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. This can be granted either by a government body called the Medicines and Healthcare Products Regulatory Agency (MHRA) www.mhra.gov.uk, or by a European authority under the European regulatory process.
The regulatory authority (either the MHRA or a European authority) 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. A number of other potential new treatments for MS are also going through clinical trials at present: you can find out more about these by asking your neurologist.
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 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.
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 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
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 is commonly used in people with psoriasis and rheumatoid arthritis. Adverse effects include bone marrow suppression and pulmonary fibrosis (scarring of the lungs). One small trial of 60 patients with progressive MS suggested a positive benefit in slowing the development of disability affecting the upper limbs (arms). More trials are needed before we can be sure whether Methotrexate is effective in MS. (Cochrane Gray 2004)
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 and after the course of treatment. Mitoxantrone is also
associated with nausea and vomiting, hair loss, the development of infertility and rarely the development
of leukaemia, a cancer of blood cells.
