Ligelizumab improves angioedema, disease severity and quality-of-life in patients with chronic spontaneous urticaria

Abstract

Background: Disease burden is particularly high in Chronic Spontaneous Urticaria (CSU) patients with angioedema, and patients whose signs and symptoms are inadequately controlled by H₁-antihistamines need new treatment options. Here we report an exploratory analysis, from the ligelizumab Phase 2b study, investigating angioedema occurrence in patients with CSU and describe the changes in angioedema following treatment with ligelizumab, omalizumab, or placebo.

Methods: Data from the ligelizumab Phase 2b core (ligelizumab 72 mg, 240 mg, omalizumab 300 mg and placebo) and extension study (ligelizumab 240 mg) were used. Changes in Weekly Angioedema Activity Score (AAS7), the Dermatology Life Quality Index (DLQI), and Weekly Urticaria Activity Score (UAS7) among each time point were analyzed for each treatment arm.

Results: From a total of 297 patients analyzed, 165 (55.6%) reported angioedema occurrence at baseline, with mean AAS7 ranging 30.6-42.2 across treatment arms. At Week 12 of the core study 87.5%, 84.6%, 75.0%, and 61.0% of patients were angioedema free for ligelizumab 72 mg, 240 mg, omalizumab 300 mg, and placebo arms, respectively. In CSU patients with angioedema at baseline, the largest change from baseline in AAS7 score was observed with ligelizumab 72 mg (-31.9) at week 16 in the core study. Patients with angioedema had a higher mean DLQI at baseline (14.9-16.1) vs. patients without angioedema (10.6-12.0). In patients with angioedema, low AAS7 was significantly associated with complete response on UAS7 (UAS7 = 0) and complete normalization of DLQI (DLQI 0-1).

Conclusion: In the Phase 2b study, ligelizumab effectively reduced angioedema and urticaria symptoms, and improve health related quality of life in patients with moderate-to-severe CSU.

Clinicaltrailsgov nct number: NCT02477332; NCT02649218.

Keywords: Angioedema; Chronic spontaneous urticaria; Dermatology life quality index; IgE; Ligelizumab.

Fig. 1

Angioedema status of patients in the ligelizumab Phase 2b studies: (a) median (IQ range), mean ± SD of AAS7 at baseline in the core and extension studies, (b) LS mean CFB AAS7 in the core Phase 2b study, (c) LS mean CFB AAS7 in the extension study, (d) mean rate of weeks with or without angioedema in the core and extension studies. Presented at EAACI 2022: https://www.urticariaknowledgecenter.novartis.com/EAACI/presentations/2022/Posters/EAACI_2022_Angioedema_control_Poster.pdf. Box-and-whisker plot shows medians (horizontal line) with Q1-Q3 range (edges of box), error bars represent SD, with a diamond marker within the box depicting mean. LS means from Mixed model of repeated measures (MMRM model): CFB in AAS7 score, considering treatment, visit, baseline total IgE, baseline AAS7 score, age as covariates for core study, and visit and extension baseline AAS7 score as covariates for the extension. Only patients with angioedema at baseline were considered for this analysis. Rate of angioedema is defined as (number of weeks with angioedema in core treatment phase)/(number of completed weeks in core treatment phase). Rate of non-angioedema is defined as: (number of weeks without angioedema in core treatment phase)/(number of completed weeks in core treatment phase). Blue dotted line indicates primary endpoint. Red dotted line indicates the end of the treatment period of the core study. AAS7, weekly angioedema activity score; CFB, change from baseline; Ext., extension; LIG, ligelizumab; LS Mean, least squares mean; n, number of patients; OMA, omalizumab; Q1-Q3, 1st to 3rd interquartile range; SD, standard deviation.

Fig. 2

Urticaria activity and co-occurrence of angioedema: (a) median (IQ range), mean ± SD UAS7 at baseline in the Phase 2b and studies; mean CFB UAS7 in patients (b) with angioedema and (c) without angioedema in the core Phase 2b study, and (d) with or without angioedema in the extension study; AAS7 by UAS7 responder status among patient with angioedema at baseline in (e) core study, and (f) extension study. Presented at AAD 2022: https://www.urticariaknowledgecenter.novartis.com/AAD/presentations/2022/AAD_2022_Patients_treated_Poster.pdf. Box-and-whisker plot shows medians (horizontal line) with Q1-Q3 range (edges of box). Error bars represent SD. Diamond marker within the box depicts mean. Blue and red dotted line indicates primary endpoint (Week 12) and end of the treatment period (Week 20), respectively. Patients who remained in the follow-up period for at least 12 weeks and had active disease (UAS7≥12), could enter the extension study from Week 32 onwards for the core study. UAS7 disease activity categories; complete response (UAS7 = 0); well-controlled (UAS7 = 1–6); mild (UAS7 = 7–15); moderate (UAS7 = 16–27); severe (UAS7 = 28–42). AAS7, Weekly Angioedema Activity score; BL, baseline; CFB, change from baseline; Ext., extension; LIG, ligelizumab; LS mean, least squares mean; n, number of patients; OMA, omalizumab; SD, standard deviation; SE, standard error; UAS7, weekly urticaria activity score.

Fig. 3

Dermatology-QoL by angioedema status at baseline: (a) Median (IQ range), mean ± SD in the Phase 2b core and extension studies. AAS7 comparison by DLQI categories among patient with angioedema at baseline (b) in the Phase 2b core study, and (c) in the extension study. Presented at EAACI 2022: https://www.urticariaknowledgecenter.novartis.com/EAACI/presentations/2022/Posters/EAACI_2022_Angioedema_control_Poster.pdf. Box-and-whisker plot shows medians (horizontal line) with Q1-Q3 range (edges of box), error bars represent SD, with a diamond marker within the box depicting mean. DLQI categories for effect on QoL (DLQI score 0–1: no effect; 2–5: small effect; 6–10: moderate effect; 11–20: very large effect; and 21–30: extremely large effect). AAS7, weekly angioedema activity score; BL, baseline; DLQI, Dermatology Life Quality Index; Ext., extension; LIG, ligelizumab; OMA, omalizumab; QoL, quality of life; SE, standard error; SD, standard deviation