Articles on Medical Diseases and Conditions

Tag: beta-interferons

  • Steroids

    Types

    The use of steroid-based drugs for ‘attacks’ or ‘relapses’ of MS has been the standard treatment for MS for some years, and many people may still find that this is the first line of treatment offered to them.
    There are several types of steroid drugs:

    • Adrenocorticosteroids (such as ACTH – AdrenoCorticoTrophic Hormone), used to be one of the most commonly used steroids in MS.
    • Glucocorticosteroids (such as prednisolone, given by mouth; or methylprednisolone, usually given through a drip, intravenously) are used more commonly now.

    Effects of steroids

    There is substantial evidence that both types reduce the inflammation at active disease sites in the CNS and, in particular, reverse disruptions of the blood–brain barrier (see Chapter 1) that may occur when the disease is active. These effects, in turn, should reduce the duration and degree of symptoms. However, most studies suggest that the effects of steroids are relatively short term, perhaps lasting a few weeks, although there have been one or two studies which suggest tantalizingly that there may be far longer positive effects of the combined short-term use of methyl- prednisolone and prednisolone.
    There is also some interesting evidence from a trial on the use of steroids (methylprednisolone and prednisolone) following an initial episode of ‘optic neuritis’ (inflammation of the optic nerve, which makes things seem blurred). This is a significant symptom, which often acts as a forerunner of MS. There is more information on this trial in Chapter 18.
    Overall there is a sense, at the moment, that further definitive trials to assess the most effective steroid, as well as its dose and mode of administration in MS, are now almost a waste of time and resources, as newer drugs – such as the beta-interferons, glatiramer acetate and others – show so much more promise for the control of MS, in relation not only to relapses, but also to the course of the disease.

    How are steroids given?

    ACTH has now been replaced by the use of methylprednisolone and prednisolone, but there is widespread debate amongst neurologists about the most appropriate steroid and mode of administration in MS. People with MS are likely to come across different ways in which steroids are currently given – intravenously administered methylprednisolone (called IVMP for short) normally requires a hospital stay for one to several days, depending on precisely how the drug is administered. There may need to be other hospital stays for assessment purposes.

    Side effects

    As with all powerful drugs, side effects – that is unwanted effects – can occur. Side effects appear to depend very much on both the type of steroid and how it is administered. When methylprednisolone is given in the usual short-term high intravenous doses, facial flushes, a metallic taste in the mouth during the treatment and sometimes acne occur. Most other reactions are not serious, but occasionally sleep disturbances, stomach upsets and mild mood changes occur. Very occasionally more serious psychological changes are seen.
    With longer term administration of methylprednisolone, often followed by oral prednisolone, a range of unwanted effects may occur. These are very highly dependent on exactly how the steroids are given, for how long and the level of dose. Often signs of some water retention may occur: a ‘moon-shaped face’ and modest swelling (oedema) in several parts of the body. Normally, the cells of the body are bathed inside and outside in water, and this water is regulated by hormones, sodium (salt) levels and the kidneys. Steroids tend to cause the kidneys to retain
    sodium: an increase in sodium levels leads to an increase in water retention in the body, resulting usually in a modest but noticeable swelling – the oedema.
    Steroids can also produce a temporary ‘masculinization’ in women through their hormonal effects, which can include increased body hair, menstrual irregularities, acne and, paradoxically, a loss of scalp hair. Very prolonged administration can produce a range of other effects, some of them very serious.
    There is always a balance to be struck between probable improvement in some MS symptoms following a relapse, and the avoidance of as many of these side effects as possible. It may not be an easy decision for either the clinician or the person with MS. Usually the pressing nature of the symptoms produced by a relapse decides the immediate outcome. Nevertheless, the use of steroids must be very carefully monitored. The objective is to gain the maximum possible beneficial effects following dosage for the shortest possible time. However, longer term administration of steroids is thought on balance to be important in special circumstances, to try to contain the Multiple Sclerosis.

  • The beta-interferons and the management of Multiple Sclerosis

    What are beta-interferons?

    Interferons are naturally occurring substances in the body, produced in response to ‘invasion’ by a foreign substance, such as a virus. Two different kinds of beta-interferons have shown a significant effect in MS by reducing the number and severity of its ‘attacks’: beta-interferon 1b (trade name Betaferon) and, more recently, beta-interferon 1a (trade names Avonex and Rebif). They seem to stabilize the immune system but there is conflicting evidence as to whether it also slows disease progression.

