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 nonmelanoma 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.

A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19

“…Data sets reported included the placebo-controlled data set (placebo [ n = 743], baricitinib 2 mg [ n = 576] and baricitinib 4 mg [ n = 489]), the ‘extended data set’ and ‘All baricitinib’ data set [ 99 ]. An additional integrated safety analysis of baricitinib 2 mg utilising data from 1598 patients with 1434.2 PYE to baricitinib 2 mg (maximum 869 days) was also included in this review [ 116 ].…”

“…No further MACE were identified during the extended follow-up of patients receiving baricitinib 2 mg for up to 2.4 years. One patient with a history of peripheral arterial occlusive disease had an arterial bypass occlusion (IR, 0.07/100 PYE) [ 116 ].…”

Clinical Tailoring of Baricitinib 2 mg in Atopic Dermatitis: Baseline Body Surface Area and Rapid Onset of Action Identifies Response at Week 16

“…Dependent upon country-specific approvals, the recommended starting dose of baricitinib for adults with moderate-to-severe AD is 2 mg or 4 mg [14 -16]. In BREEZE-AD5, an ongoing, randomized, placebo-controlled, phase 3 trial of moderate-to-severe AD patients who had an inadequate response or intolerance to TCS, once-daily oral baricitinib 2-mg monotherapy improved several clinical signs and symptoms of AD at week 16 compared with placebo, with a safety profile consistent with previous studies of baricitinib 2 mg in AD [17,18]. The objective of this post-hoc analysis was to identify patients who are most likely to benefit from baricitinib 2 mg, using a proposed clinical tailoring approach based on baseline body surface area (BSA) affected at drug initiation and early clinical improvement, in the phase 3 monotherapy trial BREEZE-AD5.…”

Current and Emerging Strategies to Inhibit Type 2 Inflammation in Atopic Dermatitis

“…Some serious AEs have been reported with pan-JAK inhibitors, including cytopenias (which may arise due to disrupted JAK-mediated signaling of hematopoietic growth factors), gastrointestinal tract perforation (which may arise due to altered JAK signaling for IL-6, IL-22, IL-10, and IL-9, all of which are involved in intestinal barrier function), and malignancy (which may result from T-cell and NK cell dysregulation) [ 238 ]. Although these events are uncommon (generally < 5% incidence), they tend to occur at frequencies larger than those observed with biologics [ 159 , 180 , 238 , 239 , 246 , 247 ].…”