Dupilumab for Atopic Dermatitis: The Silver Bullet We Have Been Searching for? (original) (raw)
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Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis
New England Journal of Medicine, 2014
BACKGROUND Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels. The blockade by dupilumab of these key drivers of type 2 helper T-cell (Th2)-mediated inflammation could help in the treatment of related diseases, including atopic dermatitis. METHODS We performed randomized, double-blind, placebo-controlled trials involving adults who had moderate-to-severe atopic dermatitis despite treatment with topical glucocorticoids and calcineurin inhibitors. Dupilumab was evaluated as monotherapy in two 4-week trials and in one 12-week trial and in combination with topical glucocorticoids in another 4-week study. End points included the Eczema Area and Severity Index (EASI) score, the investigator's global assessment score, pruritus, safety assessments, serum biomarker levels, and disease transcriptome. RESULTS In the 4-week monotherapy studies, dupilumab resulted in rapid and dose-dependent improvements in clinical indexes, biomarker levels, and the transcriptome. The results of the 12-week study of dupilumab monotherapy reproduced and extended the 4-week findings: 85% of patients in the dupilumab group, as compared with 35% of those in the placebo group, had a 50% reduction in the EASI score (EASI-50, with higher scores in the EASI indicating greater severity of eczema) (P<0.001); 40% of patients in the dupilumab group, as compared with 7% in the placebo group, had a score of 0 to 1 (indicating clearing or near-clearing of skin lesions) on the investigator's global assessment (P<0.001); and pruritus scores decreased (indicating a reduction in itch) by 55.7% in the dupilumab group versus 15.1% in the placebo group (P<0.001). In the combination study, 100% of the patients in the dupilumab group, as compared with 50% of those who received topical glucocorticoids with placebo injection, met the criterion for EASI-50 (P = 0.002), despite the fact that patients who received dupilumab plus glucocorticoids used less than half the amount of topical glucocorticoids used by those who received placebo plus the topical medication (P = 0.16). Adverse events, such as skin infection, occurred more frequently with placebo; nasopharyngitis and headache were the most frequent adverse events with dupilumab. CONCLUSIONS Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity. Side-effect profiles were not doselimiting.
Severe atopic dermatitis: Dupilumab is not just safer, but more efficient
Allergologia et Immunopathologia, 2020
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by relapsing eczema and pruritus. Until the development of Dupilumab, a new monoclonal antibody targeting IL-4 and IL-13 receptors, the current treatment of severe cases was based on immunosuppressant agents. Our main goal was to build a case series of five patients with severe atopic dermatitis, who were using immunosuppressive drugs with significant adverse effects and only partially controlled AD, and compare their symptoms, SCORAD index, treatment regimens, total and specific IgE, and blood cell count before and after the introduction of Dupilumab. SCORAD index and topical corticosteroids used on a daily basis had a significant decrease after 16 weeks of Dupilumab. Adverse effects were mild: conjunctivitis, local reaction and regional dermatosis. All patients with severe atopic dermatitis achieved better control of AD with Dupilumab than with immunosuppressive drugs. Adverse effects, secondary infections, total and specific IgE levels were greatly reduced.
Dupilumab for treatment of atopic dermatitis
Expert Review of Clinical Pharmacology, 2018
Atopic dermatitis (AD) is a common, chronic, inflammatory skin disorder with high physical and emotional burden. AD usually starts in early childhood and has a heterogeneous course. Emerging evidence suggests that IL-4 and IL-13 are key cytokines in the immunopathogenesis of AD. Dupilumab is a monoclonal antibody directed against IL-4 receptor ␣ subunit, that blocks both IL-4 and IL-13 signaling. Data from Phase I-III studies revealed that dupilumab, administered as monotherapy or with topical corticosteroids, is effective and well tolerated in the treatment of adult patients with moderate-to-severe AD. A large proportion of patients receiving dupilumab had significant improvements in multiple efficacy indexes, including Eczema Area and Severity Index, Investigator's Global Assessment and SCORing Atopic Dermatitis scores. These results introduce a new era of targeted therapies in the management of AD.
Journal of the American Association of Nurse Practitioners, 2018
Objective: Atopic dermatitis is a chronic, relapsing inflammatory skin disease characterized by intense pruritus, excoriations and limited therapies. Dupilumab, a monoclonal antibody against interleukin-4 receptor alpha, is a promising new treatment option for atopic dermatitis. We sought to systematically summarize the efficacy, safety, and influence on quality of life of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults. Results: A total of 7 RCTs containing 2705 subjects were identified. Significantly more patients receiving dupilumab (611/1789) achieved Investigator's Global Assessment response compared with the control (89/916; RR, 3.95; P < 0.001). Dupilumab was significantly more effective in reducing Eczema Area and Severity Index, peak pruritus numerical rating scale score, and body surface area. Treatment duration rather than administration frequency slightly influenced the efficacy. Dupilumab treatment also contributed to marked improvement in patients' quality of life and psychological symptoms. Incidence of adverse events was similar in dupilumab group and control group. Conclusions: Dupilumab is effective and safe for the treatment of moderate-tosevere atopic dermatitis in adults. This meta-analysis supports the role of dupilumab as a primary targeted biologic therapy in adult patients with moderate-to-severe atopic dermatitis. Materials and Methods: We searched Pubmed, Embase, and the Cochrane Library for eligible trials. Only double-blinded randomized controlled trials (RCTs) investigating the efficacy and safety of dupilumab in treating moderate-to-severe atopic dermatitis were included in this analysis. We made a comparison of dupilumab with control based on the pooled relative risk (RR), weighted mean difference, and their corresponding 95% confidence intervals of different measurements.
