Annals of Allergy Asthma & Immunology最新文献_第7页

CHARACTERISTICS OF PATIENTS WITH CHRONIC SPONTANEOUS URTICARIA WHO ARE EARLY RESPONDERS TO OMALIZUMAB 对奥马珠单抗早期应答的慢性自发性荨麻疹患者的特征

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2024-10-25 DOI: 10.1016/j.anai.2024.08.109

S. Saini , T. Casale , M. Holden , B. Trzaskoma , J. Bernstein

Introduction

Omalizumab, an anti-immunoglobulin E (IgE) antibody, is approved for the treatment of H1-antihistamine-refractory chronic spontaneous urticaria (CSU), and studies suggest that time to response may vary across patient subgroups. Patient characteristics associated with an early response to omalizumab are not well understood.

Methods

We conducted a post-hoc analysis of pooled phase 3 ASTERIA I/II trials (NCT01287117/01292473). Patients with H1-antihistamine-refractory CSU received omalizumab or placebo for up to 24 weeks. Response to omalizumab was defined as a weekly Urticaria Activity Score (UAS7) of ≤6. Baseline demographics and clinical characteristics were assessed among early responders and non-responders at Week 4. Analyses were conducted within the omalizumab 300 mg treatment group by evaluating baseline variables one at a time and P values were generated using 2-sample t-tests for continuous baseline variables and chi-square tests for categorical variables.

Results

A higher proportion of early responders had a negative chronic urticaria (CU) index or angioedema at baseline versus non-responders (for negative CU index, 87.0% [n=60/69] vs 66.7% [n=60/90], P=0.0032; for angioedema, 51.4% [n=36/70] vs 33.3% [n=30/90], P=0.0211). Among patients with both a negative CU index and angioedema at baseline, 68.3% were early responders (n=28/41); however, there was only 1 early responder among patients with the opposite characteristics (both a positive CU index and no angioedema, 7.1% [n=1/14]). Overall safety results for ASTERIA I/II: Maurer NEJM 2013;368:924-35 and Saini JID 2015;135;67-75.

Conclusions

Patients with CSU with a negative CU index and/or angioedema at baseline may be more likely to be early responders after initiating treatment with omalizumab 300 mg.

导言奥马珠单抗是一种抗免疫球蛋白E（IgE）抗体，已被批准用于治疗H1-抗组胺难治性慢性自发性荨麻疹（CSU）。我们对ASTERIA I/II期试验（NCT01287117/01292473）进行了事后分析。H1-抗组胺难治性CSU患者接受了长达24周的奥马珠单抗或安慰剂治疗。对奥马珠单抗的反应定义为每周荨麻疹活动评分（UAS7）≤6。在第4周对早期应答者和非应答者进行了基线人口统计学和临床特征评估。在奥马珠单抗 300 毫克治疗组内进行分析，每次评估一个基线变量，对连续基线变量采用双样本 t 检验，对分类变量采用卡方检验得出 P 值。结果早期应答者与非应答者相比，基线慢性荨麻疹（CU）指数或血管性水肿为阴性的比例更高（CU指数阴性，87.0% [n=60/69] vs 66.7% [n=60/90]，P=0.0032；血管性水肿，51.4% [n=36/70] vs 33.3% [n=30/90]，P=0.0211）。在基线CU指数和血管性水肿均为阴性的患者中，68.3%为早期应答者（n=28/41）；但在具有相反特征（CU指数均为阳性且无血管性水肿，7.1% [n=1/14]）的患者中，只有1例早期应答者。ASTERIA I/II的总体安全性结果：Maurer NEJM 2013;368:924-35和Saini JID 2015;135;67-75.结论基线时CU指数为阴性和/或血管性水肿的CSU患者在开始使用奥马珠单抗300毫克治疗后更有可能成为早期应答者。

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引用次数: 0

RACIAL AND ETHNIC DISPARITIES IN SUBCUTANEOUS ALLERGEN IMMUNOTHERAPY FOR PEDIATRIC PATIENTS WITH ALLERGIC RHINITIS 儿科过敏性鼻炎患者皮下过敏原免疫疗法的种族和民族差异

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2024-10-25 DOI: 10.1016/j.anai.2024.08.080

K. Nguyen , T. Al-Shaikhly

Introduction

Racial and ethnic disparities in treatment are commonly found across multiple atopic diseases. Herein, we explore discrepancies in initiation of subcutaneous allergen immunotherapy (SCIT) among various races and ethnicities of pediatric patients with allergic rhinitis.

Methods

In this retrospective matched cohort study, we utilized the TriNetX US Collaborative Network (TriNetX LLC, Cambridge, MA), a multicenter electronic health record database, to identify pediatric patients with allergic rhinitis (age 1-17 years). Patients were stratified into study groups according to their racial and ethnic identification. The study groups were further matched for baseline demographics, atopic comorbidities, heart diseases, and use of beta-blockers and angiotensin-converting enzyme inhibitors. Relative risk (RR) and Confidence Interval (CI) for SCIT initiation were contrasted across study groups.

Results

Among 544,360 pediatric patients with allergic rhinitis (mean age (± standard deviation) was 7.6 (4.5) years; % females, 46.9%), ethnicity data was available for 88.3% of patients with 79.7% identified as non-Hispanic. Over a 3-year observation period, fewer pediatric Black patients [RR, 0.30; 95% CI, 0.24-0.38)] were started on SCIT as compared to pediatric non-Hispanic White patients. Similarly, the proportion of Hispanic [RR, 0.46; 95% CI, 0.37-0.58)] and Asian [RR, 0.49; 95% CI, 0.30-0.81)] pediatric patients with allergic rhinitis who were initiated on SCIT were lower than their non-Hispanic White counterparts.

Conclusion

In the United States, racial and ethnic disparities in SCIT prescription extend to pediatric patients with allergic rhinitis with underutilization of SCIT among under-represented races and ethnicities in comparison to White patients. Barriers to treatment should be further explored and mitigated.

