Short-Term Administration of Mycophenolate Is Well-Tolerated in CLN3 Disease (Juvenile Neuronal Ceroid Lipofuscinosis).
JIMD Rep
; 43: 117-124, 2019.
Article
en En
| MEDLINE
| ID: mdl-29923092
ABSTRACT
Mycophenolate, an immunosuppressant, is commonly used off-label for autoimmune neurological conditions. In CLN3 disease, a neurodegenerative disorder of childhood, preclinical and clinical data suggest secondary autoimmunity and inflammation throughout the central nervous system are key components of pathogenesis. We tested the short-term tolerability of mycophenolate in individuals with CLN3 disease, in preparation for possible long-term efficacy trials of this drug. We conducted a randomized, double-blind, placebo-controlled, crossover study of mycophenolate in 19 ambulatory individuals with CLN3 disease to determine the safety and tolerability of short-term administration (NCT01399047). The study included two 8-week treatment periods with a 4-week intervening washout. Mycophenolate was well tolerated. 89.5% of participants completed the mycophenolate arm, on the assigned study dose (95% CI 66.9-98.7%), and there were no significant differences in tolerability rates between mycophenolate and placebo arms (10.5%; 95% CI -3.3-24.3%, p = 0.21). All reported adverse events were mild in severity; the most common adverse events on mycophenolate were vomiting (31.6%; 95% CI 12.6-56.6%), diarrhea (15.8%; 95% CI 3.4-39.6%), and cough (15.8%; 95% CI 3.4-39.6%). These did not occur at a significantly increased frequency above placebo. There were no definite effects on measured autoimmunity or clinical outcomes in the setting of short-term administration. Study of long-term exposure is needed to test the impact of mycophenolate on key clinical features and CLN3 disease trajectory.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Tipo de estudio:
Clinical_trials
Idioma:
En
Revista:
JIMD Rep
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos