Soegiharto Reineke, Alizadeh Aghdam Mehran, Sørensen Jennifer Astrup, van Lindonk Esmee, Bulut Demir Ferhan, Porras Nasser Mohammad, Matsuo Yoshimi, Kiefer Lea, Knulst André C, Maurer Marcus, Ritchie Carla, Rudenko Michael, Kocatürk Emek, Criado Roberta F J, Gregoriou Stamatis, Bobylev Tatjana, Kleinheinz Andreas, Takahagi Shunsuke, Hide Michihiro, Giménez-Arnau Ana M, Salman Andaç, Kara Rabia O, Sevimli Dikicier Bahar, van Doorn Martijn B A, Thomsen Simon F, van den Reek Juul M P A, Röckmann Heike
Department of Dermatology/Allergology, University Medical Centre Utrecht, Utrecht University, Utrecht, Netherlands.
Department of Dermato-Venereology and Wound Healing Centre, University of Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark.
JAMA Dermatol. 2024 Sep 1;160(9):927-935. doi: 10.1001/jamadermatol.2024.2056.
Treating patients with chronic urticaria using omalizumab has been shown to be safe and effective in randomized clinical trials. Multinational studies on long-term omalizumab performance in chronic urticaria in clinical practice settings are lacking, especially on drug survival. Drug survival, which refers to the length of time that patients are treated with a specific drug, is a comprehensive outcome covering effectiveness, safety, and patient and physician preferences. Furthermore, little is known about the reasons and potential predictors for omalizumab discontinuation.
To investigate omalizumab drug survival as well as reasons and potential predictors for discontinuation in a large, diverse population.
DESIGN, SETTING, AND PARTICIPANTS: This international multicenter cohort study was conducted at 14 Urticaria Centers of Reference and Excellence in 10 countries, including all patients with chronic urticaria from these centers who were ever treated with omalizumab.
Drug survival analysis was performed to assess time to discontinuation. Patient characteristics and treatment protocols were investigated by Cox regression analysis to identify potential predictors for omalizumab discontinuation.
In 2325 patients with chronic urticaria who started omalizumab between June 2009 and July 2022, the mean (SD) age of the cohort was 42 (6) years, and 1650 participants (71%) were female. Overall omalizumab survival rates decreased from 76% to 39% after 1 to 7 years, respectively (median survival time, 3.3 [95 % CI, 2.9-4.0] years), primarily due to discontinuation from well-controlled disease in 576 patients (65%). Ineffectiveness and adverse effects were reasons for discontinuation in a far smaller proportion of patients, totaling 164 patients (18%) and 31 patients (4%), respectively. Fast treatment response was associated with higher rates of omalizumab discontinuation due to well-controlled disease (hazard ratio, 1.45 [95% CI, 1.20-1.75]), and disease duration of more than 2 years was associated with lower rates of discontinuation due to well-controlled disease (HR, 0.81 [95% CI, 0.67-0.98]). Immunosuppressive cotreatment at the start of omalizumab and autoimmune disease was associated with a higher risk for discontinuation due to ineffectiveness (HR, 1.65 [95% CI, 1.12-2.42]). The presence of spontaneous wheals (HR, 0.62 [95% CI, 0.41-0.93]) and access to higher dosages (HR, 0.40 [95% CI, 0.27-0.58) were both associated with a lower risk for discontinuation of omalizumab due to ineffectiveness.
This multinational omalizumab drug survival cohort study demonstrated that treatment of chronic urticaria with omalizumab in a clinical setting is effective and safe, and well-controlled disease is the main reason for treatment discontinuation. These findings on omalizumab drug survival rates and reasons and potential predictors for discontinuation may guide patients and physicians in clinical decision-making and expectation management. These results may call for the identification of biomarkers for chronic urticaria remission in complete responders to omalizumab treatment.
在随机临床试验中，已证明使用奥马珠单抗治疗慢性荨麻疹患者是安全有效的。缺乏关于奥马珠单抗在临床实践环境中治疗慢性荨麻疹的长期疗效的跨国研究，尤其是关于药物留存率的研究。药物留存率是指患者接受特定药物治疗的时间长度，是一个涵盖有效性、安全性以及患者和医生偏好的综合结果。此外，对于奥马珠单抗停药的原因和潜在预测因素知之甚少。
在一个大型、多样化的人群中调查奥马珠单抗的药物留存率以及停药的原因和潜在预测因素。
设计、设置和参与者：这项国际多中心队列研究在10个国家的14个荨麻疹参考和卓越中心进行，纳入了这些中心所有曾接受奥马珠单抗治疗的慢性荨麻疹患者。
进行药物留存率分析以评估停药时间。通过Cox回归分析研究患者特征和治疗方案，以确定奥马珠单抗停药的潜在预测因素。
在2009年6月至2022年7月开始使用奥马珠单抗的2325例慢性荨麻疹患者中，队列的平均（标准差）年龄为42（6）岁，1650名参与者（71%）为女性。奥马珠单抗的总体留存率在1至7年后分别从76%降至39%（中位留存时间，3.3[95%CI，2.9 - 4.0]年），主要原因是576例患者（65%）因病情得到良好控制而停药。无效和不良反应导致停药的患者比例要小得多，分别为164例患者（18%）和31例患者（4%）。快速的治疗反应与因病情得到良好控制而停用奥马珠单抗的较高发生率相关（风险比，1.45[95%CI，1.20 - 1.75]），病程超过2年与因病情得到良好控制而停药的较低发生率相关（HR，0.81[95%CI，0.67 - 0.98]）。在开始使用奥马珠单抗时进行免疫抑制联合治疗以及患有自身免疫性疾病与因无效而停药的较高风险相关（HR，1.65[95%CI，1.12 - 2.42]）。出现自发性风团（HR，0.62[95%CI，0.41 - 0.93]）和能够使用更高剂量（HR，0.40[95%CI，0.27 - 0.58]）均与因无效而停用奥马珠单抗的较低风险相关。
这项跨国奥马珠单抗药物留存率队列研究表明，在临床环境中用奥马珠单抗治疗慢性荨麻疹是有效且安全的，病情得到良好控制是治疗停药的主要原因。这些关于奥马珠单抗药物留存率、停药原因和潜在预测因素的发现可能会指导患者和医生进行临床决策和预期管理。这些结果可能需要识别奥马珠单抗治疗完全缓解的慢性荨麻疹患者的生物标志物。