导言：在多种特应性疾病中，治疗中的种族和民族差异很常见。在这项回顾性匹配队列研究中，我们利用多中心电子健康记录数据库 TriNetX US Collaborative Network（TriNetX LLC，马萨诸塞州剑桥市）来识别过敏性鼻炎儿科患者（1-17 岁）。根据患者的种族和民族身份将其分为不同的研究组。各研究组的基线人口统计学、特应性合并症、心脏病以及β-受体阻滞剂和血管紧张素转换酶抑制剂的使用情况进一步匹配。结果在 544,360 名过敏性鼻炎儿科患者中（平均年龄（± 标准差）为 7.6 (4.5) 岁；女性占 46.9%），88.3% 的患者有种族数据，其中 79.7% 被认定为非西班牙裔。在 3 年的观察期内，与非西班牙裔白人儿科患者相比，黑人儿科患者开始使用 SCIT 的比例较低 [RR，0.30；95% CI，0.24-0.38]。同样，西班牙裔[RR，0.46；95% CI，0.37-0.58]和亚裔[RR，0.49；95% CI，0.30-0.81]儿科过敏性鼻炎患者开始使用 SCIT 的比例也低于非西班牙裔白人患者。结论在美国，过敏性鼻炎儿科患者在SCIT处方方面存在种族和民族差异，与白人患者相比，代表性不足的种族和民族对SCIT的使用率较低。应进一步探索和减少治疗障碍。

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引用次数: 0

PROPHYLACTIC TREATMENT WITH ORAL DEUCRICTIBANT IMPROVES HEREDITARY ANGIOEDEMA DISEASE CONTROL AND HEALTH-RELATED QUALITY OF LIFE 口服杜冷丁预防性治疗可改善遗传性血管性水肿的病情控制和与健康相关的生活质量

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2024-10-25 DOI: 10.1016/j.anai.2024.08.131

H. Wedner , J. Anderson , H. Chapdelaine , M. Magerl , M. Manning , M. Riedl , P. Lu , E. Aygoren-Pursun

Introduction

Hereditary angioedema (HAE) attacks are caused by excess bradykinin activating bradykinin B2 receptors. Deucrictibant is a selective, orally-administered bradykinin B2 receptor antagonist under development for on-demand and prophylactic treatment of HAE attacks.

Methods

CHAPTER-1 (NCT05047185) is an ongoing 2-part Phase 2 study evaluating efficacy and safety of deucrictibant for long-term prophylaxis of HAE attacks. In part 1, participants received double-blinded placebo or deucrictibant 20mg/day or 40mg/day (immediate-release capsule formulation) for 12 weeks. Thirty-four participants were enrolled. In the ongoing part 2, participants receive treatment with open-label deucrictibant 40mg/day. Disease control, health-related quality of life (HRQoL), and patient treatment satisfaction were assessed using Angioedema Control Test (AECT); Patient Global Assessment of Change (PGA-Change) and Angioedema QoL Questionnaire (AE-QoL); and Treatment Satisfaction Questionnaire for Medication (TSQM).

Results

In placebo-controlled part 1, at 12 weeks, 9/10 participants in both deucrictibant 20mg/day and 40mg/day dose-groups had well-controlled disease by AECT vs 3/8 receiving placebo (P=0.0430 both doses). By PGA-Change, 8/10 and 7/9 participants reported feeling “much better” in the deucrictibant 20mg/day and 40mg/day groups vs 1/8 in the placebo group. Mean AE-QoL total score improved from baseline to week 12 by 19.0, 25.9, and 11.9 points in participants receiving deucrictibant 20mg/day, 40mg/day, and placebo. Participants receiving deucrictibant experienced greater treatment satisfaction, with mean TSQM Global Scores of 89.2 and 85.8 with deucrictibant 20mg/day and 40mg/day vs 59.4 with placebo.

Conclusion

Prophylaxis with oral deucrictibant for 12 weeks resulted in improvement in disease control, HRQoL, and treatment satisfaction vs placebo in people with HAE.

导言垂体性血管性水肿（HAE）发作是由过量缓激肽激活缓激肽 B2 受体引起的。方法CHAPTER-1（NCT05047185）是一项正在进行的二期研究，由两部分组成，评估缓激肽B2受体拮抗剂用于长期预防HAE发作的疗效和安全性。在第一部分中，参与者接受双盲安慰剂或20毫克/天或40毫克/天（速释胶囊剂）的脱昔利班治疗，为期12周。共有 34 人参加。在正在进行的第2部分中，参与者将接受40毫克/天的开放标签地屈孕酮治疗。使用血管性水肿控制测试（AECT）、患者总体变化评估（PGA-Change）和血管性水肿生活质量问卷（AE-QoL）以及药物治疗满意度问卷（TSQM）评估疾病控制、健康相关生活质量（HRQoL）和患者治疗满意度。结果在安慰剂对照的第一部分中，12周时，根据AECT，9/10名服用20毫克/天和40毫克/天剂量组的患者与3/8名服用安慰剂的患者相比，病情得到了很好的控制（两种剂量的P=0.0430）。在PGA-Change中，8/10和7/9的参与者报告说，每天服用20毫克和40毫克剂量组的患者感觉 "好多了"，而安慰剂组只有1/8的患者感觉 "好多了"。从基线到第12周，接受杜克瑞班特20毫克/天、40毫克/天和安慰剂治疗的参试者平均AE-QoL总分分别提高了19.0分、25.9分和11.9分。结论：与安慰剂相比，在HAE患者中口服12周的右旋瑞班可改善疾病控制、HRQoL和治疗满意度。

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引用次数: 0

EFFICACY AND SAFETY OF A THREE-STEP ASPIRIN CHALLENGE PROTOCOL IN A MONITORED CLINIC SETTING 在受监控的诊所环境中，三步阿司匹林挑战方案的有效性和安全性

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2024-10-25 DOI: 10.1016/j.anai.2024.08.038

A. Irace, I. Thapar, J. Bosso, J. Douglas

Introduction

Aspirin challenge is the gold standard procedure to diagnose aspirin-exacerbated respiratory disease in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and an unclear history of aspirin/NSAID drug reactions. The goal of this study is to establish the efficacy and safety of a 3-step in-clinic aspirin challenge protocol.

