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Management of Relapsing-Remitting Multiple Sclerosis

Defining the Role of Subcutaneous Recombinant Interferon-β-1a (Rebif®)

  • Drugs in Disease Management
  • Published:
Disease Management and Health Outcomes

Summary

Abstract

Multiple sclerosis (MS) is a chronic neurological disease of adults that affects over 1 million people worldwide. Relapsing-remitting MS, characterized by acute attacks (relapses) followed by complete or partial remissions, is the most common type of MS at disease onset. Over time, most patients develop secondary-progressive disease. Costs for patients, caregivers, healthcare providers and insurers, and society in general are high because of the progressive disability and long-term care associated with MS. Historically, drug therapy has represented a relatively small component of the overall cost of the disease and indirect costs have accounted for most of the costs. Although not curative, disease-modifying agents are available for first-line use in patients with relapsing-remitting MS; the goals of therapy are to reduce the frequency and severity of relapses and postpone disease progression. All of the disease-modifying agents are associated with high cost-utility ratios.

Subcutaneous (SC) interferon-β-1a (Rebif®1) is a disease-modifying therapy that demonstrates significant benefits on all outcome measures of clinical trials [relapse rate, relapse severity, progression of disability, magnetic resonance imaging (MRI) burden of disease and MRI activity] in patients with relapsing-remitting MS. In a large, 2-year, double-blind trial, SC interferon-β-1a 44μg three time weekly decreased the number of relapses by 32% and delayed disease progression by 9.4 months with compared with placebo. In addition, patients treated with SC interferon-β-1a had 78% fewer active lesions than placebo recipients when evaluated by MRI scans. A 2-year extension of this trial demonstrated the persistence of positive effects with treatment.

Results from a large, assessor-blinded, randomized trial in patients with relapsing-remitting MS show a significant short-term therapeutic advantage for SC interferon-β-1a over IM interferon-β-1a. At week 24 of treatment, 74.9% of patients who received SC interferon-β-1a 44μg three times weekly were relapse-free compared with 63.3% of those who received intramuscular (IM) interferon-β-1a 30μg (Avonex®) once weekly. Moreover, there were fewer mean active lesions per MRI scan in SC interferon-β-1a recipients than in DVI interferon-β-1a recipients (0.7 vs 1.3 lesions).

The most frequently reported adverse event with SC interferon-β-1a is injection site inflammation (>60% of patients). SC interferon-β-1a treatment is associated with the well recognized adverse events which accompany interferon therapy including flu-like syndrome and dose-related effects on elevation of liver enzymes and reduction in white blood cell indices.

The reduction in relapses, hospital admissions and courses of corticosteroid therapy seen with SC interferon-β-1a compared with placebo results in decreased costs within the healthcare system. The delay in disease progression may reduce both direct (e.g. paid caregivers and adaptive equipment) and indirect (e.g. disability payments and lost income) costs and will likely be distributed across multiple healthcare and non-healthcare systems.

In conclusion, SC interferon-β-1a is a valuable first-line disease-modifying therapy in the treatment of patients with relapsing forms of MS. The high acquisition costs of interferon-β-1a must be weighed against the long-term benefits of therapy.

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Notes

  1. Use of tradenames is for product identification purposes only, and does not imply endorsement.

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Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Katherine A. Lyseng-Williamson & Greg L. Plosker

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  1. Katherine A. Lyseng-Williamson
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  2. Greg L. Plosker
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Correspondence to Katherine A. Lyseng-Williamson.

Additional information

Various sections of the manuscript reviewed by: D.N. Bourdette, Department of Veteran Affairs Medical Center, Neurology Service, Portland, Oregon, USA; B. Brochet, Hopital Pellegin, Bordeaux, France; G. Comi, Scientific Institute Ospedale San Raffaele, University of Milan, Department of Neuroscience, Milan, Italy; R. Hohlfeld, University of Munich, Institute for Clinical Neuroimmunology, Munich, Germany; G.L. Mancardi, University of Genoa, Department of Neurological Sciences and Vision, Genoa, Italy; R. Milo, Assaf Harofeh Medical Center, Zerifin, Israel; D.W. Paty, Department of Medicine, University of British Columbia, Division of Neurology, Vancouver, British Columbia, Canada; B. Weinstock-Guttman, Baird Multiple Sclerosis Center, Buffalo, New York, USA.

Data Selection

Sources: Medical literature published in any language since 1980 on interferon-beta-1a, identified using AdisBase (a proprietary database of Adis International) and Medline. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: AdisBase search terms were ‘multiple sclerosis’ and (‘guideline’ or ‘guideline-utilisation’ or ‘practice-guideline’ or ‘disease-management-programmes’ or ‘treatment-algorithms’ or ‘reviews-on-treatment’ or ‘drug-evaluations’ or ‘epidemiology’ or ‘cost-of-illness’ or ‘pathogenesis’), or ‘interferon-β-1a’ and (‘review’ or ‘clinical-study’). Medline search terms were ‘multiple sclerosis’ and (‘guidelines’ or ‘decision-making’ or ‘health-policy’ or ‘managed-care-programmes’ or ‘epidemiology’ or ‘outcome-assessment-health-care’ or ‘clinical-protocols’ or ‘guideline in pt’ or ‘polic* in ti’ or ‘expert panel’ or ‘utilization review’ or ‘algorithms’ or ‘disease management’ or ‘quality of life’), or ‘interferon-beta-1a’ and ‘review in pt’. Searches were last updated 11 March 2002.

Selection: Studies in patients with multiple sclerosis who received subcutaneous interferon-β-1a. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic, pharmacokinetic, pharmacoeconomic and epidemiological data are also included.

Index terms: Multiple sclerosis, interferon-β-1a, disease management, review on treatment.

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Lyseng-Williamson, K.A., Plosker, G.L. Management of Relapsing-Remitting Multiple Sclerosis. Dis-Manage-Health-Outcomes 10, 307–325 (2002). https://doi.org/10.2165/00115677-200210050-00004

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