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Management of chronic spontaneous urticaria (CSU): a treat to target approach using a patient reported… Lima, Hermenio; Gooderham, Melinda; Dutz, Jan; Lynde, Charles; Chapdelaine, Hugo; Ellis, Anne; Gilbert, Martin; Ho, Vincent; Papp, Kim; Poulin, Yves; Sussman, Gordon Aug 24, 2017

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Lima et al.  Allergy Asthma Clin Immunol  (2017) 13:38 DOI 10.1186/s13223-017-0210-0SHORT REPORTManagement of chronic spontaneous urticaria (CSU): a treat to target approach using a patient reported outcomeHermenio Lima1* , Melinda Gooderham2, Jan Dutz3, Charles Lynde4, Hugo Chapdelaine5, Anne Ellis6, Martin Gilbert7, Vincent Ho3, Kim Papp8, Yves Poulin9 and Gordon Sussman10Abstract Background: Treat-to-target therapy approaches are established for chronic diseases such as diabetes, hypertension, and more recently rheumatoid arthritis, resulting in improved patient outcomes. These approaches do not use patient reported outcomes (PRO) as targets of therapy. Chronic spontaneous urticaria (CSU), also called chronic idiopathic urticaria (CIU), is defined as recurrent urticaria of known and unknown cause, lasting more than 6 weeks. Treatment of CSU can be challenging. However, with the advent of proven therapies and validated instruments for measuring disease activity, the concept of treat-to-target (T2T) can be successfully applied to CSU. Herein, we propose a poten-tial PRO therapeutic target and suggest a T2T approach for the management of patients with CSU.Methods: Principles and recommendations for a treat-to-target approach in CSU (T2T/CSU) were developed by a Canadian task force, consisting of dermatologists, immunologists, and allergists. The task force formulated recommen-dations for therapeutic targets in CSU on the basis of a systematic literature review and expert opinion.Results: The key features of these T2T/CSU recommendations are the use of a PRO as the principal target, with symp-tom control as measured by Urticaria Activity Score 7 (UAS7 ≤ 6), targeting symptom remission (UAS7 = 0).Conclusion: Treatment targets such as UAS7 ≤ 6 and UAS7 = 0 provide a benchmark for success in the care of patients with CSU, and will permit the evaluation of a PRO-based T2T approach in the care of these patients and the effect of this approach on improved patient care as seen in other chronic diseases.Keywords: Chronic spontaneous urticaria, Chronic idiopathic urticaria, Urticaria, Urticaria Activity Score, CSU, CIU, UAS© The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.IntroductionOptimal treatment of chronic diseases requires tight con-trol of disease activity beyond improvement of patients’ symptoms. Treat-to-target (T2T) treatment strategy aims to achieve complete symptom control and improve the patient’s quality of life (QoL). When compared to the traditional symptom-based approach, target-based strategies have been shown to lead to better treatment and patient outcomes in diseases with complex clinical presentations and a paucity of overt symptoms [1]. T2T has been established for chronic diseases in which clini-cal severity correlates with biomarkers or aggregate measurements of disease activity [2]. Designing a treat-ment target requires tight control of disease activity based on values of specific quantitative measures [3]. T2T approach in hypertension, diabetes, and rheumatoid arthritis (RA) has led to a reduction of organ damage, improvement in patient’s QoL and decrease in mortality rates [4]. Such an approach has been less common in der-matologic disease.Chronic spontaneous urticaria (CSU); a mast-cell driven disease, characterized by recurrent itchy wheals (hives), is defined as spontaneous appearance of wheals, Open AccessAllergy, Asthma & Clinical Immunology*Correspondence:  hlima@mcmaster.ca 1 Division of Dermatology, Department of Medicine, McMaster University, HSC-3U8, 1280 Main St. West, Hamilton, ON L8S 4K1, CanadaFull list of author information is available at the end of the articlePage 2 of 7Lima et al. Allergy Asthma Clin Immunol  (2017) 13:38 angioedema, or both, for 6 or more weeks, with no apparent external trigger [5, 6]. Common therapeutic goals are reduction in