Safety of Baricitinib for the Treatment of Atopic Dermatitis in Adults Over a Median of 1.6 and up to 4.6 Years Treatment: Final Integrated Analysis of Eight Clinical Trials

Abstract

Background: Baricitinib is a selective Janus kinase (JAK)1/JAK2 inhibitor approved in more than 70 countries for the treatment of moderate-to-severe atopic dermatitis (AD) in adults, and in over 30 countries for adolescents and children from age 2 years with moderate-to-severe AD, who are candidates for systemic therapy. Objectives: We report the final integrated safety profile of the AD clinical programme in adult patients up to 4.6 years of treatment. Methods: The analysis includes three data sets from the integrated AD baricitinib clinical trial programme, described previously. All-bari AD included patients that received at least one dose of baricitinib (1-, 2-, or 4-mg). We report the proportion of patients with events and incidence rates (IRs)/100 patient-years (PY) at risk. Results: In total, 2637 patients received baricitinib for 5216.2 PY, with a median exposure duration of 594 days (1.6 years) and a maximum exposure of 1688 days (4.6 years). In All-bari AD, the rate of discontinuation due to adverse events (AEs) was low (IR = 3.3). The IR for serious adverse events (SAEs) in All-bari AD was 5.0. The most frequently reported SAEs were in the infections System Organ Class (IR = 1.7), and the IR for any infection was 64.0, whereas IRs for herpes simplex, herpes zoster and opportunistic infection were 6.2, 2.7 and 0.3, respectively. AEs of special interest in All-bari AD included 10 positively adjudicated major adverse cardiovascular events (MACEs) (IR = 0.19), 3 of which were categorised as myocardial infarctions (IR = 0.06) and 6 stroke (IR = 0.11); 4 pulmonary embolisms (PEs; 1 patient experienced both a deep vein thrombosis [DVT] and PE) (IR = 0.07); 21 malignancies excluding nonmelanoma skin cancer (IR = 0.39), and 6 deaths (IR = 0.1). Conclusions: In this final analysis, baricitinib continues to demonstrate a consistent and well-established safety profile, with no new safety signals. Rates of serious infections, DVT/PE, MACE and malignancies were within ranges of background rates in patients with AD. Trial Registration: NCT02576938 (JAHG), NCT03334396 (JAHL; BREEZE-AD1), NCT03334422 (JAHM; BREEZE-AD2), NCT03334435 (JAHN; BREEZE-AD3), NCT03428100 (JAIN; BREEZE-AD4), NCT03435081 (JAIW; BREEZE-AD5), NCT03559270 (JAIX; BREEZE-AD6) and NCT03733301 (JAIY; BREEZE-AD7).