Oral Janus kinase inhibitors and venous thromboembolic events in atopic dermatitis: protocols for a case-time control study and a nested case-control study based on the French national health insurance (SNDS) cohort

Pauline Berthe (1) , Lucie-Marie Scailteux (1, 2, 3) , Alain Lescoat (2, 3, 1) , Delphine Staumont-Salle (4, 5) , Guillaume Coiffier (6, 7) , Pierre Gueret (1) , Alain Dupuy (1, 2, 3) , Emmanuel Oger (1, 2, 3) , Catherine Droitcourt (1, 2, 3)

1 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
2 Irset - Institut de recherche en santé, environnement et travail
3 EHESP - École des Hautes Études en Santé Publique [EHESP]
4 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
5 INFINITE (Ex-Liric) - Institute for Translational Research in Inflammation - U 1286
6 Centre hospitalier Rene Pleven de Dinan
7 NuMeCan - Nutrition, Métabolismes et Cancer

Introduction Atopic dermatitis (AD) is a highly prevalent, chronic, inflammatory skin disease. Several orally administered Janus kinase inhibitors (JAKis, including baricitinib, upadacitinib and abrocitinib) have received a marketing authorisation for AD. Clinical trials in rheumatoid arthritis (RA) have flagged up a potential risk of JAKi-induced venous thromboembolic events (VTEs). Accordingly, the summary of product characteristics for a JAKi must mention VTEs as potential adverse drug reactions. In contrast to RA, AD per se is not associated with an elevated risk of VTEs. Assessing this potential risk among patients with AD would shed further light on the putative underlying relationship between JAKis and VTEs. Our research question is to investigate whether JAKi administration increases the risk of VTEs in adults with AD. Our primary objective is to assess the risk of VTEs in adults with AD exposed to JAKis compared to AD adults not exposed to JAKis, and our secondary objective is to evaluate whether JAKi initiation acts as a trigger of VTEs in adults with AD within 3 months. Methods and analysis Hence, we have designed (1) a nested case-control study and (2) a case-time control study in a cohort of adults with AD with data from the French national health insurance system (2017-2025). Here, we describe the study protocol, our methodological choices and certain novel aspects, including the combined value of the two assumptions and the use of an exhaustive national health insurance database with potentially greater statistical power for studying rare events in the population of patients with AD at a low risk of VTEs (thus limiting the influence of confounding factors). Ethics and dissemination The protocol has been approved by an independent ethics committee and registered with the French National Data Protection Commission. The study's findings will be published in peer-reviewed scientific journals and presented at international conferences.

Mots clés: Adult dermatology; Eczema; Thromboembolism; Risk management; CLINICAL PHARMACOLOGY

Domaines: Sciences du Vivant [q-bio]

Pauline Berthe, Lucie-Marie Scailteux, Alain Lescoat, Delphine Staumont-Salle, Guillaume Coiffier, et al.. Oral Janus kinase inhibitors and venous thromboembolic events in atopic dermatitis: protocols for a case-time control study and a nested case-control study based on the French national health insurance (SNDS) cohort. BMJ Open, 2022, 12 (9), pp.e059979. ⟨10.1136/bmjopen-2021-059979⟩. ⟨hal-03799022⟩