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      The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 2. Management of H1-Antihistamine-Refractory Chronic Urticaria

      review-article
      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , , 42 ,
      Allergy, Asthma & Immunology Research
      The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
      Urticaria, antihistamine, treatment, guideline, evidence, leukotriene, IgE, cyclosporine

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          Abstract

          Quite a few patients with chronic spontaneous urticaria (CSU) are refractory to H 1-antihistamines, even though the dose of H 1-antihistamines is increased up to 4-fold. CSU that is not controlled with H 1-antihistamines results in increased disease burden. Several immunomodulators have been used to manage these patients. The guidelines reported herein are connected to Part 1 of the KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children, and aimed to provide evidence-based recommendations for the management of H 1-antihistamine-refractory CSU. Part 2 focuses on the more commonly used additional treatment options for refractory CSU, including omalizumab, cyclosporine, leukotriene receptor antagonist, dapsone, methotrexate, and phototherapy. The evidence to support their efficacy, dosing, safety, and selection of these agents is systematically reviewed. To date, for patients with refractory CSU, the methodologically sound data to evaluate the use of omalizumab has been growing; however, the evidence of other immunomodulators and phototherapy is still insufficient. Therefore, an individualized stepwise approach with a goal of achieving complete symptom control and minimizing side effects can be recommended. Larger controlled studies are needed to elevate the level of evidence to select a rational therapeutic agent for patients with refractory CSU.

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          Most cited references80

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          The EAACI/GA²LEN/EDF/WAO Guideline for the Definition, Classification, Diagnosis and Management of Urticaria. The 2017 Revision and Update

          This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
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            The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update.

            This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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              Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria.

              Many patients with chronic idiopathic urticaria (also called chronic spontaneous urticaria) do not have a response to therapy with H-antihistamines, even at high doses. In phase 2 trials, omalizumab, an anti-IgE monoclonal antibody [corrected] that targets IgE and affects mast-cell and basophil function, has shown efficacy in such patients. In this phase 3, multicenter, randomized, double-blind study, we evaluated the efficacy and safety of omalizumab in patients with moderate-to-severe chronic idiopathic urticaria who remained symptomatic despite H-antihistamine therapy (licensed doses). We randomly assigned 323 patients to receive three subcutaneous injections, spaced 4 weeks apart, of omalizumab at doses of 75 mg, 150 mg, or 300 mg or placebo, followed by a 16-week observation period. The primary efficacy outcome was the change from baseline in a weekly itch-severity score (ranging from 0 to 21, with higher scores indicating more severe itching). The baseline weekly itch-severity score was approximately 14 in all four study groups. At week 12, the mean (±SD) change from baseline in the weekly itch-severity score was -5.1±5.6 in the placebo group, -5.9±6.5 in the 75-mg group (P=0.46), -8.1±6.4 in the 150-mg group (P=0.001), and -9.8±6.0 in the 300-mg group (P<0.001). Most prespecified secondary outcomes at week 12 showed similar dose-dependent effects. The frequency of adverse events was similar across groups. The frequency of serious adverse events was low, although the rate was higher in the 300-mg group (6%) than in the placebo group (3%) or in either the 75-mg or 150-mg group (1% for each). Omalizumab diminished clinical symptoms and signs of chronic idiopathic urticaria in patients who had remained symptomatic despite the use of approved doses of H-antihistamines. (Funded by Genentech and Novartis Pharma; ClinicalTrials.gov number, NCT01292473.).
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                Author and article information

                Journal
                Allergy Asthma Immunol Res
                Allergy Asthma Immunol Res
                AAIR
                Allergy, Asthma & Immunology Research
                The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
                2092-7355
                2092-7363
                September 2020
                30 March 2020
                : 12
                : 5
                : 750-770
                Affiliations
                [1 ]Department of Pulmonology and Allergy, Hallym University Dongtan Sacred Heart Hospital, Allergy and Clinical Immunology Research Center, Hallym University College of Medicine, Chuncheon, Korea.
                [2 ]Department of Dermatology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
                [3 ]Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
                [4 ]Department of Dermatology, Inje University Ilsan Paik Hospital, Ilsan, Korea.
                [5 ]Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
                [6 ]Department of Internal Medicine, St. Carollo General Hospital, Suncheon, Korea.
                [7 ]Department of Dermatology, Dankook University College of Medicine, Cheonan, Korea.
                [8 ]Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
                [9 ]Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea.
                [10 ]Department of Internal Medicine, Korea University Medical Center Anam Hospital, Seoul, Korea.
                [11 ]Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
                [12 ]Department of Dermatology, Hanyang University Guri Hospital, Guri, Korea.
                [13 ]Department of Dermatology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
                [14 ]Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Korea.
                [15 ]Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.
                [16 ]Institute for Evidence-based Medicine, Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea.
                [17 ]Department of Dermatology, Hallym University College of Medicine, Seoul, Korea.
                [18 ]Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea.
                [19 ]Department of Dermatology, Gil Medical Center, Gachon University School of Medicine, Incheon, Korea.
                [20 ]Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
                [21 ]Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea.
                [22 ]Department of Allergy and Clinical Immunology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea.
                [23 ]Department of Dermatology, SMG-SNU Boramae Medical Center, Seoul, Korea.
                [24 ]Department of Dermatology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea.
                [25 ]Department of Dermatology, College of Medicine, Ewha Womans University, Seoul, Korea.
                [26 ]Department of Pediatrics, Korea University College of Medicine, Seoul, Korea.
                [27 ]Department of Pediatrics, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea.
                [28 ]Division of Pulmonology and Allergy, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea.
                [29 ]Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
                [30 ]Department of Dermatology, School of Medicine, Eulji University, Daejeon, Korea.
                [31 ]Department of Dermatology, Seoul St. Mary's Hospital, Brain Korea 21 PLUS Project for Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Korea.
                [32 ]Wirye Seoul Doctors Hospital, Seongnam, Korea.
                [33 ]Department of Dermatology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
                [34 ]Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
                [35 ]Department of Pediatrics, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea.
                [36 ]Department of Dermatology, Korea University College of Medicine, Seoul, Korea.
                [37 ]Department of Dermatology, Veterans Health Service Medical Center, Seoul, Korea.
                [38 ]Department of Pediatrics, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, Korea.
                [39 ]Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
                [40 ]Department of Pediatrics, School of Medicine, Inha University, Incheon, Korea.
                [41 ]Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
                [42 ]Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
                Author notes
                Correspondence to Young-Min Ye, MD, PhD. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Korea. Tel: +82-31-219-5155; Fax: +82-31-219-5154; ye9007@ 123456ajou.ac.kr
                Correspondence to Young Min Park, MD, PhD. Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. Tel: +82-2-2258-6223; Fax: +82-2-599-9950; yymmpark6301@ 123456hotmail.com

                Jeong-Hee Choi and Dong Hun Lee equally contributed to the article.

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                Article
                10.4168/aair.2020.12.5.750
                7346997
                32638557
                11ca2234-8e1b-41f1-85e9-064442584ff9
                Copyright © 2020 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 February 2020
                : 25 February 2020
                Categories
                Review

                Immunology
                urticaria,antihistamine, treatment,guideline,evidence,leukotriene,ige,cyclosporine
                Immunology
                urticaria, antihistamine, treatment, guideline, evidence, leukotriene, ige, cyclosporine

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