einstein (São Paulo), 2019
Case report of a patient with severe atopic dermatitis who showed a good response to dupilumab. She had already used two immunosuppressive agents, cyclosporine A and mycophenolate mofetil, for the treatment of atopic dermatitis with no proper control of the disease. She had also been taking all measures to control severe cases of the disease: bath and environmental controls, topical potent corticosteroids and emollients. She presented constant pruritus and skin lesions, frequent skin infections e poor quality of life. She also developed depression due to her disease. Recently, dupilumab, a new biological agent, was approved for the treatment of moderate/severe atopic dermatitis in many countries, including Brazil. Dupilumab is a monoclonal antibody with a common alpha chain of interleukin (IL) 4 and IL-13 receptors, two cytokines involved in the Th2 profile immune response that promote atopic inflammation. In a pioneer way in Brazil, the patient initiated the treatment with an attack dose of 600mg subcutaneous of dupilumab and 300mg subcutaneous every other week. Up to now, she has taken four applications, presenting a great improvement of the disease and her quality of life. There were no adverse effects, nor in the injection site nor of other kind. Patient and her family are very satisfied, and the medical team evaluates that the treatment is being well succeed. The case report described here subsidizes the use of dupilumab in the treatment of severe atopic dermatitis refractory to use of immunosuppressive agents.
2019
Introduction Atopic dermatitis is a chronic inflammatory skin disease characterized by intense pruritus. Dupilumab is a human monoclonal antibody specifically targeted to block the interleukin-4 alpha receptor (IL-4), inhibiting signalling for interleukin-4 and interleukin-13 in the treatment of atopic dermatitis. Materials and method Longitudinal study performed under routine clinical practice in the dermatology department of the Royo Villanova Hospital. Eleven adult patients with moderate-severe AD are being treated in a program of extended use of medication authorized by the Spanish Agency of Medicines and Health Products (AEMS). Patients are treated with dupilumab 300 mg subcutaneous injection every 2 weeks with an initial loading dose of 600 mg. artificial tears are recommended for the preventive management of conjunctivitis, and emollient creams for the skin. Results Week 16 analysis shows a reduction in pruritus (p=0.003) and in the severity of the disease (91% reduction, p&l...
Severe atopic dermatitis and dupilumab
Revista da Associação Médica Brasileira
Is there an indication for the drug dupilumab in the treatment of severe atopic dermatitis? Is its constant use effective and safe? METHODS Eligibility criteria The eligibility criteria used to select the evidence and data were as follows: patients with severe atopic dermatitis (refractory to conventional treatment); intervention: dupilumab; comparison: placebo; outcomes: reduction of the effects of the disease and adverse events; study design: randomized clinical trials and no period and language restriction.
Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis
New England Journal of Medicine, 2016
BACKGROUND Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. METHODS In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment and a reduction of 2 points or more in that score from baseline at week 16. RESULTS We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups. CONCLUSIONS In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743; SOLO 2 ClinicalTrials .gov number, NCT02277769.
Dupilumab progressively improves systemic and cutaneous abnormalities in atopic dermatitis patients
The Journal of allergy and clinical immunology, 2018
Dupilumab is an IL-4Rα monoclonal antibody inhibiting signaling of IL-4/IL-13, key drivers of Type 2-driven inflammation, as demonstrated by its efficacy in atopic/allergic diseases. This placebo-controlled, double-blind trial (NCT01979016) evaluated efficacy, safety, and effects of dupilumab on molecular/cellular lesional and nonlesional skin phenotypes and systemic Type 2 biomarkers of moderate-to-severe atopic dermatitis (AD) patients. Skin biopsies and blood were evaluated from 54 patients randomized 1:1 to weekly subcutaneous 200 mg dupilumab or placebo for 16 weeks. Dupilumab (versus placebo) significantly improved AD clinical signs and symptoms, was well tolerated, and progressively shifted the lesional transcriptome toward a nonlesional phenotype (weeks 4-16). Mean improvements in a meta-analysis-derived AD transcriptome (genes differentially expressed between lesional and nonlesional skin) were 68.8% and 110.8% with dupilumab and -10.5% and 55.0% with placebo (weeks 4 and 1...