Self-administered DMDs
What evidence is there
that DMDs work?
DMDs have been around for over a decade. Their use in the USA dates back to the early 1990s, the first interferon beta drug was licensed in the UK in 1995. Glatiramer acetate was licensed in the UK in 2000.
However, there is still a great deal to be learned about the benefits and risks of DMDs. Our understanding of how well they work is mainly based on studies of people receiving treatment for 2-4 years only. Although there are now many patients who have been taking DMDs for 15 years or more, the long term evidence is biased by the fact that only patients who do well on treatment tend to keep taking the drugs over a long period.
Any benefits of DMDs reported by research can also not be guaranteed for individual patients. Some people have a better experience than others and there is no way to predict who will find the treatment very helpful and who may find that it has little or no effect on them. The results of studies show the average effect that the drug has had on all the people taking part - it does not mean that this effect occurs in every patient.
Many research studies have been conducted to look at the benefits of the different licensed DMDs. However, comparing the findings of these studies with each other can be extremely difficult. This is because of differences in the way these studies were designed and conducted. For example, they have not all studied similar patients, and different measures of the benefits of treatment have been used. For more information about Research studies, use the link at the bottom of the page to go the supplementary section.
The information below is therefore based only on the work of important groups who have reviewed all the evidence from Grade 1 clinical trials. In general, they give us the average benefit of groups of drugs rather than individual drugs. These groups are:There are three major outcomes that studies consider when assessing the effectiveness of MS treatments:
Most studies also use MRI scans of the brain to provide additional information about the effects of the drug on MS. MRI is helpful because it is very sensitive in detecting new MS lesions when they occur. Specific MRI criteria are also a part of deciding whether someone is eligible to be treated with natalizumab.
However, a beneficial effect of a treatment on disease activity as measured by MRI is not enough for a drug to be licensed to treat MS. Although changes measured on MRI can be linked partly with clinical attacks, they do not correlate well with the development of disability.
Therefore, MRI scanning should not be used on its own to assess the effectiveness of a particular drug and MRI scanning usually is not used in the UK as a measure of MS disease activity in routine clinical practice, although it can sometimes be useful in addition to clinical evaluation.
In general, treatment decisions are primarily based on clinical factors - in other words things that the patient can feel (NICE 2002, Cochrane Munari 2004, Cochrane Rice 2004).
All of these five licensed drugs have been shown to reduce the rate of relapse in patients with
relapsing remitting MS by about 30% (just under one-third); in an average patient, if you've had
just one relapse, you have about a 50% chance of having another one over the next two to three years.
But if you take interferon beta, you have only a 35% chance of another relapse. This reduction has
been demonstrated for the first 2 years of therapy.
The interferon beta products have also been shown to reduce relapse frequency and severity in secondary
progressive MS.
The number of severe attacks - those requiring hospital admission or steroid treatment - is reduced by 50%.
The major trials of interferon betas have found that using them slows the development of disability in MS, although there is still debate about how much this happens. Looking at all the major trials together, the Cochrane review (Cochrane Rice 2004) found that interferon betas slow the development of disability by about 31% in people who stayed on treatment for 2 years. However, some doubt exists over how accurate this result is because some people dropped out of the studies before the end of two years, and we don't know how their disability changed.
The National Institute for Clinical Excellence found that open label studies (i.e. studies where both the patient and the medical team knew which drug the patient was taking) suggested that interferon betas continue to have a positive effect beyond 2 years. For people who have taken the drug in studies for approximately 4 years, disease activity appears to be lower than might otherwise be expected.
Whether glatiramer acetate has an effect on the development of disability is still unclear. As
a result of this, the product license for the drug in the UK does not cover this outcome.
The Cochrane review (Cochrane Munari 2004) concluded from its review of
the research that glatiramer acetate did not show any significant effect
on disability increase, measured as a sustained worsening on the
EDSS.
Over time, the human immune system may react to treatment with interferons. The body can then produce antibodies against them in the bloodstream. There is evidence that these antibodies reduce the effectiveness of the DMDs in preventing relapses. These antibodies develop in about 30% of people on Betaferon® or Extavia®, 20% on Rebif® and 5% on Avonex®. Neutralising antibodies do not occur witih Copaxone®. A laboratory test to measure antibody levels is available, and the results are usually available within 2-3 weeks.
Positive tests for neutralising antibodies to interferon beta, especially if sustained and in high levels, strengthen the case for stopping therapy. (See the FAQ section for more details).
At present there is debate amongst experts around how important neutralising antibodies are. In
about 30-40% of cases the antibodies disappear with time; this is more likely to occur in patients
with neutralising antibodies receiving Betaferon® or Extavia®
compared to those on Rebif® or Avonex®.
The evidence from grade 1 clinical trials doesn't yet give us the answer to this very important question.
There are four grade 1 trials (EVIDENCE, INCOMIN, BEYOND and REGARD) which have compared treatment with different DMDs. In two of the trials (BEYOND and REGARD), no significant difference in outcomes was shown between interferon beta and glatiramer acetate.
The other two trials showed that, up to the first 2 years of treatment, interferon beta seems to be marginally more effective when injected every other day or three times a week than when given once a week.
However, it is not known whether this difference lasts beyond 2 years of treatment. For example, the effects of neutralizing antibodies, which don't appear until treatment has been carried out for some time, would not be noted in trials less than 2 years long. See the References page for links to these trials.
The DMDs can reduce the chances of having new problems from MS in the future, especially to reduce the relapse rate by about 30%. They do not reverse the effects and symptoms of MS that have developed and become permanent before the treatment is started.
Also see the FAQs page and the supplementary page on Research Studies for more detailed information.
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