Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials

Abstract

Background Janus kinase (JAK) inhibition is a new mode of action in atopic dermatitis (AD); clarity about drug class safety considerations in the context of AD is important. Baricitinib, an oral, reversible, selective inhibitor of JAK1/JAK2, is in late‐stage development for adult patients with moderate‐to‐severe AD. Objective To report pooled safety data for baricitinib in patients with moderate‐to‐severe AD in the clinical development program including long‐term extension (LTE) studies. Methods This analysis included patient‐level safety data from six double‐blinded, randomized, placebo‐controlled studies (one phase 2 and five phase 3), one double‐blinded, randomized, LTE study and one open‐label LTE study, reported in three data sets: placebo‐controlled, 2‐mg – 4‐mg extended and All‐bari AD. Safety outcomes include treatment‐emergent adverse events, adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates were calculated. Results Data were collected for 2531 patients who were given baricitinib for 2247 patient‐years (median duration 310 days). The frequency of serious infections, opportunistic infections and conjunctival disorders was low and similar between treatment groups in the placebo‐controlled period. The most common serious infections were eczema herpeticum [n = 11, incidence rates (IR) = 0.5], cellulitis (n = 6, IR = 0.3) and pneumonia (n = 3, IR = 0.1). There were four opportunistic infections (IR = 0.2). No malignancies, gastrointestinal perforations, positively adjudicated cardiovascular events or tuberculosis were reported in the placebo‐controlled period in baricitinib‐treated patients. Frequency of herpes simplex was higher in the 4‐mg group (6.1%) vs. the 2‐mg (3.6%) and placebo group (2.7%); IRs in the extended data set (2‐mg IR = 9.6; 4‐mg IR = 14.5) were lower vs. the placebo‐controlled data set (2‐mg IR = 12.4; 4‐mg IR = 21.3). In the All‐bari AD data set, there were two positively adjudicated major adverse cardiovascular events (2‐mg group): two venous thrombosis events (4‐mg group) and one death. Conclusion This integrated safety analysis in patients with moderate‐to‐severe AD confirms the established safety profile of baricitinib.

Itch and Sleep Improvements with Baricitinib in Patients with Atopic Dermatitis: A Post Hoc Analysis of 3 Phase 3 Studies

“…Baricitinib treatment consistently resulted in a rapid onset of action, typically 1 day after the first dose, in the improvement of the clinically burdensome symptoms of itch and sleep disturbance. Together with the primary outcome data [ 13 , 14 ] and safety profile [ 23 ], the findings from this study support the use of baricitinib, with or without topical corticosteroids, in the treatment of moderate-to-severe atopic dermatitis.…”

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

“…In this integrated analysis from eight clinical trials, we provide safety data for baricitinib 2 mg, including long-term data on over 1500 patients with a median followup of 330 days and maximum of 2.4 years. Baricitinib 2 mg demonstrated a safety profile in moderate-to-severe AD in this extended safety analysis consistent with the established safety profile for baricitinib 2 mg [19].…”

“…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. S1 and the Methods in the Electronic Supplementary Material (ESM).…”

No association between atopic dermatitis and acne vulgaris in the general population

“…1 Oral Janus kinase inhibition in atopic dermatitis (AD) has been associated with increased occurrence of folliculitis and acne. [2][3][4] However, it is currently unknown whether individuals with AD have an increased prevalence of these conditions. In 1998, a random sample of 902 15-to 41-year-old individuals from the general population of western Copenhagen was invited to a health examination.…”