disease activity, complete symp-tom control, and improvement in QoL. CSU is a major burden to patients with significant healthcare costs and socio-economic implications [7, 8].Chronic spontaneous urticaria is similar in many aspects to chronic diseases for which a T2T approach has been established. A validated clinical activity tool, the Urticaria Activity Score 7 (UAS7), allows clinicians to monitor levels of disease activity in response to treatment in CSU and may thus be used in a treat to target approach. UAS7 is a composite measure of clinical findings similar to composite measures used to quantitate clinical activ-ity in diabetes, hypertension, coronary heart disease and rheumatoid arthritis that use a single biomarker to define treatment targets. However, unlike other markers, UAS7 is a patient-reported outcome (PRO) measure used in clinical trials evaluating the efficacy of therapy in CSU [9]. UAS7 is a validated tool that measures levels of disease activity, and includes two items—intensity of pruritus (itch) and number of wheals (hives) [10].While CSU differs from a few other chronic diseases by the absence of long-term organ damage and low mor-tality rates, a T2T approach offers an important man-agement tool guiding therapeutic modification until symptom control or remission is obtained. The task force formulated three overarching principles and five recom-mendations for therapeutic targets in CSU on the basis of a systematic literature review and expert opinion. The key component of these recommendations is to achieve complete symptom control and improve the QoL. The Canadian T2T in CSU recommendations is meant to inform physicians about therapeutic targets as a manage-ment tool used to help patients reach optimal outcomes in the treatment of CSU. The recommendations are in line with the Canadian and EAACI/GA2LEN/EDF/WAO urticaria clinical practice guidelines [11, 12].MethodsA Steering Committee (SC) involving allergists, immu-nologists and dermatologists was assembled creating a Canadian task force to developed the principles and rec-ommendations for a treat-to-target approach in CSU in November 2014. SC members were identified by their proficiency in managing CSU; participation in consensus reports; involvement in clinical trials for CSU; and rele-vant medical activity in different regions of Canada.After reviewing the published literature in CSU, and deliberating upon the treatment targets for this paper, the SC panel formulated a provisional set of recommen-dations in line with the Canadian and EAACI/GA2LEN/EDF/WAO urticaria clinical practice guidelines [13, 14].Provisional recommendations were presented for discussion, amendment and voting by SC members.  SurveyMonkey® instrument was used by SC members to submit information. Participants voted on each rec-ommendation statement. Statements receiving ≥75% of votes were approved while those with ≤25% were rejected. Any statements receiving >25 and <75% of votes were subjected to an additional debate, and only those receiving ≥67% support were accepted. Therefore, a majority of ≥50% support was required for a state-ment to be accepted. For each accepted statement, the group was required to express their level of agreement using a 5-point numerical rating scale (1 = do not agree to 5 = agree completely) and the level of agreement was expressed as the average of all voters.These T2T recommendations were discussed, amended and voted upon by Task Force members. In a final step, the statements were distributed by email to each Task Force participant for comments. Only modifications of syntax and improved clarity were considered. Changes to meaning were not accepted.ResultsThe online  SurveyMonkey® results are presented in Table  1. The overarching principles and recommenda-tions for the T2T/CSU are discussed in detail below.Overarching principlesPatient and physician must share the responsibility of treatment for CSUManagement of CSU must occur in a close collaboration between the patient and physician [15]. The patient must be involved in symptom evaluation as the key metric for success in a PRO measure (the UAS7). The patient must also be involved in the determination of treatment goals. The physician must inform