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Generalidades y pruritógenos. Parte 1" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0030" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 1085 "Ancho" => 613 "Tamanyo" => 48905 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "F.J. Navarro-Triviño" "autores" => array:1 [ 0 => array:2 [ "nombre" => "F.J." 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Keumala Budianti, S. Mahri, D. Almira" "autores" => array:3 [ 0 => array:2 [ "nombre" => "W." "apellidos" => "Keumala Budianti" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Mahri" ] 2 => array:2 [ "nombre" => "D." "apellidos" => "Almira" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0010"></elsevierMultimedia></p></span>" ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023003459?idApp=UINPBA000044" "url" => "/00017310/0000011400000006/v1_202306061231/S0001731023003459/v1_202306061231/es/main.assets" ] ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "The Role of Adjuvant Therapy in the Management of Chronic Urticaria" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "523" "paginaFinal" => "530" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "W. Keumala Budianti, S. Mahri, D. Almira" "autores" => array:3 [ 0 => array:2 [ "nombre" => "W." "apellidos" => "Keumala Budianti" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Mahri" ] 2 => array:4 [ "nombre" => "D." "apellidos" => "Almira" "email" => array:1 [ 0 => "donnalmira19@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo, Jakarta, Indonesia" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "El papel de la terapia adyuvante en el tratamiento de la urticaria crónica espontánea" ] ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0010" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 1042 "Ancho" => 1333 "Tamanyo" => 111093 ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Nowadays, second generation of H1 antihistamine as the first line therapy is recommended by the recent management of urticaria guidelines with an increase in dosage 4 times higher when there is no improvement in the clinical symptoms.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">1</span></a> Despite the dosage enhancement, chronic spontaneous urticaria (CSU) therapy still requires a complement agent to maximize its effect, necessitating the use of adjuvant therapy to increase the effectiveness of the first line therapy. Adjuvant therapy for CSU is needed, especially for refractory patients receiving increased antihistamine doses. This literature review will discuss further a variety of adjuvant therapy and their role in the management of CSU. As shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, the level of evidence (LoE) of the management is based on Oxford Centre for Evidence-Based Medicine 2011 for the therapeutic study and the simplified table of adjuvant therapy modalities can be seen in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Chronic spontaneous urticaria</span><p id="par0010" class="elsevierStylePara elsevierViewall">The goal of treating CSU is to resolve all symptoms through non-pharmacology approaches, including identification and elimination of the urticaria causes, avoiding trigger factors, and tolerance induction; then pharmacological therapy to prevent the release of mast cell mediators or the effect of mast cell mediators. The pharmacological treatment should allow the lowest dose to alleviate the symptoms. The treatment is adjustable, corresponding to the degree of disease activity.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">2</span></a> As illustrated in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, EAACI/GA2LEN/EDF/WAO guideline in 2022 recommends the second generation of H1 antihistamine to be the first line of therapy for CSU, with the dosage enhancement up to 4 times higher if there is no improvement in the clinical symptoms.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">1</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Adjuvant therapy for chronic spontaneous urticaria</span><p id="par0015" class="elsevierStylePara elsevierViewall">Adjuvant therapy is an additional therapy that is given together with the first line therapy simultaneously with the purpose of increasing the therapy effectivity.<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">3</span></a> Adjuvant therapy in CSU is needed primarily on patients with no response to the treatment or refractory towards increasing antihistamine doses. The following sections will discuss several adjuvant therapies and their roles in CSU.</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Biologic agent</span><p id="par0020" class="elsevierStylePara elsevierViewall">Biological agent comes from living things and is used to prevent, diagnose, or treat a disease. The biologic agents used to treat chronic refractory urticaria are omalizumab, rituximab, intravenous immunoglobulin (IVIG), dan inhibitor TNF-α (infliximab, adalimumab, and etanercept); all used alongside the standard antihistamine regimen.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">4</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Omalizumab</span><p id="par0025" class="elsevierStylePara elsevierViewall">Omalizumab (OMA) is a recombinant monoclonal antibody that comes from a human and acts as an anti-IgE antibody, preventing the binding of IgE to receptor cells.