Utilisation Patterns and Real-World Effects of Tezacaftor and Ivacaftor Combination Therapy (TEZ/IVA) in Patients With Cystic Fibrosis (CF)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Drug utilisation

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

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Observational study

Study drug and medical condition

• Name of medicine:
  SYMKEVI
• Medical condition to be studied:
  Cystic fibrosis

Population studied

• Short description of the study population:
  The study population included patients with cystic fibrosis (CF), aged 12 years or older, identified from the CF registries of US, UK, Germany, France and Ireland for the period of 2018 to 2022. The study included three cohorts: longitudinal safety and disease progression analyses, pregnancy analyses, and drug utilisation analyses.
• Age groups:
  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Hepatic impaired

  Immunocompromised

  Other

  Pregnant women

  Renal impaired
• Special population of interest, other:
  Patients with cystic fibrosis
• Estimated number of subjects:
  9623

Study design details

• Main study objective:
  To evaluate: 1. Safety outcomes in CF patients with mutations indicated for TEZ/IVA, and treated with TEZ/IVA, 2. Disease progression in CF patients with mutations indicated for TEZ/IVA, and treated with TEZ/IVA, 3. Frequency and outcome of pregnancies in female patients ?14 years, have mutations indicated for TEZ/IVA, and treated with TEZ/IVA, 4. Drug utilisation/potential off-label use
• Outcomes:
  Safety analyses: death, organ transplant, hospitalisations, pulmonary exacerbations, CF complications, respiratory microbiology, liver function tests. Disease progression analyses: percent predicted FEV1, BMI. Pregnancy analyses: pregnancy outcome, gestational age, congenital anomalies (data availability varies by registry). Drug utilization analyses: TEZ/IVA use outside of labeled indications.
• Data analysis plan:
  Data will be analysed separately for each registry for 5 years. The results of the annual analyses will be combined in a single study report for each year. Each annual report will include the patient data collected during the previous calendar year. Descriptive statistics will be presented for all study endpoints. All safety, CF disease progression, and pregnancy endpoints (Objectives 1, 2, and 3, respectively) will be compared within the TEZ/IVA cohort. Risks, as well as crude relative risks with 95% confidence intervals will be calculated for safety outcomes for each of the analyses years. Analyses will be stratified by patient age, percent predicted FEV1, and other variables as appropriate. Multivariate modelling and sensitivity analysis may be performed for outcomes deserving further investigation if sufficient data are available. Off-label use definition will be adjusted for each annual analysis as necessary if labelled indications change and will be region-specific.

Documents

Study results

TEZ_IVA_PASS_Abstract