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Adverse effects of treatments for multiple sclerosis

With the increasing use of new treatments for MS, GPs have an important role in helping patients cope with side-effects ­ Professor David Weller offers advice

Pharmaceutical treatments for

multiple sclerosis are almost always prescribed by neurologists, but GPs have an essential role in monitoring for adverse effects.

Disease modifying treatments for MS

(?-interferon and glatiramer acatate) have been available in the UK since 1995 but until lately their use has not been uniform because of concerns about cost and efficacy.

A risk-sharing scheme for MS was introduced in 2002 as a partnership between the NHS and pharmaceutical companies to make available four drugs: Avonex, Rebif, Betaferon and Copaxone.

Under the scheme, disease-modifying treatments are available to patients meeting the Association of British Neurology guidelines. The four available agents have all been shown to reduce the number of relapses in people with relapsing remitting MS and also in those with secondary progressive MS who are still experiencing relapses. This reduction is of the order of 30 per cent.

MS is characterised by multifocal areas of inflammatory demyelination throughout the central nervous system and these compounds have also been shown to reduce the development of new lesions as detected by MRI.

None of these four agents are licensed for use in primary progressive MS ­ recent research has shown they have no effect where progression is occurring without relapses1.

Despite the evidence that these compounds reduce relapse frequency, there is uncertainty about their long-term ability to reduce disease progression ­ a number of recent studies report negligible effects on accumulation of disability2,3.

But several studies suggest

?-interferon is most effective when given early in the disease course, even after a first clinical presentation of demyelination. Longer-term data from these trials are awaited4,5.

All four treatment options are given by injection (see table below) and have a range of potential side-effects.

Side-effects of ?-interferons

Flu-like symptoms The occurrence of a flu-like syndrome in the first few hours after injection is common to all three ?-interferons. To minimise this symptom the patient may be advised to take paracetamol or an NSAID at the time of injection and also to take the injection in the evening so as to avoid having these symptoms during the day.

Injection site reactions The site of injections may become red, swollen, or painful and lumpy. Injection site reactions are minimised by ensuring good injection technique, rotating sites and ensuring the drug is at room temperature before it is injected.

Abnormalities of FBC and LFT The ?-interferons may lead to mild anaemia and reduced white cell and platelet counts; LFTs may also become elevated. FBC and LFT are checked prior to treatment being started, at one month after the start of treatment and then every three months. If tests remain stable the period between blood tests may be increased to six months, but this will vary between centres.

Worsening of neurological symptoms ?-interferons may cause a transient worsening of symptoms or an increase in spasticity immediately after injection. This may be managed by reducing the dose administered for a period.

Mood changes Prescription of the

?-interferons is contraindicated where there is a history of significant depression or suicide attempts.

There have been reports of mood swings with ?-interferon use, although there is no evidence that these agents in themselves cause depression.

Side-effects of glatiramer acetate

Injection site reactions may occur with use of this agent. Rarely, the injection may cause a transient episode of chest tightness, shortness of breath and flushing.

This usually lasts less than one hour and usually only occurs sporadically.

Conclusion

GPs have an important role in the diagnosis and management of this complex disease and its associated co-morbidities. It is vital that this includes prompt recognition of MS patients who may benefit from pharmaceutical treatments so that swift neurology referrals can be made.

Over the course of their illness, MS patients are likely to develop

associated morbidities such as depression, and most aspects of the disease require a co-ordinated, multidisciplinary

approach.

The introduction of disease-modifying treatments for MS has to some extent changed the course of the disease, with patients on these treatments experiencing fewer relapses. However, their effectiveness in slowing progression of the illness in the long-term remains in question.

References

1 Leary SM et al. Interferon ?-1a in primary progressive MS: an exploratory, randomised, controlled trial Neurology 2003; 60; 44-51

2 Filippini G et al. Interferons in relapsing remitting multiple sclerosis; a systematic review. Lancet 2003; 361 545-52

3 Cohen JA et al. Benefit of interferon ?-1a on MSFC progression in secondary progressive MS. Neurology 2002; 59: 679-87

4 Jacobs LD et al. Intramuscular interferon

?-1a therspy initiated during a first demyelinating event in multiple sclerosis;

a randomised study. N Engl J Med 2000; 343: 898-904

5 Comi G et al. Effect of early interferon treatment on conversionto definite multiple sclerosis; a randomised study. Lancet 2001; 357: 1576-82

David Weller is head of

general practice,

University of Edinburgh

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