A Prospective Pediatric Longitudinal Evaluation to Assess the Long-Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis (APPLES™)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (D11AH01) tacrolimus

  tacrolimus
• Medical condition to be studied:
  Dermatitis atopic

Population studied

• Short description of the study population:
  To be enrolled in the study subjects had to be diagnosed with atopic dermatitis (AD), had to have been exposed to tacrolimus ointment before the age of 16, and the subject o guardian had to have given written informed consent and assent (when relevant) to comply with the program requirements, including annual physical examinations, biennial dermatological examinations and direct contact twice a year for questionnaire completion.
• Age groups:
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
• Estimated number of subjects:
  8000

Study design details

• Main study objective:
  The APPLES Study is a large cohort study to assess the long-term safety of tacrolimus ointment 0.03% or 0.1% in the treatment of subjects with atopic dermatitis under actual use conditions, including the risk of developing cutaneous or systemic malignancies.
• Outcomes:
  •Total systemic malignancies diagnosed more than 6 months after the initiation of tacrolimus ointment treatment.•Hodgkin and Non-Hodgkin lymphoma diagnosed more than 6 months after the initiation of tacrolimus ointment treatment.•Cutaneous malignancies (melanoma and non-melanoma skin cancer) diagnosed more than 6 months after initiation of tacrolimus ointment treatment.
• Data analysis plan:
  Standardized Incidence Ratios and confidence intervals will be calculated for every outcome. The expected number of events are derived from available cancer registries covering the relevant countries of residence, taking into account sex, age, and in the United States of America also race.