PhD candidate Department of Pharmacy Systems, Outcomes and Policy, University of Illinois Chicago Chicago, United States
Background: Antiviral (AV) therapy in influenza can reduce disease complications, particularly in high-risk populations. Concerns have been raised related to bleeding risk associated with these drugs. In US package inserts for oseltamivir and baloxavir marboxil, gastrointestinal (GI) bleeding events are included as possible adverse reactions.
Objectives: The aim of this study was to compare the risk of GI bleeding between influenza patients who were given AV drugs (oseltamivir, zanamivir, and baloxavir marboxil) and those who did not receive AVs.
Methods: We conducted this retrospective cohort study using the MarketScan Commercial Claims and Encounters and Medicare supplemental data. Between July 2016 and November 2019, we identified the first influenza episode for an individual based on an influenza diagnosis (ICD-10 codes) at an outpatient encounter. To be included, individuals needed continuous enrollment in the 180 days preceding their qualifying diagnosis. This baseline period was used to measure comorbidities and prior medication use. Individuals with an AV dispensing on the day of their diagnosis were included in the treated group and all others were in the untreated group. To match the AV treated patients with untreated, we used propensity score (PS) matching (ratio = 1:1, caliper 0.004) based on baseline comorbidities and medication use. Patients were followed until the first occurring of the following: GI bleed event; disenrollment; or 15days. Individuals in the untreated group were censored at the point of AV dispensing if that occurred prior to the previous events. Hazard ratios (HR) were estimated using Cox proportional hazard (PH) models within the PS matched cohorts. We also conducted a sensitivity analysis to mitigate the risk of channeling bias by excluding patients with a history of bleeds during the baseline period.
Results: We identified 1,557,883 patients with influenza diagnosis during the study period. The matched cohort had 631,470 patients in both treated and untreated groups. The mean age was 26.7 years and 55.6% of patients were female. During the follow-up period the incidence of GI bleeds per 1000 person-days were 0.08 and 0.14 in treated and untreated group respectively. From the Cox PH analysis, the hazard ratio (HR) for GI bleeds in the treated group was 0.58 (95% CI 0.53, 0.64) compared to the untreated group. When excluding patients with a history of bleeds, the HR for bleeding in the treated group was 0.59 (95% CI 0.53, 0.66) compared to the untreated group.
Conclusions: From this cohort study, we did not observe any increase in the risk of GI bleeds associated with AV treatment. Rather, those in the treated group had a lower risk of bleeding. Replication of this finding to rule out channeling bias or other concerns is important.