Development and validation of a risk prediction tool for oral corticosteroid adverse outcomes in asthma, based on real-world exposure information

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Method development or testing
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Historic longitudinal observational follow-up

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (H02) CORTICOSTEROIDS FOR SYSTEMIC USE

  CORTICOSTEROIDS FOR SYSTEMIC USE
• Medical condition to be studied:
  Asthma

Population studied

• Short description of the study population:
  United Kingdom adult (age 18-93) primary care patients with asthma registered in the Optimum Patient Care Research Database between January 1990 and June 2021.
• 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)
• Special population of interest:
  Other
• Special population of interest, other:
  Patients with active asthma
• Estimated number of subjects:
  249226

Study design details

• Study design:
  Data from UK asthma patients were used to track longitudinal changes in oral corticosteroid (OCS) use; the; largest pre–post visit change defined an index date. Risk of OCS-associated morbidities was modelled in cohorts; without pre-index diagnoses using Cox regression and survival time analyses.
• Main study objective:
  Predict future risks of oral corticosteroid-related morbidities in patients with asthma at differing projected levels; of oral corticosteroid exposure.
• Setting:
  United Kingdom primary care electronic medical records from Jan 1990 to Jun 2012:; Inclusion criteria:; • Minimum 2 years of baseline dataplus at least 3 years of follow-up.; • Active asthma: 2+ prescriptions for asthma medication within1 year before + 1 year after the index visit.; • Age 18-90 at index date (approximate as only birth year is available).
• Outcomes:
  Anxiety/depression; increased body mass index; cataracts; cerebrovascular accident; cerebro-cardiovascular; disease (any among: cerebrovascular accident, heart failure, myocardial infarction); dyslipidaemia; glaucoma;; heart failure; hypertension; myocardial infarction; osteoporosis; osteoporotic fractures; peptic ulcer; pneumonia;; renal impairment (chronic kidney disease stage ≥3a); type 2 diabetes; sleep apnoea
• Data analysis plan:
  Prediction models, regression and survival time-models will be used. Risk factors and secondary risk factors; identified during literature review will be evaluated for inclusion by backward stepwise selection using the Cox; Proportional Hazards Model. Analyses will be performed on 75% of each risk cohort as a training dataset to allow; validation in the remaining 25%.
• Summary results:
  249,226 patients with asthma met eligibility criteria for risk modelling. The pre-index to post-index OCS usage; category remained unchanged in 38.6% of patients, increased in 39.2%, and decreased in 22.2%, with 20.7%; having no further OCS prescriptions . In models, the risks of all adverse outcomes increased with projected; categoric OCS use; for example, hazard ratios for a one-category increment (none to low, low to high) were; 1.55 (1.42-1.69) for type 2 diabetes, 1.56 (1.36-1.78) for post-menopausal osteoporosis, 1.05 (1.00-1.10) for; hypertension, and 1.67 (1.52-1.83) for pneumonia (all p <0.001).