UK Clinical Trial of Rituximab
The ME Association believes that the drug Rituximab represents the most important development so far in terms of a potential disease altering treatment for at least a sub-group of people with ME/CFS.
Applications for funding from any high quality research group in the UK who wants to carry out a clinical trial would be especially welcome, and the ME Association are also willing to help fund a multicentre international trial – provided it has a UK arm.
Given the expected cost of a large scale randomised controlled trial it is likely that collaborative funding will prove necessary, and to this end the ME Association would be happy to work cooperatively with other charities or funding bodies – as has already happened in the case of the UK ME/CFS Biobank for example.
At the July 2015 board meeting of the CFS/ME Research Collaborative (CMRC) Dr Shepherd raised the subject of funding for a large UK Phase III trial of Rituximab, and the notion was very warmly received.
The MEA through its Ramsay Research Fund has currently set aside over £60,000 for a viable UK trial and these funds currently remain separate from other research funds until such time as a trial is deemed feasible.
Rituximab news updates
2017 Latest: The current plan regarding any UK clinical trial of Rituximab would appear to be to wait for publication of the Norwegian phase 3 clinical trial, which is now expected in 2018. It also appears that the chosen site for a UK trial, which could begin in 2018 if the results from Norway are favourable, will be in Norwich – with patients being recruited from Norfolk and Suffolk.
June 2016 – Invest in ME held their annual research conference which included a presentation from Dr Jo Cambridge who talked about B-cell biology and Rituximab treatment. The conference report from Dr Charles Shepherd features highlights from this and other presentations.
May 2016 – Following a public meeting in Sussex with Dr Amolak Bansal about Rituximab, MEA medical advisor Dr Charles Shepherd posted an update on the proposed UK trial.
September 2015 – MEA trustees issued a position statement relating to the £60,000+ it has ring-fenced for any suitable UK clinical trial of Rituximab. The statement also features the necessary application conditions for any clinical trials research group who are proposing to perform a clinical trial.
How you can help
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Background to Rituximab and M.E.
The ME Association has consistently maintained that the positive results emanating from Drs Fluge and Mella – coming first from the 3-patient Preliminary Case Series in 2009, and followed by the 30-patient Phase II Double-blind and Placebo-controlled Trial in 2011 reporting a strong and lasting improvement in 67% patients (and 13% of placebo controls) – demonstrated that Rituximab had exciting potential as a possible treatment for at least a sub-group of people with ME/CFS.
These initial studies were followed by an Open-label Phase II Study from the same Norwegian team, who wanted to see what the optimal dose of Rituximab might be and if this maintenance dose would also have a lasting effect on those treated.
29 people with ME/CFS were included in this study and all of them, with the exception of one, had been in the 2011 study. Those that had received the placebo in the last study were this time treated with Rituximab.
Published in July 2015, this open-label study successfully produced additional evidence that Rituximab was very effective for a significant proportion (64%) of those with ME/CFS over the medium term (up to 36 months), and with very minor reported side-effects.
However, as an open-label study it was not blinded – patients knew they were receiving Rituximab and that it had previously demonstrated benefit, which could have affected the reported benefits – and there was no control group. Also, as mentioned above, the study did not employ new patients; it relied on those who had been in the previous trial.
It should also be noted that those few patients considered very severely affected – bedbound – in this latest study were deemed ‘non-responders’ to the drug, which would seem to match previous observations for this patient group; although Drs Fluge and Mella plan to conduct a separate study to try and discover why this might be the case.
Despite the generally positive results, the authors continue to express necessary caution:
“We do not encourage the use of Rituximab for ME/CFS outside of approved clinical trials, and this is especially important for the group with very severe disease.”
The main purpose of this 2015 study was to help the researchers’ with the much larger multi-centre Phase III trial, which is currently underway and has been financed by the Norwegian Government and private donations. This gold-standard randomised placebo-controlled trial (RCT) will recruit 152 patients and follow their progress for 24 months after they have received treatment. The results – expected in 2018 – will represent the most significant yet and could provide further incentive to central funding bodies in other countries to attempt equally large replication studies.
The Norwegians have also began looking at a different drug – cyclophosphamide – which was again, and coincidentally, observed as bringing benefit to ME/CFS symptoms in people subsequently diagnosed and treated for cancer. This Phase II Open-label Trial began in March 2015 and will follow 40 people with ME/CFS during treatment and for 12 months after. It should complete in 2016 and will offer an interesting comparison to Rituximab.
What might Rituximab mean to M.E. and possible disease mechanisms?
The Norwegians were clear from the start that they felt the positive results from treatment could mean a sub-set of people with ME/CFS were struggling with some form of autoimmune disease process.
They reiterated this position in their 2015 paper:
“The observed patterns of delayed responses and relapse after B-cell depletion and regeneration, a three times higher disease prevalence in women than in men, and a previously demonstrated increase in B-cell lymphoma risk for elderly ME/CFS patients, suggest that ME/CFS may be a variant of an autoimmune disease.”
However, the method by which Rituximab appears to be a safe and effective form of treatment for some people with ME/CFS remains uncertain, and establishing precisely how it works is another aspect to the research on this drug that needs to be completed.
Note: An autoimmune disease occurs when the body’s immune system starts producing harmful antibodies – autoantibodies – which are directed against the body’s own tissue. There is some evidence to indicate that low levels of some autoantibodies are present in some people with ME/CFS. In our current state of knowledge, this is best described as saying that there may be an autoimmune component in some cases of ME/CFS. However, we are not yet in a position to say that ME/CFS is an autoimmune disease.
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