IMPORTANCE Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease with an unmet need for treatments that provide rapid and high levels of skin clearance and itch improvement.OBJECTIVE To assess the safety and efficacy of upadacitinib vs dupilumab in adults with moderate-to-severe AD.DESIGN, SETTING, AND PARTICIPANTS Heads Up was a 24-week, head-to-head, phase 3b, multicenter, randomized, double-blinded, double-dummy, active-controlled clinical trial comparing the safety and efficacy of upadacitinib with dupilumab among 692 adults with moderate-to-severe AD who were candidates for systemic therapy. The study was conducted from February 21, 2019, to December 9, 2020, at 129 centers located in 22 countries across Europe, North and South America, Oceania, and the Asia-Pacific region. Efficacy analyses were conducted in the intent-to-treat population.INTERVENTIONS Patients were randomized 1:1 and treated with oral upadacitinib, 30 mg once daily, or subcutaneous dupilumab, 300 mg every other week. MAIN OUTCOMES AND MEASURESThe primary end point was achievement of 75% improvement in the Eczema Area and Severity Index (EASI75) at week 16. Secondary end points were percentage change from baseline in the Worst Pruritus Numerical Rating Scale (NRS) (weekly average), proportion of patients achieving EASI100 and EASI90 at week 16, percentage change from baseline in Worst Pruritus NRS at week 4, proportion of patients achieving EASI75 at week 2, percentage change from baseline in Worst Pruritus NRS (weekly average) at week 1, and Worst Pruritus NRS (weekly average) improvement of 4 points or more at week 16. End points at week 24 included EASI75, EASI90, EASI100, and improvement of 4 points or more in Worst Pruritus NRS from baseline (weekly average). Safety was assessed as treatment-emergent adverse events in all patients receiving 1 or more dose of either drug. RESULTSOf 924 patients screened, 348 (183 men [52.6%]; mean [SD] age, 36.6 [14.6] years) were randomized to receive upadacitinib and 344 were randomized to receive dupilumab (194 men [56.4%]; mean [SD] age, 36.9 [14.1] years); demographic and disease characteristics were balanced among treatment groups. At week 16, 247 patients receiving upadacitinib (71.0%) and 210 patients receiving dupilumab (61.1%) achieved EASI75 (P = .006). All ranked secondary end points also demonstrated the superiority of upadacitinib vs dupilumab, including improvement in Worst Pruritus NRS as early as week 1 (mean [SE], 31.4% [1.7%] vs 8.8% [1.8%]; P < .001), achievement of EASI75 as early as week 2 (152 [43.7%] vs 60 [17.4%]; P < .001), and achievement of EASI100 at week 16 (97 [27.9%] vs 26 [7.6%]; P < .001). Rates of serious infection, eczema herpeticum, herpes zoster, and laboratory-related adverse events were higher for patients who received upadacitinib, whereas rates of conjunctivitis and injection-site reactions were higher for patients who received dupilumab.CONCLUSIONS AND RELEVANCE During 16 weeks of treatment, upadacitinib demonstrated superior efficacy vs dup...
IMPORTANCE Clinical trials of dupilumab for atopic dermatitis (AD) have reported an increased incidence of conjunctivitis in patients who received dupilumab compared with those who received placebo.OBJECTIVE To describe the characteristics of patients who develop conjunctivitis secondary to dupilumab treatment for AD. DESIGN, SETTING, AND PARTICIPANTS Case series of 12 patients who reported development of conjunctivitis from a cohort of 142 patients treated with dupilumab for AD at a secondary care center from March 14, 2017, to March 29, 2018.EXPOSURES Patients received a 600-mg injection of dupilumab as a loading dose and a 300-mg injection every 2 weeks thereafter.MAIN OUTCOMES AND MEASURES Primary outcome measures were severity of AD as measured by the Investigator Global Assessment (IGA) score, a 5-point scale from 0 (clear) to 4 (severe), at the time of dupilumab initiation and at conjunctivitis onset. RESULTSOf the 12 patients included in this series, 7 (58%) were male. The mean (SD) age of patients was 30 (8.1) years at the time conjunctivitis developed. All patients showed improvement of their AD at the time of conjunctivitis diagnosis, with a mean (SD) 1.9 (0.8)-point decrease in IGA score and 47.8% (11.2%) decrease in body surface area affected. Nine of the 12 patients (75%) had severe baseline AD with an IGA score of 4. All patients who discontinued treatment had severe AD at the time of initial dupilumab administration and had at least 1 atopic condition in addition to AD.CONCLUSIONS AND RELEVANCE Conjunctivitis that develops after administration of dupilumab to treat AD may be severe enough to necessitate stopping therapy. Severe conjunctivitis was more likely to develop in patients with more severe baseline AD who had a good response to dupilumab and an increased atopic phenotype. Studies are needed to confirm risk factors associated with development of conjunctivitis and to determine effective treatment.
Itch is a common clinical symptom and major driver of disease-related morbidity across a wide range of medical conditions. A substantial unmet need is for objective, accurate measurements of itch. In this article, we present a noninvasive technology to objectively quantify scratching behavior via a soft, flexible, and wireless sensor that captures the acousto-mechanic signatures of scratching from the dorsum of the hand. A machine learning algorithm validated on data collected from healthy subjects (n = 10) indicates excellent performance relative to smartwatch-based approaches. Clinical validation in a cohort of predominately pediatric patients (n = 11) with moderate to severe atopic dermatitis included 46 sleep-nights totaling 378.4 hours. The data indicate an accuracy of 99.0% (84.3% sensitivity, 99.3% specificity) against visual observation. This work suggests broad capabilities relevant to applications ranging from assessing the efficacy of drugs for conditions that cause itch to monitoring disease severity and treatment response.
Biologic agents, monoclonal antibodies that target highly-specific molecular pathways of inflammation, are becoming integrated into care pathways for multiple disorders that are relevant in otolaryngology and allergy. These conditions share common inflammatory mechanisms of so-called Type 2 inflammation with dysregulation of immunoglobulin E production and eosinophil and mast cell degranulation leading to tissue damage. Biologic agents are now available for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, eosinophilic granulomatosis with polyangiitis (EGPA), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). This paper summarizes the diagnosis and management of these conditions and critically reviews the clinical trial data that has led to regulatory approval of biologic agents for these conditions.
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