Risk of Skin Cancer and Lymphoma in Users of Topical Tacrolimus, Pimecrolimus, and Corticosteroids: Protopic JOint European Longitudinal Lymphoma and skin cancer Evaluation (JOELLE) Study

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Safety 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:
  PROTOPIC
• Medicinal product name, other:
  Elidel; Topical tacrolimus; Topical pimecrolimus
• Anatomical Therapeutic Chemical (ATC) code:
  (D11AH01) tacrolimus

  tacrolimus

  (D11AH02) pimecrolimus

  pimecrolimus
• Medical condition to be studied:
  Malignant melanoma

  Neoplasm skin

  Hodgkin's disease nodular sclerosis

  Hodgkin's disease lymphocyte predominance type stage unspecified

  Hodgkin's disease lymphocyte depletion type stage unspecified

  Non-Hodgkin's lymphoma stage I

  Non-Hodgkin's lymphoma stage II

  Non-Hodgkin's lymphoma stage III

  Non-Hodgkin's lymphoma stage IV

Population studied

• Short description of the study population:
  The study will be conducted following a common protocol in populations covered in population-based health databases and cancer registries in four countries in Europe that are available for research and that provide access to health-related data including prescription drug data: the PHARMO Database Network in the Netherlands, the Danish health databases, the Swedish health databases, and the Clinical Practice Research Datalink (CPRD) in the UK. The study population is all individuals of any age registered in the study databases from the date topical tacrolimus became available in each country through 31 December 2014 (period of inclusion), and who have at least 12 months of continuous enrollment in the study databases, except for children 0 to 12 months of age. Because the study is focused on incident cases of skin cancer and lymphoma, patients with a history of any of these conditions any time before the start date (date of cohort entry) will be excluded from the study population. The study will include four primary cohorts identified from all eligible individuals in the study population who are prescribed topical tacrolimus, topical pimecrolimus, or moderate- to high-potency topical corticosteroids during the study period, and one secondary cohort of untreated patients.
• Age groups:
  • Children (2 to < 12 years)
  • 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)
• Estimated number of subjects:
  250000

Study design details

• Main study objective:
  To estimate the incidence rate ratios of skin cancer and lymphoma in the pediatric and adult populations for new users of topical tacrolimus and topical pimecrolimus compared with users of moderate- to high-potency topical corticosteroids diagnosed with atopic dermatitis.
• Outcomes:
  Skin Malignancies: Malignant melanoma, Nonmelanoma skin cancer, Lymphomas: Cutaneous T cell lymphomas (CTCL), Hodgkin lymphomas (HL), Non Hodgkin lymphomas
• Data analysis plan:
  Incidence rates of each study malignancy will be estimated in users of topical tacrolimus, topical pimecrolimus, moderate- to high-potency topical corticosteroids, and in the general population. Incidence rate ratios and 95% CIs will be estimated comparing the rates between users of topical tacrolimus and topical pimecrolimus and users of moderate- to high-potency corticosteroids, and between users of moderate- to high-potency corticosteroids and the general population. Propensity scores will be used to match the study cohorts. Each research center will produce stratified data that will be analysed by the coordination center using standard stratified methods. The effect of cumulative dose and duration of use of topical tacrolimus and topical pimecrolimus will be estimated.