the patient of all available treatment options, potential complications of therapy, and the rationale for recommending a particular thera-peutic approach based on patient’s disease severity.Achieve symptom control and normalize patient’s long‑term health‑related quality of lifeThe therapeutic objective in CSU is to attain symp-tom control and symptom remission, while minimizing treatment-related side effects to ultimately improve qual-ity of life (QoL). Symptom control and symptom remis-sion are based on both patient’s feedback (PRO—using the UAS7) and physical examination. While symptom remission should be a clear target (UAS7 = 0), based on analysis of the minimal clinically important difference in UAS7 scores, low disease activity (UAS7 ≤ 6) may be an acceptable alternative therapeutic goal [16, 17]. In addi-tion, use of the validated chronic urticaria quality of life Page 3 of 7Lima et al. Allergy Asthma Clin Immunol  (2017) 13:38 questionnaire (CU-Q2oL) to assess the effect of CSU on QoL is recommended to monitor aspects of QoL such as anxiety and stress that are not captured by the UAS7 [11, 18, 19].Record of UAS7 must be part of any urticaria treatment to target management plan for measuring disease activity and adjusting therapy accordinglyManagement of CSU is aimed primarily at symptom control while minimizing treatment-related side effects. Recent guidelines recommend a step-wise pharmacologi-cal approach to the management of CSU with assessment of disease activity and QoL at each stage [13]. In a T2T/CSU approach, a record of UAS7 could be used as an indicator of disease activity, and as a tool to guide treat-ment decisions and to modify therapy based on response to treatment with a goal of complete symptom control (UAS7 ≤ 6) or symptom remission (UAS7 = 0) [16].Recommendation statementsThe primary target for treatment of CSU should be clinical remissionSymptom remission is a critical goal for all patients Clin-ical symptom remission is defined as complete symptom control and the lack of significant disease activity [11]. Few studies have reported symptom remission as the clin-ical trial primary endpoint [20]. The majority of the trials have evaluated the frequencies of symptom remission in response to different therapies, or had symptom remis-sion as the primary endpoint, but this was investigated by static management and not by strategic therapy escalation as in a treat to target approach [21–24].A significant proportion of  patients can achieve symp‑tom remission A meaningful proportion of patients can attain sustained symptom remission, and avoid the mor-bidity associated with CSU, when treatment is initiated early in the course of the disease. Therefore, symptom remission (UAS7 = 0) should be a meaningful and attain-able target for all patients with CSU [25].Significant residual disease activity is not accepta‑ble Only a few studies have dealt with the natural course of CSU, which can be active for as long as 20  years in the absence of therapy despite a tendency of spontane-ous recovery [26]. Any level of disease activity (UAS7 > 6) may contribute to recurrence of acute flare-ups. The aim of therapy for CSU is to achieve symptom control (UAS7 ≤ 6) and sustained remission (UAS7 = 0), with the ultimate goal of improving patient’s QoL [27].The patient should be knowledgeable about the treatment target under physician supervisionImportance of  discussing the therapeutic options, treat‑ment strategies, and  the reason for  selected treatment target with  the patient T2T approach includes patient involvement in shared decision-making [28]. Minimiza-tion of symptoms is a target of treatment in CSU and can be monitored using measures of disease activity such as UAS7, and Urticaria Control Test (UCT). However, due to its recent introduction, the UCT has not yet been widely used [29, 30].The role of the physician is to define the treatment target with the patient, choose the appropriate therapy and follow the patient over time to monitor disease activity Physi-cians following the T2T principles should help the patient to understand the goal of the treatment of CSU. A patient-friendly version of T2T/CSU including UAS7, the risks and benefits of treatment, and control of