Comparing the Incidence between Tiotropium and ICS/LABA in Real world Use in South Korea (CITRUS study)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

  Healthcare resource 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:
  Prescription event monitoring

Study drug and medical condition

• Medicinal product name, other:
  Spiriva
• Medical condition to be studied:
  Pneumonia

  Death

  Tuberculosis
• Additional medical condition(s):
  COPD exacerbations, lung cancer, non-tuberculosis mycobacteria (NTM) lung disease

Population studied

• Short description of the study population:
  COPD patient aged ≥55 years with a prescription of LAMA or ICS/LABA during the selection period and received LAMA or ICS/LABA more than twice within 12 months from the index date were identified for the study.
• Age groups:
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Estimated number of subjects:
  10.000

Study design details

• Study design:
  Retrospective cohort study
• Main study objective:
  To see the effectiveness of tiotropium compare to ICS/LABA in terms of prevention of COPD acute exacerbation and reducing incidence of pneumonia. The study will be conducted in a general practice setting, Korea National Health Insurance claim data & mortality data from the Bureau of Statistics, which includes computerized medical records of more than half million patients in South Korea
• Setting:
  Korean national health insurance claims data
• Outcomes:
  The primary outcomes were pneumonia, COPD exacerbations, and time to initiating triple combination therapy from the index date, and the secondary outcomes were the healthcare utilization (HCRU), all-cause mortality, lung ; cancer, tuberculosis (TB), and non-tuberculosis mycobacteria (NTM).
• Data analysis plan:
  All analyses will be performed with SAS and R . All variables will be summarized descriptively through displays of mean(± standard deviations), median, and ranges for continuous variables, and frequency distributions of categorical variables. To address the imbalance of potential confounders between LAMA ICS/LABA groups, we matched treatment groups using propensity scores estimated as by multiple logistic regression analysis based on as age, sex, socioeconomics status, Charlson Comorbidity Index, and asthma, and history of COPD exacerbation. Cox proportional hazards regression analyses will be used to estimate hazard ratios (HRs) HRs and 95% confidence intervals (95% CIs) for all outcomes. For (possibly) repeating events (such as exacerbation event) additionally a Poisson regression model will be fitted for the number of events (taking into account the matching). Detailed methodology for summary and statistical analyses of data in this study will be documented in an SAP.
• Summary results:
  After matching with propensity scores, a total of 4,888 patients were selected for this study. The mean (SD) age of LAMA group (N=2,444) was 69.57 (7.85) whereas ICS/LABA group (N=2,444) was 69.73 (7.91) after matching. Among LAMA group, 1,854 (75.86%) was male and 590 (24.14%) was female. Similarly, ; 1,822 (74.55%) was male and 622 (25.45%) was female in ICS/LABA group. ICS/LABA group showed significantly higher risks for pneumonia events (overall hazard ratio [HR] 1.475, 95% confidence interval [CI] 1.308-1.663; inpatient HR 1.517, 95% CI 1.314-1.751; outpatient HR 1.358, 95% CI 1.187-1.554) , COPD ; exacerbations (overall HR 1.145, 95% CI 1.059-1.237; moderate exacerbations HR 1.151, 95% CI 1.057-1.253; severe exacerbations HR 1.166, 95% CI 1.022-1.330) , and escalation to triple combination (HR 1.601, 95% CI 1.404-1.826) compared to LAMA group, whereas no significant difference between study groups were observed for lung cancer, pneumonia-related or all-cause mortality, TB, and NTM. LAMA significantly delayed the time to initiation of triple combination therapy (LAMA 450.44±510.56; ICS/LABA 358.12±418.70), and ; patients of LAMA group spent less on medical care on average than those on ICS/LABA group.