Fluoroquinolone-Associated Injuries of Tendon, Muscles and Synovium: Recent Evidence From a Large German Claims Data Cohort Study

Fluoroquinolones have been associated with certain injuries of tendon, muscles and synovium (MTS), but the comparative risk relative to other antibiotics remains limited. The aim of this study was to examine the association between newly prescribed fluoroquinolones and the occurrence of MTS injuries with focus on length of follow-up, active comparators, age and gender. This is a cohort study in active comparator new-user design based on data from the German statutory health insurance “ Allgemeine Ortskrankenkasse ” (AOK), 2013–2019. Fluoroquinolones were compared with eight comparator antibiotic agents. Adults with incident antibiotic prescription during 2014–2018 covered by the German statutory health insurance, called “Allgemeine Ortskrankenkasse” (AOK) were followed up during the 365 days after antibiotic exposure. The primary outcome was the occurrence of incident MTS injuries. Hazard ratios with corresponding 95% confidence intervals were estimated by piece-wise exponential additive mixed models adjusted for person-time, age, comorbidities, year, and quarter at index. A 365-day follow-up was selected for the main analysis and sensitivity analyses were pre-specified including shorter follow-up windows, MTS diagnosis, comparator drug, age and gender stratification. In total, 12,007,302 antibiotic episodes of which 6.23% had incident MTS injuries were included. During the 365-day risk window of the main analysis, including inpatient and outpatient diagnoses, no increased relative risk was found (Adjusted hazard ratios (aHR) 0.99 [95% CI 0.99–1.00]). MTS mainly comprised spontaneous rupture of synovium and tendon (aHR 1.26 [1.00–1.57]), especially Achilles tendon (aHR 1.35 [1.16–1.56]). Females were at higher risk for these events compared with males, but no differences in the fluoroquinolone-specific relative risk were observed in age and gender subgroups. While no increased risk was observed over a 365-day period in the primary analysis, findings from sensitivity analyses suggest a potential short-term increase in the relative risk of specific tendon injuries following fluoroquinolone exposure within the first 30 days after initial dispensing. Risk estimates vary in further sensitivity analyses.