disease activity Table 1 Overarching principles and recommendations results of the  SurveyMonkey® online responsesa The level of agreement was expressed as the average of all voters on a 5-point numerical rating scale. A majority of ≥50% was required for a statement to be acceptedSupport (%) AgreementaOverarching principles Patient and physician must share the responsibility of treatment for CSU/CIU 100 4.9 Achieve symptom control and normalize patient’s long-term health-related quality of life 100 4.4 A record of UAS7 must be part of any urticaria treatment to target management plan by measuring  disease activity and adjusting therapy accordingly100 4.6Recommendations The primary target for treatment of CSU/CIU should be clinical symptom remission 100 4.4 The patient should be knowledgeable about the treatment target under physician supervision 100 4.8 The use of a validated tool to monitor disease activity 100 4.6 Until the treatment target is reached, drug therapy should be adjusted 77.8 3.7 The treatment target should be sustained throughout the remaining course of the disease management 100 4.6Page 4 of 7Lima et al. Allergy Asthma Clin Immunol  (2017) 13:38 should be provided to start the dialogue [31]. Studies have shown that even in a busy clinic it is possible to create a target for treatment with a patient, expressed as an activ-ity to be retained or regained [8, 32].The use of a validated tool to monitor disease activityAssessment of CSU by using the most appropriate instru‑ment is needed in routine clinical practice to guide treat‑ment decisions. We recommend the UAS7 score for moni‑toring response to therapy The UAS7 is a validated tool with which to follow CSU disease activity in clinical practice [33]. Continued measurement of disease activity is needed in routine clinical practice to guide treatment decisions. The UAS has proven to be as useful as other complex symptom scores. Patients score both their pru-ritus and number of wheals daily on a three-point scale, which gives them a daily score out of 6. The sum of the daily UAS scores gives the score for that week, with a max-imal score of 42. For symptom control the target should be UAS7 ≤ 6, and for remission, UAS7 = 0. Despite its limita-tions, this scoring system gives the clinicians and patients a quantitative method of monitoring disease activity and response to treatment [29].Disease activity must be regularly measured and  moni‑tored Pruritus and wheals are manifestations of inflam-mation in CSU [8]. Inflammation can be monitored by a regular assessment of disease activity using UAS7. To help control disease activity, one suggestion is to follow patients with UAS7  ≥  6 as frequently as monthly, and less frequently (e.g. every 3–6 months) for patients with sustained symptom control (UAS7  ≤  6) or remission (UAS7 = 0) [34].The target value of disease activity level may be influenced by  comorbidities Other conditions should be considered when making clinical decisions, in addition to assessing com-posite measures of disease activity. A target value of UAS7 may have to be less stringent in patients with comorbidities (e.g. chronic infections, renal or hepatic functional impair-ment, chronic congestive heart failure, anxiety or depression, etc.) or associated therapies. The practice parameters devel-oped by the joint task force on practice parameters (JTFPP), include omalizumab as a fourth-line treatment option, stressing that the benefits need to be weighed against the potential for burden and cost [35, 36]. However, omalizumab is relevant in all CSU/CIU guidelines [37].Until the treatment target is reached, drug therapy should be adjusted using a ladder approach according to current AACI/GA2LEN/EDF/WAO therapy guidelinesDose adjustment of existing medication A change to the treatment plan should be made for patients who have not achieved the well-controlled primary target of symptom control (UAS7 ≤ 6) or remission (UAS7 = 0). The type of adjustment depends on the applied strategy and patient’s individual response. However, a change in drug therapy is not always necessary. For patients who have not achieved the primary target of remission but show significant improvement over the previous 2 weeks, dose