Methods

From 2016-2023, 145 patients with CRSwNP and asthma underwent aspirin challenge. Increasing aspirin dosages, from 30 to 325 mg, were administered with a 60-minute (after 30 mg), 90-minute (after 81 mg), and 3-hour (after 325 mg) dosing interval in clinic. Patient demographics, vitals, symptoms and symptom scores, FEV1, peak nasal inspiratory flow rate (PNIFR), and treatments administered were analyzed. A positive reaction was defined as an increased symptom score ≥5 points from baseline, decreased FEV1 by ≥15%, or decreased PNIFR by ≥20%.

Results

Among 145 patients, 67 (46.2%) had positive challenges. The most common provoking dose was 30 mg (47.8%), followed by 81 mg (43.3%). Among reactors, symptoms usually presented at the 1-hour (n=26, 38.8%) or 2-hour timepoint (n=18, 26.9%). From baseline to nadir, mean decrease in FEV1 was 8.9%, and mean decrease in PNIFR was 24.5%. The most common symptoms were nasal congestion (n=51, 76.1%) and rhinorrhea (n=23, 34.3%). Epinephrine was infrequently required (n=9, 13.4%). No patients required ED transfer or hospitalization, and mean challenge duration was 4.76 hours.

Conclusion

With a mean duration <5 hours and excellent safety profile, our study demonstrates an efficient, 3-step aspirin challenge protocol that was safely performed in an outpatient clinic setting.

导言阿司匹林挑战是诊断慢性鼻炎伴鼻息肉（CRSwNP）、哮喘和阿司匹林/非甾体抗炎药物反应史不明确的患者阿司匹林加重呼吸道疾病的金标准程序。本研究的目的是确定诊所内阿司匹林挑战三步方案的有效性和安全性。方法从 2016 年至 2023 年，145 名 CRSwNP 和哮喘患者接受了阿司匹林挑战。阿司匹林剂量从 30 毫克到 325 毫克不断增加，临床给药间隔分别为 60 分钟（30 毫克后）、90 分钟（81 毫克后）和 3 小时（325 毫克后）。对患者的人口统计学特征、生命体征、症状和症状评分、FEV1、鼻吸气流量峰值 (PNIFR) 和治疗方法进行了分析。阳性反应的定义是症状评分比基线增加≥5分，FEV1下降≥15%，或PNIFR下降≥20%。最常见的激起剂量是 30 毫克（47.8%），其次是 81 毫克（43.3%）。在反应者中，症状通常在 1 小时（26 人，占 38.8%）或 2 小时（18 人，占 26.9%）时出现。从基线到最低点，FEV1 平均下降 8.9%，PNIFR 平均下降 24.5%。最常见的症状是鼻塞（51 人，占 76.1%）和鼻出血（23 人，占 34.3%）。需要肾上腺素的情况不多（9 人，占 13.4%）。没有患者需要转送急诊室或住院治疗，平均挑战持续时间为 4.76 小时。结论我们的研究展示了一种高效的三步阿司匹林挑战方案，其平均持续时间为 5 小时，安全性极佳，可在门诊环境中安全实施。

{"title":"EFFICACY AND SAFETY OF A THREE-STEP ASPIRIN CHALLENGE PROTOCOL IN A MONITORED CLINIC SETTING","authors":"A. Irace, I. Thapar, J. Bosso, J. Douglas","doi":"10.1016/j.anai.2024.08.038","DOIUrl":"10.1016/j.anai.2024.08.038","url":null,"abstract":"<div><h3>Introduction</h3><div>Aspirin challenge is the gold standard procedure to diagnose aspirin-exacerbated respiratory disease in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and an unclear history of aspirin/NSAID drug reactions. The goal of this study is to establish the efficacy and safety of a 3-step in-clinic aspirin challenge protocol.</div></div><div><h3>Methods</h3><div>From 2016-2023, 145 patients with CRSwNP and asthma underwent aspirin challenge. Increasing aspirin dosages, from 30 to 325 mg, were administered with a 60-minute (after 30 mg), 90-minute (after 81 mg), and 3-hour (after 325 mg) dosing interval in clinic. Patient demographics, vitals, symptoms and symptom scores, FEV1, peak nasal inspiratory flow rate (PNIFR), and treatments administered were analyzed. A positive reaction was defined as an increased symptom score ≥5 points from baseline, decreased FEV1 by ≥15%, or decreased PNIFR by ≥20%.</div></div><div><h3>Results</h3><div>Among 145 patients, 67 (46.2%) had positive challenges. The most common provoking dose was 30 mg (47.8%), followed by 81 mg (43.3%). Among reactors, symptoms usually presented at the 1-hour (n=26, 38.8%) or 2-hour timepoint (n=18, 26.9%). From baseline to nadir, mean decrease in FEV1 was 8.9%, and mean decrease in PNIFR was 24.5%. The most common symptoms were nasal congestion (n=51, 76.1%) and rhinorrhea (n=23, 34.3%). Epinephrine was infrequently required (n=9, 13.4%). No patients required ED transfer or hospitalization, and mean challenge duration was 4.76 hours.</div></div><div><h3>Conclusion</h3><div>With a mean duration <5 hours and excellent safety profile, our study demonstrates an efficient, 3-step aspirin challenge protocol that was safely performed in an outpatient clinic setting.</div></div>","PeriodicalId":50773,"journal":{"name":"Annals of Allergy Asthma & Immunology","volume":"133 6","pages":"Page S3"},"PeriodicalIF":5.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ASSESSMENT OF POTENTIAL CROSS-REACTIVITY REACTIONS AND CHARACTERISTICS OF HOSPITAL INPATIENTS CLAIMING A QUINOLONE DRUG ALLERGY 评估潜在的交叉反应和声称对喹诺酮类药物过敏的住院病人的特征

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2024-10-25 DOI: 10.1016/j.anai.2024.08.076

A. Jain

Introduction

While penicillin allergy research has established the crucial utility of accurate registration of prevalence, characteristics, and diagnosis of ß-lactam allergy, other types of antibiotic allergies have only been partially investigated. The primary objective of this study is to better assess quinolone cross-reactivity.

