P1802 - Serum Creatinine ≥ 5 mg/dL Is Associated With Decreased Safety and Efficacy in Patients Treated With Terlipressin for Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI) in the United Kingdom (UK)
Andrew S. Allegretti, MD, MPH1, Khurram Jamil, MD2, Katharina Verleger, MS3, Shelby L. Corman, PharmD, MS4, Nehemiah Kebede, MS5, Sneha S. Kelkar, MS, MPH6, Marieke Heisen, PhD7, Xingyue Huang, PhD2, Kevin Moore, MD8 1Massachusetts General Hospital, Boston, MA; 2Mallinckrodt Pharmaceuticals, Hampton, NJ; 3OPEN Health, Berlin, Berlin, Germany; 4OPEN Heath, Bethesda, MD; 5OPEN Health, Bethesda, MD; 6OPEN Health, New York, NY; 7OPEN Health, Rotterdam, Zuid-Holland, Netherlands; 8UCL Institute of Liver and Digestive Health, Royal Free Hospital, University College London, London, England, United Kingdom
Introduction: Clinical practice guidelines emphasize the importance of prompt treatment of HRS-AKI with vasoactive medications and albumin. The objective of this analysis was to describe efficacy and safety outcomes in patients with an SCr ≥ 5 mg/dL at the time of vasopressor initiation, which may be a tipping point for clinical outcomes in terlipressin clinical trials.
Methods: This was a post hoc analysis of a retrospective, UK-based chart review study conducted at 26 sites throughout England and Scotland. Patients were included if admitted to the hospital with a diagnosis of HRS-AKI and were treated with terlipressin between January 1, 2013 and December 31, 2017. Data were collected from hospital admission to 90 days post-discharge, and included demographics, baseline clinical characteristics, treatment history, procedures, and adverse events. The primary outcome was HRS response, defined as complete response (SCr decreased to ≤ 1.5 mg/dL), partial response (SCr decreased ≥ 20% but > 1.5 mg/dL), and no response (SCr decreased < 20% from presentation), stratified by SCr at hospital admission (< 5 mg/dL vs. ≥ 5 mg/dL). Other outcomes included the incidence of adverse events and survival from hospital admission.
Results: Among 203 patients who received terlipressin, 181 (89%) had an SCr < 5 mg/dL at presentation and 22 (11%) had an SCr ≥ 5 mg/dL. Baseline characteristics were similar between the groups. Patients with presenting SCr < 5 mg/dL were significantly more likely to achieve complete response compared to those with SCr ≥ 5 mg/dL (54.7% vs. 13.6%; p< 0.001). Patients with presenting SCr ≥ 5 mg/dL were more likely to develop fluid overload or pulmonary edema (27.3%) and multi-organ failure (31.8%) compared to patients with SCr < 5 mg/dL (14.4% [p=0.126] and 6.1% [p=0.001], respectively). Overall survival was significantly longer in patients with presenting SCr < 5 mg/dL than in patients with presenting SCr ≥ 5 mg/dL (hazard ratio, 0.48; 95% CI, 0.23-1.00; p=0.04).
Discussion: The results of this study confirm those of previous trials linking higher presenting SCr to poorer efficacy in patients with HRS-AKI. Importantly, patients with SCr ≥ 5 mg/dL also were significantly more likely to develop adverse events compared to those with a presenting SCr < 5 mg/dL. These findings highlight significant unmet need for effective medical therapy for HRS-AKI and the importance of earlier initiation of vasoconstrictors to optimize patient outcomes.
Andrew Allegretti: Mallinckrodt Pharmaceuticals – Advisory Committee/Board Member.
Kevin Moore: Mallinckrodt Pharmaceuticals – Advisory Committee/Board Member.
Andrew S. Allegretti, MD, MPH1, Khurram Jamil, MD2, Katharina Verleger, MS3, Shelby L. Corman, PharmD, MS4, Nehemiah Kebede, MS5, Sneha S. Kelkar, MS, MPH6, Marieke Heisen, PhD7, Xingyue Huang, PhD2, Kevin Moore, MD8. P1802 - Serum Creatinine ≥ 5 mg/dL Is Associated With Decreased Safety and Efficacy in Patients Treated With Terlipressin for Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI) in the United Kingdom (UK), ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.