Real-World Clinical Outcomes in Patients with Severe Asthma Treated with Tezepelumab: A Retrospective Observational Study of CHRONICLE and ISAR (SYNERGY)

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:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  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:
  Study Population: Patients with severe asthma enrolled in CHRONICLE and ISAR who initiated tezepelumab and meet all the inclusion criteria will be included in this study. ; ; Inclusion Criteria: Enrolled in CHRONICLE or ISAR; Aged ≥18 years at the index date; Received at least one tezepelumab injection; Have medical records available for the ≥6 months preceding the index date; Documented history of ≥1 asthma exacerbation during the 12 months prior to index date
• 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:
  1000

Study design details

• Study design:
  This is a multi-country, multi-centre, single-arm, retrospective, observational cohort study in patients with severe asthma who initiated tezepelumab while enrolled in CHRONICLE and ISAR.
• Main study objective:
  To describe asthma exacerbations in the 12-month periods before (baseline period) and after the initiation of tezepelumab (study period).
• Setting:
  This is a multi-country, multi-centre, single-arm, retrospective, observational cohort study in patients with severe asthma who initiated tezepelumab while enrolled in CHRONICLE and ISAR.; ; CHRONICLE (NCT03373045) is a non-interventional, US-based severe asthma registry that collected data from February 2018 through February 2025. It included adult patients (18 years or older) either receiving biologic therapy or maintenance systemic corticosteroids or who remain uncontrolled despite high-dose inhaled corticosteroids plus additional controllers. Between February 2018 and 2025, CHRONICLE enrolled 4366 evaluable patients with severe asthma from 142 sites, with more than 400 patients having initiated tezepelumab.; ; The International Severe Asthma Registry (ISAR) is a global collaborative project established to collect ongoing data from patients with severe asthma. To be included in the registry, patients must be at least 18 years of age, visit a participating centre, and have a diagnosis of severe asthma. In addition, patients must provide informed consent for their data to be used in ISAR research. Severe asthma is defined by either persistent uncontrolled symptoms despite optimal therapy or the need for intensive treatment, as described in steps 4 and 5 of the GINA guidelines. Data collection began in January 2018 and is ongoing. ISAR has enrolled 34,649 patients with severe asthma from 29 countries to date, with an estimated 500 non-US patients having initiated tezepelumab.
• Comparators:
  None
• Outcomes:
  Exacerbations – number of asthma exacerbations in the baseline and study periods. The definition of exacerbation is the worsening of asthma that leads to one of the following:; • Use of systemic corticosteroids for 3 days or more or a temporary increase in a stable, background dosage of oral corticosteroids,; • An emergency department or urgent care visit (<24 hours) due to asthma that required SCS, or; • An inpatient admission to hospital (≥24 hours) due to asthma.
• Data analysis plan:
  Annualized asthma exacerbation rate (AAER) for each of these exacerbation classifications will be defined as the total number of exacerbations × 365.25 / total duration of baseline/study (days). Total number of exacerbations and rates will be reported crude. In addition, AAER and 95% confidence intervals (CIs) will be estimated using negative binomial regression (or other appropriate regression). The logarithm of time at risk (follow up time) for an exacerbation during the study will be added as an offset variable. The absolute change in AAER will be reported between the baseline period and study period. The relative change in AAER from index will also be reported for these timepoints. The relative change will be calculated as a ratio, (e.g., 52-week/baseline) and proportion change with 95% CIs based on a negative binomial model.