Rituximab reference vs biosimilar utilization for oncology vs nononcology indications.

OBJECTIVES: Limited data exist on the adoption of rituximab biosimilars vs the reference product by indication. Available data from real-world studies comparing rituximab biosimilar and reference use have focused predominantly on oncology indications. This is the first study to assess the utilization of the 3 US rituximab biosimilars vs the reference product. STUDY DESIGN: Comparative analysis. METHODS: Deidentified real-world data of rituximab, rituximab-abbs, rituximab-pvvr, and rituximab-arrx dispensations between December 31, 2018, and February 1, 2022, were extracted using Trisus Medication Compare (The Craneware Group). The primary outcome was rituximab reference vs biosimilar utilization for oncology vs nononcology indications. Results were stratified by on-label and off-label use and treatment settings. RESULTS: A total of 28,025 encounters were captured for rituximab and its biosimilars across 193 facilities (rituximab: n = 23,395; biosimilars, n = 4631 [rituximab-abbs: n = 2550; rituximab-pvvr, n = 2081; rituximab-arrx: n = 0]). Rituximab reference had higher dispensations for oncology (78.4%) and nononcology (88.3%) indications than its biosimilars (21.6% and 11.7%, respectively; P < .01). The 3-year annual trends from 2019 to 2021 revealed decreased rituximab reference utilization (99.99% to 40.1%) and increased biosimilar use (0.01% to 59.9%). Most oncology dispensations were on label (94.5%), whereas most nononcology dispensations were off label (73.6%; P < .01). A higher proportion of biosimilar use was attributed to on-label indications (67.7%; off-label, 32.2%) compared with rituximab reference (58.0% vs42.0%, respectively; P < .01). Nonacademic settings showed higher biosimilar adoption than academic settings (22.2% vs 10.3%, respectively; P < .01). CONCLUSIONS: Real-world evidence shows an increase in rituximab biosimilar adoption over time, with higher adoption for oncology vs nononcology indications and in nonacademic settings.

Angiotensin II Use in Treatment of Refractory Shock Due to Benazepril and Amlodipine Toxic Ingestion.

INTRODUCTION: Calcium channel blockers (CCB) are a leading cause of ingestion-associated fatality. Angiotensin-converting enzyme inhibitor (ACEi) overdose as part of co-ingestion is common and associated with refractory shock. Treatment options to manage this profound vasoplegia are limited. We describe the first case of use of newly formulated Angiotensin II for treatment of severe ACEi and CCB poisoning. CASE REPORT: A 57-year-old man presented after suicide attempt by ingesting 20 tablets each of amlodipine 10 mg and benazepril 20 mg. His hypotension was initially managed with 35 mL/kg of crystalloid, norepinephrine, and hyperinsulinemic euglycemic therapy (HIET). His hemodynamics further deteriorated, and he developed lactic acidosis, electrolyte derangements, and renal dysfunction. Further complications of his ingestion included cardiac arrest, subsequent requirement for emergency cricothyrotomy, and renal replacement therapy. Maximal hemodynamic support with HIET therapy insulin drip 4.4 units/kg/hour, norepinephrine 2 mcg/kg/min, epinephrine 1 mcg/kg/min, vasopressin .06 units/hour, and intravenous lipid emulsion was unsuccessful. Ang II was started and titrated to maximal doses with dramatic improvement in hemodynamics. Within hours of starting Ang II, epinephrine was stopped and norepinephrine decreased by 50%. He was downgraded from the intensive care unit without any ongoing end-organ dysfunction. DISCUSSION: Isolated CCB overdoses have high complication rates and well-established treatments. Therefore, management of CCB and ACEi co-ingestion is typically driven by CCB poisoning algorithm. There are multiple reports of CCB and ACEi co-ingestions causing treatment-refractory shock. Therapeutic options are limited by toxicities and availability of salvage therapies. Ang II is a safe and highly effective option to manage these patients.

Effect of Nonselective ß-Blockers on Mortality in Patients With End-Stage Cirrhosis.

Background: Data regarding safety of nonselective ß-blockers (NSBBs) in patients with end-stage cirrhosis are conflicting, making it difficult for practitioners to justify if benefits outweigh the risks. Objective: Evaluate the effect of NSBB use on mortality in patients with end-stage cirrhosis. Methods: We performed a dual-center retrospective study of patients who received octreotide for a variceal bleed. Patients were stratified into 2 groups based on whether or not a NSBB was prescribed at hospital discharge. The primary outcome was 24-month mortality. Multivariable logistic regression, with 24-month mortality as the dependent variable, was performed to identify independent risk factors for the primary outcome. Results: 255 patients met inclusion criteria; 24-month mortality was 32.8%. The NSBB and no-NSBB groups had similar mortality rates at 24 months (32.0% vs 38.5%, P = 0.51). Mortality at 3 months (11.6% vs 23.3%, P = 0.08) and 12 months (22.2% vs 30.0%, P = 0.36) were similar, and there were no differences in rate of variceal bleeding (22.7% vs 13.3%, P = 0.34) or cirrhosis-related cause of death (20.4% vs 23.3%, P = 0.81). In the multivariable model, age, model for end-stage liver disease with sodium and hepatocellular carcinoma were independent risk factors for 24-month mortality. NSBB therapy had no effect on 24-month mortality (adjusted odds ratio = 1.05; 95% CI = 0.32 to 3.40). Conclusion and Relevance: In patients with end-stage cirrhosis, use of NSBBs did not affect 24-month mortality. More research is needed to determine when, and if, NSBBs should be discontinued in end-stage cirrhosis.

Evaluation of prophylactic antibiotic regimens on recurrence and mortality in spontaneous bacterial peritonitis.

INTRODUCTION AND OBJECTIVES: Limited data describe current SBP epidemiology and specific secondary SBP prophylactic regimens, leading to variable prescribing practices. This work aims to compare 90-day and one-year SBP recurrence and mortality based on secondary SBP antibiotic prophylaxis regimens. MATERIALS AND METHODS: We performed a retrospective cohort of patients >18 years with an SBP diagnosis from 2010 to 2015 at two academic institutions. Eligible patients had ascitic PMN counts ≥250cells/mm3 or a positive ascitic culture. Patients were compared based on secondary SBP prophylaxis regimens (i.e., daily, intermittent, or no prophylaxis). RESULTS: Of 791 patients with ascitic fluid samples, 86 patients were included. Antibiotic prophylaxis included daily (n=34), intermittent (n=36), or no prophylaxis (n=16). Nearly half of SBP episodes had a positive ascitic fluid culture; 50% were gram-negative pathogens, and 50% were gram-positive pathogens. Daily and intermittent regimens had similar rates of recurrence at 90-days (19.4% vs. 14.7%, p=0.60) and one-year (33.3% vs. 26.5%, p=0.53). Similarly, mortality did not differ among daily and intermittent regimens at 90-days (32.4% vs. 30.6%, p=0.87) or one-year (67.6% vs. 63.9%, p=0.74). When comparing any prophylaxis vs. no prophylaxis, there were no differences in 90-day or one-year recurrence or mortality. CONCLUSIONS: In patients with a history of SBP, our data indicate similar outcomes with daily, intermittent, or no secondary antibiotic prophylaxis. With available data, including ours, demonstrating a changing epidemiology for SBP pathogens, further data is required to determine if traditional approaches to secondary SBP prophylaxis remain appropriate.