    Who is helped by beta-interferons?

    At present, this is not entirely clear. The drugs have been extensively tested on people with specific kinds of relapsing-remitting MS, mainly those in the earlier stages of MS and who can walk (in the jargon, those who were ‘ambulant’). This was because it was easier to demonstrate the effectiveness of the drugs on people who were more mildly affected and who were having relatively regular ‘relapses’. Findings of several trials showed that these people had a (statistically) significantly lower rate of relapses compared to a group of others who did not take the drugs and, furthermore, when they did have a relapse, it was likely to be less severe.
    In the case of secondary progression, as it is preceded by a relapsing- remitting phase, such people may benefit through some of the therapies, which could have some effect on modifying the earlier phase of the disease.
    In primary progressive MS, there is less compelling evidence at present that beta-interferons substantially affect the longer term course of the disease.
    These current findings mean ‘statistically’ that there are still some people who took the drugs and who did not benefit a great deal from them. Beta-interferons may have less effect on people whose disease pro- gression is substantial.
    Nevertheless, at present, drug therapy for primary progressive MS is still mainly to manage any symptoms as they appear. However, given the evidence that beta-interferons can produce some benefits for both relapsing-remitting and secondary progressive MS, research is now increasingly interested in their potential effects in primary progressive MS.

    Effects of beta-interferons

    Expectations of the drugs have been so high that many people have been disappointed that they do not feel much better when they take them, but the drugs do not cure MS nor do they appear to repair existing damage: they just seem to slow down further damage and symptoms in some people, so both the original symptoms and any internal damage to your CNS will still be there. The drugs are working ‘silently’, thus, we anticipate, preventing some future symptoms and damage. You might wonder why you are taking drugs that you may think have no effect on your present symptoms!
    The effect of beta-interferons, as far as we know, is to encourage the immune system to become more ‘placid’. This seems to reduce the number and extent of the periodic ‘inflammations’ that lead to more MS symptoms; however, they do not necessarily eliminate those ‘inflammations’. So relapses may still occur, even if they are fewer in number and less in degree than they would otherwise have been. The problem is that neither the doctor treating you, nor you yourself, know what would
    ‘otherwise have been’. All you may know is that you now have (perhaps a minor) relapse, and are feeling worse. Your relapses might well have been worse without beta-interferon but, of course, you might feel that it was not effective at all.
    Beta-interferons appear to work best when the disease is active, when (although not always) there are recognizable symptoms. The predominant medical opinion at present is that beta-interferons should be given only when there is evidence of recent disease activity, but the increasing research evidence that beta-interferons may slow down the development of symptoms over the medium term (3–5 years) is prompting a serious review of this position. Indeed, there are now scientifically influential voices arguing for the administration of beta- interferons at the earliest possible stage of the disease.

    Longer term effects of beta-interferon

    More studies will be needed to assess ef fects of beta-interferon over
    15–20 years. We have data, at the time of writing this book, only on small groups of people who have had beta-interferons for 8–10 years, and this is not sufficient to make very long-term judgements. However, there are some promising signs. It does appear from current clinical trials that the onset or progression of disability, as measured by a range of tests, is slowed down by the beta-interferons and this slow-down is statistically significant – for at least 4 or 5 years after taking the drug. In addition, disease activity in the CNS as measured by magnetic resonance scans also seems to be reduced, but remember that most of these very positive results were obtained from people with milder forms of MS at an earlier stage of their disease.
    A problem that has arisen in about a third of people being given beta- interferon 1b (Betaferon) is that they have developed ‘antibodies’ to the drug after about a year or so. It appears that their bodies are resisting the ef fects of beta-interferon, attacking beta-interferon as an ‘invader’. In such cases, the positive ef fects of the drug disappear, and rate of relapses and disease progression returns – as far as we can see – to their previous state.
    Another problem is that, at present, there is no test available to ascertain which people will develop these antibodies. It is mainly by the return of increased disease activity and symptoms that these people would recognize this problem. It is not clear whether exactly the same problems will occur with other types of beta-interferon, but the first signs are that they will.

    How is beta-interferon given?

