Comparative safety of extrafine beclometasone fixed dose combinations (FDC) and fluticasone FDC in COPD

A historical cohort study, comparing time to pneumonia events in patients with COPD who initiated a fixed dose combination containing beclometasone (Fostair® or Trimbow®) with • Patients initiating a fixed dose combination containing fluticasone • Patients initiating a long-acting bronchodilator The primary outcome is time until a pneumonia event. The secondary outcome is time until a respiratory infection. The following exploratory outcomes will be used: Time until the first pneumonia related hospitalisation: a primary care recorded hospital admission within one month of a physician diagnosed pneumonia Time to first primary care recorded hospital admission. The rate of moderate/severe COPD exacerbations and pneumonia events during the entire follow-up period (to be used for a benefit/harm comparison). A set of confounding handling approaches will be evaluated, and the best one with regard to residual bias will be chosen. Superiority will be tested in a per protocol analysis comparing the FDC beclomethasone group with the FDC fluticasone reference group, with a superiority margin of 10% (or loge(1.1) on the log scale). Patients will be censored at the end of data availability (due to leaving the practice, or the last time data were extracted for the practice), 4 weeks after the last prescription containing ICS or 4 weeks after the patient switches to the comparator medication. This four-week period is to ensure we will capture a pneumonia event, even if early symptoms have caused discontinuation of ICS or switching to the other medication. Non-inferiority will be tested in per protocol analyses comparing the FDC beclometasone group with the LABD reference group, with a non-inferiority margin of a relative difference of 15%. Patients will be censored at the end of data availability (due to leaving the practice, or the last time data were extracted for the practice) or on addition of an ICS.