adjustment or continuation for another 2 weeks instead of changing therapy may be sufficient.Assessment follow‑up using T2T—utility of  UAS7 The effect of treatment on symptoms of CSU should be meas-ured based on the UAS scores. While the UAS scores is a patient-reported outcome measure, physician evaluations are independent of the opinion of the patient. Thus, the pro-cess by which the physician and the patient make a decision together for therapeutic modification is based on a dialogue, builds on the preferences of the patient, and the knowledge of the doctor. While remission is a desired treatment target, low disease activity and symptom control (UAS7 ≤ 6) may be an acceptable alternative therapeutic goal [38].However, until the desired treatment target is reached, therapy should be adjusted at least biweekly [39]. UAS7 > 6 warrants frequent follow-up and assessment of the disease status in order to adjust or modify treatment accordingly. If symptom control (UAS7  ≤  6) or remis-sion (UAS7 =  0) is reached and sustained, fewer evalu-ations are acceptable. If UAS7 ≤ 6 is not reached within 2–4 weeks from starting or adjusting therapy, treatment should be modified.The treatment target should be sustained throughout the remaining course of the disease managementMaintaining the state of symptom control or remission con‑tinuously Once CSU disease activity has been titrated to a target of symptom control or remission, this state should be maintained continuously.Further studies are needed to help direct decisions to reduce or discontinue treatment for CSU Studies evaluating dis-continuation of therapy once remission is reached, patient follow-ups to monitor flare-ups, and re-initiation of therapy, are scarce [39]. Furthermore, few studies address the fre-quency of relapses with a particular therapy or duration of treatment [40, 41]. One approach, particularly for patients with long-standing CSU, is to manage patients who have achieved remission with a specific therapeutic agent for an additional 3 months before tapering the dosage [42].DiscussionTreating-to-target, as in other chronic diseases, should be the goal of CSU management. Such a T2T strategy has been shown to lead to better patient outcomes when Page 5 of 7Lima et al. Allergy Asthma Clin Immunol  (2017) 13:38 clinically relevant targets such as biomarkers of disease activity, and composite clinical disease activity measures are used. While guidelines for treating CSU have been established, none discuss a treatment to target approach to achieve the therapeutic goal of symptom remission or disease control. These principles and recommendations for a treat-to-target approach were based on the best treatment outcome of CSU in a busy clinical practice. These T2T/CSU recommendations, however, are based on a literature review and expert opinion of the current treatment guidelines, and they evolved from discussions among experts from across Canada. The requirement of a high level of agreement from the expert opinion on most of the statements implies a broad acceptance and consensus.Treatment strategies improve compliance and achieve a better result when the patient has access to thera-peutic strategies suggested in guidelines. However, a Canadian task force was aware of potential financial constraints or access to particular treatments, which would only allow a certain proportion of patients to achieve the desired targets. These T2T guidelines differ from those of other chronic disease in which biomark-ers or physician determined composite disease activ-ity scores are commonly used to establish therapeutic targets [1]. These guidelines also differ from recent guidelines for the treatment of psoriasis where physi-cian-assessed disease activity is combined with a PRO score, the DLQI [43]. The nature of CSU symptoms and intermittent clinical findings, lends itself best to a T2T guideline relying on a PRO, the UAS7, with the possi-ble adjunct use of an additional QoL questionnaire, the CU-Q2ol (Table 2).These recommendations are meant to provide guid-ance towards therapeutic goals in CSU, enabling itera-tive physician evaluation and treatment modification, based upon a PRO. We propose that bringing them into practice will help enable