Omalizumab response in patients with chronic idiopathic urticaria: Insights from the XTEND-CIU study

To the Editor: We describe results from a phase IV study in patients with chronic idiopathic urticaria (CIU) that provide an expanded view of the benefits of omalizumab treatment in protocol-defined responders and nonresponders and offer insight that may be useful to clinicians when deciding treatment duration for omalizumab nonresponders. The Xolair Treatment Efficacy of Longer Duration in Chronic Idiopathic Urticaria (XTEND-CIU) study was a US–based, multicenter, randomized, double-blind, placebo-controlled trial (Fig 1) that included patients with CIU between the ages of 12 and 75 years. After the 24-week open-label period during which patients received omalizumab 300 mg every 4 weeks, they were stratified by their 7-day Urticaria Activity Score (UAS7): a UAS7 of 6 or lower (protocol-defined responder) versus a UAS7 higher than 6 (nonresponders); the responders entered a double-blind phase. Symptoms were recorded electronically by patients using the Urticaria Patient Daily Diary1Mathias S.D. Dreskin S.C. Kaplan A. Saini S.S. Spector S. Rosén K.E. Development of a daily diary for patients with chronic idiopathic urticaria.Ann Allergy Asthma Immunol. 2010; 105: 142-148Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar, 2Mathias S.D. Tschosik E.A. Zazzali J.L. Adaptation and validation of the Urticaria Patient Daily Diary for adolescents.Allergy Asthma Proc. 2012; 33: 186-190Crossref PubMed Scopus (13) Google Scholar and by paper-based clinician- and patient-reported instruments. A total of 206 patients were enrolled in the open-label period, and 205 were treated with omalizumab. At baseline, patients enrolled in the XTEND-CIU study reported a substantial disease burden, reflected in the UAS7 (mean, 32.2; standard deviation, 7.0) and patient-reported outcome (PRO) scores, despite treatment with H1 antihistamines, H2 blockers, and/or leukotriene receptor modifiers. By week 1, 3.9% of patients had achieved a UAS7 of 6 or lower; complete response was evident as early as week 2 in 13.7% of patients, and improvements continued to week 24. The percentages of patients meeting the definition of protocol-defined responder or complete responder, respectively, were as follows: 38.2% and 17.6% at week 4, 58.8% and 36.8% at week 12, and 73.0% and 52.0% at week 24 (Fig 2). Among protocol-defined nonresponders (ie, nonrandomized patients), 64% experienced an improvement in their UAS7 of 10 or more between baseline and the end of week 24. PRO measures showed improvement in all evaluated areas; the most notable improvement occurred between baseline and week 12, with additional improvement achieved by week 24. Even protocol-defined nonresponders reported evidence of clinically meaningful improvement (achievement of a minimally important difference response) in Dermatology Life Quality Index and Insomnia Severity Index scores through 24 weeks of omalizumab treatment. Mean activity and productivity impairment scores improved in responders and nonresponders. No new safety signals were detected. Patients in the XTEND-CIU study had a disease burden consistent with that described in other large studies.3Kaplan A. Ledford D. Ashby M. et al.Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy.J Allergy Clin Immunol. 2013; 132: 101-109Abstract Full Text Full Text PDF PubMed Scopus (417) Google Scholar, 4Maurer M. Rosén K. Hsieh H.J. et al.Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria.N Engl J Med. 2013; 368: 924-935Crossref PubMed Scopus (728) Google Scholar, 5Maurer M. Staubach P. Raap U. et al.H1-antihistamine-refractory chronic spontaneous urticaria: it's worse than we thought – first results of the multicenter real-life AWARE study.Clin Exp Allergy. 2017; 47: 684-692Crossref PubMed Scopus (76) Google Scholar, 6Saini S.S. Bindslev-Jensen C. Maurer M. et al.Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study.J Invest Dermatol. 2015; 135: 925Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar The rate of protocol-defined response at randomization was 65% at week 24, exceeding the expected 57% response rate at week 24 according to data from the GLACIAL study, which enrolled a population similar to that of the current study.3Kaplan A. Ledford D. Ashby M. et al.Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy.J Allergy Clin Immunol. 2013; 132: 101-109Abstract Full Text Full Text PDF PubMed Scopus (417) Google Scholar These preliminary findings from the XTEND-CIU study, reflecting the initial 24-week open-label period, demonstrate that in patients with evidence of moderate-to-severe CIU symptoms at baseline, improvements in the UAS7 were observed as early as week 1 and continued to week 24, with PROs following a similar trend. Even among protocol-defined nonresponders there was evidence of a treatment response. Data from the double-blind period of the XTEND-CIU study will enhance understanding of the safety and efficacy of longer-term (48 weeks) administration of omalizumab in patients with CIU. The authors acknowledge the contributions of study participants and the XTEND-CIU study investigators. The authors also would like to acknowledge the contributions of Noelle M. Griffin, PhD, Boris Polman, MD, and Ha Tran, MD, MS, to the data analyses. Third-party writing assistance was provided by Linda Wagner, PharmD, of Envision Pharma Group (Excel Scientific Solutions, Inc), and funded by Genentech, Inc, and Novartis Pharmaceuticals Corporation.