This was a retrospective observational study using the Optum Research Database. Study inclusion requirements (see Figure 1) were:

• Initiation of COPD treatment (LAMA monotherapy, ICS+LABA, LAMA+LABA [TIO+OLO is a subset], TT – free or fixed dose combinations) with ≥30 days of treatment between 01/01/2014 and 03/31/2018 (identification period).
  • The date of treatment initiation was the index date.

• ≥2 diagnoses for COPD on separate dates of service, in any position on the medical claim between 01/01/2013 and 05/31/2018 (study period).
• ≥40 years old as of the index date, complete demographic information.
• Continuous medical/pharmacy coverage for 12-months pre-index and for ≥30 days post-index.
• MAPD insurance coverage.
• No asthma, cystic fibrosis, or lung cancer (identified with ≥2 diagnoses on separate dates of service) during the study period.

Exacerbations were defined as:

• Severe - an inpatient admission with a COPD diagnosis code in the primary position on the claim.
• Moderate - an emergency department visit with a primary COPD diagnosis code or an office visit with a COPD diagnosis code in any position on the claim plus a pharmacy claim for an oral corticosteroid or COPD-guideline recommended antibiotic within 7 days of the visit.

Exacerbation categories were defined according to baseline COPD exacerbation history as follows:

• None - 0 exacerbations.
• Single - 1 moderate and no severe exacerbations.
• Multiple/severe - ≥2 moderate or ≥1 severe exacerbations.

• This post-hoc analysis directly matched TIO+OLO and TT cohorts on baseline exacerbation history and maintenance naïve status before being propensity score matched 1:1.
• Kaplan-Meier log-rank test was applied for all comparisons. Cox proportional hazard models was used adjusting for residual baseline differences.