1. Comparative safety of oral Janus kinase inhibitors versus dupilumab in patients with atopic dermatitis: A population-based cohort study.
- Author
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Tsai SY, Phipatanakul W, Hawryluk EB, Oyoshi MK, Schneider LC, and Ma KS
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Administration, Oral, Cohort Studies, Pyrazoles therapeutic use, Pyrazoles adverse effects, Pyrimidines therapeutic use, Pyrimidines adverse effects, Pyrimidines administration & dosage, Adolescent, Sulfonamides adverse effects, Sulfonamides therapeutic use, Sulfonamides administration & dosage, Young Adult, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Heterocyclic Compounds, 3-Ring, Purines, Dermatitis, Atopic drug therapy, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized administration & dosage, Janus Kinase Inhibitors therapeutic use, Janus Kinase Inhibitors adverse effects, Azetidines adverse effects, Azetidines therapeutic use, Azetidines administration & dosage
- Abstract
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.)
- Published
- 2024
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