David H Miller, professor of clinical neurology.
Institute of Neurology and National Hospital for Neurology and Neurosurgery, London WC1N 3BG
Multiple sclerosis is a chronic demyelinating disease of the central nervous system that affects one in 800 people in the United Kingdom. It usually presents in young adults, and although the course is highly variable, most people develop serious and irreversible neurological disabilities over 10 to 30 years. It has a major adverse impact on the quality of life of affected individuals and their carers. The loss of productivity and independence has important socioeconomic consequences.
Three interferon betas and glatiramer acetate are licensed as disease modifying treatments for multiple sclerosis. They are given by injection and have shown few serious adverse effects over observation periods that are currently up to 10 years. In placebo controlled trials over two years, the agents reduced the relapse rate by 30%; interferon beta reduced the rate at which new lesions were detected by magnetic resonance imaging by 50-80% and modestly slowed the accumulation of disability in relapsing remitting but not secondary progressive non-relapsing multiple sclerosis.1
The use of these agents has evoked debate. Firstly, it is not known whether treatment in early relapsing remitting multiple sclerosis delays the development of secondary progression and irreversible disabilitylonger term studies are needed. Secondly, the treatments are expensive, and in 2002 the National Institute for Clinical Excellence concluded that they were not cost effective.2 Chilcott et al performed the health economics analysis for the National Institute for Clinical Excellence and show that the cost per quality adjusted life year gained is high but decreases with prolonged treatment up to 20 years. This makes sense because it takes many years to develop the disabilities that account for the major costs of the disease. The model is, however, weakened by extrapolating treatment effects over longer periods than those for which data are available, using a single study of the clinical course of the disease to derive disease progression rates, and by the unpredictability of the disease and the difficulty in capturing all aspects of its impact on patients.
In the face of such uncertainties, the Department of Health has introduced a scheme for providing disease modifying treatments in the NHS. This risk sharing scheme provides treatment for ambulant patients with clinically active relapsing disease,3 with annual monitoring of neurological status over 10 years, calculation of cost effectiveness based on actual long term data, and adjustment of the cost of the drugs (if required) to make them cost effective. The scheme has important scientific and practical limitations and will need substantial investment to generate reliable data. Nevertheless, it is a constructive approach in addressing a difficult problem, and it is hard to see a realistic alternative. Providing no disease modifying treatments to patients with frequent and disabling relapses would seem unreasonable, and a long term placebo controlled trial is unlikely to be acceptable to many patients or neurologists.
Research is needed to identify those who will benefit most from disease modifying treatments. This may be possible by independent meta-analysis of large datasets from clinical and magnetic resonance imaging studies derived from multiple trials and natural history studies of the clinical course of multiple sclerosis.4 Work must also go on to develop more effective treatments.
Competing interests: DHM has received grants from Elan, Biogen, and Schering, honoraria for giving expert advice to Biogen, Schering, Wyeth, and Bristol Myers Squibb, and lecture fees from Serono.
1. Rice GPA, Incorvaia B, Munari L, Ebers G, Polman C, D'Amico
R, et al. Interferon in relapsing-remitting multiple sclerosis. In: Cochrane
Library. Issue 4. Oxford: Update Software, 2001.
2. National Institute for Clinical Excellence. Beta interferon and glatiramer acetate for the treatment of multiple sclerosis. Technology appraisal guidance. www.nice.org.uk [No 32, Jan 2002.]
3. Association of British Neurologists. Guidelines for the use of beta interferons and glatiramer acetate in multiple sclerosis. Jan 2001. www.theabn.org
4. Noseworthy J, Kappos L, Daumer M. Competing interests in multiple sclerosis research. Lancet 2003; 361: 350-351[Medline].
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