Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis

Abstract

IMPORTANCE Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies. OBJECTIVE To assess the efficacy and safety of 4 mg and 2 mg of baricitinib in combination with background topical corticosteroid (TCS) therapy in adults with moderate to severe AD who previously had an inadequate response to TCS therapy. DESIGN, SETTING, AND PARTICIPANTS This double-blind, placebo-controlled, phase 3 randomized clinical trial, BREEZE-AD7 (Study of Baricitinib [LY3009104] in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis) was conducted from November 16, 2018, to August 22, 2019, at 68 centers across 10 countries in Asia, Australia, Europe, and South America. Patients 18 years or older with moderate to severe AD and an inadequate response to TCSs were included. After completing the study, patients were followed up for up to 4 weeks or enrolled in a long-term extension study. INTERVENTIONS Patients were randomly assigned (1:1:1) to receive 2 mg of baricitinib once daily (n = 109), 4 mg of baricitinib once daily (n = 111), or placebo (n = 109) for 16 weeks. The use of low-to-moderate potency TCSs was allowed. MAIN OUTCOMES AND MEASURES The primary end point was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear), with a 2-point or greater improvement from baseline at week 16. RESULTS Among 329 patients (mean [SD] age, 33.8 [12.4] years; 216 [66%] male), at week 16, a vIGA-AD score of 0 (clear) or 1 (almost clear) was achieved by 34 patients (31%) receiving 4 mg of baricitinib and 26 (24%) receiving 2 mg of baricitinib compared with 16 (15%) receiving placebo (odds ratio vs placebo, 2.8 [95% CI, 1.4-5.6]; P = .004 for the 4-mg group; 1.9 [95% CI, 0.9-3.9]; P = .08 for the 2-mg group). Treatment-emergent adverse events were reported in 64 of 111 patients (58%) in the 4-mg group, 61 of 109 patients (56%) in the 2-mg group, and 41 of 108 patients (38%) in the placebo group. Serious adverse events were reported in 4 patients (4%) in the 4-mg group, 2 (2%) in the 2-mg group, and 4 (4%) in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and folliculitis. CONCLUSIONS AND RELEVANCE A dose of 4 mg of baricitinib in combination with background TCS therapy significantly improved the signs and symptoms of moderate to severe AD, with a safety profile consistent with previous studies of baricitinib in AD.

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

“…In multiple randomized, placebo-controlled, phase II and phase III clinical trials in adults with moderate-to-severe AD, baricitinib as monotherapy or in combination with topical corticosteroids improved clinical signs and symptoms of AD [15][16][17][18]. An integrated safety analysis of baricitinib clinical trials, including two ongoing long-term extension (LTE) trials with exposure up to 2 years, informs the safety profile of baricitinib in AD [19]; the objective of this integrated analysis was to further evaluate the safety of oncedaily baricitinib 2 mg from these trials with LTE exposure up to 2.4 years.…”

Pooled Results of Two Randomized Phase III Trials Evaluating VP-102, a Drug-Device Combination Product Containing Cantharidin 0.7% (w/v) for the Treatment of Molluscum Contagiosum

“…Once applied, the acetone evaporates quickly, leaving a thin dry film that is then washed off within roughly 24 h. Gentian violet is a surgical dye inside the film that allows for distinction between treated and untreated lesions during application. Denatonium benzoate, one of the most bitter agents on the planet, is included to deter oral ingestion [ 21 ].…”

Biologika-Therapie der atopischen Dermatitis

“…Baricitinib ist bereits als Monotherapie seit Februar 2017 global zur Therapie der rheumatoiden Arthritis zugelassen. Die placebokontrollierten randomisierten Phase-3-Studien bei erwachsenen AD-Patienten mit moderater bis schwerer atopischer Dermatitis über 16 Wochen wurde bereits erfolgreich abgeschlossen und zeigten eine Verbesserung des EASI um 75 % bei 48 % der Patienten mit Baricitinib 4 mg [38].…”

“…Im Nebenwirkungsprofil zeigt sich Baricitinib relativ sicher: Häufige Nebenwirkungen sind Herpes-Infektionen, Übelkeit, Infektionen der oberen Atemwege sowie CKund Lipid-Erhöhungen. Die zuvor in Studien der rheumatoiden Arthritis vermehrt berichteten thromboembolischen Ereignisse (tiefe Beinvenenthrombose, Pulmonalembolie) konnten in den Zulassungsstudien bei der atopischen Dermatitis nicht in ähnlichem Ausmaß gezeigt werden [38]. Es gab jedoch einen Fall einer Pulmonalembolie nach 10-wöchiger Einnahme von Baricitinib 4 mg bei einer 51-jährigen Patientin, die Kontrazeptiva einnahm und starke Raucherin war [38].…”

“…Die zuvor in Studien der rheumatoiden Arthritis vermehrt berichteten thromboembolischen Ereignisse (tiefe Beinvenenthrombose, Pulmonalembolie) konnten in den Zulassungsstudien bei der atopischen Dermatitis nicht in ähnlichem Ausmaß gezeigt werden [38]. Es gab jedoch einen Fall einer Pulmonalembolie nach 10-wöchiger Einnahme von Baricitinib 4 mg bei einer 51-jährigen Patientin, die Kontrazeptiva einnahm und starke Raucherin war [38]. Baricitinib ist der erste JAK-Inhibitor, der von der europäischen Arzneimittelkommission EMA für die Therapie der moderaten bis schweren AD in einer Dosierung von 4 mg täglich im Oktober 2020 zugelassen wurde.…”