Ligelizumab improves angioedema, disease severity and quality-of-life in patients with chronic spontaneous urticaria
Martin MetzJonathan A. BernsteinAna M. Giménez‐ArnauMichihiro HideMarcus MaurerKarl SitzWeily SoongGordon SussmanEva HuaAvantika BarveNathalie BarbierMaria‐Magdalena BalpThomas Severin
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BackgroundDisease 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.MethodsData 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.ResultsFrom 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).ConclusionIn the Phase 2b study, ligelizumab effectively reduced angioedema and urticaria symptoms, and improved health related quality of life in patients with moderate-to-severe CSU.Clinicaltrails.gov NCT numberNCT02477332; NCT02649218.Keywords:
Omalizumab
Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied.The primary objective was to evaluate the efficacy of omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU-Q2oL) questionnaire. Number of angioedema-burdened days, time interval between successive angioedema episodes, disease activity, angioedema-specific and overall QoL impairment were secondary objectives.X-ACT was a phase III, randomized, double-blind study conducted in 24 centres (Germany), which selectively included CSU patients with angioedema and wheals. Patients were randomized (1 : 1) to omalizumab 300 mg or placebo (every 4 weeks up to week 24) (ClinicalTrials.gov number: NCT01723072).Of the 91 patients randomized to omalizumab (n = 44) or placebo (n = 47) at baseline, 68 completed the 28-week treatment phase (omalizumab, 35; placebo, 33). Omalizumab was superior to placebo in improving CU-Q2oL scores at week 28 (P < 0.001). There was a threefold improvement in angioedema-burdened days/week with omalizumab (0.3) vs placebo (1.1). The median time to first recurrence of angioedema was 57-63 days with omalizumab and <5 days with placebo. Omalizumab significantly improved angioedema-specific QoL (P < 0.001). The adverse events reported are in line with the established safety profile of omalizumab.Omalizumab was an effective treatment option for patients with moderate-to-severe CSU symptoms and angioedema unresponsive to high doses of antihistamine treatment.
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Background
Chronic urticaria (CU) is a common disorder characterized by recurrent episodes of urticaria pruritic erythematous lesions, associated with angioedema1. It affects 0.1% of the population, it is estimated that approximately 15 to 25% of the population will have hives at some point in their lives.2 About 80% of UC patients are diagnosed as idiopathic chronic urticaria and that no cause is identified, 3 experiencing deterioration in their quality of life affecting your work, social relationships, schemes requiring multiple medications and doses higher than usual. This study proposes Omalizumab (anti-IgE humanized antibody) as a treatment for Refractory Chronic Urticaria (RCU)
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In order to identify the etiologic factors in childhood chronic urticaria, we studied 226 children, 122 boys and 104 girls, aged 1 to 14 (mean = 8.14) years with chronic urticaria and/or angioedema. The initial evaluation consisted of a thorough history, physical examination, and basic laboratory tests. Specific in vivo and in vitro tests were done according to the findings of the initial evaluation. Urticaria alone was present in 78.4% of the patients, angioedema alone in 6.6%, and both urticaria and angioedema in 15% of the patients. Chronic urticaria was attributed to physical factors in 6.2% of the patients, infections in 4.4%, aeroallergens in 2.2%, foods in 4%, food additives in 2.6%, and drugs in 1.8% of the patients. Overall, causal factors of chronic urticaria were found in 21.2% of the patients.
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Treatment of chronic urticaria refractory to antihistamines presents a challenge to both people affected with the disease as well as the physicians who treat them. Omalizumab, a monoclonal antibody against IgE, has emerged as one potential solution to this challenge. In several clinical trials published between 2011 and 2013, omalizumab significantly reduced or eliminated symptoms of chronic urticaria. The optimal dose for chronic urticaria is 300 mg administered every 4 weeks, a dose that differs from those used in asthma, which are based on the patient's weight and IgE level. Omalizumab does not appear to cause lasting symptom remission, and the ideal duration of treatment for chronic urticaria has not been defined.
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Angioedema with swelling of larynx is a serious allergic reaction and can be life-threatening. It can occur after exposure to various triggers and usually it is very difficult for the patient and the doctor to find the trigger and maintain complete remission. In idiopathic recurring angioedema presenting with frequent attacks, prophylaxis with H1 antihistamines recommended. However, not all patients respond to antihistamines. Omalizumab is an anti-immunoglobulin (Ig)-E-Ig-G antibody approved for the treatment of asthma and also effective treatment in chronic spontaneous urticaria. We report a 47-year-old male patient with severe idiopathic angioedema controlled by corticosteroid and proggressed after discontining of corticosteroid because of its side effects. Omalizumab at a dose of 300 mg every 4 weeks was administrated and omalizumab provided a rapid clinical response after first injection. During the 4 months of omalizumab therapy, he had no further attacks and any other treatment needs. After 3 months of stopping omalizumab therapy, during the 4-week period he had two mild lip swelling in his lips that resolved with antihistamines.
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