<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">5,6</span></a> The effectiveness of OMA is proven and well tolerated in patients with refractory CSU. The EAACI/GA2LEN/EDF/WAO guidelines in 2022 recommend OMA as the third-line therapy for patients with chronic refractory urticaria towards the increase of H1 antihistamine dosage.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The mechanism of action of OMA is not fully understood. Kaplan et al. have reported the mechanism of actions of OMA in the CSU treatment is by decreasing the free IgE and IgE receptors, reducing the mast cell ability to release histamine, restoring basopenia, restoring the IgE receptors function in basophile, reducing the activity of auto-antibody IgG towards IgE and its receptors, reducing the abnormal IgE intrinsic activity, reducing the auto-antibody IgE towards an antigen or an unknown auto-antigen, and reducing abnormal coagulation which related to the disease activity through in vitro.<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The effectivity of the OMA addition in the CSU treatment was reported in many phases II<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">8,9</span></a> and phase III<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">10–12</span></a> clinical trials, as well as meta-analysis.<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">13</span></a> The three phase III clinical trials observed CSU/CindU moderate–severe patients who did not respond to the standard treatment and other additional therapies were given OMA 75<span class="elsevierStyleHsp" style=""></span>mg, 150<span class="elsevierStyleHsp" style=""></span>mg, or 300<span class="elsevierStyleHsp" style=""></span>mg for 12–24 weeks, and there was a decrease in the itch severity score (ISS) on the 12-week treatment. Casale et al.<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">14</span></a> have reported that there were more patients with urticaria activity score 7 (UAS7) ≤6 (symptoms are well controlled) or UAS7 0 (symptoms are perfectly controlled) when treated with OMA 300<span class="elsevierStyleHsp" style=""></span>mg compared to placebo.</p><p id="par0040" class="elsevierStylePara elsevierViewall">OMA is effective in the dosage of 150–300<span class="elsevierStyleHsp" style=""></span>mg per month. The dosage and duration of the therapy may vary between countries. Generally, OMA is well tolerated, and the most common side effects are nasopharyngitis, sinusitis, URTI, headache, and cough.<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">14</span></a> The risk of anaphylactic may occur 2<span class="elsevierStyleHsp" style=""></span>h after the first administration of OMA; thus, careful observation is needed.<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Rituximab</span><p id="par0045" class="elsevierStylePara elsevierViewall">Rituximab is a chimeric monoclonal antibody to CD20. The mechanism of action of rituximab in CSU prevents the production of autoantibody.<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">15</span></a> The rituximab treatment result varies widely. A case report of a patient with pressure urticaria who failed in the first and second line of therapy had received rituximab 375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/week infusion 4 times; however, there was no improvement. A case report of CSU and immunodeficiency treated by rituximab 375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/week, 4 times, showed a perfect recovery of urticaria symptoms within 1 week, with remission of more than 1 year, and later the symptoms will be easily treated by an antihistamine.<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">16</span></a> Another case report of refractory autoimmune CSU was given rituximab per week (4 times in dosage, within 4 weeks) along with the administration of methotrexate showed a perfect remission 6 weeks after the last administration.<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">17</span></a> There was no randomized controlled trials (RCT) study of rituximab in CSU.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Inhibitor TNF-α</span><p id="par0050" class="elsevierStylePara elsevierViewall">Some TNF-α inhibitors drugs such as etanercept, infliximab, and adalimumab were used to treat CSU or vasculitis urticaria based on the postulation that TNF may have important roles in some types of urticaria.<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">18,19</span></a> For example, etanercept 2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>25<span class="elsevierStyleHsp" style=""></span>mg/week is useful to treat delayed pressure urticaria and psoriasis. On the 5-day of treatment, the urticaria was resolved and did not appear until the end of the therapy.<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">20</span></a> A case series of 6 patients with chronic idiopathic urticaria or vasculitis urticaria treated by inhibitor TNF-α showed a dramatic clinical improvement in all patients.<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">21</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Serious infections such as tuberculosis, fungal infection, lymphoma, and malignancy were reported. This drug is not recommended for CSU treatment due to its lack of evidence to support the safety and efficacy of the treatment. Furthermore, there is no clinical trial comparing this drug to OMA, in which the safety and efficacy have been tested.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="el