Making treatment choices
David Footit, Consultant Neurologist, Preston
Open Door - August 2010 pages 8-9
Picture: Horia Varlan
New tablet gives fresh hope to MS patients...
I can just see the headlines in the press as one of the 'orals' comes to market. The question is should all my patients simply form an orderly queue for their prescription of a wonder cure, or is there more to it than that? I guess most of you know the answer to this, but here's how I'll be approaching it with patients.
What's on offer?
Well nothing yet, but two drugs are coming, perhaps within the year, and more are in the pipeline. Both work by suppressing the body's immune response and have been tested in patients with relapsing MS. Sadly patients with progressive forms of MS will not benefit from them. There is some tantalising experimental evidence that some of the agents in development may promote remyelination, but as most people around MS have found out, what works for mice may not for men.
Cladribine is already used as therapy for some forms of leukaemia. It works by interfering with DNA synthesis, damaging subtypes of lymphocytes thought to be important in producing MS relapses. The result of the CLARITY trial was that treatment with cladribine in short courses over two years reduced the average number of relapses per year from 0.33 to 0.15, compared to placebo.
Fingolimod is a new drug which prevents lymphocytes from leaving the lymph nodes; as with cladribine, if the number of lymphocytes in the blood is reduced, brain inflammation will be less. The result of the FREEDOMS study showed that daily treatment with low or higher dose fingolimod reduced annual relapse rate from 0.40 to 0.17. The TRANSFORMS trial showed that both doses were superior to intramuscular interferon 1a - reducing average relapse rate from 0.33 to 0.18.
For both cladribine and fingolimod there were also effects upon disability, but patients were only followed for two years, so this has to be treated with caution.
You don't get 'owt for nowt', so there are downsides. As with anything interfering with the immune system there are concerns about infection, blood test abnormalities and malignancy, mainly of the skin. In the trials, fingolimod was occasionally associated with a slowing of the heart rate or macular oedema (an eye condition threatening vision); both these will require monitoring. Cladribine was associated with an excess of shingles infection.
So what choices do I face with patients?
The starting point, whether the patient is freshly diagnosed or on an established drug, is to attempt to predict what is likely to happen if we change nothing. As now, if my very best crystal ball suggests a reasonably good prognosis, 'watchful waiting' is probably the choice most patients will follow. Basically 'if it ain't broke don't try to fix it'.
Patients who have an intermediate prognosis and who meet criteria for 'injectables' have more of a dilemma - whether to hang on for the convenience of an oral or go with what they can have right away. Lots of factors come into play, but over the years experience has shown the vast majority can come to terms with needles, given adequate support. I will be reminding patients that drugs don't always come as swiftly to the market as predicted and problems can arise even at the last minute - many will remember the suspension of natalizumab (Tysabri) just as it was about to launch in the UK. Even after a drug is licensed there may be delays - NICE will have to determine whether the treatment is cost-effective, and this may take time and the outcome is uncertain. I expect many people will still choose an injectable, and then consider at a later date whether to switch.
The big question for those with an intermediate prognosis is whether the orals will mimic Nick Clegg and become a 'game-changer'. The evidence for fingolimod being more effective than one of the injectables is quite compelling; cladribine has not been compared to another active drug. We cannot be sure about long term safety and effectiveness for either oral. For all the arguments about how effective they are, the injectables are certainly safe and generally well tolerated. For that reason alone many patients, and indeed neurologists may prefer to wait for others to test the water with the orals.
The final group of patients to consider are those with aggressive disease, many of whom currently choose therapy with natalizumab. Clearly oral therapy will be more convenient, but will it be as effective? In the trials, the relapse rate on orals and natalizumab is comparable, however the relapse rate in the placebo patients was much lower in the trials of orals than in the natalizumab trials. This suggests that in the oral trials the patients had less aggressive disease. Until a trial is done comparing one with another we cannot say which treatment is more powerful, but I suspect the orals will prove to be intermediate between injectables and natalizumab.
Choice and information
Choice was the buzzword in the noughties, offered by politicians as the means to improve services from education to the NHS. The trouble is that choice without clear information can become bewildering - anyone who has bought a mobile phone recently will know what I mean. The new options for MS treatment are of course welcome, but as a doctor I still can't give a clear answer to the question every patient wants - which drug will best reduce my chances of disability. When I left the shop with my shiny new phone I had a sneaking feeling there was something better in there for me, but I had missed it. Now more than ever it will be vital that patients get sufficient time with their neurologist and specialist nurse to come to the decision that suits them best.
Treatment choices - the point of view of a person with MS
Picture: Marcel Germain
I currently take one of the injectable disease modifying drugs. Although initially not keen on the idea of regularly injecting myself, I have come to terms with needles, am able to manage the side effects and have been relapse free for over three years. The idea of an oral treatment is a very attractive proposal. However, the lack of long-term safety data and the growing list of side effects that are being talked about make me very cautious of even bringing up the possibility of an oral treatment with my neurologist at the present time. I don't think I want to be faced with making that choice just yet.
I can't guarantee I will feel the same if my disease progresses more quickly. If I started to have more frequent relapses, I might be inclined to take a more 'risky' approach and push for one of the new treatments. At the moment I'm not sure if that would be Tysabri or one of the orals. My gut feeling is for Tysabri. Despite the risk of serious side effects, at least more is known about this drug and procedures are in place to spot problems early.
When I was choosing which of the injectable drugs to take, my neurologist told me they were all pretty much the same and left the decision up to me. The risks and benefits of the new drugs are very different from what is already available. It's not just a case of preferring a pill to an injection but understanding what the drug will do to me and what will be the implications for future treatment if I chose one drug and not another. I would want a lot more input from my neurologist when making this decision.
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