Category: Archive

Multiple sclerosis ‘blood blockage theory’

http://news.bbc.co.uk/1/hi/health/8374980.stm

We remain sceptical about this theory; venous outflow obstruction does not explain the epidemiology of MS and falls down short on many other observations.

The interventions required to relieve venous obstruction are not without risks. The ‘blood blockage theory’ remains a theory and any involvement with the theory should be via ethically approved research studies.

The earlier use of natalizumab!

Biogen-Idec and Elan have announced the eminent start of a clinical trial, called Surpass, to assess the effectiveness of switching to natalizumab (Tysabri) in patients that have experienced disease breakthrough with either glatiramer acetate or interferon beta.

I interpret this as a show of confidence by the companies that we can overcome the PML problem; there are now 31 confirmed cases of post-marketing PML in patients with MS receiving natalizumab.

What dose of vitamin D?

After our MS Research Day on the 30th January we have been asked by several people about the correct dose of vitamin D to take to try and prevent MS and related disorders. Unfortunately we don’t know. Until we do the appropriate clinical trials any recommendations will not be evidence-based. At present we defer to the Vitamin D Council’s recommendations (www.vitamindcouncil.org):

“…. if you have little UVB exposure, my advice is as follows: healthy children under the age of 1 years should take 1,000 IU per day—over the age of 1, 1,000 IU per every 25 pounds of body weight per day. Well adults and adolescents should take 5,000 IU per day…..”

Before starting vD supplementation at this level we would urge you to see your doctor to discuss things formally; ideally this should be done in conjunction with blood monitoring.

Do you think placebo-controlled trials are ethical?

I received a strongly worded email criticising our site for participating in placebo-controlled MS clinical trials; in the opinion of the critic as there are licensed disease-modifying therapies for people with MS, placebo-controlled trials are unethical.

What do you think?

I responded as follows:

“Yes, there are several ethical considerations that need to be taken into account in relation to placebo-controlled MS trials; this issue has been extensively debated and discussed in the literature and there are International guidelines on the conduct of placebo-controlled trials.

In the UK, ethics committees make us insert a statement in the patient information sheet stating that there are licensed therapies and that by participating in a particular study people with MS could be denying themselves active treatment. In addition, we have to reconsent study participants after each relapse and/or confirmed disease progression. In addition, contemporary placebo-controlled trials have rescue arms, which allow study subjects active treatment within a study if their disease becomes active.

It is important to recognise that despite there being licensed therapies some patients don’t want to go onto them because they are injectables; if we did all trials with an active comparator, i.e. an injectable, we would exclude these patients from participating. People with needle phobia and those that have failed injectables because of side effects make up the majority of patients volunteering for placebo-controlled trials. I suspect, however, that once oral therapies are licensed for MS it will become very difficult to recruit subjects for placebo-controlled trials.

The issue of placebo-controlled trials should also be viewed on the background of the limited efficacy of the current injectables and the fact that we still don’t have data on whether or not they impact on the long-term prognosis of the disease.

In summary, I don’t think it is unethical to do placebo-controlled trials. However, you have to do them with carefully designed trials and informed consent. People with MS are perfectly capable of making an informed decision about not taking up the option of going on to a moderately effective first-line therapy and volunteering for a placebo-controlled trial of a new agent. At the end of the day we need to be pragmatic; without clinical trials we won’t advance the field and people living with MS are very aware of this. “

Please have your say if you agree or disagree with this stance!

FDA approves dalfampridine

On the 22nd January the FDA approved dalfampridine (Ampyra, Elan/Acorda Therapeutics) extended-release tablets to improve walking in people with MS. Dalfampridine is a potassium channel blocker, that has been shown to improve walking speeds vs placebo. The drug was previously known as fampridine sustained release. Given at doses greater than the recommended 10 mg twice a day, dalfampridine can cause seizures. The most common adverse events reported in clinical trials were urinary tract infection, insomnia, dizziness, headache, nausea, weakness, back pain, balance disorder, swelling in the nose or throat, constipation, diarrhoea, indigestion, throat pain, and burning, tingling, or itching of skin. Dalfampridine, should not be used in patients with moderate or severe kidney disease. In these patients, blood levels with the drug approach those associated with the occurrence of seizures.

Please see previous posting below discussing the concerns with dalfampridine.

Primary EBV infection and MS

A NEW STUDY ON INITIAL EBV INFECTION AND MS

Ascherio et al. Primary EBV infection and MS. Ann Neurol 2010; in press.

“In this study all EBV-negative subjects (10 out of 10) who developed MS became EBV positive before MS onset. In contrast, only 36% (10 of the 28) controls subjects who were EBV-negative became EBV-positive with follow-up. Ascherio and colleagues conclude that MS risk is extremely low among individuals not infected with EBV, but it increases sharply in the same individuals following EBV infection.”

Interpretation: This study is very important with regard to pinning down whether or not EBV causes MS. It ticks one of the criteria for causation; i.e. the correct temporal sequence. You need to get infected with EBV prior to MS onset.

Prof G

Which oral?

I am often asked which oral would you prescribe? There is no simple answer to this question. The answer will depend on several factors some of which are still to emerge; to mention a few:

1. If and when these agents get licensed and the conditions of licensing; i.e. a first- or second-line indication.
2. The price and more importantly the cost-effectiveness of the agents; NICE will dictate the conditions of use in the UK.
3. Level of disease activity; inactive vs. active vs. highly-active disease.
4. Perceived long-term risk; infections and possible risk of malignancy.
5. Local infrastructure to start the orals.
6. Requirements and intensity of monitoring whilst on medication.
7. Fertility issues.
8. Previous use of other disease-modifying agents.
9. Underlying medical problems.
10. Etc, etc.

It is clear from the above that the decisions about which agent to use will be personalised and will depend largely on patient choice. It is important to ensure that patients have choice and that the choice is an informed one.

Prof G