Disclosures: The study was funded by Mallinckrodt Pharmaceuticals.
June 12, 2020
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Study shows terlipressin improves kidney function in hepatorenal syndrome

Disclosures: The study was funded by Mallinckrodt Pharmaceuticals.
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Newly published research from the United Kingdom demonstrates terlipressin is effective for improving kidney function in hospitalized patients with hepatorenal syndrome type 1.

“Acute kidney injury (AKI) is a complication of advanced liver disease, occurring in approximately 3.23% of hospitalized adult patients with chronic liver disease including cirrhosis,” Kevin Moore, MD, of the UCL Institute of Liver and Digestive Health at the Royal Free Hospital, University College London, and colleagues wrote. “Hepatorenal syndrome (HRS) is a type of functional AKI that results from portal hypertension leading to decreased effective circulating arterial volume, and renal vasoconstriction.”

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According to the researchers, although terlipressin is the most frequently prescribed vasoconstrictor for patients with hepatorenal syndrome in the United Kingdom, “more straightforward AKI definitions” have led to a different understanding of HRS-AKI.

While previous clinical trials examined the effectiveness of the drug at more advanced stages of kidney injury, they wrote the new definition “is more in line with conventional medicine, and in effect recognizes that earlier diagnosis and presumably treatment is better.”

With this in mind, Moore and colleagues conducted a multicenter chart review of 225 hospitalized patients who had an HRSAKI episode between January 2013 and December 2017. All patients had serum creatinine of greater than 1.5 mg/dL and were treated with a vasoconstrictor (203 treated with terlipressin for a median of 6 days; mean serum creatinine at vasopressor initiation, 3.25 mg/dL).

The primary outcome of the study was improvement of kidney function, which was further categorized as complete response (serum creatinine improved to 1.5 mg/dL), partial response (serum creatinine reduction of 20% but >1.5 mg/dL) and overall response (complete or partial response).

Overall, the researchers found the terlipressin response rate was 73%, with a higher response seen in those with mild AKI (defined as baseline serum creatinine < 2.25 mg/dL) compared to those with moderate or severe AKI.

It was also determined patients who were taking terlipressin were more likely to achieve complete response than patients on other vasopressors (50% vs. 23%).

Regarding survival rates, 90-day survival was 86% for all patients (93% for overall responders vs. 66% for treatment non-responders).

Adverse events due to terlipressin occurred in 25% of patients, while 41% of those treated with other vasopressors experienced adverse events. The most commonly reported adverse events were fluid overload/pulmonary edema and multi-organ failure.

Severe AKI was associated with higher rates of adverse events, according to the researchers.

“This retrospective analysis of the use of terlipressin in HRS-1 patients, where it is approved and available, provides important insight into the real-world treatment patterns and outcomes in this rare, acute syndrome,” Tunde Otulana, MD, senior vice president and chief medical officer at Mallinckrodt, said in a related press release. “Mallinckrodt is committed to advancing the science to benefit patients with this devastating and rapidly progressing syndrome for which effective treatment options are limited.”

Moore also commented on the recent findings in the release.

“While there are limitations to medical chart study,” he said, “the findings from this real-world data are encouraging for patients with HRS-1 who have limited treatment options and are often facing a poor prognosis.”

Though Mallinckrodt received a new drug application for terlipressin in April 2020 following positive results from the Confirm trial, the FDA continues to evaluate the drug for use in the United States.