Patient characteristics and treatment pathways in patients with asthma or asthma-COPD overlap treated with Medium-Strength ICS/LABA and switching to High-StrEngth ICS/LABA or Medium-Strength TRImbow (BETRI)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  Trimbow
• Name of medicine, other:
  High-dose inhaled corticosteroid / long-acting beta-agonist combinations
• Study drug International non-proprietary name (INN) or common name:
  BECLOMETASONE

  FORMOTEROL

  GLYCOPYRRONIUM BROMIDE
• Anatomical Therapeutic Chemical (ATC) code:
  (R03AL09) formoterol, glycopyrronium bromide and beclometasone
• Medical condition to be studied:
  Asthma

  Asthma-chronic obstructive pulmonary disease overlap syndrome

Population studied

• Short description of the study population:
  This study will include all patients in the Optimum Patient Care Research Database that fulfil all the inclusion criteria and none of the exclusion criteria below.; ; Inclusion criteria:; • Prescription of medium-dose Trimbow or high-dose ICS/LABA in OPCRD on or after 1 Jan 2017; • Recorded with asthma prior to index date; • Patients with at least one year of prescription of medium dose ICS/LABA therapy in the year prior to index date; • Aged 18 years old or older at index date; • With at least one year of available data prior to index date; ; Exclusion criteria:; • Diagnosis of other chronic respiratory conditions, including interstitial pulmonary fibrosis, lung cancer, and bronchiectasis
• Age groups:
  Adult and elderly population (>18 years)

  Adults (18 to < 65 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Elderly (≥ 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  16914

Study design details

• Study design:
  This is a retrospective cohort study with a new-user, active-comparator design.
• Main study objective:
  Objective 1: To identify predictors of clinical success in step-up therapy from medium dose inhaled corticosteroid / long-acting beta-agonist (ICS/LABA) to medium dose Trimbow.; ; Objective 2: To evaluate whether stepping up from medium dose ICS/LABA to medium dose Trimbow is not inferior to stepping up to high dose ICS/LABA in terms of annualized rate of exacerbations and asthma control in real-world clinical practice. Superiority to be examined if non-inferiority achieved.
• Setting:
  The index date is the date of study entry, i.e. the date of initiating medium-dose Trimbow or high-dose ICS/LABA, which is on or after 1 Jan 2017.; ; The study / follow-up period starts from the index date to death or the end of data availability (that is, the date of data extraction), whichever earlier.; ; The baseline period is the entire period available for each patient prior to the index date and will be of at least one year.
• Comparators:
  The exposures of interest will be the first recorded prescription of medium-dose Trimbow (i.e. the presence of Trimbow 100) or high-dose ICS/LABA (>800mcg/day Beclomethasone dipropionate-equivalent), which are to occur on / after 1 Jan 2017. Exposures (prescriptions) will be ascertained from prescription records. Exposures are ascertained from OPCRD using SNOMED-International codes, SNOMED-UK codes, and Read codes v2 and v3.
• Outcomes:
  • Severe exacerbation rate as defined according to the ERS/ATS task force definitions, that is:; o an asthma-related hospital attendance/admission and/or ; o an asthma-related accident and emergency (A&E) attendance and/or ; o a primary care consultation with an acute OCS course of ≥3 days; ; • Risk domain asthma control, defined by not having any asthma-related hospitalization, acute oral steroid use, nor lower respiratory tract infection (LRTI); ; • Overall asthma control as both an aggregated and disaggregated outcome; controlled asthma is defined by fulfilling all of the following components: ; o No asthma-related hospitalization,; o No acute oral steroid use, or LRTI, and; o Average salbutamol-equivalent SABA dosage ≤200 μg/day; ; • Reliever use, referring to the average daily SABA dosage in the follow-up period; ; • Mean daily ICS exposure (µg/day; i.e. all prescribed ICS divided by number of follow-up days); ; • Mean daily OCS exposure (µg/day; i.e. all prescribed OCS divided by number of follow-up days)
• Data analysis plan:
  For objective 1, multivariable models consisting of pre-specified candidate predictors will be fitted for each outcome to identify predictors of each outcome.; ; For objective 2, a target trial emulation approach will be used. All baseline variables will be described by treatment groups (medium-dose Trimbow, vs high-dose ICS/LABA) for all analyzed patients. To minimize confounding, in particular confounding by indication, propensity score weighting with overlap weights will be used to minimize imbalances in baseline covariates between treatment groups, so that the treatments will be compared at the point of clinical equipoise. Primary analyses will be performed with the intention-to-treat principle, allowing patients in each treatment group to change their therapy during follow-up without being censored. Per protocol analyses will also be reported in line with guidelines for non-inferiority studies. Propensity score-weighted generalised linear modelling will be performed to estimate the associations between the clinical outcomes and treatment.