Methods

A retrospective chart review was performed for all adult inpatients with an index documented history of immediate hypersensitivity to quinolone(s) who received a subsequent systemic quinolone. The primary outcome was immediate hypersensitivity reaction to a second quinolone other than the index quinolone allergy.

Results

A total of 54 cases met inclusion criteria, with a mean age of 67 years old, 74.1% female, and average hospital LOS 3.8 days. Index fluoroquinolone allergy history, in order of prevalence, included rash, hives, anaphylaxis, tendonitis, syncope, unknown, mental status changes, and hemolytic anemia. Of the 54 cases, 3.7% (2/54) experienced an immediate hypersensitivity reaction after second quinolone exposure to ciprofloxacin, levofloxacin, and/or moxifloxacin. Within the ciprofloxacin, levofloxacin, and moxifloxacin index allergy cohorts, the frequency of cross-reactivity was 0% for each index allergy cohort (0/18, 0/25, and 0/0 respectively). The only immediate hypersensitivity reactions noted were for patients claiming an allergy to levofloxacin, who received subsequent reexposure to levofloxacin (18.2%; 2/11).

Conclusion

Our data demonstrated a quinolone cross-reactivity frequency of 0%. Despite our relatively small sample size, these results highlighted the likely low risk of experiencing a cross-reaction when exposed to a different quinolone. With further research and larger sample sizes, this low cross-reactivity frequency can offer practitioners clinical guidance for implications of in-class alternatives.

导言：青霉素过敏研究证实了准确登记ß-内酰胺过敏的患病率、特征和诊断的重要作用，但对其他类型的抗生素过敏仅进行了部分调查。本研究的主要目的是更好地评估喹诺酮类药物的交叉反应性。研究方法：对所有对喹诺酮类药物过敏的成人住院患者进行回顾性病历审查，这些患者均有对喹诺酮类药物过敏的病史记录，且随后接受了系统性喹诺酮类药物治疗。结果共有 54 例符合纳入标准，平均年龄为 67 岁，74.1% 为女性，平均住院时间为 3.8 天。氟喹诺酮类药物过敏的病史依次为皮疹、荨麻疹、过敏性休克、肌腱炎、晕厥、不明原因、精神状态改变和溶血性贫血。在 54 例病例中，有 3.7%（2/54）的患者在第二次接触环丙沙星、左氧氟沙星和/或莫西沙星等喹诺酮类药物后立即出现超敏反应。在环丙沙星、左氧氟沙星和莫西沙星指数过敏队列中，每个指数过敏队列的交叉反应频率均为 0%（分别为 0/18、0/25 和 0/0）。唯一发现的即刻超敏反应是对左氧氟沙星过敏的患者，他们随后再次接触了左氧氟沙星（18.2%；2/11）。尽管我们的样本量相对较小，但这些结果突显出在接触不同喹诺酮类药物时发生交叉反应的风险可能很低。随着进一步的研究和样本量的增加，这种低交叉反应频率可为从业人员提供临床指导，帮助他们了解课内替代药物的影响。

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引用次数: 0

EVALUATION OF AUTOMATED INFUSION PUMP FOR RAPID DESENSITIZATION TO ANTICANCER AGENTS 评估用于抗癌剂快速脱敏的自动输液泵

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2024-10-25 DOI: 10.1016/j.anai.2024.08.077

J. Lee , S. Ban , J. Han , S. Paik , J. Park , J. Jeong , Y. Kim , H. Kang

Introduction

Desensitization presents a promising strategy for reintroducing essential medications to patients experiencing hypersensitivity reactions. However, the process demands significant manual intervention from medical staff in order to adjust dosage and rate of each step. We aimed to assess the efficacy of a novel automated infusion pump (AIP) designed to streamline this process by automating drug administration.

Methods

We conducted a comparative evaluation of AIP versus manual infusion for rapid desensitization of anticancer agents at Seoul National University from November 2022 to February 2024. AIP is programmed to initiate and execute various specified protocols, progressing through predetermined steps automatically.

Results

Analysis of 754 desensitization procedures involving 182 patients revealed that 406 cases (53.8%) utilized the AIP; carboplatin (137 cases, 18.2%), oxaliplatin (127 cases, 16.8%), and rituximab (66 cases, 8.8%) were the most frequently administered medications. Breakthrough reaction (BTR) incidence did not significantly differ between manual and AIP methods for platinum-based agents such as carboplatin, oxaliplatin, and cisplatin (34.1% vs. 25%, p = 0.088) or taxanes such as paclitaxel and docetaxel (12.7% vs. 16.4%, p = 0.456). However, rituximab desensitization exhibited a significantly lower BTR rate with AIP (14.3%) compared to manual infusion (52.6%, p = 0.001), with similar up-dosing steps and infusion duration. Three instances of machine error necessitated a switch to manual infusion, but no adverse effects from infusion errors were reported.

Conclusions

The use of AIP for desensitization presents a safe and labor-saving alternative for manual desensitization, with particularly enhanced efficacy observed in rituximab desensitization compared to manual infusion.

导言：脱敏疗法是向出现过敏反应的患者重新提供必需药物的一种有前途的策略。然而，这一过程需要医务人员大量的人工干预，以调整每个步骤的剂量和速度。我们的目的是评估新型自动输液泵（AIP）的疗效，该泵旨在通过自动给药来简化这一过程。方法我们于 2022 年 11 月至 2024 年 2 月在首尔国立大学对 AIP 与手动输液进行了比较评估，以快速脱敏抗癌药物。结果对涉及 182 名患者的 754 个脱敏程序进行分析后发现，406 例（53.8%）患者使用了 AIP；卡铂（137 例，18.2%）、奥沙利铂（127 例，16.8%）和利妥昔单抗（66 例，8.8%）是最常用的药物。对于卡铂、奥沙利铂和顺铂等铂类药物（34.1% vs. 25%，p = 0.088）或紫杉醇和多西他赛等类固醇类药物（12.7% vs. 16.4%，p = 0.456），人工方法和 AIP 方法的突破性反应（BTR）发生率没有明显差异。不过，利妥昔单抗脱敏疗法的 BTR 率与人工输注（52.6%，p = 0.001）相比，AIP（14.3%）要低得多，而且加药步骤和输注持续时间相似。结论使用 AIP 进行脱敏是一种安全、省力的人工脱敏替代方法，与人工输注相比，利妥昔单抗脱敏的疗效尤其显著。

