Omalizumab for the treatment of chronic spontaneous urticaria: A meta-analysis of randomized clinical trials Zuo-Tao Zhao, MD, PhD, Chun-Mei Ji, M Pharm,

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Omalizumab for the treatment of chronic spontaneous urticaria: A meta-analysis of randomized clinical trials Zuo-Tao Zhao, MD, PhD, Chun-Mei Ji, M Pharm, Wen-Jun Yu, MD, Ling Meng, M Pharm, Tomasz Hawro, MD, Ji-Fu Wei, PhD, Marcus Maurer, MD Journal of Allergy and Clinical Immunology Volume 137, Issue 6, Pages 1742-1750.e4 (June 2016) DOI: 10.1016/j.jaci.2015.12.1342 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Study selection process. We identified 202 potentially relevant studies, of which 7 were included in the meta-analysis. Journal of Allergy and Clinical Immunology 2016 137, 1742-1750.e4DOI: (10.1016/j.jaci.2015.12.1342) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Studies included in this meta-analysis show a low risk of bias. A, Risk of bias summary for each included study. B, Begg funnel plot. The largest studies are plotted near the average, and smaller studies are spread evenly on both sides of the average, creating a roughly funnel-shaped distribution. Deviation from this shape can indicate publication bias. The funnel plot and Egger test showed no evidence of publication bias. Journal of Allergy and Clinical Immunology 2016 137, 1742-1750.e4DOI: (10.1016/j.jaci.2015.12.1342) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Meta-analysis of efficacy outcomes of 7 RCTs with omalizumab- and placebo-treated patients with CSU. A, WMD WIS. B, WMD WWS. C, Rates of complete responders (UAS7 = 0) and RRs of complete response. Horizontal lines represent 95% CIs of the RR estimates. Diamonds represent the meta-analysis summary effect estimate; green dots represent the WMD, and blue dots represent the RR. Journal of Allergy and Clinical Immunology 2016 137, 1742-1750.e4DOI: (10.1016/j.jaci.2015.12.1342) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Meta-analysis of efficacy outcomes of 7 RCTs with omalizumab- and placebo-treated patients with CSU. A, WMD WIS. B, WMD WWS. C, Rates of complete responders (UAS7 = 0) and RRs of complete response. Horizontal lines represent 95% CIs of the RR estimates. Diamonds represent the meta-analysis summary effect estimate; green dots represent the WMD, and blue dots represent the RR. Journal of Allergy and Clinical Immunology 2016 137, 1742-1750.e4DOI: (10.1016/j.jaci.2015.12.1342) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Meta-analysis of the RCTs comparing rates of patients with at least 1 AE between the omalizumab- and placebo-treated groups. Horizontal lines represent 95% CIs of the RR estimates. Diamonds represent the meta-analysis summary effect estimate, and blue dots represent the RR. Journal of Allergy and Clinical Immunology 2016 137, 1742-1750.e4DOI: (10.1016/j.jaci.2015.12.1342) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Galbraith radial plot. The figure shows the contribution of results from the patient groups treated with different doses of omalizumab in the different studies to the heterogeneity of efficacy of treatment. The group receiving 75 mg of omalizumab in the ASTERIA II study was found to be the main cause of the heterogeneity. ASI75, ASTERIA I 75 mg; ASI150, ASTERIA I 150 mg; ASI300, ASTERIA I 300 mg; ASII75, ASTERIA II 75 mg; GL300, GLACIAL 300 mg; MOA300, MOA 300 mg; MY75, MYSTQUE 75 mg; MY300, MYSTQUE 300 mg; MY600, MYSTQUE 600 mg; XA300, X-ACT 300 mg; XC150, XCUISITE 150 mg; XC300, XCUISITE 300 mg; XC600, XCUISITE 600 mg. Journal of Allergy and Clinical Immunology 2016 137, 1742-1750.e4DOI: (10.1016/j.jaci.2015.12.1342) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Subgroup analysis of time point. A, WIS. B, Weekly hive score. C, Number of complete responders. D, At least 1 AE. Horizontal lines represent 95% CIs of the RR estimates. Diamonds represent the meta-analysis summary effect estimate; green dots represent the WMD, and blue dots represent the RR. Journal of Allergy and Clinical Immunology 2016 137, 1742-1750.e4DOI: (10.1016/j.jaci.2015.12.1342) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Subgroup analysis of time point. A, WIS. B, Weekly hive score. C, Number of complete responders. D, At least 1 AE. Horizontal lines represent 95% CIs of the RR estimates. Diamonds represent the meta-analysis summary effect estimate; green dots represent the WMD, and blue dots represent the RR. Journal of Allergy and Clinical Immunology 2016 137, 1742-1750.e4DOI: (10.1016/j.jaci.2015.12.1342) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Subgroup analysis of UAS standard. A, WIS. B, Weekly hive score. Horizontal lines represent 95% CIs of RR estimates. Diamonds represent the meta-analysis summary effect estimate; green dots represent WMDs. Journal of Allergy and Clinical Immunology 2016 137, 1742-1750.e4DOI: (10.1016/j.jaci.2015.12.1342) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions