The Comparative Risk of Urinary Tract Infections with Degarelix and Gonadotropin-Releasing Hormone Agonists among Patients Diagnosed with Prostate Cancer: A Population-Based Cohort Study

Background: Gonadotropin-releasing hormone (GnRH) antagonist (degarelix) and GnRH agonists (leuprolide, goserelin, histrelin, triptorelin) are mainstay prostate cancer treatments. Evidence from RCTs have indicated a potential differential effect of these drugs on the risk of urinary tract infections (UTI). We examined this safety concern in detail in this study.

Objectives: To examine the risk of UTI with degarelix compared with GnRH agonists among patients diagnosed with prostate cancer.

Methods: Using Medicare (2008-2020), we conducted a retrospective cohort study and implemented an active comparator, new user design. Cohort entry date corresponded to date of initiation with either degarelix or GnRH agonists. We included male patients at least 18 years of age with a diagnosis of prostate cancer and a minimum of 365 days of continuous enrollment in Medicare Parts A and B prior to the cohort entry date. 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 including demographics, history of prostate cancer treatments, comorbidities, co-medications, and healthcare system encounters.

Results: The study population included 18,875 patients initiating on degarelix and 141,773 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 experienced 134 severe UTI events (incidence rate [IR]/1,000 person-years [95% CI]: 19.8 [16.7-23.4]) compared with 1,939 events in the GnRH agonists group (IR [95% CI]: 13.0[12.5-13.6]), with a weighted HR of 1.08 (95% CI: 0.84-1.38). Degarelix was also associated with an increased risk of outpatient treated UTI (weighted HR: 1.18, 95% CI: 1.07-1.30). Consistent results were observed across sensitivity analyses extending the grace period for defining treatment discontinuation, with individual GnRH agonists as the comparator, and when excluding patients with history of UTI prior to cohort entry date.

Conclusions: In this population-based study, degarelix in comparison with GnRH agonists, was associated with a modest increased risk of severe and non-severe UTI.