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Background: Systemic Janus kinase inhibitors (JAKi) and dupilumab both have emerged as promising therapeutics for atopic dermatitis (AD). Dupilumab has a favorable safety profile, but oral JAKi therapy has been established in other diseases that carry potential comorbid susceptibilities that influence safety., Objective: We sought to provide real-world evidence of the comparative safety of oral JAKi versus dupilumab in patients with AD., Methods: The study used observational data from multiple healthcare organizations in the US. Patients with AD treated with either oral JAKi (upadacitinib, abrocitinib, and baricitinib) or dupilumab were enrolled. The 2 treatment groups were propensity score matched 1:1 on the basis of demographics, comorbidities, and prior medications. Safety outcomes within 2 years after the initiation of medications were measured by hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: A total of 14,716 patients were included, with 942 patients treated with oral JAKi and 13,774 with dupilumab. The 2 treatment groups respectively included 938 patients after matching. Treatment with oral JAKi was not associated with increased risks of mortality, malignancies, major adverse cardiovascular events, venous thromboembolism, renal events, or serious gastrointestinal events. However, patients receiving oral JAKi showed significantly higher risks of skin and subcutaneous tissue infection (HR = 1.35, 95% CI = 1.07-1.69), herpes infection (herpes simplex, HR = 1.64, 95% CI = 1.03-2.61; herpes zoster, HR = 2.51, 95% CI = 1.14-5.52), acne (HR = 2.09, 95% CI = 1.54-2.84), cytopenia (anemia, HR = 1.83, 95% CI = 1.39-2.41; neutropenia, HR = 4.02, 95% CI = 1.91-8.47; thrombocytopenia, HR = 1.76, 95% CI = 1.08-2.89), and hyperlipidemia (HR = 1.45, 95% CI = 1.09-1.92); the risk of ophthalmic complications was higher in those receiving dupilumab (HR = 1.49, 95% CI = 1.03-2.17)., Conclusion: Oral JAKi did not exhibit concerning safety issues in treating patients with AD but increased the risk of infections and abnormalities in laboratory findings. Long-term follow-up data are required to validate these results., Competing Interests: Disclosure statement M.O. was supported by grants NIH/NIAID R01 AI142872, R01 AI172938, and R21 AI151591. W.P. was supported by grant NIH/NIAID K24 AI106822. Disclosure of potential conflict of interest: E. B. Hawryluk is on the advisory board of Apogee; consults for Skin Analytics; and receives royalties from UpToDate as an author and reviewer. L. C. Schneider is an investigator for Regeneron and DBV Technologies; and is on the advisory boards of Sanofi, Triveni Bio, DBV, Alladapt Immunotherapeutics, BioThea Pharmaceuticals, Ukko, Leo Pharmaceuticals, DAIT/NIAID, and the National Eczema Association. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Dupilumab is the first and only biologic agent approved for the treatment of atopic dermatitis (AD) in pediatric patients aged from 6 months to 17 years. The study aimed to evaluate the impact of dupilumab on the occurrence of comorbidities in pediatric patients with AD., Methods: In this population-based cohort study, we utilized electronic health records from multiple healthcare organizations across the United States. Pediatric patients (<18 years of age) with a diagnosis of AD initiating dupilumab were propensity-score matched 1:1 to those initiating other systemic agents (azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, or systemic corticosteroids). The primary outcomes were new-onset comorbidities emerging during the study period measured by the risk ratio (RR) and its confidence interval (CI). Subgroup analyses were stratified by age (0-5 years, 6-11 years, and 12-17 years), sex, and race., Results: A total of 3575 pediatric patients with AD treated with dupilumab were matched to 3575 patients treated with other systemic agents. The dupilumab cohort was associated with a lowered risk of new-onset atopic comorbidities (including asthma [RR, 0.72; 95% CI, 0.59-0.89] and allergic rhinitis [RR, 0.62; 95% CI, 0.52-0.74]), infections (e.g., skin and soft tissue infection [RR, 0.70; 95% CI, 0.63-0.76] and respiratory tract infection [RR = 0.56; 95% CI, 0.51-0.61]), psychiatric disorders (e.g., mood disorder [RR, 0.52; 95% CI, 0.39-0.70] and anxiety [RR, 0.57; 95% CI, 0.46-0.70], sleep disturbance [RR, 0.60; 95% CI, 0.47-0.77]), neurologic and developmental disorders (e.g., attention deficit hyperactivity disorder [RR, 0.54; 95% CI, 0.38-0.75]). Furthermore, the positive effects are found to be more pronounced in younger children (aged 0-5 years) with AD., Conclusions: Treatment with dupilumab compared to systemic agents resulted in reductions in AD-related comorbidities in pediatric patients., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Biologic therapies targeting tumor necrosis factor (TNF)-alpha have become a mainstay in the management of a number of autoimmune diseases. We report a series of adverse skin eruptions in six patients (four females, two males, age: 21-58 years, mean: 39) receiving 4 months to 10 years (mean 3.1 years) of anti-TNF-alpha therapies (infliximab, n = 4; adalimumab, n = 1 or etanercept, n = 1). The following drug-associated diagnoses were made in eight skin biopsies performed at Massachusetts General Hospital between 3/2007 and 10/2010: pustular folliculitis, psoriasis, interface dermatitis, neutrophilic eccrine hidradenitis, Sweet's syndrome, lupus, vasculitis and palmoplantar pustulosis. The descriptions of neutrophilic eccrine hidradenitis-like and Sweet's-like hypersensitivity eruptions induced by anti-TNF-alpha therapies are the first such cases described in the literature. Each cutaneous eruption improved or resolved with switching to a different TNF-alpha inhibitor, discontinuation of the anti-TNF-alpha agent, and/or topical or systemic steroids. There was a clear chronologic relationship with, and clinical remission upon withdrawal or steroid suppression of the anti-TNF-alpha agents. The mechanism for such diverse cutaneous eruptions among this class of medications remains poorly understood. The cutaneous adverse reaction profile of TNF-alpha inhibitors is broad and should be considered in the histopathologic differential in this clinical setting., (Copyright © 2012 John Wiley & Sons A/S.)