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引用次数: 0

DRUG DESENSITIZATION CHARACTERIZATION: AN INSTITUTIONAL EXPERIENCE 药物脱敏特征描述：机构经验

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2024-10-25 DOI: 10.1016/j.anai.2024.08.070

A. Heffes-Doon, S. Lee, J. Chin-Hon, E. Banta

Introduction

Chemotherapy desensitization is utilized following hypersensitivity reactions (HSR) to allow for continued administration of medication following type 1 reactions (type 1), cytokine release reactions (CRR) and mixed reactions (both type 1 and CRR). We describe our institutional experience with desensitization.

Methods

We reviewed the charts of patients with HSR referred to allergy and immunology for desensitization, 18-95 years of age, between 2018 to 2024.

Results

Forty-four patients with immediate HSR and desensitization were reviewed; 10 (23%) males, and 34 females (77%), with a mean age of 62.7 years. Indications for treatment were malignancy (80%), autoimmune disease (18%) and anemia (2%). Index reactions (IR) were type 1 (n= 29, 65.9%), mixed (n=10, 22.7%), and CRR (n= 4, 9.1%). Grade 2 IR severity was most common (30.2%), followed by grade 4 (25.6%) and grade 3 (25.6%). Trigger medications included platinum agents (45.4%), anti-CD20 monoclonal antibodies (mAbs) (38.6%) and taxanes (11.4%). The most common desensitization protocol used was a 12-step (93.2%). Forty-one (93%) patients completed desensitization. Three patients (2 rituximab, 1 ocrelizumab) did not due to reactions during desensitization. Nine breakthrough reactions (BR) occurred, of these, 6 completed the desensitization. No mortality related to desensitization occurred.

Conclusion

Desensitization performed in a facility with anaphylaxis-preparedness is an effective method of administering medications to patients with HSR. All patients undergoing desensitization to platinum agents and taxanes completed desensitization, while 3 patients receiving an anti-CD20 mAb did not due to BR symptoms.

导言化疗脱敏是在超敏反应（HSR）发生后进行的，以便在发生1型反应（1型）、细胞因子释放反应（CRR）和混合反应（1型和CRR）后继续用药。我们介绍了本机构在脱敏治疗方面的经验。方法我们回顾了 2018 年至 2024 年间转诊至过敏与免疫科进行脱敏治疗的 HSR 患者病历，患者年龄在 18-95 岁之间。结果回顾了 44 名立即接受 HSR 和脱敏治疗的患者；其中男性 10 人（23%），女性 34 人（77%），平均年龄 62.7 岁。治疗指征为恶性肿瘤（80%）、自身免疫性疾病（18%）和贫血（2%）。指数反应（IR）为1型（29例，65.9%）、混合型（10例，22.7%）和CRR（4例，9.1%）。IR 严重程度 2 级最常见（30.2%），其次是 4 级（25.6%）和 3 级（25.6%）。触发药物包括铂类药物（45.4%）、抗CD20单克隆抗体（mAbs）（38.6%）和类固醇类药物（11.4%）。最常用的脱敏方案是 12 步疗法（93.2%）。41名患者（93%）完成了脱敏治疗。三名患者（2 名利妥昔单抗患者，1 名奥克利珠单抗患者）因脱敏过程中出现反应而未完成脱敏。发生了 9 例突破性反应 (BR)，其中 6 例完成了脱敏治疗。结论在有过敏性休克准备的机构中对 HSR 患者进行脱敏治疗是一种有效的用药方法。所有接受铂类药物和类固醇类药物脱敏治疗的患者都完成了脱敏治疗，而3名接受抗CD20 mAb治疗的患者因出现BR症状而没有完成脱敏治疗。

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引用次数: 0

OUTCOMES OF PATIENTS WITH HEREDITARY ANGIOEDEMA WITH NORMAL C1-INHIBITOR FUNCTION AND ANGIOEDEMA OF UNKNOWN ETIOLOGY c1 抑制剂功能正常的遗传性血管性水肿患者和病因不明的血管性水肿患者的治疗结果

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2024-10-25 DOI: 10.1016/j.anai.2024.08.101

A. Adatia , J. Boursiquot , A. El-Zoeiby , D. Goodyear , C. Kalicinsky , A. Kanani , S. Waserman , S. Betschel

Introduction

Clinical outcomes of patients with hereditary angioedema with normal C1-inhibitor function (HAE nC1-INH) and angioedema of unknown etiology (AE-UNK) in Canada are poorly understood.

Methods

Real-world data on patient characteristics, treatments and outcomes were extracted from electronic heath records of patients with HAE nC1-INH and AE-UNK from Canadian HAE-treating specialist practices.

Results

Of 37 patients with HAE nC1-INH and 23 with AE-UNK, median (range) age at symptom onset was 21.5 (5.0–57.0) and 23.0 years (10.0–54.0), and time to diagnosis from symptom onset was 7.0 (0.0–43.0) and 2.0 years (-10.0–50.0), respectively. Attack characteristics differed between HAE nC1-INH vs. AE-UNK: 65% vs. 26% (p=0.007) reported stress; and 35% vs. 9% (p=0.031) reported estrogen therapy as the predominant attack trigger. Fewer AE-UNK vs. HAE nC1-INH had GI sites affected by attacks (before treatment: p=0.015, after initiation: p=0.032). Pre-diagnosis, most patients received antihistamines. Post-diagnosis, 73% and 74% of HAE nC1-INH and AE-UNK patients received long-term prophylaxis (LTP) (most common were subcutaneous pdC1-INH and tranexamic acid), and 22% and 13% were receiving >1 LTP concurrently. Three-months post-treatment, attack duration and frequency significantly decreased for HAE nC1-INH from 1.00 day (range: 0.00–7.00) to 0.29 (range: 0.02–4.00; p=0.001) and 10.50 attacks (range: 0.00–90.00) to 6.00 (range: 0.00–60.00; p=0.004).

