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After Decades Without any Developments, New Drugs May Revolutionize the Treatment of Atopic Dermatitis
FR-Después de décadas sin novedades, nuevos fármacos prometen revolucionar el tratamiento de la dermatitis atópica
D. Morgado-Carrasco, X. Fustà-Novell, J. Riera-Monroig, P. Iranzo
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Dermatology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain
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Note the multiple erosions, excoriated papules, and marked xerosis on the back.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Atopic dermatitis (AD) is an inflammatory skin disease characterized by pruritic eczematous lesions that can affect large surface areas of the body (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Etiologic and pathogenic mechanisms include epithelial dysfunction, alterations to gut microbiota, and inadequate immune activation with overexpression of interleukin 4 (IL-4), IL-13, and IL-31.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Severe AD requires systemic treatment with oral corticosteroids and immunosuppressive agents, but the long-term use of these drugs can cause considerable adverse effects. Despite the prevalence of AD, no new drugs have been developed in recent decades. The US Food and Drug Administration, however, recently approved 2 novel drugs, dupilumab and crisaborole, for use in AD, and other drugs have shown promising results in preliminary studies.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Dupilumab blocks the IL-4 receptor α subunit, thereby inhibiting IL-4 and IL-13 signaling and reducing not only the production of immunoglobulin E but also inflammatory responses mediated by type 2 helper T cells. Two randomized placebo-controlled clinical trials of dupilumab in patients with moderate to severe AD, SOLO-1 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>671) and SOLO-2 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>708), found that dupilumab 300<span class="elsevierStyleHsp" style=""></span>mg administered subcutaneously every week or every 2 weeks resulted in an investigator's global assessment (IGA) score of 0 or 1 (clear or almost clear) at 16 weeks in 38% of patients (vs. 10% for placebo) in SOLO-1 and 36% (vs. 8% for placebo) in SOLO-2 (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001).<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> It was also associated with a greater percent reduction in the Eczema Area and Severity Index (EASI) score (67% to 72% vs. 30% to 37% for placebo, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001) and better results on all the clinical evaluation, quality of life, and pruritus scales. Adverse effects were similar in both groups, although dupilumab was inexplicably associated with a higher incidence of conjunctivitis.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Topical crisaborole 2% is a nonsteroidal anti-inflammatory drug that inhibits phosphodiesterase (PDE) 4 (mainly PDE4B), reducing the release of proinflammatory cytokines, such as tumor necrosis factor, IL-12, and IL-23. Two clinical trials in patients older than 2 years with mild to moderate AD, AD:301 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>763) and AD:302 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>764), found crisaborole to be superior to placebo in terms of reducing IgA after 28 days (AD:301: 32.8% vs. 25.4%, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.038; AD:302: 31.4% vs. 18.0%, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001) and improving pruritus.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> In addition, adverse effects were minimal.</p><p id="par0020" class="elsevierStylePara elsevierViewall">One interesting drug currently being investigated in clinical trials is nemolizumab. Nemolizumab is a monoclonal anti-IL-31 receptor antibody that has been shown to be superior to placebo in a phase II trial of 264 patients with moderate to severe AD. It was more effective in improving pruritus (percentage improvement from baseline of 63% in the high-dose group vs. 21% for placebo), although it did not reduce the body surface area affected.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> Another promising drug is topical tofacitinib 2%, which inhibits janus kinases 1 and 3 and the activity of IL-2, IL-4, and other proinflammatory cytokines. The results of a phase IIa trial of 69 adults with mild to moderate AD showed that topical tofacitinib 2% was significantly superior to placebo in terms of improving EASI score (−81.7% vs. −29.9%) and pruritus. There were also few treatment-related effects.