Oral disease modifying treatments in the management of MS
Richard Nicholas, neurologist, Imperial Healthcare Trust,
David Wilkie, trial administrator, Imperial College London
Open Door - August 2011 page 6-7
Picture by tschörda
The development of disease modifying treatments (DMTs) for people with relapsing remitting multiple sclerosis has revolutionised its management in the last 15 years. Until April 2011, all licensed treatments were injectable. Now the first oral therapy, fingolimod (Gilenya), is available in Europe, and three further oral drugs have completed their final trials (BG12, laquinimod, teriflunomide) and may be licensed in the near future.
Though promising, how these oral medications will be used in the newly diagnosed and those already on therapy is unclear and raises many questions for doctors and people with MS considering treatment options.
Why start a DMT at all?
There are two events of concern in MS:
- Relapses - an acute worsening of function lasting more than 24 hours, followed by an improvement.
- Accumulation of disability - where MS affects not just day to day function but becomes increasingly problematic over time.
DMT treatment can potentially stop these events occurring.
Why does starting a DMT need some thought?
There are two issues with starting DMTs. Firstly, 10- 15% of people with MS will never experience any disability and, secondly, the aim of DMTs is to prevent relapses and ultimately prevent further disability that may or may not occur in the future.
As there may not be any perceived benefits and as MS is a long lasting and often very variable condition, any side effects can become a major issue.
When should you be thinking about starting a DMT?
DMTs have been shown to reduce relapses, and it is increasingly evident that DMTs started after disability begins to accumulate do not stop the progress of further disability. Thus ideally they should be started early on.
Why should you continue to take them?
It is currently believed for DMTs to be effective that they need to be taken for many years. Current DMTs are not perfect and unfortunately occasional relapses can occur, but DMTs may still have a benefit on the condition.
Should you be thinking about switching treatments?
Changing treatment is increasingly common as options for treatment widen. The aim of starting effective DMTs early on means that if a DMT does not work for you or causes significant side effects, you should discuss changing sooner rather than later. The challenge is that each DMT has its own benefits and risks.
Benefits and risks of DMTs
Our knowledge about the benefits of DMTs comes from trials performed over one to three years, a relatively short time in the lifespan of MS, whereas knowledge of side effects accumulates over years as the drug is used.
We know about side effects of first line DMTs (interferons and Copaxone) and have increasing knowledge about side effects of natalizumab, but we have less knowledge about fingolimod.
First line DMTs
- Cut relapses by about 30%.
- They help some people with MS a lot and some not at all.
- It takes six months to a year to see if they are being helpful.
- They have significant day to day side effects causing flu-like symptoms and injection site problems and as a result about 35% of people do not take them long-term.
- They are generally safe with no major issues when taken for more than 15 years.
Natalizumab (Tysabri)
- Cuts relapses by about 68% and can improve function for some with MS.
- Natalizumab takes about six months to work.
- Natalizumab has to be given into the vein every 28 days and can cause allergic reactions.
- The main risk is that of PML (progressive multifocal leukoencephalopathy): a severe, potentially fatal condition caused by a virus, the JC virus, entering the brain. This risk is being understood more as blood tests have been developed to check if people have ever had the JC virus infection. We also better understand the warning signs so treatment can be stopped if required.
Fingolimod (Gilenya)
- Cuts relapses by 55% and has few issues day to day.
- Potentially it can cause more infections, slow the heart rate when it is first given and cause macular oedema (a swelling at the back of the eye) affecting vision. It may also upset the liver enzymes.
- It has in rare instances been associated with serious herpes infections but we need to gather more data to get a better understanding as we use the drug.
Where does fingolimod fit in?
First line DMTs all have similar potency but fingolimod appears to be more effective and natalizumab - at least on paper - is more effective than fingolimod.
Currently in the UK our use of the drugs and who will get access to these is determined by their licence and by the views of The National Institute for Health and Clinical Excellence (NICE) who are due to report on fingolimod in December 2011.
Your decision about DMTs
You need to consider the day to day impact of the condition and the potential side effects of treatment.
There are other considerations in choosing or changing a DMT. If you are stable on a therapy it may be that the DMT you are using suits you and changing may not be the best option. You may want to reconsider when we have more knowledge of the new DMTs.
If you are considering having children in the future, our knowledge from first line DMTs and natalizumab means that they can be used prior to pregnancy. In the case of fingolimod we have little knowledge so far about its effects in pregnancy and it is recommended that it is stopped at least two months before conception.
A shared decision with your neurologist
MS is different for everyone and to identify the best strategy for your particular circumstances you need to consider the options and discuss them with your neurologist. Importantly, a decision about DMTs is not final and with our increasing choice of DMTs any decision should be reviewed in the future.
Fingolimod factfile
What is fingolimod?
Fingolimod (Gilenya) is a disease modifying treatment for people with relapsing remitting MS. It is also undergoing trials as a potential treatment for primary progressive MS.
How does fingolimod work?
Fingolimod binds to lymphocytes (white blood cells) causing a large proportion of them to be retained in the lymph glands. The number of lymphocytes reaching the brain is decreased, resulting in reduced immune attack on nerve cells in the brain and spinal cord.
How is fingolimod taken?
Fingolimod is taken as a capsule 0.5mg daily. The first dose is taken under medical supervision to check for side effects.
Who can be treated with fingolimod?
Fingolimod is licensed for people who continue to have relapses or find their relapse rate has increased despite a year's treatment with one of the first line drugs (Avonex, Betaferon, Copaxone, Extavia, Rebif). It can also be used for people with rapidly evolving severe relapsing remitting MS - two or more relapses a year.
Side effects of fingolimod
Common side effects include headache, liver enzyme increases, influenza, diarrhoea, back pain, and cough. Fingolimod can cause temporary changes in heart rate, blood pressure, shortness of breath and macular oedema (a swelling in the eye affecting vision).
In August 2011, NICE produced a draft recommendation that fingolimod was not a cost effective drug for the NHS to provide.
Read the MS Trust's press release about this decision.
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Disclaimer
Open Door articles are reproduced as published. They are not updated to take account of subsequent developments. Use appropriate caution in acting on the information in any article.
In August 2011, NICE produced a draft recommendation that fingolimod was not a cost effective drug for the NHS to provide.
Read the MS Trust's press release about this decision.