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

BACKGROUND: Upadacitinib is a selective reversible Janus kinase (JAK) inhibitor with established efficacy in moderate-to-severe atopic dermatitis (AD). OBJECTIVE: We evaluated 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 weeks) and longer-term safety data from patients receiving upadacitinib during the blinded extension periods of the three 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 latter 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 by both adults and adolescents. TEAEs and discontinuation due to AEs were reported more frequently in patients receiving 30 mg upadacitinib (respectively, 311.9 and 5.7 events per 100 PY) versus 15 mg (respectively, 274.6 and 4.4 events per 100 PY). Serious adverse event rates (15/30 mg, 7.1/7.7 events per 100 PY) were similar in both groups. Acne was the most frequently reported adverse event (15/30 mg, 13.3/20.2 events per 100 PY). Serious infection rates were similar across treatment groups. Adjudicated major adverse cardiovascular event and venous thromboembolic event rates were ≤0.1 events per 100 PY. Rates of malignant neoplasms were within the expected range for the general population. CONCLUSIONS: 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 to the known safety profile of upadacitinib.

Pretibial angioplasia: a novel entity encompassing the clinical features of necrobiosis lipoidica and the histopathology of venous insufficiency.

BACKGROUND: Necrobiosis lipoidica (NL) presents clinically as waxy yellow-brown plaques, commonly on the shins. Venous insufficiency also involves the legs; however, it has distinct clinical and pathologic features. OBJECTIVE: We present a series of eight patients who had lesions that clinically resembled NL but on pathology showed features resembling venous insufficiency. METHODS: Between 1997 and 2008, eight patients were identified at St. Paul's Hospital, Vancouver, to have had skin lesions clinically diagnosed as NL, or a similar morphologic entity, but showing histopathologic features resembling venous insufficiency on biopsy. The clinical records and pathology reports of these patients were reviewed. RESULTS: The patients' ages ranged from 39 to 73 years. Only one patient was female. Members of the group held diagnoses of diabetes, renal failure, or venous or arterial disease. All patients had lesions on the legs, most on the anterior aspect. The clinical diagnosis was generally NL; other clinical impressions included lichen planus, morphea, and Kaposi sarcoma. All patients had features on pathology resembling venous insufficiency and no features of NL. CONCLUSION: We propose that this unique combination of clinical features of NL and histopathologic features resembling venous insufficiency represents a novel entity for which we propose the name pretibial angioplasia.