Prednisone bests anakinra, zinc for 90-day survival in severe alcohol-related hepatitis
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WASHINGTON — Prednisone induced a higher 90-day survival rate and lower incidence of acute kidney injury compared with anakinra and zinc sulfate in patients with severe alcohol-associated hepatitis, according to late-breaking data.
“Alcohol-associated hepatitis (AH) is an acute clinical syndrome resulting from heavy and sustained alcohol consumption. Severe AH has a 90-day mortality rate of up to 30%, and treatment with corticosteroids improved 30- but not 90-day survival,” Samer Gawrieh, MD, associate professor of medicine at Indiana University School of Medicine and gastroenterology specialist at IU Health Physicians & Digestive Disorders, said at The Liver Meeting. “Anakinra, an IL-1 inhibitor, reduced alcohol-induced hepatic steatosis, alanine transaminase and inflammatory cytokines in a mouse model of AH, and it also demonstrated efficacy signals in phase 2 study, but there are no large trials comparing anakinra to standard of care.”
With funding from the National Institute on Alcohol Abuse and Alcoholism, the Alcoholic Hepatitis Network conducted a double-blind, randomized, placebo-controlled trial at eight U.S. sites between July 2020 and August 2022. Of 147 patients with severe AH and MELD scores of 20 to 35, 74 received subcutaneous anakinra 100 mg daily for 14 days with oral ZnSO4 220 mg daily for 90 days (A+Z), and 73 received oral prednisone 40 mg daily for 30 days (discontinued if day 7 Lille score > 0.45). Researchers administered matching placebo for each group. The primary endpoint was survival at 90 days.
Following a planned interim analysis, significant differences in 90-day survival among groups (69.9% vs. 91%, respectively) prompted study discontinuation. In addition, four patients in the A+Z group underwent liver transplant compared with one patient in the prednisone group, with patients in the A+Z group experiencing lower transplant-free survival (P = .0007).
Eleven patients in the prednisone group discontinued participation due to an elevated Lille score, but survived 90 days. Serious adverse events occurred in 66.2% of A+Z patients vs. 56.2% of prednisone patients, with 41% and 21%, respectively, developing acute kidney injury. Of those in the A+Z group who died, 79% had acute kidney injury.
“Participants with severe alcoholic hepatitis treated with prednisone had a significantly higher 90-day survival than those treated with anakinra,” Gawrieh said. “The prednisone arm had lower incidence of acute kidney injuries, and the 90-day survival rate was higher in both study arms than reported in previous treatment trials of severe alcoholic hepatitis.”
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Gawrieh S, et al. Anakinra plus zinc vs. prednisone for treatment of severe alcohol-associated hepatitis: A randomized controlled trial. Presented at: The Liver Meeting; Nov. 4-8, 2022; Washington (hybrid meeting).
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