Intramuscular interferon beta‐1a for disease progression in relapsing multiple sclerosis

Abstract

The accepted standard treatment of relapsing multiple sclerosis consists of medications for disease symptoms, including treatment for acute exacerbations. However, currently there is no therapy that alters the progression of physical disability associated with this disease. The purpose of this study was to determine whether interferon beta-1a could slow the progressive, irreversible, neurological disability of relapsing multiple sclerosis. Three hundred one patients with relapsing multiple sclerosis were randomized into a double-blinded, placebo-controlled, multicenter phase III trial of interferon beta-1a. Interferon beta-1a, 6.0 million units (30 micrograms¿, was administered by intramuscular injection weekly. The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Expanded Disability Status Scale (EDSS). Interferon beta-1a treatment produced a significant delay in time to sustained EDSS progression (p = 0.02). The Kaplan-Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9% in the placebo group and 21.9% in the interferon beta-1a-treated group. Patients treated with interferon beta-1a also had significantly fewer exacerbations (p = 0.03) and a significantly lower number and volume of gadolinium-enhanced brain lesions on magnetic resonance images (p-values ranging between 0.02 and 0.05). Over 2 years, the annual exacerbation rate was 0.90 in placebo-treated patients versus 0.61 in interferon beta-1a-treated patients. There were no major adverse events related to treatment. Interferon beta-1a had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity measured by gadolinium-enhanced lesions on brain magnetic resonance images. This treatment may alter the fundamental course of relapsing multiple sclerosis.

IFN‐β regulates CD73 and adenosine expression at the blood–brain barrier

“…It reduces the relapse rate, the relapse severity and the progression of disability [2,3], but the underlying mechanisms of the drug are not yet fully understood [9]. In this study we demonstrate both in vitro and in vivo that IFN-b increases the expression of CD73 (ecto-5 0 -nucleotidase) on human EC.…”

“…Moreover, gadolinium enhancement of magnetic resonance imagins lesions is indicative of BBB damage, and treating MSpatients with IFN-b in vivo leads to an early reduction in the appearance of gadolinium-enhancing lesions [2,8]. Thus far, the mechanism of action on the barrier stabilizing effect of IFN-b is not well understood although some mechanisms have been discovered.…”

“…Moreover, recent reports describe IFN-b as a suppressor of both myeloid [6] and Th17-cells [7]. IFN-b also reduces the number of gadolinium enhancing lesions in brain magnetic resonance imaging of MS patients [2,3,8], which is thought to reflect its ability to regulate the blood-brain barrier (BBB) function [9]. Ecto-5 0 -nucleotidase (CD73; EC 3.1.3.5) is a 70 kDa GPI-anchored glycoprotein.…”

“…MS is generally thought to be an autoimmune disease in which the immune system attack against self-antigens results in inflammation and neurological symptoms [1]. First line treatment of MS is subcutaneous or intramuscular administration of IFN-b, which leads to a reduced number of relapses and a slower disease progression [2][3][4]. The proposed beneficial effects of IFN-b include a decrease in antigen presentation, MHC class II expression, T-cell proliferation, IFN-b production, ECM degradation, and the expression of adhesion molecules [5].…”

Interferon Beta and Glatiramer Acetate Therapy

“…Beginning in November 1990, the randomized, doubleblind, placebo-controlled trial began testing the next IFNB formulation, IFN beta-1a intramuscular (IM) 30 μg [20]. The MS Collaborative Research Group (MSCRG) study used ARR and a longer time frame for EDSS sustained disability of six months.…”