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

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 6 double-blinded, randomized, placebo-controlled, studies (one phase 2 and five phase 3), 1 double-blinded, randomized, LTE study, and 1 open-label LTE study, reported in 3 datasets: 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, IR=0.5), cellulitis (n=6, IR=0.3) and pneumonia (n=3, IR=0.1). There were 4 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%) versus the 2-mg (3.6%) and placebo group (2.7%); IRs in the extended dataset (2-mg IR=9.6; 4-mg IR=14.5) were lower versus the placebo-controlled dataset (2-mg IR=12.4; 4-mg IR=21.3). In the All-bari AD dataset there were 2 positively adjudicated major adverse cardiovascular events (2-mg group): 2 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.