Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies.

BACKGROUND: Disease-modifying therapies are thought to reduce the conversion rate to secondary progressive multiple sclerosis. OBJECTIVE: To explore the rate, chronology, and contributing factors of conversion to the progressive phase in treated relapsing-remitting multiple sclerosis patients. METHODS: Our study included 204 patients treated for relapsing-remitting multiple sclerosis between 1995 and 2002, prospectively followed to date. Kaplan-Meier analysis was applied to estimate the time until secondary progressive multiple sclerosis conversion, and multivariate survival analysis with a Cox regression model was used to analyse prognostic factors. RESULTS: Relapsing-remitting multiple sclerosis patients were continuously treated for 13 years (SD 4.5); 36.3% converted to secondary progressive multiple sclerosis at a mean age of 42.6 years (SD 10.6), a mean time of 8.2 years (SD 5.2) and an estimated mean time of 17.2 years (range 17.1-18.1). A multifocal relapse, age older than 34 years at disease onset and treatment failure independently predicted conversion to secondary progressive multiple sclerosis but did not influence the time to reach an Expanded Disability Status Scale of 6.0. CONCLUSIONS: The favourable influence of disease-modifying therapies on long-term disability in relapsing-remitting multiple sclerosis is well established. However, the time to progression onset and the subsequent clinical course in treated patients seem similar to those previously reported in natural history studies. More studies are needed to clarify the effect of disease-modifying therapies once the progressive phase has been reached.

Tratamiento de la esclerosis múltiple remitente recurrente con fingolimod en la práctica clínica habitual / Treatment of relapsing-remitting multiple sclerosis with fingolimod in routine clinical practice

Introducción. El fingolimod es un inmunosupresor selectivo dirigido contra el receptor SP-1, indicado en el tratamiento de la esclerosis múltiple remitente recurrente (EMRR) agresiva y tras el fracaso del tratamiento con fármacos de primera línea. Objetivo. Investigar la seguridad y efectividad del fingolimod en condiciones de práctica clínica habitual. Pacientes y métodos. Estudio observacional con seguimiento prospectivo de pacientes con EMRR que recibieron fingolimod desde enero de 2011 hasta febrero de 2014. Se evaluó la tasa anual de brotes (TAB), la discapacidad medida por la escala expandida del estado de discapacidad (EDSS), la actividad en la resonancia magnética y la aparición de efectos adversos. Resultados. Incluimos 122 pacientes, el 79,5% mujeres y con una edad media de 26,8 años. Se clasificaron según el último tratamiento recibido en: naïve (EMRR agresiva; n = 17), fracaso a terapias previas (n = 67) y retirada de natalizumab por riesgo de leucoencefalopatía multifocal progresiva (n = 38). Tras un seguimiento medio de 29,9 ± 15,9 meses, se redujo de forma significativa la TAB y la aparición de nuevas lesiones con realce de gadolinio en el grupo naïve y el de fracaso a terapias previas. No ha habido diferencias en la evolución de la EDSS ni en el tiempo hasta el primer brote o el fracaso terapéutico entre los diferentes subgrupos. El riesgo a fracaso terapéutico es mayor con la EDSS basal > 3 (hazard ratio: 4,24; p = 0,001) y presencia de bandas oligoclonales IgM (hazard ratio: 2,45; p < 0,022). Conclusiones. El fingolimod es un fármaco eficaz y seguro en la EMRR en condiciones de práctica clínica habitual. Tener una EDSS basal > 3 y bandas oligoclonales IgM predice una mala respuesta al fingolimod (AU)

Introduction. Fingolimod is a selective immunosuppressant that targets the S1P receptor, and is indicated in the treatment of aggressive relapsing-remitting multiple sclerosis (RRMS) and following treatment failure with first-order drugs. Aim. To investigate the safety and effectiveness of fingolimod under the conditions of routine clinical practice. Patients and methods. We conducted an observational study with prospective follow-up of patients with RRMS who received fingolimod from January 2011 until February 2014. Data assessed were the annualised relapse rate (ARR), disability measured by the Expanded Disability Status Scale (EDSS), magnetic resonance activity and the appearance of side effects. Results. Our sample consisted of 122 patients, 79.5% of them females and with a mean age of 26.8 years. They were classified, according to the last treatment received, as being: naïve (aggressive RRMS; n = 17), previous treatment failure (n = 67) and withdrawal of natalizumab due to risk of progressive multifocal leukoencephalopathy (n = 38). After a mean follow-up of 29.9 ± 15.9 months, the ARR and the appearance of new lesions with gadolinium enhancement were reduced in both the naïve and the previous treatment failure groups. There were no differences between the various subgroups as regards the progression of EDSS or the time elapsed until the first attack or treatment failure. The risk of treatment failure is higher with a baseline EDSS > 3 (hazard ratio: 4.24; p = 0.001) and presence of IgM oligoclonal bands (hazard ratio: 2.45; p < 0.022). Conclusions: Fingolimod is an effective and well-tolerated drug under conditions of routine clinical practice. Having a baseline EDSS > 3 and IgM oligoclonal bands is predictive of a poor response to fingolimod (AU)