P4675 - Retreatment Following Initial Treatment With Terlipressin Improved Clinical Outcomes Among Patients With Hepatorenal Syndrome-Acute Kidney Injury: A Pooled Post Hoc Analysis
Kimberly Brown, MD1, Zachary P.. Fricker, MD2, Shehzad N.. Merwat, MD3, Manhal J.. Izzy, MD4, Sanaz Cardoza, PharmD5 1Henry Ford Health, Detroit, MI; 2Beth Israel Deaconess Medical Center, Boston, MA; 3The University of Texas Health Science Center at Houston, Houston, TX; 4Vanderbilt University, Nashville, TN; 5Mallinckrodt Pharmaceuticals, Bridgewater, NJ
Introduction: Terlipressin is used to treat hepatorenal syndrome-acute kidney injury (HRS-AKI), a potentially lethal form of AKI. In 3 Phase III clinical studies of terlipressin treatment of patients with HRS-AKI, retreatment with the same blinded study drug was allowed for patients who initially responded to treatment with a ≥30% reduction in serum creatinine (SCr), but then met the HRS diagnosis criteria again (≤90 days from the first dose of study drug). This study assessed retreatment with terlipressin and its associated clinical outcomes using pooled data from the 3 Phase III clinical studies.
Methods: The intent-to-treat (ITT) population of 3 Phase III studies (ie, OT-0401, REVERSE, and CONFIRM), in which patients with HRS-AKI were treated with terlipressin at 1–2 mg every 6 hours via intravenous bolus or matched placebo, were pooled for the analysis. Retreatment was allowed if patients responded initially with a ≥30% reduction in SCr but then subsequently developed a recurrence of HRS-AKI. HRS reversal was defined as ≥1 SCr value of ≤1.5 mg/dL on treatment (≤24 h after the last dose of study drug), for both the initial treatment and subsequent retreatment period. Assessments also included: durable HRS reversal, defined as HRS reversal without renal replacement therapy up to Day 30; and the proportion of patients alive at Day 90 (from start of initial treatment).
Results: There was a significant improvement in HRS reversal and durable HRS reversal with initial terlipressin treatment versus placebo (HRS reversal: 33.2% [117/352] vs 16.4% [42/256], P< .001; durable HRS reversal, 30.1% [106/352] vs 15.2% [39/256], P< .001). Moreover, HRS reversal was durable among most patients with initial reversal (terlipressin, 90.6% [106/117]; placebo, 92.9% [39/42]). Ten patients eligible for retreatment with terlipressin were retreated, with a median time to retreatment of 21 days (range: 12–75 days). Among those retreated with terlipressin, 60% (6/10) achieved HRS reversal. Most patients (70.1% [82/117]) with initial HRS reversal in response to terlipressin treatment were alive at Day 90. Similarly, most patients (90% [9/10]) who initially responded but later required retreatment with terlipressin were also alive at Day 90.
Discussion: Terlipressin retreatment significantly improved HRS reversal, which was durable. Among patients eligible for retreatment with terlipressin due to recurrent HRS-AKI, 6/10 achieved HRS reversal and 9/10 were alive at Day 90.
Kimberly Brown, MD1, Zachary P.. Fricker, MD2, Shehzad N.. Merwat, MD3, Manhal J.. Izzy, MD4, Sanaz Cardoza, PharmD5. P4675 - Retreatment Following Initial Treatment With Terlipressin Improved Clinical Outcomes Among Patients With Hepatorenal Syndrome-Acute Kidney Injury: A Pooled Post Hoc Analysis, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.
