Medicines, which meet the standards of safety, quality and efficacy, are granted a marketing authorisation (previously called a product licence), which is normally necessary before they can be prescribed or sold.
The MHRA carries out an assessment of the medicine's safety, quality and efficacy, examining all the research and test results in detail, before a decision is made on whether the product should be granted a marketing authorisation. The authorisation which is issued defines who the drug can be prescribed to, and for what conditions and uses.
However, under certain special conditions, medicines can be prescribed on an individual patient basis, where there is a particular reason, for a condition or use where the medicine does not have a marketing authorisation. This is called 'off licence' or 'unlicensed' prescribing, and this sometimes happens in MS. This website cannot advise you about unlicensed drugs - they are only used in very special circumstances and should be discussed with your specialist. A list of those which are sometimes used in the UK is given below.
With the exception of mitoxantrone, which is licensed for use in people with MS in some European countries and the United States, none of the immunomodulators is licensed specifically for the treatment of MS. Immunomodulators used in MS include azathioprine, cyclophosphamide, cyclosporine, methotrexate, and mitoxantrone.
Azathioprine (Imuran®)
Azathioprine is an immune suppressive agent; the main adverse event with this
agent is suppression of white blood-cell production in the bone marrow which
results in an increased susceptibility to infections. Other side effects include
damage to the liver, nausea/vomiting, and a slightly increased risk of some
types of cancer.
An analysis of all the studies involving the use of azathioprine in MS found a slight decrease in relapse rates and a slight slowing down of disability progression with this drug (Yudkin1991). However, many neurologists have concluded that the level of treatment effect is unlikely to outweigh the adverse effects of this drug.
Cyclophosphamide (Endoxana®)
This is an anticancer agent with potentially serious side effects, which include
suppression of the bone marrow, infertility, damage to the foetus in woman
who become pregnant whilst on the medication, severe chemical irritation of
the bladder, which can lead to bleeding (haemorrhagic cystitis), hair loss
and nausea/vomiting. Its use as a treatment of MS is controversial. Some controlled
trials have shown a small clinical benefit with this drug but one large trial
did not. As a result of the serious side effects and uncertain benefits, most
centres no longer use cyclophosphamide.
Cyclosporine (Sandimmune®; Neoral®)
Cyclosporine is an immunoregulator commonly used to prevent rejection of organs
after transplantation. Cyclosporine is frequently associated with high blood
pressure and damage to the kidneys. Although cyclosporine has been shown to
have a small, positive effect on MS, the adverse effects associated with this
drug can be very problematic for patients. It is almost never used nowadays
Intravenous Immunoglobulin
Immunoglobulin (obtained from the blood of healthy human donors) is available,
but not licensed, for use in MS. Some studies suggest that immunoglobulin
may be effective in reducing MS relapse rate (Fazekas 1997). However, a recent
trial in people with secondary progressive MS was negative. Because of these
different results, further trials are necessary to assess the effectiveness
of immunoglobulin as a treatment option in MS.
Methotrexate
Methotrexate is commonly used in people with psoriasis and rheumatoid arthritis.
One small trial with 60 patients with primary progressive MS suggested a positive
benefit in the development of disability and number of relapses, but the results
were not statistically significant. More trials are needed before we can be
sure whether Methotrexate is effective in MS. (Cochrane Gray 2004)
Mitoxantrone (Novantrone®)
This is another anti-cancer drug that is being used more commonly in the larger
Neurology Centres in the UK. Trials have shown it to be a powerful immune
suppressive therapy and for this reason, it has been tested in patients with
MS. It is mainly used for people with MS who are experiencing a rapid accumulation
of disability over a short period of time due to severe relapses. All the
hospitals using the drug in the UK have specific policies controlling its
usage. Patients are admitted onto the ward for the treatment as it is intravenous
(given through a drip). Some Trusts require that it is administered by a trained
chemotherapy nurse and not by neurology staff. The main disadvantage of mitoxantrone
is its safety profile, in particular its effect on the heart, which means
that there is a restriction on the total amount of treatment that can be given.
As a result echocardiograms are performed on patients prior to receiving the
drug, and later during or after the course of treatment. Mitoxantrone is also
associated with nausea and vomiting, hair loss and the development of infertility.