Conclusions

This study demonstrates differing clinical trajectories between HAE nC1-INH and AE-UNK, including attack characteristics, diagnostic delays, and treatment responses. Despite treatment response, many patients still experienced attacks. Unmet need exists for tailored guidelines, therapies, and understanding of pathophysiological differences.

方法从加拿大HAE治疗专科的HAE nC1-INH和AE-UNK患者的电子病历中提取了有关患者特征、治疗和预后的真实数据。结果在37名HAE nC1-INH患者和23名AE-UNK患者中，症状出现时的中位年龄（范围）分别为21.5岁（5.0-57.0岁）和23.0岁（10.0-54.0岁），从症状出现到确诊的时间分别为7.0年（0.0-43.0年）和2.0年（-10.0-50.0年）。HAE nC1-INH 与 AE-UNK 的发作特征有所不同：65% 与 26% （P=0.007）报告说压力是主要的发作诱因；35% 与 9% （P=0.031）报告说雌激素治疗是主要的发作诱因。与 HAE nC1-INH 相比，较少的 AE-UNK 患者的消化道部位受到发作的影响（治疗前：p=0.015；治疗后：p=0.032）。诊断前，大多数患者接受了抗组胺药治疗。诊断后，73%和74%的HAE nC1-INH和AE-UNK患者接受了长期预防（LTP）治疗（最常见的是皮下注射pdC1-INH和氨甲环酸），22%和13%的患者同时接受了>1 LTP治疗。治疗后三个月，HAE nC1-INH的发作持续时间和频率明显减少，从1.00天（范围：0.00-7.00）减少到0.29（范围：0.02-4.00；P=0.001），10.50次发作（范围：0.00-90.00）减少到6.结论本研究显示了 HAE nC1-INH 和 AE-UNK 之间不同的临床轨迹，包括发作特征、诊断延迟和治疗反应。尽管有治疗反应，但许多患者仍会发作。对于量身定制的指南、疗法和对病理生理学差异的理解仍有未满足的需求。

{"title":"OUTCOMES OF PATIENTS WITH HEREDITARY ANGIOEDEMA WITH NORMAL C1-INHIBITOR FUNCTION AND ANGIOEDEMA OF UNKNOWN ETIOLOGY","authors":"A. Adatia , J. Boursiquot , A. El-Zoeiby , D. Goodyear , C. Kalicinsky , A. Kanani , S. Waserman , S. Betschel","doi":"10.1016/j.anai.2024.08.101","DOIUrl":"10.1016/j.anai.2024.08.101","url":null,"abstract":"<div><h3>Introduction</h3><div>Clinical outcomes of patients with hereditary angioedema with normal C1-inhibitor function (HAE nC1-INH) and angioedema of unknown etiology (AE-UNK) in Canada are poorly understood.</div></div><div><h3>Methods</h3><div>Real-world data on patient characteristics, treatments and outcomes were extracted from electronic heath records of patients with HAE nC1-INH and AE-UNK from Canadian HAE-treating specialist practices.</div></div><div><h3>Results</h3><div>Of 37 patients with HAE nC1-INH and 23 with AE-UNK, median (range) age at symptom onset was 21.5 (5.0–57.0) and 23.0 years (10.0–54.0), and time to diagnosis from symptom onset was 7.0 (0.0–43.0) and 2.0 years (-10.0–50.0), respectively. Attack characteristics differed between HAE nC1-INH vs. AE-UNK: 65% vs. 26% (p=0.007) reported stress; and 35% vs. 9% (p=0.031) reported estrogen therapy as the predominant attack trigger. Fewer AE-UNK vs. HAE nC1-INH had GI sites affected by attacks (before treatment: p=0.015, after initiation: p=0.032). Pre-diagnosis, most patients received antihistamines. Post-diagnosis, 73% and 74% of HAE nC1-INH and AE-UNK patients received long-term prophylaxis (LTP) (most common were subcutaneous pdC1-INH and tranexamic acid), and 22% and 13% were receiving >1 LTP concurrently. Three-months post-treatment, attack duration and frequency significantly decreased for HAE nC1-INH from 1.00 day (range: 0.00–7.00) to 0.29 (range: 0.02–4.00; p=0.001) and 10.50 attacks (range: 0.00–90.00) to 6.00 (range: 0.00–60.00; p=0.004).</div></div><div><h3>Conclusions</h3><div>This study demonstrates differing clinical trajectories between HAE nC1-INH and AE-UNK, including attack characteristics, diagnostic delays, and treatment responses. Despite treatment response, many patients still experienced attacks. Unmet need exists for tailored guidelines, therapies, and understanding of pathophysiological differences.</div></div>","PeriodicalId":50773,"journal":{"name":"Annals of Allergy Asthma & Immunology","volume":"133 6","pages":"Page S24"},"PeriodicalIF":5.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142529621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

INDIRECT TREATMENT COMPARISON OF ORAL SEBETRALSTAT AND INTRAVENOUS RHC1-INH AS ON-DEMAND TREATMENTS FOR HEREDITARY ANGIOEDEMA 按需治疗遗传性血管性水肿的口服sebetralstat和静脉注射rhc1-inh的间接治疗比较

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2024-10-25 DOI: 10.1016/j.anai.2024.08.114

A. Wang , H. Li , M. Magerl , T. Craig , M. Manning , N. Hummel , P. Audhya , J. Bernstein

Introduction

Substantial heterogeneity in hereditary angioedema (HAE) on-demand trial designs and endpoints make indirect treatment comparison (ITC) challenging. Sebetralstat, an investigational oral on-demand plasma kallikrein inhibitor, demonstrated efficacy and safety in a phase 3 randomized placebo-controlled trial, in which the primary endpoint of time to beginning of symptom relief was measured by the Patient Global Impression of Change scale. Based on a systematic literature review, among published phase 3 HAE on-demand trials, only one, the pivotal trial for intravenous recombinant human C1 esterase inhibitor (IV-rhC1-INH), reported relevant data for a comparable primary endpoint to enable an ITC with sebetralstat.

