Safety of upadacitinib in moderate-to-severe atopic dermatitis: An integrated analysis of phase 3 studies

Document Type

Journal Article

Publication Date



The Journal of allergy and clinical immunology




Atopic dermatitis; Janus kinase inhibitor; safety; upadacitinib


BACKGROUND: Upadacitinib is a selective, reversible, Janus kinase (JAK) inhibitor with established efficacy in moderate-to-severe atopic dermatitis (AD). OBJECTIVE: Evaluate the safety of upadacitinib in patients with moderate-to-severe AD. METHODS: Integrated safety data from the 16-week placebo-controlled periods of 1 phase 2b and 3 ongoing phase 3 studies (16-Week) and longer-term safety data from patients receiving upadacitinib during the blinded extension periods of the 3 phase 3 studies were analyzed (All Upadacitinib Exposure). Treatment-emergent adverse events (TEAEs) were presented as exposure-adjusted rates per 100 patient years (PY). RESULTS: Safety results were similar between the 16-week and All Upadacitinib Exposure groups. The All Upadacitinib Exposure group included 2485 patients (333 adolescents), receiving upadacitinib 15 mg (n=1239) or 30 mg (n=1246) for a mean duration of approximately 1 year. Upadacitinib was well tolerated in both adults and adolescents. TEAEs and discontinuation due to AEs were reported more frequently in patients receiving 30-mg upadacitinib (311.9 and 5.7 events per 100 PY) versus 15 mg (274.6 and 4.4 events per 100 PY). Serious AE rates (15/30 mg, 7.1/7.7 per 100 PY) were similar in both groups. Acne was the most frequently reported AE (15/30 mg, 13.3/20.2 per 100 PY). Serious infection rates were similar across treatment groups. Adjudicated major adverse cardiovascular event and venous thromboembolic event rates were ≤0.1 per 100 PY. Rates of malignant neoplasms were within the expected range for the general population. CONCLUSION: Upadacitinib was well tolerated, and no new important safety risks were observed among adults and adolescents with moderate-to-severe AD treated for approximately 1 year compared with the known safety profile of upadacitinib. CLINICAL IMPLICATIONS: Integrated safety data support the use of both upadacitinib 15-mg and 30-mg doses in patients with moderate-to-severe atopic dermatitis who are candidates for longer-term systemic therapy.