(297) Use of systemic fluoroquinolones in primary care and hospital settings in the UK: A population-level cohort study

Background: Fluoroquinolones (FQ) have been associated with an increased risk of serious adverse events, leading to risk minimisation measures (RMM) being issued by the UK’s Medicines and Healthcare products Regulatory Agency in March 2019 to restrict their use in some mild or moderate infections as well as in people aged ≥60.

Objectives: This study aimed to assess the impact of the RMM by:
1- Estimating the incidence rates (IRs) of FQ use for the period 2012-2022.
2- Describing the patient characteristics and indications for FQ use in the study population before and after the publication of RMM.

Methods: Data were extracted from five UK databases, including primary care: CPRD GOLD and CPRD AURUM, secondary care: Barts Health and Lancashire Teaching Hospitals, or both: HIC Dundee. All adult subjects included in any of the databases between 01/01/2012 and 31/12/2022 and with at least 30 days of previous database visibility before index date were included. The exposure of interest was FQ use. Index date was the date of FQ prescription/dispensation with no prior use in the previous 30 days. Annual IRs of FQ were calculated per 100000 person-years. A segmented regression analysis with a step and slope change using interrupted time series methods was used to compare IRs before vs. after RMM. New users were characterised including socio-demographics and selected comorbidities, and conditions recorded 7 days prior to index date were extracted as proxies for potential FQ indications. Patient characteristics and indications were compared before and after RMM for all new users in CPRD GOLD, AURUM and Barts Health, and the analyses were stratified by age 18-59 vs. ≥60 years.

Results: During the study period, there were 384744, 1044142, 7007, 2287, and 67394 new FQ users in CPRD GOLD, AURUM, Barts Health, Lancashire Teaching Hospitals, and HIC Dundee, respectively.
IRs of FQ dropped after RMM introduction. IR was 1289 /100000 person-years (95%CI 1278 to 1300) in 2018 vs. 1149 (1138 to 1160) in 2019 for CPRD GOLD, 977 (972 to 982) vs. 881 (876 to 885) for AURUM, 210 (201 to 220) vs. 79 (73 to 85) for Barts Health, and 1314 (1290 to 1338) vs. 1034 (1013 to 1056) for HIC Dundee. There were significant step changes after RMM in CPRD AURUM, Barts Health and HIC Dundee.
After RMM, primary care new users were younger, had lower proportions of chronic kidney disease diagnoses, and glucocorticoid use. There were fewer urinary tract (UTI) and respiratory infections indications for FQ use after RMM. In CPRD AURUM, for example, 19.1% of new users aged ≥60 were prescribed FQ within one week of a UTI diagnosis before RMM vs. 15.6% after the measures’ introduction.

Conclusions: The study results support the conclusion that RMM introduction contributed to lower FQ prescriptions, especially for those at an increased risk of adverse events.