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, MD^8
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.


Disclosures:


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.