Monday, 5 June 2017

Our Quick Survey for June: Prescribing Experimental and Speculative Drug Treatments | 05 June 2017

MEA Quick Survey for June – Why are we asking about experimental and speculative drug treatments?

Despite some significant research advances in our understanding of the underlying disease process in ME/CFS, doctors still do not have a safe and effective form of drug treatment for this illness.

However, there are a number of drugs which are being (or have been) assessed in clinical trials.

Some of these drugs are creating a great deal of interest – antiviral treatment with valganciclovir and the use of rituximab and cyclophosphamide in particular.

Not surprisingly, this means that we are frequently dealing with questions about new forms of drug treatment and why most UK doctors refuse to even consider prescribing one of these potentially disease modifying drugs – even if the patient is willing to take responsibility for any adverse effects that may occur.

There are several reasons why doctors refuse to prescribe experimental or speculative forms of treatment:

First is that all drugs have to be assessed in large scale clinical trials to make sure that they are both safe and effective before they are given what is called a product license for use in a specific condition such as ME/CFS, along with an approval or recommendation from NICE.

In the case of ME/CFS, whilst there is some evidence of benefit from clinical trials in relation to antiviral drugs and with rituximab, we don’t yet have enough consistent evidence on safety and efficacy from several high quality clinical trials carried out by independent research groups to meet this requirement.

Second is the fact that in the absence of this type of evidence from clinical trials, the NICE guideline on ME/CFS does not recommend the use of antiviral drugs or drugs that affect the immune system such as rituximab or cyclophosphamide.

Third is that doctors could end up being sued for negligence if anything went wrong with the use of a drug that has not been given this form of official approval.

My personal view is that in the case of rituximab, where the Norwegian research group have made it very clear that this drug should not be prescribed outside a clinical trial in our current state of knowledge, it would be highly irresponsible to do so.

The phase 3 clinical trial in Norway will finish in September. Will know the results in 2018. If rituximab is shown to be safe and effective, we hope that a large scale clinical trial can then be set up here in the UK.

A considerable amount of money has already been raised by Invest in ME and the MEA Ramsay Research Fund has £60,000 set aside to help fund a UK clinical trial if it is required. However, the cost of a large scale multi-centre clinical trial, which would be needed to obtain the necessary approval for ME/CFS, would be considerable in view of the cost of the drug and the way it has to be administered in hospital.

So, even if all goes to plan and a phase 3 UK clinical trial takes place, it seems that it will take around 5 years before there is any likelihood of this drug being approved for NHS treatment for what could be a sub-group of people with ME/CFS.

However, there are other situations where I think a more flexible approach should apply.

For example, in the case of antiviral drugs such as valganciclovir, where there is some evidence of benefit from clinical trials, and from physicians in America who use this drug on selective cases, I take the view that infectious diseases specialists who are familiar with the use of this type of potentially toxic antiviral medication should be able to do so in carefully selected patients with ME/CFS where there is both clinical and virological/immunological evidence to support a decision to do so.

So this is why we would like to assess patient opinion on the important issue as to whether there are situations where a more flexible approach to the use of experimental forms of treatment should be adopted here in the UK.

You can vote on this poll on the home page on the MEA website.

Dr Charles Shepherd
Hon Medical Adviser, MEA

Further Information:

The Treatment section of the 2017 edition of MEA purple booklet has a detailed summary of all clinical trials relating to drugs aimed at the underlying disease process in ME/CFS:

Section on antiviral treatment from MEA purple booklet

7.4.6 Antiviral drugs

Although viral infections commonly trigger ME/CFS, there is very little scientific evidence to indicate that a persisting viral infection is involved in perpetuating ME/CFS. The first antiviral drug to be assessed in a clinical trial was acyclovir (Straus et al 1988a). No benefits were found. Intravenous ganciclovir was found to be of benefit in a subset of patients with abnormal aberrant T-waves in a small pilot trial (Lerner et al 1997).

Valganciclovir (VGCV), which is active against human herpes virus type-6 infection, is currently being assessed in the USA following a report that it could be of benefit in ME/CFS patients with evidence of persisting EBV infection (Kogelnik et al 2006).

A more recent study investigated whether antibody titres against HHV-6 and EBV were associated with a clinical response to valganciclovir in a subset of ME/CFS patients (Watt et al 2012). Antibody titres were considered high if HHV-6 IgG was > 1:320, EBV capsid antigen IgG was > 1:640 and EBV early antigen IgG was > 1:160. Treatment with valganciclovir, independent of baseline antibody titres, was associated with self-rated improvement in physical and cognitive functioning in those who had positive HHV-6 and/or EBV serologies.

Montoya et al (2013) randomised (2:1) 30 ME/CFS patients with elevated IgG antibody titres against HHV-6 and EBV to receive valganciclovir or placebo for six months in a double-blind, placebo-controlled trial. Statistically significant differences between groups were observed in mental fatigue sub-scores and cognitive function. The VGCV patients experienced improvements within the first three months and maintained that benefit for the remaining nine months. In the VGCV arm, monocyte counts decreased, neutrophil counts increased and cytokines were more likely to evolve towards a Th-1 profile.

NICE does not recommend the use of antiviral treatment in ME/CFS (National Institute for Health and Care Excellence 2007b), and this has had a very negative impact on any interest here in the UK regarding a clinical trial that would aim to replicate these very interesting findings. The MEA has met with a representative from the pharmaceutical company that manufactures Valcyte (one of the brand names of VGCV) to discuss the possibility of a UK clinical trial.

 



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