symptom control and normali-zation of patient’s QoL. The utility and efficacy of a T2T strategy using a PRO as prime indicator of success will need to be evaluated in formal studies, but promises to conceptually extend the framework for T2T approaches to treatment.The UAS7, a validated, clinically relevant, and readily applied PRO measurement tool, can be used to define a treatment target in CSU. We propose here that a relevant PRO can be used in defining a T2T strategy for CSU. An appropriate and achievable treatment target is symptom control (UAS7 ≤ 6) or symptom remission (UAS7 = 0). Successful management of CSU is to achieve and main-tain this target.Authors’ contributionsHL, MG, JD and KP proposed the paper format and framework for data collec-tion. HL assisted with data collection. HL analyzed the data and completed the statistical analysis. GS, YP, KP, VH, MG, AE, HC and CL complete the statistical analysis, abstract and manuscript. All authors read and approved the final manuscript.Author details1 Division of Dermatology, Department of Medicine, McMaster University, HSC-3U8, 1280 Main St. West, Hamilton, ON L8S 4K1, Canada. 2 SKiN Centre for Dermatology and Probity Medical Research, Peterborough, ON, Canada. 3 Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada. 4 Lynde Institute for Dermatology, Markham, ON, Canada. 5 Division of Allergy & Immunology, Department of Medicine, Univer-sité de Montréal, Montreal, QC, Canada. 6 Division of Allergy & Immunology, Department of Medicine, Queen’s University, Kingston, ON, Canada. 7 Hôpital du Saint-Sacrement du CHU de Québec, Quebec City, QC, Canada. 8 Clinical Research and Probity Medical Research, Waterloo, ON, Canada. 9 Depart-ment of dermatology, Hôpital Hôtel-Dieu du CHU de Québec, and Centre de Recherche Dermatologique du Québec métropolitain, Quebec City, QC, Canada. 10 Division of Allergy and Clinical Immunology, St. Michael’s Hospital, Toronto, ON, Canada. AcknowledgementsNot applicable.Competing interestsThe author(s) disclosed receipt of the following financial support related to the publication of this article: All authors attended the First Global Urticaria Forum, November 27–29, 2014 in Prague, The Czech Republic. Novartis Pharma AG sponsored this meeting. Travel to and from the meeting was reimbursed. The idea for the article was proposed and developed by the authors present at the meeting independent of the meeting sponsor. The authors drafted, reviewed and edited the article; determined final content; and all authors read and approved the final publication. The authors maintained complete control over the article and its content. The authors paid for the editorial assistant.Availability of data and materialsThe datasets analyzed during the current study are available from the cor-responding author on reasonable request.Ethics approvalNot applicable.FundingThe authors paid for the editorial assistant.Table 2 Treat-to-target strategies for chronic diseases [1, 39]BP blood pressure, CSU chronic spontaneous urticaria, DAS28 disease activity score-28, HbA1c hemoglobin A1c, PASI psoriasis area severity index, PROQOL patient reported outcomes quality of life, UAS7 weekly urticaria activity scorea Recommendation from this publicationDisease Diabetes Hypertension Rheumatoid arthritis Psoriasis CSUTarget HbA1c BP level DAS28 PASI + PROQOL UAS7aComment Biologic marker Biologic marker Clinical score Clinical scorePatient inputPatient inputPage 6 of 7Lima et al. Allergy Asthma Clin Immunol  (2017) 13:38 Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in pub-lished maps and institutional affiliations.Received: 26 March 2017   Accepted: 4 August 2017References 1. Atar D, Birkeland KI, Uhlig T. ‘Treat to target’: moving targets from hypertension, hyperlipidaemia and diabetes to rheumatoid arthritis. Ann Rheum Dis. 2010;69:629–30. 2. Garber AJ. Treat-to-target trials: uses, interpretation and review of con-cepts. Diabetes Obes Metab. 2013;16:193–205. 3. van Vollenhoven RF, Mosca M, Bertsias G, Isenberg D, Kuhn A, Lerstrom K, Aringer M, Bootsma H, Boumpas D, Bruce IN, et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis. 2014;73:958–67. 4. Uhlig T, Sokka T. ‘Rheumatologist go home!’ Coming up next? Ann Rheum Dis. 2013;72:1111–2. 