High-profile gastroenterologists and hepatologists have rejected a Cochrane Review which claims direct acting antivirals do not reduce morbidity or mortality in people with hepatitis C.
The Gastroenterological Society of Australia has labelled the review “flawed” and is urging doctors not to stop prescribing DAAs, seen as the key to eliminating hepatitis C in Australia.
The Cochrane Collaboration’s systematic review published this month reviewed 138 trials which randomised over 25,000 participants investigating 51 different DAAs, the majority against placebo, with an average intervention and follow-up period of 34 weeks.
The aim was to assess impact on morbidity, mortality, serious adverse events and secondary outcomes including sustained virological load.
The authors identified all trials as very low quality and at high risk of bias, acknowledging an absence of data on hepatitis C-morbidity and all-cause mortality – just 11 studies recording 16 deaths.
Fifty-seven of the trials looked at drugs that have been discontinued or withdrawn from the market.
The review concludes DAAs “do not seem to have any effects on the risk of hepatitis C-related morbidity or all-cause mortality” and no impact on serious adverse events, with the exception of simeprevir which may have an impact.
Meanwhile, DAAs seemed to reduce the risk of no sustained virological response, but claimed the clinical relevance of this response was “questionable, as it is a non-validated surrogate outcome”.
“It is questionable if an eradication of hepatitis C virus in the blood leads no hepatitis C in the body and improved survival and fewer complications,” it concluded.
The Gastroenterological Society of Australia has come out strongly against the review.
Chair of the Australian Liver Association, a GESA special interest group, Professor Alex Thompson says it is “flawed”, a criticism echoed by clinicians in the UK.
“The clinical trials analysed were designed as short-term studies to demonstrate antiviral efficacy in terms of curing hepatitis C. They were never intended to assess mortality and therefore it is not surprising that a mortality benefit was not identified.”
“Cohort studies and real world studies have shown clearing hepatitis C reduces the risk of liver cancer, liver failure and liver transplants,” he told the limbic.
“In RCTs it has been shown to decrease and improve patient reported outcomes including quality of life measures and remove stigma.”
There is also clear evidence that curing hepatitis C prevents transmission.
A group of UK clinicians raised similar criticism of the review – which they described as “fundamentally flawed” – in a letter published last week in The Guardian.
“The trials were neither designed, nor powered, to assess mortality, so it is hardly surprising that the Cochrane review was unable to identify any impact on mortality” wrote Graham R Foster, Professor of hepatology at the Queen Mary University of London.
Professor Thompson said he was worried the results could have a serious detrimental impact on the headway being made in Australia to eradicate the disease since DAAs were listed on the PBS in March last year.
More than 30,000 patients have been treated with the antivirals since then.
“As someone who has dedicated my career to treating viral hepatitis, I am worried that misinformation stemming from this report may sway doctors away from prescribing DAAs and discourage patients from seeking and continuing treatment.”
“The risk-share agreement struck between government and industry means that public expenditure on DAA treatment is capped annually – in effect, the more treatments that are prescribed per year, the cheaper the cost per treatment.”
“Australia is in a unique position where all people living with hepatitis C can access antiviral treatment. We have the potential to become one of the first countries in the world to eliminate hepatitis C as a public health threat, but only if treatment rates remain high.”
You can read the full review here.