D0499 - Treatment Response to Terlipressin Plus Albumin Varies by Precipitating Factor in Patients With Hepatorenal Syndrome Type 1

Tuesday, October 25, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

R. Todd Frederick, MD

Fellowship Director
California Pacific Medical Center
San Francisco, CA

Richard T. Frederick, MD¹, Nicholas Lim, MD², Mohammad Khan, MD³, Zunaira Zafar, MD⁴, Khurram Jamil, MD⁵
¹California Pacific Medical Center, San Francisco, CA; ²University of Minnesota, Minneapolis, MN; ³Jefferson Northeast, Newtown, PA; ⁴St. Mary Medical Center, Yardley, PA; ⁵Mallinckrodt, Hampton, NJ

Introduction: Hepatorenal syndrome (HRS) is a rapidly progressive form of renal failure that occurs in patients (pts) with advanced cirrhosis. Many cases of HRS are believed to be precipitated by an event such as infection, diuretic use, large volume paracentesis (LVP), or gastrointestinal bleeding (GIB). Terlipressin (TERLI) significantly reverses the renal and circulatory dysfunction in pts with HRS more effectively than placebo (PBO), although response rates may vary based on the presence of an underlying precipitant at baseline.

Methods: Using pooled data from 3 Phase III PBO-controlled studies (OT-0401, REVERSE, and CONFIRM), the incidence of HRS reversal—defined as >1 serum creatinine value of ≤1.5 mg/dL while on treatment—and HRS reversal without renal replacement therapy (RRT) by Day 30 after treatment with TERLI + albumin (n=352) vs PBO + albumin (n=256) was evaluated in subgroups of pts with HRS who presented with either infection, LVP (with or without diuretic use), GIB, or no identifiable precipitant.

Results: In the pooled population, pt age (mean±SD) was 54±11 years in each of the TERLI and PBO groups; 61% vs 65% of pts, respectively, were male; baseline MELD score was 33±6 in each group; and alcohol was the cause of cirrhosis in 60% vs 59% of pts, respectively. HRS reversal was achieved by 33% of pts in the TERLI group vs 16% in the PBO group (P< .001). HRS reversal without RRT was higher in the TERLI group (30%) vs the PBO group (15%; P< .001). Pts in the TERLI group who presented with infection had a higher incidence of HRS reversal and HRS reversal without RRT vs the PBO group (P=.018 and P=.014, respectively; Table). For LVP/diuretic use, HRS reversal was higher in the TERLI group vs the PBO group (P=.025), while a higher trend for HRS reversal without RRT was observed in the TERLI group (P=.077). HRS reversal and HRS reversal without RRT were similar between groups in pts with GIB, although the numbers in this group were small (P=.347 and P=.234, respectively). HRS reversal and HRS reversal without RRT were higher in TERLI-treated pts who presented without an identifiable precipitant vs the PBO group (P< .001 and P=.007, respectively).

Discussion: TERLI-treated pts who presented with infection, LVP, or no identifiable precipitant for HRS achieved HRS reversal and avoided RRT more frequently than pts in the PBO group. Few pts who presented with GIB achieved HRS reversal, regardless of treatment. Precipitants for HRS may modify the clinical response to TERLI in pts with HRS.

Parameter	Infection			LVP and/or Diuretic Treatment			GIB			No Identifiable Precipitant
Parameter	TERLI (n=59)	PBO (n=44)	P Value*	TERLI (n=83)	PBO (n=59)	P Value*	TERLI (n=19)	PBO (n=16)	P Value*	TERLI (n=177)	PBO (n=107)	P Value*
HRS Reversal†	24 (41)	8 (18)	.018	30 (36)	11 (19)	.025	4 (21)	1 (6)	.347	61 (35)	17 (16)	< .001
HRS Reversal without RRT through Day 30‡	21 (36)	6 (14)	.014	26 (31)	10 (17)	.077	3 (16)	0	.234	54 (31)	17 (16)	.007

Table: HRS Reversal and HRS Reversal without RRT through Day 30 by Possible Precipitating Factors for HRS and Treatment Group, Pooled ITT Population.
Data are presented as n (%). Data are pooled from the Phase III studies: OT-0401, REVERSE, and CONFIRM.
*Calculated using a Fisher’s exact test.
†The incidence of HRS reversal is defined as at least 1 SCr value of ≤1.5 mg/dL on treatment (up to 24 hours after the last dose of study medication). Any SCr values obtained posttransplant or RRT are excluded.
‡For OT-0401 and CONFIRM, dates/times are used to determine 30 days. For REVERSE, RRT is recorded with dates/times through the end of the treatment period at the Day 30 visits without an RRT date.
GIB, gastrointestinal bleeding; HRS, hepatorenal syndrome; ITT, intent-to-treat; LVP, large volume paracentesis; PBO, placebo; RRT, renal replacement therapy; SCr, serum creatinine; TERLI, terlipressin.

Disclosures:

Richard Frederick: Evidera – Consultant. Mallinckrodt – Consultant, Grant/Research Support. Seal Rock Therapeutics – Consultant. TenNor Therapeutics – Consultant.

Nicholas Lim indicated no relevant financial relationships.

Mohammad Khan: Mallinckrodt – Advisor or Review Panel Member.

Zunaira Zafar indicated no relevant financial relationships.

Khurram Jamil: Mallinckrodt – Employee.

Richard T. Frederick, MD¹, Nicholas Lim, MD², Mohammad Khan, MD³, Zunaira Zafar, MD⁴, Khurram Jamil, MD⁵. D0499 - Treatment Response to Terlipressin Plus Albumin Varies by Precipitating Factor in Patients With Hepatorenal Syndrome Type 1, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.