An Observational Multi-Country Post-Authorisation Safety Study to Evaluate the Risk of Serious Adverse Cardiovascular Events in Adolescent and Adult Patients with Severe Asthma taking Tezepelumab (TRESPASS)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  TEZSPIRE
• Study drug International non-proprietary name (INN) or common name:
  TEZEPELUMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (R03DX11) tezepelumab

  tezepelumab
• Medical condition to be studied:
  Asthma

Population studied

• Short description of the study population:
  The source population will consist of patients with a diagnosis of asthma receiving tezepelumab or high-intensity SOC treatment for severe asthma at any point during the study inclusion period. From this source population, the exposed study population (i.e. patients who initiate tezepelumab treatment) and the unexposed study population (i.e. comparable patients who are unexposed to tezepelumab) will be identified. Inclusion of patients who are unexposed to tezepelumab will be based on the presence of a trigger exposure designed to mirror the start of tezepelumab in exposed patients (i.e. augmentation or change of the non-biologic high-intensity treatment that does not represent treatment de-escalation). Unexposed patients are required to have matching clinical and treatment characteristics to the exposed patients, including a similar baseline risk of cardiovascular events.
• Age groups:
  • Paediatric Population (< 18 years)

    • Adolescents (12 to < 18 years)
  • 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:
  95574

Study design details

• Study design:
  Non-interventional, longitudinal, population-based, cohort design using secondary data sources. It will use a descriptive and a prevalent new-user design for comparative analyses of serious cardiovascular events outcomes in patients with severe asthma exposed and unexposed to tezepelumab.
• Main study objective:
  To estimate and compare the risk of a composite of major adverse cardiovascular events (MACE) in adolescent and adult patients with severe asthma who initiated tezepelumab vs. matched patients unexposed to tezepelumab (treated with standard of care for severe asthma).
• Setting:
  A total of four large longitudinal patient-level data sources have been selected for this study, representing four countries: Denmark, France, Germany, and USA.; ; The included data sources are:; 1. Danish National Registries (Denmark); 2. French National Health Data System (SNDS) (France); 3. Statutory Health Insurance (SHI) (Germany); 4. Carelon (USA); The start of the study period corresponds to tezepelumab market launch date in each country of interest (i.e. between 2022 – 2023). An approximately five-year study period is planned in each country, with an anticipated last date of study period in 2029.
• Comparators:
  Patients with severe asthma on Standard of Care, i.e., on high-intensity treatment, defined as: concomitant use of high dose ICS + LABA; concomitant use of medium to high dose ICS + low dose OCS at least 50% of the past year; concomitant use of medium to high dose ICS + LABA + low dose OCS at least 50% of the past year; concomitant use of medium to high dose ICS + LABA + third controller other than low dose OCS; biologics.; Comparators must additionally present a trigger exposure, defined as change of the non-biologic high-intensity treatment that does not represent treatment de-escalation. For the comparative analyses, patients exposed to non-tezepelumab biologics will be excluded from the comparator group.
• Outcomes:
  The primary outcome of interest is the composite outcome MACE, consisting of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. ; The secondary outcomes of interest are a composite of four serious adverse cardiovascular events, including arrhythmias, coronary artery disease, heart failure and myocardial disorders, and the individual components of the primary and secondary composite outcomes.
• Data analysis plan:
  A full description of the analytical approach will be developed and described in the SAP. Details on data derivations, category definitions, analyses, handling of missing data, and presentation of the study results will be provided in SAP. SAP will be finalised prior to the conduct of the study analyses. All study results will be presented separately for each country in the study reports, as appropriate when data become available. The final study report will include all descriptive, comparative, exploratory and sensitivity analyses as well as the meta-analysis for all the data sources.