Intranasal Fluticasone Propionate Observational Cohort Safety Studies: Reviewing Evidence from Databases on Two Continents.

Purpose: Our objective was to highlight the importance of database selection in observational research and to determine the incidence of corticosteroid-related events in patients exposed to fluticasone propionate intranasal spray (FPNS) compared with other intranasal steroids (INS).

Methods: After a feasibility study using an electronic medical record database in the UK (1990-2002), a retrospective cohort study was conducted using a large administrative claims database in the USA from 1994 to 2002 comparing the incidence and rate ratios of steroid-related events among intermittent, sub-chronic, and chronic FPNS use and other INS use episodes.

Results: Most patients used INS intermittently; power was low to evaluate risk associated with chronic use. Significantly elevated adjusted rate ratios were observed in the US study comparing FPNS with other INS for hypercorticism, sinusitis, abscess, and empyema, as well as a significantly decreased rate ratio for cataracts. The US claims database provided greater granularity on covariates and markers of severity to improve control of confounding for this study and time period, but neither database was able to assess the indication for prescription and the UK study could not address the use of INS without a prescription.

Conclusions: The FPNS results were consistent with the risk profile for INS and did not raise any new safety signals at the time of study conduct, which is consistent with the current safety profile. We were not able to discern the extent of potential off-label use of FPNS or other INS. Differences in the available data and healthcare systems highlight important considerations for database selection in the feasibility phase to assess the precision and limitations prior to formal risk evaluation.