Study identification

PURI

https://redirect.ema.europa.eu/resource/46412

EU PAS number

EUPAS4357

Study ID

46412

Official title and acronym

Risk of Skin Cancer and Lymphoma in Users of Topical Tacrolimus, Pimecrolimus, and Corticosteroids (JOELLE)

DARWIN EU® study

No

Study countries

Denmark
Netherlands
Sweden
United Kingdom

Study description

Protopic JOint European Longitudinal Lymphoma and skin cancer Evaluation (JOELLE) Study is a European, multinational cohort study to assess the risk of skin cancer and lymphoma in the pediatric and adult population treated with topical tacrolimus, pimecrolimus, and corticosteroids and in the not-treated population. The study design is a cohort study in populations from four automated health databases: the PHARMO Record Linkage System in the Netherlands, Clinical Practice Research Datalink (CPRD), in the UK, the Danish National Health Database (through research center Southern Denmark University) in Denmark, and the Swedish National Health Databases (through research center Karolinska Institutet) in Sweden. The study will be coordinated by RTI Health Solutions in Spain and the United States. The study endpoints are nonmelanoma skin cancer, malignant melanoma, Hodgkin lymphoma, non-Hodgkin lymphoma, and cutaneous T cell lymphoma. Exposure propensity scores will be used to frequency match users of tacrolimus and users of pimecrolimus with users topical corticosteroids. The not-treated cohort will be individually matched to the corticosteroids cohort identified for comparison with users of tacrolimus. The study cohorts will be followed from the start date for the first occurrence of any one of the study endpoints. A minimum lag time of 6 months will be assumed between the start of exposure and the occurrence of the study endpoints. Person-years of follow-up will be classified according to ever use, single use, and switching/multiple use of tacrolimus and pimecrolimus and to cumulative dose and duration of exposure. The main exposure of interest will be the cumulative dose of topical tacrolimus and pimecrolimus. Stratified analysis and Mantel-Haenszel methods will be used to estimate crude and adjusted incidence rate ratios for each study endpoint and exposure category comparing users of tacrolimus and users of pimecrolimus with users of corticosteroids.

Study status

Finalised
Research institutions and networks

Institutions

RTI Health Solutions (RTI-HS)
France
Spain
Sweden
United Kingdom
United Kingdom (Northern Ireland)
United States
First published:
13/03/2025
InstitutionNot-for-profitENCePP partner

Contact details

Jordi Castellsague

Primary lead investigator
Study timelines

Date when funding contract was signed

Planned:
Actual:

Study start date

Planned:
Actual:

Data analysis start date

Planned:
Actual:

Date of final study report

Planned:
Actual:
Sources of funding
Pharmaceutical company and other private sector 

More details on funding

Astellas Pharma Europe B.V.
Study protocol
Initial protocol

Protopic JOELLE Protocol V04 2013_04_10_2_redacted

English (1.33 MB - PDF)View document
Updated protocol

Protopic JOELLE Protocol V4.3_2014-06-06_Ammendment

English (1.19 MB - PDF)View document
Regulatory

Was the study required by a regulatory body?

Yes

Is the study required by a Risk Management Plan (RMP)?

EU RMP category 3 (required)