Pharmacoepidemiology
Degarelix and the Risk of Severe Urinary Tract Infections Among Patients Diagnosed with Prostate Cancer: A Population-Based Cohort Study Farzin Khosrow-Khavar* Farzin Khosrow-Khavar Elisa Bandera Chintan Dave
Background: Gonadotropin-releasing hormone (GnRH) antagonist (degarelix) and agonists (leuprolide, goserelin, histrelin, triptorelin) are mainstay prostate cancer treatments. Results from RCTs have indicated a potential differential effect of these drugs on risk of urinary tract infections (UTI). We examined this safety concern in detail in this study.
Methods: Using Medicare (2008-2020), we conducted a retrospective cohort study among male patients with prostate cancer initiating either degarelix or GnRH agonists. The primary outcome corresponded to severe UTI events, defined as a hospitalization for primary UTI, urosepsis, or pyelonephritis. Secondary outcome corresponded to outpatient treated UTI. Patients were followed from date of treatment initiation until the earliest of the study outcome, treatment switch or discontinuation, disenrollment, or end of the study period. Cox proportional hazards models incorporating inverse probability of treatment (IPT) weights were used to estimate weighted HRs and 95 CIs accounting for 65 a priori defined baseline confounders.
Results: The study included 18,875 patients initiating on degarelix and 141,764 on GnRH agonists with mean (std) age corresponding to 76.1 (7.5) and 75.7 (7.5), respectively. Patients’ characteristics between exposure groups were balanced after IPT weighing (standardized differences <0.05). Patients receiving degarelix had 134 severe UTI events (incidence rate [IR]/1,000 person-years [95% CI]: 19.8 [16.7-23.4]) compared to 1,939 events in the GnRH agonists group (IR [95% CI]: 13.0[12.5-13.6]), with a weighted HR of 1.17 (95% CI: 1.08-1.27). Degarelix was also associated with an increased risk of outpatient treated UTI (weighted HR: 1.16, 95% CI: 1.13-1.19). Consistent results were observed across range of sensitivity analyses.
Conclusion: In this population-based study, degarelix in comparison with GnRH agonists, was associated with an increased risk of severe and non-severe UTI.