Modeling demonstrates clinical, financial benefits of long-term treatment for NASH

SAN DIEGO – A treatment regimen that demonstrates lasting efficacy for patients with advanced non-alcoholic steatohepatitis would increase quality of life and result in billions of dollars saved, according to findings presented at Digestive Disease Week.

“[Patients with NASH] are at increased risk [for] advanced fibrosis, cirrhosis and its complications,” the researchers wrote. “Treatment of NASH is limited to lifestyle modifications, which is the current standard of care. Nevertheless, several drug regimens for patients with NASH are undergoing clinical trials. Our aim was to estimate gains in clinical and quality of life outcomes and the associated value by curing NASH with advanced fibrosis in the United States.”

Zobair M. Younossi, MD, chairman of the department of medicine at Inova Fairfax Hospital, Fairfax, Virginia, and colleagues developed two Markov models to evaluate changes in lifetime quality-adjusted life years (QALYs) with a hypothetical treatment that would eventually reduce fibrosis stage, therefore halting progression to negative liver-related outcomes. Fibrosis stage could be decreased by any mechanism, according to the authors. The decrease in progression would be evaluated in comparison with standard of care treatment for NASH.

The models developed by the researchers used 1-year cycles of treatment and a lifetime horizon for seven age cohorts, ranging from 18-29 years to 80 years and older, in the United States in 2017. Ten health states for NASH were modeled, including fibrosis stages 0-3, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplant and post-liver transplant. Transition probabilities were obtained from the literature; utility values for each health state was taken from the literature as well and reduced by 0.02 every 20 years.

In the active treatment group, patients with NASH and stage 3 fibrosis were treated for 2 years. At that point, there were three outcomes outlined for them: stay in the same state, regress to fibrosis stages 0-2 or die from cardiovascular disease or age-related conditions. Following active treatment, patients were either cured of NASH or remained stable – defined as no fibrosis progression – while on long-term maintenance therapy.

Younossi and colleagues evaluated various situations by changing the treatment effect from 10% to 200%. This was done by increasing regression transition probabilities from fibrosis stage 3 to fibrosis stages 2/1 and reducing progression transition probabilities from fibrosis stage 3 to compensated cirrhosis, which led to a net regression effect. The percentage of patients being treated was also altered as part of this evaluation.

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QALYs gained through active treatment were evaluated by comparing the number of years gained in the active treatment group vs. the standard of care group. The value of a cure for NASH was determined by multiplying lifetime QALYs gained by the monetary value per QALY “according to accepted willingness-to-pay thresholds of $50,000, $100,000 and $150,000 per QALY,” the researchers wrote. The base case scenario outlined by Younossi and colleagues used a treatment effect of 100% and presumed that 30% of advanced cases would be treated.

Treating 30% of patients with advanced NASH – or approximately 1.9 million people – would result in an additional 5 million QALYs compared with standard of care, according to the base case scenario outlined by the researchers.

“At a [willingness to pay] threshold of [$50 thousand per QALY], a cure for NASH would create $250 billion in value over the lifetime of this NASH cohort,” the researchers wrote. “At higher thresholds [of $100,000 and $150,000], this value increases to $500 and $751 billion, respectively.”

In absolute terms, the group of patients aged 30 to 39 years gained the greatest amount of lifetime QALYs – 1.3 million – with active treatment, according to the findings from Younossi and colleagues. The group of patients aged 18 to 29 years gained the greatest number of lifetime QALYs per person, however, at 16 QALYs per person.

“A regimen with sustained efficacy for advanced NASH can lead to substantial clinical and economic benefits,” the researchers wrote. - by Julia Ernst, MS

Reference:

Younossi ZM, et al. Abstract Sa1557. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Disclosures: The researchers report no relevant financial disclosures.