Multiple Sclerosis
Application of Interferon Beta-1b in Multiple Sclerosis Francesca Bagnato
Visiting Assistant Professor of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science
Abstract
Recombinant interferon beta-1b (IFNβ-1b) was the first approved disease-modifying therapy for patients with multiple sclerosis (MS) by the world regulatory agencies for medical drugs and devices. IFNβ-1b significantly decreases the inflammatory component of MS but still has doubtable effect on the neurodegenerative component. This article appraises the beneficial effects of IFNβ-1b on clinical and imaging measures of disease. Upon only briefly discussing the side effects of the drug, it will conclude with some crucial scientific aspects warranting urgent investigations to precisely address the potentials of IFNβ-1b in MS patients.
Keywords Multiple sclerosis, interferon beta-1β (IFNβ-1b), magnetic resonance imaging (MRI), inflammation, neurodegeneration
Disclosure: Francesca Bagnato acts as a consultant for reading and interpretation of scans in a six-month magnetic resonance imaging initiative project with Biogen Idec and has no other conflicts of interest to declare. The views and opinions expressed are solely those of the author in accordance with the reviewers’ suggestions. Acknowledgements: The author thanks Professor Carlo Pozzilli (La Sapienza University of Rome) for critically revising the manuscript. The Intramural Research Program of the NINDS-NIH supported this research. Received: 1 September 2010 Accepted: 31 January 2011 Citation: European Neurological Review, 2011;6(1):36–44 Correspondence: Francesca Bagnato, Department of Radiology and Radiological Sciences, Institute of Imaging Science, Vanderbilt University, 1161 21st Avenue South, AA 1105 MCN, Nashville, TN 37232-2310, US. E:
Francesca.r.bagnato@
vanderbilt.edu
Multiple sclerosis (MS) is a chronic illness of the central nervous system affecting approximately 2.5 million young people worldwide.1 Regarded as exclusively a white matter (WM) disease, clinicians are now facing the notion, known to pathologists for over a century, that MS may affect the grey matter (GM) as well.2
Currently, MS is an incurable disease. It is, however, to some extent treatable. The past 20 years have witnessed a remarkable expansion of the horizons of pharmacological treatments aimed at delaying disease progression. Recombinant interferon beta-1b (IFNβ-1b) was the first disease-modifying therapy approved in MS by the US Food and Drug Administration (FDA).3
Today, IFNβ-1b is the drug
for which clinicians have the most experience with in chronically treating patients.
This article will attempt to appraise the status of IFNβ-1b application in MS patients today. Upon reviewing the clinical-radiological presentation of the illness and its evolution over time, the effects of IFNβ-1b on clinical and imaging measures of disease, as reported in the largest clinical trials, will be discussed. Then the side effects of the drug will briefly be covered. This review will conclude by addressing some crucial scientific aspects that are still open for investigation to estimate the actual potentials of IFNβ-1b treatment in MS patients.
Two types of IFNβ are currently available for MS treatment, namely IFNβ-1a and IFNβ-1b. Their mechanisms of actions and clinical efficacy almost entirely overlap but, for the purpose of the present review, IFNβ-1b will be focused on.
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Clinical-radiological Presentation and Evolution of Multiple Sclerosis
The first clinically manifest event of MS is the relatively acute or subacute occurrence of one or more combined neurological symptoms, lasting at least 24 hours, in the absence of fever and infection, and suggestive of demyelination and inflammation. Such an event, namely clinical relapse, defines the status of clinically isolated syndrome (CIS). This is not considered clinically definite MS (CDMS) until a second attack occurs. Approximately 44% of CIS patients will remain free from a second attack within the following three years.4
Up
to 10% of CIS patients will not convert to CDMS over the course of the subsequent 20 years.5
Patients not converting to CDMS within the
following three years tend to have fewer active lesions during the six months following the first attack (see Figure 1) than those who do convert to CDMS.4
In 85–90% of CDMS patients (MS hereafter) the disease starts and evolves with a relapsing-remitting (RR) course. RRMS is characterised by repeated and time-interleaved clinical relapses. These relapses may last from a few days to a few months and are sustained by inflammation directed against either the spinal cord or the brain tissue.
Contrast-enhancing Lesions and Clinical Attacks Magnetic resonance imaging (MRI) mirrors inflammation by showing sharply demarcated focal WM contrast-enhancing lesions (CELs) in T1-weighted (T1-w) images obtained upon the injection of the contrast agent gadolinium-DTPA (see Figure 2A). CELs (brain CELs more than spinal cord ones) may be visible even in the absence of a
© TOUCH BRIEFINGS 2011
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