5. Zuberbier T. A summary of the new international EAACI/GA2LEN/EDF/WAO guidelines in urticaria. World Allergy Organ J. 2012;5:S1–5. 6. Kolkhir P, Balakirski G, Merk HF, Olisova O, Maurer M. Chronic sponta-neous urticaria and internal parasites—a systematic review. Allergy. 2016;71:308–22. 7. DeLong LK, Culler SD, Saini SS, Beck LA, Chen SC. Annual direct and indirect health care costs of chronic idiopathic urticaria. Arch Dermatol. 2008;144:35–9. 8. Maurer M, Magerl M, Metz M, Siebenhaar F, Weller K, Krause K. Practical algorithm for diagnosing patients with recurrent wheals or angioedema. Allergy. 2013;68:816–9. 9. Vena GA, Cassano N, Colombo D, Peruzzi E, Pigatto P, Neo ISG. Cyclo-sporine in chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial. J Am Acad Dermatol. 2006;55:705–9. 10. Mathias SD, Crosby RD, Rosen KE, Zazzali JL. The minimal important differ-ence for measures of urticaria disease activity: updated findings. Allergy Asthma Proc. 2015;36:394–8. 11. Sussman G, Hébert J, Gulliver W, Lynde C, Waserman S, Kanani A, Ben-Shoshan M, Horemans S, Barron C, Betschel S, et al. Insights and advances in chronic urticaria: a Canadian perspective. Ann Allergy Asthma Immu-nol. 2015;11:7. 12. Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, Church MK, Ensina LF, Gimenez-Arnau A, Godse K, et al. The EAACI/GA(2) LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014;69:868–87. 13. Bernstein JA, Lang DM, Khan DA, Craig T, Dreyfus D, Hsieh F, Sheikh J, Weldon D, Zuraw B, Bernstein DI, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014;133:1270–7. 14. Staevska M, Popov TA, Kralimarkova T, Lazarova C, Kraeva S, Popova D, Church DS, Dimitrov V, Church MK. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria. J Allergy Clin Immunol. 2010;125:676–82. 15. Zuberbier T, Greaves MW, Juhlin L, Merk H, Stingl G, Henz BM. Manage-ment of urticaria: a consensus report. J Investig Dermatol Symp Proc. 2001;6:128–31. 16. Mathias SD, Crosby RD, Zazzali JL, Maurer M, Saini SS. Evaluating the minimally important difference of the urticaria activity score and other measures of disease activity in patients with chronic idiopathic urticaria. Ann Allergy Asthma Immunol. 2012;108:20–4. 17. Kaplan A, Ferrer M, Bernstein JA, Antonova E, Trzaskoma B, Raimundo K, Rosen K, Omachi TA, Khalil S, Zazzali JL. Timing and duration of omalizumab response in patients with chronic idiopathic/spontaneous urticaria. J Allergy Clin Immunol. 2016;137:474–81. 18. Baiardini I, Pasquali M, Braido F, Fumagalli F, Guerra L, Compalati E, Braga M, Lombardi C, Fassio O, Canonica GW. A new tool to evaluate the impact of chronic urticaria on quality of life: chronic urticaria quality of life ques-tionnaire (CU-Q2oL). Allergy. 2005;60:1073–8. 19. Savic S, Marsland A, McKay D, Ardern-Jones MR, Leslie T, Somenzi O, Baldock L, Grattan C. Retrospective case note review of chronic spontaneous urti-caria outcomes and adverse effects in patients treated with omalizumab or ciclosporin in UK secondary care. Allergy Asthma Clin Immunol. 2015;11:21. 20. Juhlin L, Arendt C. Treatment of chronic urticaria with cetirizine dihydro-chloride a non-sedating antihistamine. Br J Dermatol. 1988;119:67–72. 21. Abu Shareeah AM. Comparative efficacy of loratadine and terfena-dine in the treatment of chronic idiopathic urticaria. Int J Dermatol. 1992;31:355–6. 22. Sharma V, Singh S, Ramam M, Kumawat M, Kumar R. A randomized placebo-controlled double-blind pilot study of methotrexate in the treat-ment of H1 antihistamine-resistant chronic spontaneous urticaria. Indian J Dermatol Venereol Leprol. 2014;80:122. 23. Sussman G, Hébert J, Barron C, Bian J, Caron-Guay R-M, Laflamme Sp, Stern S. Real-life experiences with omalizumab for the treatment of chronic urticaria. Ann Allergy Asthma Immunol. 2014;112:170–4. 24. Rottem M, Segal R, Kivity S, Shamshines L, Graif Y, Shalit M, Kessel A, Panasoff J, Cohen S, Toubi E, Agmon-Levin N. Omalizumab therapy for chronic spontaneous urticaria: the Israeli experience. Isr Med Assoc J. 2014;16:487–90. 25. Song CH, Stern S, Giruparajah M, Berlin N, Sussman GL. Long-term efficacy of fixed-dose omalizumab for patients with severe chronic spon-taneous urticaria. Ann Allergy Asthma Immunol. 