Methods

Based on available data, a Bayesian fixed-effects network meta-analysis (NMA) was conducted to indirectly compare the efficacy and safety outcomes of sebetralstat (NCT05259917) and IV-rhC1-INH (NCT01188564, NCT00225147, NCT00262301). Sensitivity analyses were examined with random effects models. Matching-adjusted indirect comparison (MAIC) of efficacy outcome was also performed, adjusting for differences in baseline clinical and demographic characteristics.

Results

The NMA fixed effects model found no significant differences in time to beginning of symptom relief between sebetralstat 300 mg and IV-rhC1-INH 50 IU/kg (HR [95% CI] 0.96 [0.42-2.15] to 1.19 [0.58-2.45]). After adjusting for baseline attack severity, MAIC showed numerically favorable results with sebetralstat vs IV-rhC1-INH, regardless of whether baseline demographics variables were matched. NMA found no significant differences in treatment-related adverse events. All sensitivity analyses returned consistent results.

Conclusions

This ITC study found no significant differences in time to beginning of symptom relief and overall treatment-related adverse events between sebetralstat and IV-rhC1-INH.

导言：遗传性血管性水肿（HAE）按需试验的设计和终点存在很大的异质性，这使得间接治疗比较（ITC）具有挑战性。Sebetralstat是一种按需口服血浆allikrein抑制剂，在一项3期随机安慰剂对照试验中证明了其疗效和安全性。根据系统性文献回顾，在已发表的 HAE 按需治疗 3 期试验中，只有一项试验，即静脉注射重组人 C1 酯酶抑制剂（IV-rhC1-INH）的关键性试验，报告了主要终点可比的相关数据，以实现与赛百特的 ITC。方法根据现有数据，进行了贝叶斯固定效应网络荟萃分析（NMA），间接比较了sebetralstat（NCT05259917）和IV-rhC1-INH（NCT01188564、NCT00225147、NCT00262301）的疗效和安全性结果。采用随机效应模型进行了敏感性分析。结果NMA固定效应模型发现，在症状开始缓解的时间上，sebetralstat 300 mg和IV-rhC1-INH 50 IU/kg之间没有显著差异（HR [95% CI] 0.96 [0.42-2.15] to 1.19 [0.58-2.45]）。对基线发作严重程度进行调整后，MAIC 显示，无论基线人口统计学变量是否匹配，塞贝曲司他与静脉注射-rhC1-INH 的治疗结果在数字上都更有利。NMA发现，治疗相关不良事件没有明显差异。结论这项ITC研究发现，sebetralstat和IV-rhC1-INH在症状开始缓解的时间和总体治疗相关不良事件方面没有显著差异。

{"title":"INDIRECT TREATMENT COMPARISON OF ORAL SEBETRALSTAT AND INTRAVENOUS RHC1-INH AS ON-DEMAND TREATMENTS FOR HEREDITARY ANGIOEDEMA","authors":"A. Wang , H. Li , M. Magerl , T. Craig , M. Manning , N. Hummel , P. Audhya , J. Bernstein","doi":"10.1016/j.anai.2024.08.114","DOIUrl":"10.1016/j.anai.2024.08.114","url":null,"abstract":"<div><h3>Introduction</h3><div>Substantial heterogeneity in hereditary angioedema (HAE) on-demand trial designs and endpoints make indirect treatment comparison (ITC) challenging. Sebetralstat, an investigational oral on-demand plasma kallikrein inhibitor, demonstrated efficacy and safety in a phase 3 randomized placebo-controlled trial, in which the primary endpoint of time to beginning of symptom relief was measured by the Patient Global Impression of Change scale. Based on a systematic literature review, among published phase 3 HAE on-demand trials, only one, the pivotal trial for intravenous recombinant human C1 esterase inhibitor (IV-rhC1-INH), reported relevant data for a comparable primary endpoint to enable an ITC with sebetralstat.</div></div><div><h3>Methods</h3><div>Based on available data, a Bayesian fixed-effects network meta-analysis (NMA) was conducted to indirectly compare the efficacy and safety outcomes of sebetralstat (NCT05259917) and IV-rhC1-INH (NCT01188564, NCT00225147, NCT00262301). Sensitivity analyses were examined with random effects models. Matching-adjusted indirect comparison (MAIC) of efficacy outcome was also performed, adjusting for differences in baseline clinical and demographic characteristics.</div></div><div><h3>Results</h3><div>The NMA fixed effects model found no significant differences in time to beginning of symptom relief between sebetralstat 300 mg and IV-rhC1-INH 50 IU/kg (HR [95% CI] 0.96 [0.42-2.15] to 1.19 [0.58-2.45]). After adjusting for baseline attack severity, MAIC showed numerically favorable results with sebetralstat vs IV-rhC1-INH, regardless of whether baseline demographics variables were matched. NMA found no significant differences in treatment-related adverse events. All sensitivity analyses returned consistent results.</div></div><div><h3>Conclusions</h3><div>This ITC study found no significant differences in time to beginning of symptom relief and overall treatment-related adverse events between sebetralstat and IV-rhC1-INH.</div></div>","PeriodicalId":50773,"journal":{"name":"Annals of Allergy Asthma & Immunology","volume":"133 6","pages":"Pages S28-S29"},"PeriodicalIF":5.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142529629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LOW INCIDENCE OF GARADACIMAB IMMUNOGENICITY WITH NO IMPACT ON EFFICACY, SAFETY OR PHARMACOKINETICS: INTEGRATED ANALYSIS 加拉地单抗免疫原性发生率低，对疗效、安全性或药代动力学没有影响：综合分析

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2024-10-25 DOI: 10.1016/j.anai.2024.08.125

P. Keith , A. Roberts , F. Glassman , H. Shetty , J. Lawo , L. Wieman , I. Jacobs , D. Levy

Introduction

Monoclonal antibody (mAb) treatment may induce anti-drug antibodies (ADAs). We report integrated immunogenicity data across Phase 1, Phase 2, pivotal Phase 3 (VANGUARD), and Phase 3 open-label extension (OLE) studies evaluating garadacimab (anti-activated factor XII mAb) for hereditary angioedema (HAE) long-term prophylaxis.

