ABSTRACT
Immune checkpoint inhibitor (CPI)-induced diabetes mellitus (CPI-DM) is a rare immune-related adverse event (irAE). Patients and providers fear that continuing CPIs puts patients at risk for additional irAEs and thus may discontinue therapy. Currently, there are little data to inform this decision. Therefore, this study aims to elucidate whether discontinuing CPIs after diagnosis of CPI-DM impacts the development of future irAEs and cancer outcomes such as progression and death. Patients who developed CPI-DM during cancer treatment at UCSF from 1 July 2015 to 5 July 2023 were analyzed for cancer outcomes and irAE development. Fisher's exact tests, Student t-tests, Kaplan-Meier methods, and Cox regression were used as appropriate. Of the 43 patients with CPI-DM, 20 (47%) resumed CPIs within 90 days of the irAE, 4 (9%) patients restarted after 90 days, and 19 (44%) patients never restarted. Subsequent irAEs were diagnosed in 9 of 24 (38%) who resumed CPIs and 3 of 19 (16%) who discontinued CPIs (p = 0.17). There was no significant difference in death (p = 0.74) or cancer progression (p = 0.55) between these two groups. While our single-institution study did not show worse cancer outcomes after discontinuing CPIs, many variables can impact outcomes, which our study was not adequately powered to evaluate. A nuanced approach is needed to decide whether to continue CPI treatment after a severe irAE like CPI-DM.
ABSTRACT
BACKGROUND: From 2006 to 2014, alcohol-related visits to the emergency department (ED) increased by 76% in the United States, highlighting the need for improved ED-driven interventions addressing alcohol use disorder (AUD). Naltrexone is an FDA-approved medication for AUD shown to decrease craving and self-administration of alcohol. While oral naltrexone and extended-release naltrexone have been long utilized in primary care and inpatient hospital settings, the use of naltrexone in the ED is limited. METHODS: This study implemented and analyzed a multifaceted intervention regarding ED naltrexone prescribing at a large safety net, academic, urban hospital. A baseline assessment of preintervention conditions and perspectives on naltrexone prescribing was conducted through a chart review and standardized interviews with ED providers, respectively. The interview results guided design of interventions that addressed identified barriers. These included provider education, prescribing aids, and zero-cost naltrexone tablets supplied by the ED pharmacy to patients upon discharge. RESULTS: Between September 1, 2019, and August 31, 2020, of 753 unique patients who had a primary diagnosis or chief complaint containing the word "alcohol," only five (0.66%) were prescribed naltrexone. ED providers identified lack of training regarding naltrexone, lack of a prescribing protocol, and limited patient and provider education materials as barriers to prescribing naltrexone. Following the intervention, among 278 eligible patients, 11 oral naltrexone prescriptions were written (3.96%) between April 13, 2021, and August 1, 2021. This represents a sixfold increase over the preintervention period. CONCLUSIONS: An intervention to increase ED oral naltrexone prescriptions for AUD was successfully implemented, addressing lack of provider education, lack of prescribing resources, and patient barriers to accessing prescribed medications. Longer-term follow-up is needed to assess the efficacy and sustainability of these interventions. Nevertheless, ED clinicians are well positioned to initiate naltrexone prescriptions for patients presenting with AUD.