    Beta-interferons may be currently administered in different ways. Beta- interferon 1b (Betaferon) is administered by injection subcutaneously (just below the skin) every other day. Beta-interferon 1a (Avonex) is administered by injection intramuscularly (directly into the muscles) every week. Beta-interferon 1a (Rebif) is administered subcutaneously three times a week. The different types of administration are based on what has proved in clinical trials to be the best way of ensuring the effectiveness of the drug.
    Subcutaneous injections have been given in the past by a doctor or a nurse, not only to check that it is given correctly, but to monitor whether it is given at all – people are sometimes forgetful about administering any drug. However, this is a time-consuming and expensive method and
    some people now self-administer the drug, rather like insulin for people with diabetes. Intramuscular injections have to be given by a doctor (or nurse). Newer modes of administration are now being developed and trials are taking place to test whether these other methods are better and more effective.
    None of the drugs can be taken by mouth (orally) as yet; they are proteins and likely to be broken down by the digestive processes, making them less effective, or possibly even ineffective.

    How long is beta-interferon taken for?

    Decisions will taken by your neurologist based on your personal situation, and taking into account:

    • a longer term reduction in the number and degree of relapses compared to those you had before starting the beta-interferon;
    • no substantial rise in unwanted side effects;
    • no other clinical reason why you should not continue;
    • no better therapies being available;
    • the substantial financial issues involved, i.e. the cost of the drugs.

    Side effects of beta-interferon

    There have been two main side effects noted, mainly with beta-interferon
    1b (Betaferon):

    • There are symptoms best described as ‘flu-like symptoms, which many, perhaps most, people experience in the first few months of treatment. These are generally mild and can be managed with ordinary analgesics (pain relievers), and they disappear in almost everyone after those first few months.
    • Problems at the injection site, such as blotches or pain, which most people experience initially and about half some years later.

    Such reactions are more of an irritation than anything else. Very rarely more serious reactions have been reported – only in a few cases serious enough to warrant stopping treatment.
    As far as beta-interferon 1a drugs (Avonex and Rebif) are concerned, similar types of side effects were experienced, but at a lower rate.
    We do not yet know about any longer term side effects, an important issue in MS where people usually live with their condition for several decades.

    Controversies over the prescription of beta-interferon

    As you may be aware, there has been great controversy over the availability of the expensive beta-interferons for people with MS on the NHS. An organization called NICE (the National Institute for Clinical Excellence) has been given responsibility by the UK government for the formal cost–benefit assessment of all drugs and medical devices. Only if NICE recommends that a drug or device is indeed sufficiently cost effective can it now be prescribed on the NHS, and even then there may be conditions about the circumstances in which it may be given or who may prescribe it. The issue for NICE, as far as the beta-interferons are concerned, has been what benefits occur, for what costs – remembering that the beta-interferons are very expensive drugs.
    The assessment of beta-interferons was regarded as a priority for NICE because prescribing had already begun by certain neurologists in certain areas – leading to what was considered a ‘postcode lottery’ for people with MS. In fact in a Report issued in February 2002, NICE indicated that it did not believe that there was sufficient evidence at present to prescribe beta-interferons on the NHS. In other words their judgement was that prescription by the NHS was not currently cost effective. However, it indicated that people who had already been prescribed beta- interferons, before its judgment, could continue to receive them. It also indicated that efforts were being made to find ways for the drugs to be supplied on a more cost-effective basis.
    In fact on the same day as the NICE announcement, it was also announced that what was called a ‘risk-sharing agreement’ had been reached with the relevant drug companies and the NHS to provide beta- interferons through neurologists in MS clinics for approximately 9000 people with MS (about 15% of those with the disease) on very specific criteria as follows:

    Relapsing-remitting Multiple Sclerosis
    People with MS must fulfil the following four criteria:

    • be able to walk independently
    • have had at least two clinically significant relapses in the last
    2 years
    • be 18 years old or older
    • have no contraindications.

    Secondary progressive Multiple Sclerosis
    Beta-interferon is only prescribed for people with relapsing secondary
    progressive MS. It is not ef fective in people with a non-relapsing secondary progressive course. People must fulfil the following criteria:

    • be able to walk at least 10 metres with or without assistance
    • have had at least two disabling relapses in the last 2 years
    • have had minimal increase in disability due to slow progression over the last 2 years
    • be 18 years old or older

    In relation to the agreement, a group of people with MS taking the drug will be evaluated over a period of 10 years, and the relationship of any benefits to the costs will be assessed. If the equation between costs and benefits is then considered as positive, the drugs will then be allowed to be prescribed on the NHS.
    Compared to some other countries the proportion of those with MS being prescribed beta-interferons is still relatively low, although it should be said that, in addition to issue of cost, there is still substantial debate amongst neurologists as to the frequency and extent of benefits from the beta-interferons.