Methods

ADAs against garadacimab were monitored by bridging immunogenicity assay across three Phase 1, single-ascending dose studies in healthy volunteers (follow-up 85 days). ADAs were also monitored in patients with HAE treated with garadacimab subcutaneously in a Phase 2 study (12-week placebo-controlled period, subsequent ≥44-week open-label period; 75/200/600 mg once-monthly or 400 mg every 2 weeks), pivotal Phase 3 study (6-month placebo-controlled period) and ongoing OLE study (both 200 mg once-monthly; data ≤1.8 years, cut-off February 2023).

Results

No ADAs were reported following a single dose in healthy volunteers (N=201). Low incidence of ADAs was reported in patients with HAE from Phase 2 and 3 studies (2.9%, 5/172), all with low reciprocal titers (≤320). Monthly HAE attack rate in patients with ADAs during 5.3–14.3 months of garadacimab treatment ranged 0.0–0.2 (Table), which was consistent with the attack rate in the overall population (0.2–0.3). Of patients with treatment-emergent ADAs, 2/5 experienced no treatment-emergent adverse event (TEAE); 3/5 experienced non-serious mild/moderate TEAEs (non-treatment-related, n=1; treatment-related, n=2; Table). ADAs did not impact pharmacokinetics: garadacimab concentrations were within range observed in patients without ADA.

Conclusion

Throughout the clinical development program, incidence and titers of garadacimab immunogenicity were low, with no observed impact on efficacy, safety, pharmacodynamics or pharmacokinetics.

导言：单克隆抗体（mAb）治疗可能会诱发抗药物抗体（ADA）。我们报告了评估加拉地单抗（抗活化因子 XII mAb）用于遗传性血管性水肿（HAE）长期预防的 1 期、2 期、关键性 3 期（VANGUARD）和 3 期开放标签扩展（OLE）研究的综合免疫原性数据。此外，还在一项2期研究（12周安慰剂对照期，随后≥44周开放标签期；75/200/600毫克，每月一次或400毫克，每2周一次）、关键性3期研究（6个月安慰剂对照期）和正在进行的OLE研究（均为200毫克，每月一次；数据≤1.8年，截止日期为2023年2月）中对接受加拉达西单抗皮下注射治疗的HAE患者进行了ADA监测。结果在健康志愿者（N=201）中，单次给药后未报告ADA。2期和3期研究中报告的HAE患者ADA发生率较低（2.9%，5/172），均为低互作滴度（≤320）。在加拉单抗治疗的5.3-14.3个月期间，ADA患者的HAE月发作率为0.0-0.2（表），与总体人群的发作率（0.2-0.3）一致。在出现治疗突发ADA的患者中，2/5的患者未出现治疗突发不良事件（TEAE）；3/5的患者出现非严重的轻度/中度TEAE（非治疗相关，n=1；治疗相关，n=2；表）。结论在整个临床开发项目中，加拉地单抗免疫原性的发生率和滴度都很低，对疗效、安全性、药效学或药代动力学都没有影响。

{"title":"LOW INCIDENCE OF GARADACIMAB IMMUNOGENICITY WITH NO IMPACT ON EFFICACY, SAFETY OR PHARMACOKINETICS: INTEGRATED ANALYSIS","authors":"P. Keith , A. Roberts , F. Glassman , H. Shetty , J. Lawo , L. Wieman , I. Jacobs , D. Levy","doi":"10.1016/j.anai.2024.08.125","DOIUrl":"10.1016/j.anai.2024.08.125","url":null,"abstract":"<div><h3>Introduction</h3><div>Monoclonal antibody (mAb) treatment may induce anti-drug antibodies (ADAs). We report integrated immunogenicity data across Phase 1, Phase 2, pivotal Phase 3 (VANGUARD), and Phase 3 open-label extension (OLE) studies evaluating garadacimab (anti-activated factor XII mAb) for hereditary angioedema (HAE) long-term prophylaxis.</div></div><div><h3>Methods</h3><div>ADAs against garadacimab were monitored by bridging immunogenicity assay across three Phase 1, single-ascending dose studies in healthy volunteers (follow-up 85 days). ADAs were also monitored in patients with HAE treated with garadacimab subcutaneously in a Phase 2 study (12-week placebo-controlled period, subsequent ≥44-week open-label period; 75/200/600 mg once-monthly or 400 mg every 2 weeks), pivotal Phase 3 study (6-month placebo-controlled period) and ongoing OLE study (both 200 mg once-monthly; data ≤1.8 years, cut-off February 2023).</div></div><div><h3>Results</h3><div>No ADAs were reported following a single dose in healthy volunteers (N=201). Low incidence of ADAs was reported in patients with HAE from Phase 2 and 3 studies (2.9%, 5/172), all with low reciprocal titers (≤320). Monthly HAE attack rate in patients with ADAs during 5.3–14.3 months of garadacimab treatment ranged 0.0–0.2 (Table), which was consistent with the attack rate in the overall population (0.2–0.3). Of patients with treatment-emergent ADAs, 2/5 experienced no treatment-emergent adverse event (TEAE); 3/5 experienced non-serious mild/moderate TEAEs (non-treatment-related, n=1; treatment-related, n=2; Table). ADAs did not impact pharmacokinetics: garadacimab concentrations were within range observed in patients without ADA.</div></div><div><h3>Conclusion</h3><div>Throughout the clinical development program, incidence and titers of garadacimab immunogenicity were low, with no observed impact on efficacy, safety, pharmacodynamics or pharmacokinetics.</div></div>","PeriodicalId":50773,"journal":{"name":"Annals of Allergy Asthma & Immunology","volume":"133 6","pages":"Page S32"},"PeriodicalIF":5.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142529633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0