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.