Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis.

نویسندگان

  • Nathaniel Lizak
  • Alessandra Lugaresi
  • Raed Alroughani
  • Jeannette Lechner-Scott
  • Mark Slee
  • Eva Havrdova
  • Dana Horakova
  • Maria Trojano
  • Guillermo Izquierdo
  • Pierre Duquette
  • Marc Girard
  • Alexandre Prat
  • Pierre Grammond
  • Raymond Hupperts
  • Francois Grand'Maison
  • Patrizia Sola
  • Eugenio Pucci
  • Roberto Bergamaschi
  • Celia Oreja-Guevara
  • Vincent Van Pesch
  • Cristina Ramo
  • Daniele Spitaleri
  • Gerardo Iuliano
  • Cavit Boz
  • Franco Granella
  • Javier Olascoaga
  • Freek Verheul
  • Csilla Rozsa
  • Edgardo Cristiano
  • Shlomo Flechter
  • Suzanne Hodgkinson
  • Maria Pia Amato
  • Norma Deri
  • Vilija Jokubaitis
  • Tim Spelman
  • Helmut Butzkueven
  • Tomas Kalincik
چکیده

OBJECTIVE To evaluate variability and predictability of disability trajectories in moderately advanced and advanced multiple sclerosis (MS), and their modifiability with immunomodulatory therapy. METHODS The epochs between Expanded Disability Status Scale (EDSS) steps 3-6, 4-6 and 6-6.5 were analysed. Patients with relapse-onset MS and having reached 6-month confirmed baseline EDSS step (3/4/6) were identified in MSBase, a global observational MS cohort study. We used multivariable survival models to examine the impact of disease-modifying therapy, clinical and demographic factors on progression to the outcome EDSS step (6/6.5). Sensitivity analyses with varying outcome definitions and inclusion criteria were conducted. RESULTS For the EDSS 3-6, 4-6 and 6-6.5 epochs, 1560, 1504 and 1231 patients were identified, respectively. Disability trajectories showed large coefficients of variance prebaseline (0.92-1.11) and postbaseline (2.15-2.50), with no significant correlations. The probability of reaching the outcome step was not associated with prebaseline variables, but was increased by higher relapse rates during each epoch (HRs 1.58-3.07; p<0.001). A greater proportion of each epoch treated with higher efficacy therapies was associated with lower risk of reaching the outcome disability step (HRs 0.72-0.91 per 25%; p≤0.02). 3 sensitivity analyses confirmed these results. CONCLUSIONS Disease progression during moderately advanced and advanced MS is highly variable and amnesic to prior disease activity. Lower relapse rates and greater time on higher efficacy immunomodulatory therapy after reaching EDSS steps 3, 4 and 6 are associated with a decreased risk of accumulating further disability. Highly effective immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced relapse-onset MS.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Immunomodulatory Effect of Mesenchymal Stem Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: A Review Study

Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system that may lead to disability of the patient. Current MS treatment regimens are still insufficient and research is conducted for developing more effective therapies capable of targeting neurodegeneration, inflammation, and demyelination. Recent results of experimental and clinical studies in ...

متن کامل

Curcumin ameliorates oxidative stress in animal models of multiple sclerosis

Background & Objectives: The role of oxidative stress in the pathogenesis of Multiple Sclerosis (MS) has been mentioned in previous studies. Curcumin is an active ingredient in Curcuma longa and has anti-inflammatory properties. The aim of this study was to investigate the effects of curcumin on reducing the oxidative stress in the animal model of MS. Materials & Methods: In this study, experim...

متن کامل

Oral laquinimod therapy in relapsing multiple sclerosis.

BACKGROUND Multiple sclerosis (MS) is a chronic autoimmune disease of the CNS. Early treatment reduces the number of relapses, limits progression of disability, and improves quality of life; however, existing therapies are only partially effective and require parenteral administration. OBJECTIVE To review current experience with laquinimod as a novel immunomodulatory therapy for MS. RESULTS...

متن کامل

O 9: Immunomodulatory Effects of Neural Stem Cell on Multiple Sclerosis: A Systematic Review

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are chronic inflammatory demyelinating disorders of central nervous system (CNS). While the cause is unclear, the fundamental mechanism is thought to be destruction of myelin sheaths of neurons through immune system. One of the approaches being proposed in EAE therapy is neural stem cells (NSCs) trans...

متن کامل

One-year Effectiveness and Side Effects of Fingolimod in Multiple Sclerosis Patients

 Background and purpose: Fingolimod, is one of the first oral disease-modifying treatments (DMT) that has shown efficacy in advanced clinical trials for the treatment of multiple sclerosis (MS). The present study examined the one-year effectiveness and side effects of fingolimod. Materials and methods: In this quasi-experimental study, 26 MS patients attending Kermanshah Imam Reza Hospital wer...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Journal of neurology, neurosurgery, and psychiatry

دوره 88 3  شماره 

صفحات  -

تاریخ انتشار 2017