2013;110:113–7. 26. Kozel MMA, Mekkes JR, Bossuyt PMM, Bos JD. Natural course of physical and chronic urticaria and angioedema in 220 patients. J Am Acad Derma-tol. 2001;45:387–91. 27. Kaplan AP. Clinical practice. Chronic urticaria and angioedema. N Engl J Med. 2002;346:175–9. 28. Frosch DL, Kaplan RM. Shared decision making in clinical medicine: past research and future directions. Am J Prev Med. 1999;17:285–94. 29. Mlynek A, Zalewska-Janowska A, Martus P, Staubach P, Zuberbier T, Mau-rer M. How to assess disease activity in patients with chronic urticaria? Allergy. 2008;63:777–80. 30. Weller K, Groffik A, Church MK, Hawro T, Krause K, Metz M, Martus P, Casale TB, Staubach P, Maurer M. Development and validation of the urti-caria control test: a patient-reported outcome instrument for assessing urticaria control. J Allergy Clin Immunol. 2014;133:1365–1372.e1366. 31. de Wit MPT, Smolen JS, Gossec L, van der Heijde DMFM. Treating rheuma-toid arthritis to target: the patient version of the international recommen-dations. Ann Rheum Dis. 2011;70:891–5. 32. Robinson SM, Walker DJ. Negotiating targets with patients: choice of target in relation to occupational state. Rheumatology. 2011;51:293–6. 33. Baiardini I, Braido F, Bindslev-Jensen C, Bousquet PJ, Brzoza Z, Canonica GW, Compalati E, Fiocchi A, Fokkens W, Gerth van Wijk R, et al. Recom-mendations for assessing patient-reported outcomes and health-related quality of life in patients with urticaria: a GA2LEN taskforce position paper. Allergy. 2011;66:840–4. 34. Smolen JS, Aletaha D, Bijlsma JWJ, Breedveld FC, Boumpas D, Burmester G, Combe B, Cutolo M, de Wit M, Dougados M, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69:631–7. 35. Faria R, McKenna C, Palmer S. Optimizing the position and use of omali-zumab for severe persistent allergic asthma using cost-effectiveness analysis. Value Health. 2014;17:772–82. 36. Graham J, McBride D, Stull D, Halliday A, Alexopoulos ST, Balp MM, Grif-fiths M, Agirrezabal I, Zuberbier T, Brennan A. Cost utility of omalizumab compared with standard of care for the treatment of chronic spontane-ous urticaria. PharmacoEconomics. 2016;34:815–27. 37. Gimenez-Arnau A, Ferrer M, Bartra J, Jauregui I, Labrador-Horrillo M, Fru-tos JO, Silvestre JF, Sastre J, Velasco M, Valero A. Management of chronic spontaneous urticaria in routine clinical practice: a Delphi-method ques-tionnaire among specialists to test agreement with current European guidelines statements. Allergol Immunopathol (Madr). 2017;45:134–44. 38. Kropfl L, Maurer M, Zuberbier T. Treatment strategies in urticaria. Expert Opinion Pharmacother. 2010;11:1445–50. 39. Metz M, Ohanyan T, Church MK, Maurer M. Retreatment with omalizumab results in rapid remission in chronic spontaneous and inducible urticaria. JAMA Dermatol. 2014;150:288. 40. Grattan CE, O’Donnell BF, Francis DM, Niimi N, Barlow RJ, Seed PT, Kobza Black A, Greaves MW. Randomized double-blind study of cyclosporin in chronic idiopathic urticaria. Br J Dermatol. 2000;143:365–72.Page 7 of 7Lima et al. Allergy Asthma Clin Immunol  (2017) 13:38 •  We accept pre-submission inquiries •  Our selector tool helps you to find the most relevant journal•  We provide round the clock customer support •  Convenient online submission•  Thorough peer review•  Inclusion in PubMed and all major indexing services •  Maximum visibility for your researchSubmit your manuscript atwww.biomedcentral.com/submitSubmit your next manuscript to BioMed Central and we will help you at every step: 41. Kai AC, Flohr C, Grattan CE. Improvement in quality of life impairment fol-lowed by relapse with 6-monthly periodic administration of omalizumab for severe treatment-refractory chronic urticaria and urticarial vasculitis. Clin Exp Dermatol. 2014;39:651–2. 42. Khan DA. Alternative agents in refractory chronic urticaria: evidence and considerations on their selection and use. J Allergy Clin Immunol Pract. 2013;1(433–440):e431. 43. Gulliver W, Lynde C, Dutz JP, Vender RB, Yeung J, Bourcier M, Dion PL, Hong CH, Searles G, Poulin Y. Think beyond the skin: 2014 Canadian expert opinion paper on treating to target in plaque psoriasis. J Cutan Med Surg. 2015;19:22–7.


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