Terlipressin HRS Benefit Sustained in Transplant Subgroup of CONFIRM Study

K. Rajender Reddy, MD, FACG

Treatment with terlipressin (Terlivaz) led to kidney function improvement and a reduced need for renal replacement therapy (RRT) in patients with hepatorenal syndrome (HRS) type 1 who underwent transplant after receiving treatment, according to a 12-month follow-up of the CONFIRM study presented at the American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting in Charlotte, NC.

In the transplant subgroup analysis, HRS reversal was experienced by 37% of those receiving terlipressin compared with 14% of those in the placebo group (P = .021). Verified reversal in HRS was experienced by 30% of patients treated with terlipressin compared with 17% of those treated with placebo (P = .168). At the 12-month assessment, 94% of patients remained alive in the terlipressin group compared with 83% of those receiving placebo (P = .093). At 1-year post transplant, 46% of those in the placebo arm were receiving RRT compared with 16% in the terlipressin group (P = .009).

"Among transplant recipients, overall survival through 12 months of follow-up was numerically 11% higher for those treated with terlipressin versus placebo," lead author K. Rajender Reddy, MD, FACG, Ruimy Family President's Distinguished Professor, University of Pennsylvania; Director of Hepatology; Medical Director of Liver Transplantation University of Pennsylvania, Philadelphia, PA, said during a presentation of the results. "Collectively, these data indicate that terlipressin treatment in patients with hepatorenal syndrome led to better long-term clinical outcomes in those who received a liver transplant."

In September 2022, the FDA approved terlipressin as a treatment to improve kidney function in adults with HRS who were experiencing a rapid reduction in kidney function. This approval was based on an analysis of the full population of patients enrolled in the CONFIRM trial and marked the first FDA-approved treatment available for this indication. Across the full population of the study per the FDA label, the verified HRS reversal rate was 29% with terlipressin compared with 16% for placebo.

In the CONFIRM study, patients were randomized 2:1 to receive terlipressin 1 mg (n = 199) or placebo (n = 101). Treatment was given as an intravenous bolus every 6 hours for up to 14 days. A single serum creatinine test of 1.5 mg/dL or less while on treatment was considered an HRS reversal. Verified HRS reversal was defined by 2 consecutive serum creatinine measurements at or below 1.5 mg/dL at least 2 hours apart and up to 14 days apart combined with survival without RRT for at least 10 days.

There were 46 transplant recipients in the terlipressin arm and 29 in the placebo group. Three patients in the terlipressin arm and 2 in the placebo received both a liver and kidney transplant. The remainder of transplant recipients received a liver transplant only.

The baseline characteristics in transplant recipients were balanced between groups. In the investigational arm, the median age of patients was 56 years, 28% had alcoholic hepatitis, and serum creatinine at baseline was a mean of 3.3 mg/dL. There were more patients with ACLF grade 3 disease in the placebo arm (21%) versus the terlipressin group (9%).

More patients in the placebo arm received RRT pre-transplant compared with the terlipressin arm (30% vs 62%; P = .007). After transplant, the portion of patients receiving RRT in the placebo arm gradually increased from 18% at day 30 to 46% at 1 year. In the terlipressin arm, post-transplant RRT usage remained relatively stable, at 9% on day 30 to 16% at 1 year.

"Terlipressin treatment led to a reduced need for RRT, both pretransplant and post-transplant through 12 months of follow-up," said Reddy.

An adverse event (AE) of any grade was experienced by 85% of those in the terlipressin arm and by 89% of those in the placebo group. Serious AEs of any grade were experienced by 30% of those in the terlipressin arm and by 44% of those in the placebo group. There were 4 withdrawals due to AEs in the terlipressin arm compared with 1 in the placebo group. "The incidence of post-treatment AEs and SAEs were generally similar between groups," Reddy added.

The oral abstract, “Terlipressin Treatment of Patients with Hepatorenal Syndrome Type 1 Decreased the Need for Renal Replacement Therapy in Transplant Recipients: A 12-Month Follow-up of the CONFIRM Study,” was presented at ACG 2022.