Giménez-Arnau Ana, Maurer Marcus, Bernstein Jonathan, Staubach Petra, Barbier Nathalie, Hua Eva, Severin Thomas, Joubert Yolandi, Janocha Reinhold, Balp Maria-Magdalena
Department of Dermatology, Hospital del Mar, Institut Mar d´Investigacions Mèdiques, Universitat Autònoma, Barcelona, Spain.
Department of Dermatology and Allergy, Dermatological Allergology, Allergie-Centrum-Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Clin Transl Allergy. 2022 Feb;12(2):e12121. doi: 10.1002/clt2.12121.
Chronic spontaneous urticaria (CSU) negatively impacts patients' sleep, thereby reducing health-related quality of life (HRQoL). Half of patients with inadequately controlled CSU report sleep interference often or every night, which can lead to depression, anxiety, social, and work-related problems.
This randomized, double-blind, placebo-controlled Phase 2b core study (NCT02477332) included adult patients ≥18 years with moderate to severe CSU inadequately controlled with H -antihistamines. The current analysis includes patients randomized to receive ligelizumab 72 or 240 mg, omalizumab 300 mg or placebo every 4 weeks (q4w) for five injections over 20 weeks with treatment-free follow-up for 24 weeks. Patients could enter the open-label extension study (NCT02649218) from Week 32 onwards if their weekly urticaria activity score was ≥12, which included an open-label treatment (52 weeks of ligelizumab 240 mg q4w) and a 48-week post-treatment follow-up. Weekly Sleep Interference Scores (SIS7, range 0 [no interference]-21 [substantial interference]), Weekly Activity Interference Score (AIS7), Dermatology Life Quality Index (DLQI) scores, and Overall Work Impairment were assessed.
Mean baseline SIS7 scores were balanced between the treatment arms for ligelizumab 72 mg (n = 84) and 240 mg (n = 85), omalizumab 300 mg (n = 85), and placebo (n = 43). By Week 12, patients experienced large improvements in sleep interference, with least square mean (standard error) changes from baseline (CFB) in SIS7 of -7.84 (0.58), -7.55 (0.61), -6.98 (0.60), and -5.85 (0.81), respectively. By Week 12, CFB in AIS7 were -8.25 (0.57), -8.25 (0.59), -7.30 (0.60), and -5.62 (0.79), DLQI scores were -9.79 (0.77), -9.93 (0.81), -8.35 (0.79), and -6.99 (1.11), and Overall Work Impairment scores were -28.96 (3.73), -30.76 (3.71), -25.74 (3.91), and -20.13 (5.10) for ligelizumab 72 and 240 mg, omalizumab 300 mg and placebo, respectively. Improvements in each patient-reported outcome were sustained with ligelizumab 240 mg treatment during the extension study.
Ligelizumab showed effective and sustained responses in managing sleep interference in patients with CSU, and numerically higher responses than with omalizumab and placebo. Treating the symptoms of CSU with ligelizumab improved disease burden, HRQoL, and markedly improved sleep quality.
慢性自发性荨麻疹（CSU）对患者的睡眠产生负面影响，从而降低健康相关生活质量（HRQoL）。一半控制不佳的CSU患者报告经常或每晚存在睡眠干扰，这可能导致抑郁、焦虑、社交及工作相关问题。
这项随机、双盲、安慰剂对照的2b期核心研究（NCT02477332）纳入了年龄≥18岁、使用H-抗组胺药控制不佳的中度至重度CSU成年患者。当前分析包括随机接受每4周（q4w）一次72或240mg利吉珠单抗、300mg奥马珠单抗或安慰剂治疗，共注射5次、为期20周，随后进行24周无治疗随访的患者。如果患者每周荨麻疹活动评分为≥12分，可从第32周起进入开放标签扩展研究（NCT02649218），该研究包括开放标签治疗（240mg利吉珠单抗q4w，共52周）及48周的治疗后随访。评估每周睡眠干扰评分（SIS7，范围0[无干扰] - 21[严重干扰]）、每周活动干扰评分（AIS7）、皮肤病生活质量指数（DLQI）评分及总体工作受损情况。
利吉珠单抗72mg（n = 84）和240mg（n = 85）、奥马珠单抗300mg（n = 85）及安慰剂（n = 43）治疗组的平均基线SIS7评分均衡。到第12周时，患者的睡眠干扰有显著改善，利吉珠单抗72mg、240mg，奥马珠单抗300mg及安慰剂组的SIS7自基线的最小二乘均值（标准误）变化分别为 - 7.84（0.58）、 - 7.55（0.61）、 - 6.98（0.60）及 - 5.85（0.81）。到第12周时，利吉珠单抗72mg、240mg，奥马珠单抗300mg及安慰剂组的AIS7自基线变化分别为 - 8.25（0.57）、 - 8.25（0.59）、 - 7.30（0.60）及 - 5.62（0.79），DLQI评分分别为 - 9.79（0.77）、 - 9.93（0.
