Baricitinib is a selective Janus kinase inhibitor approved in over 70 countries for treating moderate-to-severe atopic dermatitis (AD) in adults.¹ In the European Union, Saudi Arabia, and Japan, it is also approved for children and adolescents aged 2 years and older with moderate-to-severe AD who are eligible for systemic therapy.¹ Previous integrated analyses showed that baricitinib maintained a similar safety profile with no new safety signals, and the incidence of adverse events of special interest during long-term follow-up remained low.¹

The presentation reported results from the final integrated safety data for baricitinib in the adult AD clinical development program (which includes eight BREEZE-AD trials, with a median exposure of 1.6 years and maximum exposure of up to 4.6 years.¹

In the placebo (PBO)-controlled set, data were derived from one phase 2 study (JAHG) and four phase 3 studies (BREEZE-AD1, -AD2, -AD4, and -AD7) for up to 16 weeks of treatment with PBO or 2- or 4-mg baricitinib.¹ In the 2-mg and 4-mg extended set, data from patients who received 2-mg and 4-mg baricitinib in the phase 2 JAHG trial as well as five phase 3 trials (BREEZE-AD1, -AD2, -AD4 extended, -AD7 and -AD3 long-term extension [LTE]) were included.¹ Patients were censored at dose change, followed to the end of the study or through data cut-off if there was no dose change.¹ Data were analyzed without censoring at rescue.¹ In the final All-BARI-AD set, data were derived from all AD studies for which baricitinib was given to patients (all available doses, including 1-mg), including during the LTE without censoring for rescue or dose change.¹

In the PBO-controlled dataset, the median treatment exposure was 113.0 days across all groups.¹ The total patient-years of exposure (PYE) were 211.8 in the PBO group (n=743), 169.1 in the 2-mg baricitinib group (n=576), and 147.1 in the 4-mg group (n=489).¹ In the extended dataset, the 2-mg group had a median exposure of 364.0 days and a total PYE of 803.6 (n=584), while the 4-mg group had 475.0 days and 882.3 PYE (n=497).¹ In the ALL-BARI-AD dataset (n=2,637), the median exposure was 594.0 days with a total PYE of 5,216.2, including 1,681 patients (63.7%) with ≥52 weeks and 1,328 patients (50.4%) with ≥84 weeks of exposure.¹

In terms of safety, the incidence of treatment-emergent adverse events (TEAEs) was similar between arms in the PBO-controlled dataset (PBO vs. BARI 2-mg vs. BARI 4-mg adjusted incidence rate [IR] per 100 patient-years: 234.7 vs. 281.4 vs. 300.1), and this was similar in the extended dataset (BARI 2-mg adjusted IR=207.2; BARI 4-mg adjusted IR=209.1) and in All-BARI-AD (adjusted IR=140.5).¹ The incidence of serious AEs remained low in the All-BARI-AD group (adjusted IR=5.0) and the incidence of discontinuation of study drug due to AE was also maintained (adjusted IR=3.3).¹

The most common TEAEs reported in All-BARI-AD were nasopharyngitis (adjusted IR=12.5), headache (adjusted IR=4.5), upper respiratory tract infection (adjusted IR=4.3), and COVID-19 (adjusted IR=4.1).¹ One of the most commonly reported TEAEs was infections (All-BARI-AD adjusted IR=64.0), but serious infections were low in the All-BARI-AD population (adjusted IR=1.7) and remained stable compared to previous data.¹

Cardiovascular TEAEs of special interest (major adverse cardiac events adjusted IR=0.19; deep vein thrombosis/pulmonary embolism adjusted IR=0.07), malignancies (excluding non-melanoma skin cancer [NMSC] adjusted IR=0.39; NMSC adjusted IR=0.39), and gastrointestinal perforations (IR=0.02) remained low and stable compared with previous analyses in the All-BARI-AD population. These rates were within the published background IRs in the general AD population.¹

In summary, the final integrated safety analysis of the BREEZE-AD trials, which included 2637 adults with moderate-to-severe atopic dermatitis and up to 4.6 years of treatment exposure, indicated that baricitinib has a safety profile consistent with earlier studies.¹ The incidence rates of major adverse cardiovascular events, deep vein thrombosis/pulmonary embolism, malignancies, and serious infections remained stable and within the expected background incidence for this population, with no new safety signals identified.¹