Extended Safety Analysis of Baricitinib 2 mg in Adult Patients with Atopic Dermatitis: An Integrated Analysis from Eight Randomized Clinical Trials

Abstract

Background: Baricitinib, a selective Janus kinase 1/Janus kinase 2 inhibitor, is indicated in the European Union and Japan for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Objective: The objective of this study was to evaluate the safety of baricitinib 2 mg in the AD clinical program.

Methods: Six double-blind, randomized, placebo-controlled studies, and two long-term extension studies were summarized in two datasets. Placebo comparison was based on six 16-week studies with baricitinib 2 mg. All-bari-2-mg-AD included patients who received baricitinib 2 mg at any time during the eight studies.

Results: In total, 1598 patients received once-daily baricitinib 2 mg for 1434.2 patient-years of exposure (median 330 days/maximum 2.4 years). Treatment-emergent adverse events were higher for baricitinib 2 mg (57.9%) vs placebo (51.6%). Serious adverse events, serious infections, and opportunistic infections were low in frequency and similar between baricitinib 2 mg and placebo. There were no malignancies, gastrointestinal perforations, or major adverse cardiovascular events with baricitinib 2 mg in the placebo-controlled period. Herpes simplex (cluster) was higher for baricitinib 2 mg (3.8%) vs placebo (2.8%); rates decreased with extended 2 mg exposure. In All-bari-2-mg-AD, there were five malignancies other than non-melanoma skin cancer, two major adverse cardiovascular events, one peripheral venous thrombosis, one arterial thrombosis, and no pulmonary embolisms, deep vein thromboses, or deaths.

Conclusions: This integrated analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib 2 mg. Longer exposure to treatment is required to evaluate risks of malignancies and major adverse cardiovascular events.

Clinical trial registration: ClinicalTrials.gov identifiers: NCT02576938 (first posted 15 October, 2015); NCT03334396 (7 November, 2017); NCT03334422 (7 November, 2017); NCT03428100 (9 February, 2018); NCT03435081 (15 February, 2018); NCT03733301 (7 November, 2018); NCT03334435 (7 November, 2017); NCT03559270 (18 June, 2018).

Conflict of interest statement

Brett King served as a consultant for Eli Lilly and Company. Catherine Maari served as an advisory board member, investigator, and/or speaker for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Galderma, GSK Stiefel, Janssen, Novartis, and Pfizer. Edward Lain served as an advisory board member, investigator, speaker and/or consultant for AbbVie, Allergan, Almirall, Amgen, Arcutis, Athenex, Brickell Biotech, Bristol-Myers Squibb, Dermavant, Dermira, Eli Lilly and Company, Galderma, Johnson & Johnson, Kiniksa, L’Oreal, Leo Pharma, Novartis, Ortho Dermatologics, Pfizer, Pierre-Fabre, Pulse Biosciences, Regeneron/Sanofi Genzyme, Sebacia, UCB Pharma, and Vyne Therapeutics. Jonathan I. Silverberg served as a consultant and/or advisory board member for AbbVie, Arena, Asana, Bluefin, Boehringer-Ingelheim, Dermavant, Dermira, Eli Lilly and Company, Galderma, GlaxoSmithKline, Glenmark, Incyte, Kiniksa, Leo, Luna, Novartis, Pfizer, RAPT, Regeneron, Sanofi, receiving honoraria; served as a speaker for Regeneron-Sanofi; and received research grants from Galderma. Maher Issa, Katrin Holzwarth, Dennis Brinker, and Tracy Cardillo are employees and shareholders of Eli Lilly and Company. Fabio P. Nunes is a former employee of Eli Lilly and Company and is a current employee and shareholder of Janssen. Eric L. Simpson received grants and fees for participation as a consultant and principal investigator from Eli Lilly and Company, LEO Pharma, Pfizer, and Regeneron; grants for participation as a principal investigator from Galderma and Merck & Co.; and fees for consultant services from AbbVie, Boehringer Ingelheim, Dermavant Incyte, Forte Bio, Pierre Fabre Dermo, and Sanofi Genzyme.