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Dupilumab and crisaborole have emerged as novel dermatological treatments, and dupilumab in particular seems poised to revolutionize the treatment of moderate to severe AD. Further studies of IL-31, IL-13, and JAK inhibitors will determine their efficacy and safety. Patients will benefit from safe, effective drugs that are better tolerated than corticosteroids and other immunosuppressive agents.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec990664" "palabras" => array:6 [ 0 => "Atopic dermatitis" 1 => "Pruritus" 2 => "Dupilumab" 3 => "Crisaborole" 4 => "Nemolizumab" 5 => "Tofacitinib" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Morgado-Carrasco D, Fustà-Novell X, Riera-Monroig J, Iranzo P. FR-Después de décadas sin novedades, nuevos fármacos prometen revolucionar el tratamiento de la dermatitis atópica. Actas Dermosifiliogr. 2018;109:443–444.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1636 "Ancho" => 1250 "Tamanyo" => 284264 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Severe atopic dermatitis. Note the multiple erosions, excoriated papules, and marked xerosis on the back.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dupilumab in the treatment of moderate-to-severe atopic dermatitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Kraft" 1 => "M. 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Wollenberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1606490" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2017" "volumen" => "376" "paginaInicial" => "826" "paginaFinal" => "835" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28249150" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Topical tofacitinib for atopic dermatitis: A phase IIa randomized trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Bissonnette" 1 => "K.A. Papp" 2 => "Y. Poulin" 3 => "M. Gooderham" 4 => "M. Raman" 5 => "L. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 3 | 12 | 15 |
| 2024 Octubre | 87 | 41 | 128 |
| 2024 Septiembre | 77 | 20 | 97 |
| 2024 Agosto | 111 | 54 | 165 |
| 2024 Julio | 95 | 36 | 131 |
| 2024 Junio | 75 | 20 | 95 |
| 2024 Mayo | 86 | 28 | 114 |
| 2024 Abril | 86 | 27 | 113 |
| 2024 Marzo | 85 | 30 | 115 |
| 2024 Febrero | 74 | 26 | 100 |
| 2024 Enero | 65 | 28 | 93 |
| 2023 Diciembre | 88 | 26 | 114 |
| 2023 Noviembre | 85 | 25 | 110 |
| 2023 Octubre | 86 | 24 | 110 |
| 2023 Septiembre | 81 | 626 | 707 |
| 2023 Agosto | 62 | 18 | 80 |
| 2023 Julio | 188 | 29 | 217 |
| 2023 Junio | 67 | 20 | 87 |
| 2023 Mayo | 88 | 21 | 109 |
| 2023 Abril | 81 | 21 | 102 |
| 2023 Marzo | 79 | 27 | 106 |
| 2023 Febrero | 97 | 28 | 125 |
| 2023 Enero | 95 | 27 | 122 |
| 2022 Diciembre | 93 | 46 | 139 |
| 2022 Noviembre | 59 | 39 | 98 |
| 2022 Octubre | 80 | 25 | 105 |
| 2022 Septiembre | 36 | 39 | 75 |
| 2022 Agosto | 35 | 35 | 70 |
| 2022 Julio | 28 | 35 | 63 |
| 2022 Junio | 36 | 35 | 71 |
| 2022 Mayo | 75 | 47 | 122 |
| 2022 Abril | 62 | 45 | 107 |
| 2022 Marzo | 77 | 63 | 140 |
| 2022 Febrero | 71 | 26 | 97 |
| 2022 Enero | 88 | 46 | 134 |
| 2021 Diciembre | 67 | 41 | 108 |
| 2021 Noviembre | 76 | 57 | 133 |
| 2021 Octubre | 75 | 54 | 129 |
| 2021 Septiembre | 62 | 42 | 104 |
| 2021 Agosto | 63 | 37 | 100 |
| 2021 Julio | 35 | 18 | 53 |
| 2021 Junio | 43 | 30 | 73 |
| 2021 Mayo | 56 | 54 | 110 |
| 2021 Abril | 61 | 49 | 110 |
| 2021 Marzo | 57 | 28 | 85 |
| 2021 Febrero | 61 | 40 | 101 |
| 2021 Enero | 37 | 15 | 52 |
| 2020 Diciembre | 28 | 24 | 52 |
| 2020 Noviembre | 41 | 21 | 62 |
| 2020 Octubre | 28 | 7 | 35 |
| 2020 Septiembre | 58 | 13 | 71 |
| 2020 Agosto | 24 | 23 | 47 |
| 2020 Julio | 32 | 12 | 44 |
| 2020 Junio | 36 | 24 | 60 |
| 2020 Mayo | 32 | 17 | 49 |
| 2020 Abril | 27 | 18 | 45 |
| 2020 Marzo | 34 | 19 | 53 |
| 2020 Febrero | 5 | 0 | 5 |
| 2020 Enero | 2 | 0 | 2 |
| 2019 Diciembre | 4 | 0 | 4 |
| 2019 Noviembre | 2 | 0 | 2 |
| 2019 Septiembre | 5 | 2 | 7 |
| 2019 Agosto | 4 | 0 | 4 |
| 2019 Julio | 4 | 0 | 4 |
| 2019 Junio | 4 | 0 | 4 |
| 2019 Mayo | 5 | 0 | 5 |
| 2019 Abril | 2 | 0 | 2 |
| 2019 Marzo | 2 | 0 | 2 |
| 2018 Diciembre | 4 | 0 | 4 |
| 2018 Noviembre | 3 | 0 | 3 |
| 2018 Octubre | 3 | 0 | 3 |
| 2018 Septiembre | 2 | 0 | 2 |
| 2018 Julio | 1 | 0 | 1 |
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