Research: Biogen Idec; Novartis Pharmaceuticals Corp; Teva Neuroscience, Inc.; Genzyme; Sanofi; Celgene; Transparency Life Sciences; NIH; NMSS
Consulting Agreements/Advisory Boards/DSMB: Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono, Inc.; Novartis; Teva Neuroscience; Actelion; Sanofi/Genzyme; Acorda; Questcor/Malinckrodt; Roche/Genentech; MedImmune; Osmotica; Xenoport, Receptos; Forward Pharma; Akros; TG Therapeutics; Abbvie; Toyama; Amgen; Medday; Atara Biotherapeutics
Speaker: Genentech (non-promotional); Genzyme (non-promotional)
Co-Chief Editor: Multiple Sclerosis and Related Disorders
Current Financial Interests/Stock Ownership: Cognition Pharmaceuticals, Inc.
CF: nothing to disclose
SE: nothing to disclose
MM: nothing to disclose
TK: nothing to disclose
RT: nothing to disclose
LC: nothing to disclose
MF: nothing to disclose
MR: nothing to disclose
MC: nothing to disclose
Abstract: P625
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: NMO is a severe inflammatory disease affecting the CNS with the potential to cause serious neurological disability and in some cases, death. Granulocyte infiltration with subsequent neutrophil and eosinophil degranulation are critical to the ultimate destruction of astrocytes, demyelination, and neuronal/axonal loss. This trial was conducted to examine the efficacy and tolerability of cetirizine, an eosinophil-stabilizer approved for allergy treatment, as an add-on to currently-available therapies for NMO.
Methods: Eligible patients met Wingerchuk 2006 NMO criteria or had optic neuritis or longitudinally-extensive transverse myelitis with positive NMO IgG, and were stable on current NMO therapy for 3 months. Subjects were followed clinically and with serum/CSF analysis for cytokines/chemokines associated with eosinophil priming, chemotaxis, degranulation, and expression of markers of activation and degranulation by flow cytometry for 1 year. Planned endpoints included relapse rates and relapse severity before and after cetirizine, tolerability with particular attention to drowsiness, and changes in immunological parameters.
Results: 16 subjects were enrolled between April 2014 and February 2015, including 4 in the CSF sub-study. 15 were female, 7 were black, with median age 36.5. 13 were NMO IgG positive. 8 were on rituximab, 7 on mycophenolate, and 1 on azathioprine. 7 had previously experienced a total of 9 relapses while on the current treatment, 3 of which were in the year prior to study enrollment. There was 1 mild confirmed relapse during the study, characterized by eye pain with a small scotoma and red desaturation without decreased acuity. The pre and post study ARR differences were statistically significantly different from zero (p=0.047). Median EDSS was 3.0 at baseline and at study end. Mean Epworth Sleepiness Scale score was 6.5 ± 5.33 at baseline and 6.9 ± 4.50 at study end (p=0.74). There were no significant drug-related adverse events. Analysis of immunological profiling is in process.
Conclusions: Eosinophil-stabilizing properties and favorable safety profile make cetirizine an attractive add-on therapy for NMO. In our pilot study the drug was very well-tolerated with no significant increase in sleepiness. The very low pre-study relapse rates in our patient population preclude definitive conclusions related to cetirizine"s effect on relapse rates and severity, though results are promising and warrant further study.
Disclosure: This study was funded by a grant from the Guthy Jackson Charitable Foundation to Dr. Katz Sand, as well as by a philanthropic gift from the Muzio Family to Mount Sinai.
IK: has received research support from the Guthy Jackson Charitable Foundation, the National MS Society, and the US Department of Defense
FL:
Sources of Funding for Research: Biogen Idec; Novartis Pharmaceuticals Corp; Teva Neuroscience, Inc.; Genzyme; Sanofi; Celgene; Transparency Life Sciences; NIH; NMSS
Consulting Agreements/Advisory Boards/DSMB: Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono, Inc.; Novartis; Teva Neuroscience; Actelion; Sanofi/Genzyme; Acorda; Questcor/Malinckrodt; Roche/Genentech; MedImmune; Osmotica; Xenoport, Receptos; Forward Pharma; Akros; TG Therapeutics; Abbvie; Toyama; Amgen; Medday; Atara Biotherapeutics
Speaker: Genentech (non-promotional); Genzyme (non-promotional)
Co-Chief Editor: Multiple Sclerosis and Related Disorders
Current Financial Interests/Stock Ownership: Cognition Pharmaceuticals, Inc.
CF: nothing to disclose
SE: nothing to disclose
MM: nothing to disclose
TK: nothing to disclose
RT: nothing to disclose
LC: nothing to disclose
MF: nothing to disclose
MR: nothing to disclose
MC: nothing to disclose