Effectiveness and Safety of Maintenance Treatment with Combination of Tiotropium and Olodaterol in Comparison to Maintenance Treatment with a Combination of Inhaled Corticosteroids and Long-acting β2 agonists in COPD patients

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Secondary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (R03AL06) olodaterol and tiotropium bromide

  (R03AK) Adrenergics in combination with corticosteroids or other drugs, excl. anticholinergics
• Medical condition to be studied:
  Chronic obstructive pulmonary disease

Population studied

• Short description of the study population:
  The study cohort will be formed based on the following entry criteria.; Inclusion Criteria:; 1. At least one prescription for Tio+Olo combined inhaler or a LABA/ICS combined inhaler between 1 January 2013 and 31 March 2019.; a) The first dispensing of either Tio+Olo or LABA/ICS combined inhaler will be defined as the index date.; b) For the main analyses, only fixed dose combination (FDC) inhalers will be included. Sensitivity analyses will also accept free combinations ofLABA/ICS.; 2. At least one diagnosis of COPD at any time prior to the index date.; 3. At least one year of continuous medical and pharmacy health plan eligibility prior to the index date will be required to allow a baseline period for the covariates and identification of new use of the study drugs.; Exclusion Criteria:; 1. To increase the likelihood of a true diagnosis of COPD, we will exclude:; a) All patients less than 40 years of age on the index date, and; b) All patients with a diagnosis of asthma in the year prior to the index date; 2. To limit the population to those without severe lung compromise outside of COPD, we will exclude individuals with lung cancer, interstitial lung disease, or; lung transplant identified at any time prior to the index date; 3. To restrict the cohort to new users of Tio+Olo or LABA/ICS, we will exclude any individual with use of either Tio+Olo, LABA/ICS, or LABA/LAMA/ICS combination therapy in free or fixed form for at least one year prior to the index date.
• Age groups:
  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Chronic obstructive pulmonary disease (COPD) patients
• Estimated number of subjects:
  60000

Study design details

• Main study objective:
  The primary objective was to compare the effectiveness of new use of maintenance therapy initiation with the combination treatment Tiotropium and Olodaterol (Tio+Olo) compared with new use of LABA/ICS combination therapy in COPD as the time to the first COPD exacerbation.
• Outcomes:
  The primary outcome event for effectiveness was time to first COPD exacerbation after cohort entry, hospitalization for community-acquired pneumonia (serious pneumonia),escalation to triple therapy, and a composite outcome including exacerbation, hospitalization for pneumonia, or escalation to triple therapy
• Data analysis plan:
  Patient characteristics at baseline in patients treated with Tio+Olo and patients treated withLABA/LAMA/ICS will be described using standard descriptive statistics. High-dimensionalpropensity scores including both pre-specified and data-derived variables will then becalculated. We will use fine stratification and reweighting of the exposure propensity score to control for measured covariates.Cox proportional hazard regression model will be used to perform an as-treated analysis that assesses the effect of current use of LABA-ICS combination versus the Tio+Olo combination on the risk of a first COPD exacerbation. It will provide an estimate of the hazardratio (HR) of a COPD exacerbation.

Documents

Study results

1237-0093_c33177266-01_redacted