ANTECEDENTES: El fingolimod (FTY720) ha mostrado previamente su eficacia clínica en fase II / III estudios de poblaciones predominantemente caucásicas con esclerosis múltiple (EM).
OBJETIVO: Presentación de los resultados de eficacia y seguridad de seis meses en pacientes japoneses con EM recurrente tratados con fingolimod.
MÉTODOS: En este estudio doble ciego, de grupos paralelos, estudio de fase II, 171 pacientes japoneses con EM recidivante fueron aleatorizados para recibir una dosis diaria fingolimod 0,5 mg o 1,25 mg, o placebo durante seis meses. Los criterios de valoración primarios y secundarios fueron el porcentaje de pacientes libres de gadolinio (Gd) lesiones -Mejora en los meses 3 y 6, y las recaídas de más de seis meses, respectivamente; También se evaluaron los resultados de seguridad.
Resultados: 147 pacientes completaron el estudio. Una mayor proporción de los pacientes estaban libres de las lesiones realzadas Di-s en los meses 3 y 6 con fingolimod (0,5 mg: 70%, p = 0,004; 1,25 mg: 86%, p <0,001) que con placebo (40%). La odds ratio para las proporciones de pacientes sin recaídas durante seis meses favorecieron fingolimod versus placebo, pero no fueron significativas. Los eventos adversos relacionados con fingolimod incluyeron bradicardia transitoria y bloqueo auriculoventricular al inicio del tratamiento, y los niveles elevados de enzimas hepáticas.
CONCLUSIONES: Este estudio demostró la eficacia clínica de fingolimod por primera vez en pacientes japoneses con EM, en consonancia con los efectos establecidos de fingolimod en pacientes caucásicos.
BACKGROUND: A 6-month phase 2 study of fingolimod demonstrated efficacy and safety in Japanese patients with relapsing-remitting multiple sclerosis (MS). Here we report a 6-month observational extension that evaluated efficacy and safety in patients who received fingolimod continuously for 12 months or who switched from placebo to fingolimod.
METHODS: Of 147 patients who completed the 6-month core study, 143 entered the extension. Those originally randomized to placebo were re-randomized to fingolimod 1.25 mg or 0.5 mg. During the extension, all patients were switched to open-label fingolimod 0.5 mg.
RESULTS: Magnetic resonance imaging (MRI) and relapse outcomes were maintained or improved in patients treated with fingolimod for 12 months versus those treated for 6 months. No new safety events were reported over 12 months of treatment. Infections occurred in similar proportions of continuously treated and switched patients, while cardiac and liver adverse events occurred in fewer continuously treated than switched patients. Four patients were aquaporin-4 (AQP4) antibody-positive, three of whom showed rapid disease exacerbations within 10 days of fingolimod initiation.
CONCLUSION: Continuous fingolimod treatment for up to 12 months was associated with maintained or improved efficacy and a manageable safety profile, consistent with that previously seen. Results in a small number of patients suggest lack of benefit in AQP4 antibody-positive patients. Meaningful statistical interpretation was limited by the small sample size in each treatment group, owing to the number of patients who completed the core study.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00670449.
