Atopic dermatitis (AD) is a chronic, systemic disease that has a multifactorial etiology, where immune system disorders and epidermal barrier dysfunction are added to the influence of genetic and environmental factors. Dupilumab has been approved by United States and the European Union regulatory agencies in 2017 for the treatment of moderate‐to‐severe AD in adult patients who are candidates for systemic treatment. In this short report, we present a retrospective, multicentric study, in which five hospitals in Andalusia, Spain, have taken part. Our objective is to evaluate the safety and effectiveness of dupilumab in patients with moderate‐to‐severe AD treated with dupilumab with at least 52 weeks of follow‐up.
Background: Some Network Meta-analysis (NMA) has been published regarding atopic dermatitis (AD). These studies have considered drugs under investigation both in monotheraphy or in combination with topical corticosteroids, as well as systemic immunosuppressant therapies. The objective of this study is to evaluate the efficacy and safety of biological agents and small molecules in AD. Methods: A systematic review and NMA of biologics agents and small molecules in AD was performed. A literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for clinical trials and systematic reviews between January 2000 and 19 December 2020. Only randomized clinical trials (RCTs) were included. It was limited to English language and adult human subjects. Two networks were evaluated: monotherapy and combination with TCS. The two primary outcomes were Eczema Area and Severity Index (EASI) 75 and EASI 90 change from baseline to week 12–16, depending on source study cut-off. The Cochrane’s Risk of Bias tool 2011 update was used to analyze the risk of bias, focused on the primary objectives. Results: 30 RCTs (included in 26 publications) were included in the systematic review. Finally, 23 RCTs were included in the quantitative analysis (14 RCTs including 3582 patients in monotherapy; and 9 RCTs including 3686 patients with TCS). In monotherapy, a higher percentage of patients achieving EASI-75 was obtained with Upadacitinib 30 mg [OR: 18.90 (13.94; 25.62)] followed by Abrocitinib 200 mg [OR = 11.26 (7.02; 18.05)] and Upadacitinib 15 mg [OR: 10.89 (8.13; 14.59)]. These results were also observed in studies where the use of topical corticosteroid (TCS) was allowed (OR Upadacitinib 30 mg = 9.43; OR Abrocitinib 200 mg = 6.12; OR Upadacitinib 15 mg = 5.20). Regarding IGA, the percentage of patients achieving IGA0/1 was higher with both doses of Upadacitinib 30 mg [OR: 19.13 (13.14; 27.85)] and 15 mg [OR = 10.95 (7.52; 15.94). In studies where the use of TCS were allowed, however, the dose of Abrocitinib 200 mg [OR = 6.10 (3.94; 9.44)] showed higher efficacy than Upadacitinib 15 mg [OR = 5.47 (3.57; 8.41)]. Regarding safety, the drugs with the highest probability of presenting adverse effects were the Janus kinases (JAK) inhibitors, Upadacitinib and Abrocitinib in monotherapy and Baricitinib in combination with TCS. Discussion: Some risks of bias have been found, which must be taken into account when interpreting the results. The funnel plot shows a possible publication bias that may underestimate the efficacy of drugs. Upadacitinib and Abrocitinib are the drugs with the highest efficacy, both in monotherapy and in association with TCS. However, they were also those associated with the highest risk of adverse effects, showing monoclonal antibodies better safety profile. Limitations: We have included molecules still in the development phase as well studies completed and presented at conferences and with data available in Trialsgov® but not published yet. Several molecules’ development had included a small number of patients from 12 to 17 years of age, without being able to differentiate the results from the adult population. Other: Founding: None. PROSPERO database registration number CRD42021225793.
Atopic dermatitis (AD) is a chronic, inflammatory, and pruritic skin disease. Recently, upadacitinib, a selective JAK-1 inhibitor, has been incorporated for AD treatment. Real clinical practice studies are scarce, with only a few case series. [1][2][3][4] In this multicenter retrospective study, upadacitinib was evaluated in a series of patients with moderate to severe AD included in premarketing programs in Spain. Data collected included age, disease duration, comorbidities, and previous treatments. Disease severity was measured by SCORing Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), investigator's global assessment (IGA) body surface area, Dermatology Life Quality Index, Peak Pruritus Numerical Rating Scale (PP-NRS), and blood test parameters (eosinophil count, total immunoglobulin E, hemoglobin, low-density lipoprotein and high-density lipoprotein cholesterol, triglycerides, creatine phosphokinase, gamma-glutamyl transferase, glutamic oxaloacetic transaminase and glutamic pyruvic transaminase levels) at the baseline visit and at weeks 4, 16, 24, and 52.Twenty-two patients were included in the study. Demographic and baseline characteristics are shown in Table 1. Approved 15-or 30-mg daily doses were prescribed at the discretion of the prescribing physician, with no changes during the follow-up period. All values improved rapidly from week 4 of follow-up (Figs. 1A-D). Mean EASI decreased to 4.4 ± 5.2 (84.2% improvement), SCORAD to 18.5 ± 22.8 (69.2% improvement), and PP-NRS to 2.4 ± 2.9 (70.0% improvement) at week 52 ( P < 0.0001 for
Introduction: Atopic dermatitis (AD) is a genetically based chronic inflammatory dermatosis associated with multiple triggers and complex pathophysiological mechanisms. Nowadays, an authentic therapeutic revolution is taking place with the incorporation of biological drugs for the treatment of moderate and severe atopic dermatitis. A new systematic revision (RS) is necessary to support decision-making for specialists treating AD. Methods: A literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was performed between 1 January 2000 and 30 April 2022. Phase III randomized clinical trials (RCTs) of EMA-approved molecules were included. The main variables analyzed were a 75% improvement in the Eczema Area and Severity Index (EASI 75) and the number of patients who reached 0 in the Investigator Global Assessment (IGA) (fully cleared patients) or IGA 1 (almost cleared patients) at the end of the study period (week 48–60). The risk of bias was analyzed with the Cochrane Risk of Bias Assessment (ROB-2) tool, focused on the primary objectives. Before carrying out the study, the protocol was registered in PROSPERO with the number CRD42022331109. Results: A total of 3299 studies were systematically identified via databases and registers (442 from PubMed/MEDLINE, 2857 from Embase and 719 from CENTRAL). Finally, five publications containing seven RCTs were included in the final sample of detailed data extraction and data analyses. Regarding efficacy, the best results are obtained with Upadacitinib 30 mg (84.7% (77.3–92.1)) at 52 weeks, slightly improving its results when TCS is added (84.9% (80.3–89.5)). These results are replicated in the measurement of vIGA 0/1 for Updacitinib 30 mg + TCS, where 65.5% (55.7–75.2) of patients maintain it at 52 weeks. Of the four drugs, no long-term safety results have been reported for baricitinib. In relation to the safety findings, there were no significant differences in the dropout rates for this reason in the remaining three drugs. Discussion: Today, different therapeutic options for AD patients can be prescribed. Individualizing the treatment allows for better therapeutic consistency, in addition to being cost-efficient to avoid primary therapeutic failures. The results of the present SR may provide us with a useful basis for the preparation of management guidelines for the use of new generation therapies in moderate to severe atopic dermatitis.
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