Original Paper Received: December 19, 2014 Accepted: January 18, 2015 Published online: March 13, 2015

Eur Neurol 2015;73:220–229 DOI: 10.1159/000375371

Effectiveness of Natalizumab in Patients with Highly Active Relapsing Remitting Multiple Sclerosis Álvaro Cobo-Calvo a Laura Bau a Elisabet Matas a Lucía Romero-Pinel a M. Alba Mañé Martínez a, c Carles Majós b Sergio Martínez Yélamos a   

 

 

a

 

 

 

 

Unidad de Esclerosis Múltiple, Departamento de Neurología, Hospital Universitario de Bellvitge-IDIBELL, and Institut de Diagnòstic per la Imatge (IDI), Hospital Duran i Reynals, L’Hospitalet de Llobregat, Barcelona, c Servicio de Neurología y Neurofisiología Clínica, Hospital de Tarragona Joan XXIII, Tarragona, Spain  

b

 

 

Abstract Introduction: We evaluated the effectiveness of natalizumab in patients with highly active, relapsing-remitting multiple sclerosis (HA-RRMS) to identify baseline predictors associated with freedom from disease activity. Methods: We analyzed 70 patients treated with natalizumab and followed for at least 1 year with progression of disability of ≥1 point on the EDSS before starting therapy. We recorded freedom from clinical activity, radiological activity, and disease activity (clinical and radiological). Results: The median (IQR) follow-up was 2.3 (2.0–3.8) years. Of the 52 patients who completed 2 years of treatment, 25 were free of disease activity (48.1%). The ARR decreased from a mean ± SD of 2.49 ± 0.86 at baseline to 0.47 ± 0.83 at the end of the first year (p < 0.001) and 0.34 ± 0.69 at the end of the second year (p < 0.001). The percentage of patients with gadolinium-enhanced lesions decreased from 21 at baseline to 5.7 at the end of the first year (p < 0.001) and to 5.8 during the second year (p < 0.005). Baseline EDSS ≤3.0 was significantly associ-

© 2015 S. Karger AG, Basel 0014–3022/15/0734–0220$39.50/0 E-Mail [email protected] www.karger.com/ene

ated with freedom from disease activity (OR, 2.49; 95% CI, 1.24–4.99; p = 0.010). Conclusions: Natalizumab is effective in patients with HA-RRMS. Baseline EDSS ≤3.0 increases the probability of remaining disease-free in HA-RRMS treated with natalizumab. © 2015 S. Karger AG, Basel

Introduction

Natalizumab (NTZ) (Tysabri®, Biogen Idec) is a recombinant humanized monoclonal antibody that inhibits the binding of subunit α4 of the integrins α4β1 and α4β7 to its endothelial receptors (vascular-cell adhesion molecule 1 and mucosal adhesion-cell adhesion molecule 1, respectively), thus blocking the passage of leukocytes across the blood-brain barrier and reducing inflammation of the central nervous system [1]. Results of the pivotal phase III AFFIRM study showed the efficacy of NTZ in patients diagnosed with relapsing-remitting multiple sclerosis (RRMS), a 68% reduction in the annualized relapse rate (ARR) at 1 year, and a 42–54% reduction in the risk of progression at 2 years [2]. A subsequent post-hoc analysis introduced the concept of freedom from disease Álvaro Cobo-Calvo Department of Neurology, Multiple Sclerosis Unit Hospital Universitari de Bellvitge-IDIBELL Feixa Llarga s/n, ES–08907 L’Hospitalet de Llobregat, Barcelona (Spain) E-Mail acobo @ bellvitgehospital.cat

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Key Words Natalizumab · Predictors · Disease activity · Prognosis · Multiple sclerosis

95 patients started treatment with NTZ

11 patients 3.0. The clinical variables that were recorded after the initiation of treatment were number of relapses, increased disability according to the EDSS (increase of 1 point sustained for at least 6 months), time to the following relapse, and time to an increase of at least 1 point on the EDSS. We recorded the details about the immunomodulatory treatment taken before initiation of NTZ, as well as the need for corticosteroids to treat relapses. We defined a relapse as the onset of new or recurrent neurological symptoms for more than 24 hours in the absence of fever or infection. We defined progression of disability as an increase of at least 1 point in EDSS sustained for at least 6 months. C-MRI scans were performed in accordance with the multiple sclerosis protocol of Hospital Universitario de Bellvitge. All the studies were performed at the same center (Intstitut de Diagnòstic per la Imatge) using a 1.5-tesla system. The protocol included sequences obtained in T1, T2, FLAIR, and T1 after the administration of gadolinium, and images were acquired in the axial and sagittal planes. All patients underwent a baseline C-MRI scan within the 3 months preceding initiation of NTZ and annually thereafter. T2 lesions and gadolinium-enhanced lesions in both the baseline and

Eur Neurol 2015;73:220–229 DOI: 10.1159/000375371

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Effectiveness of natalizumab in patients with highly active relapsing remitting multiple sclerosis.

We evaluated the effectiveness of natalizumab in patients with highly active, relapsing-remitting multiple sclerosis (HA-RRMS) to identify baseline pr...
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