Freneslerbart

——Allergy期刊最新发表（2026年3月），国内多中心专家共识，建议收藏 本文为2026年3月23日发表于 Allergy 期刊的《Chinese Position Paper on Biologic Therapy for Allergic Rhinitis》完整中文译文。由国内变应性鼻炎领域多位权威专家联合撰写，涵盖生物制剂适应证、疗效评估、安全监测等核心内容，是目前国内变应性鼻炎生物制剂应用最权威的临床指导文件。作者信息 摘要 变应性鼻炎（AR）是一种常见的持续性鼻部疾病，在全球范围内构成重大的公共卫生挑战。现有治疗方案在相当一部分患者中常难以实现充分的症状控制。在过去二十年中，靶向2型炎症通路的生物制剂已被用于治疗在标准治疗下症状控制不佳的患者。尽管AR的生物制剂治疗选择在全球范围内仍十分有限，但stapokibart（司普奇拜）获批用于季节性变应性鼻炎（SAR）等新型药物的近期上市，已加速了该领域的临床研究与开发进程。目前，关于生物制剂治疗常年性变应性鼻炎（PAR）的证据仍较为匮乏。 为规范生物制剂在AR治疗中的应用并促进其循证使用，一个多学科专家组应运而生。本立场文件评估了生物制剂治疗AR的当前证据，纳入了国际和国内临床研究数据，并就生物制剂治疗的适当适应证提供了建议，着重强调其在难治性SAR患者中的作用，旨在支持临床决策并促进生物制剂融入日常诊疗实践。一、前言 变应性鼻炎（AR）是一种由季节性或常年性过敏原触发的慢性IgE介导的鼻黏膜炎症。在古代中国文献中即有记载，19世纪被称为“枯草热（hay fever）”，其免疫学基础于1873年得以阐明。其全球患病率目前为5%～50%，自19世纪末以来显著上升。在中国，AR影响约18%的人口，城市化地区患病率高于农村地区。流行病学研究发现工业化地区患病率更高，这可能与环境污染、气候影响、卫生假说和上皮屏障假说等因素有关。 AR按季节分为季节性（SAR）和常年性（PAR）两种亚型，这一分类方式已被用于医疗产品疗效评价和监管审批。与PAR相比，SAR具有季节性发作的特点，会导致明显的鼻部炎症加剧，并显著影响患者的生活质量。1.1 吸入性过敏原的流行情况 中国吸入性过敏原致敏情况存在显著的地区差异。尘螨在南方地区普遍流行，而花粉过敏原则主要分布在西北地区。在北方草原开展的一项研究发现，艾蒿（78%）、葎草（71%）和藜（71%）是主要的花粉过敏原，其中艾蒿与严重的临床表现相关。推荐使用包含5～8种过敏原的地区特异性皮肤点刺试验组合（如针对东北、西北和南方地区分别定制，涵盖粉尘螨、艾蒿及其他适配过敏原）进行经济高效的筛查。1.2 疾病负担 AR的经济负担相当沉重，涵盖直接费用以及因生产力下降和缺勤所致的间接费用。在美国和欧洲，AR每年造成约95亿美元的直接医疗费用和生产力损失。仅北京一个主要城市，AR相关总支出即约达4.41亿欧元。AR显著损害睡眠质量、工作效能和生活质量。共病的存在进一步加重了这一负担：约30%～40%的AR患者会发展为哮喘，约80%的哮喘患者存在AR症状，这进一步强化了“统一气道疾病”的概念。同时伴发慢性鼻窦炎（CRS）、特应性皮炎（AD）和阻塞性睡眠呼吸暂停等疾病可加重患病率，因此需要采取综合性管理策略。1.3 传统治疗 目前AR管理的标准治疗（SoC）包括：过敏原回避、药物治疗、过敏原特异性免疫治疗（AIT）和患者教育。AR的一线药物治疗主要包括H1-抗组胺药（口服和鼻用）及鼻用糖皮质激素（INCS）。近期一项Meta分析提供了证据表明，一线药物联合治疗的总体疗效优于单药治疗，其中鼻用H1-抗组胺药与INCS的联合方案在症状改善方面具有最显著的优势。AIT（皮下注射和舌下含服）被认为是唯一具有疾病修饰作用的治疗方式，但受制于疗程较长和过敏原疫苗种类有限等因素。 尽管上述治疗能缓解症状，仍有超过60%的患者症状控制不充分，表现为持续性慢性鼻塞、睡眠障碍和生活质量下降。当前治疗的局限性在于：症状缓解不完全、长期依从性差以及以2型（T2）发病机制为导向的个体化治疗不足。这些问题凸显了对新型治疗策略的迫切需求。1.4 生物制剂治疗 生物制剂通过选择性抑制过敏级联反应中的关键分子，标志着AR治疗的范式转变。靶向IgE（奥马珠单抗）、IL-4/IL-13通路（度普利尤单抗、司普奇拜）、IL-5（美泊利珠单抗）、胸腺基质淋巴细胞生成素（TSLP；特泽鲁单抗）和IL-33/ST2通路（伊特奇单抗）的单克隆抗体均已显示出调节T2炎症的前景。 图 1 | 过敏性鼻炎发病中的 2 型炎症机制及靶向关键分子的生物制剂 TSLP：胸腺基质淋巴细胞生成素IL：白细胞介素ILC2：2 型固有淋巴细胞DC：树突状细胞IgE：免疫球蛋白 ETh：辅助性 T 细胞IL-4Rα：白细胞介素 4 受体 α 亚基 奥马珠单抗在随机试验、真实世界研究和Meta分析中，对SAR和PAR均展现出显著疗效，可改善鼻部症状和生活质量。度普利尤单抗在哮喘试验的事后分析中证实了对PAR症状的缓解作用，但其与AIT的联合方案并未在SAR患者中带来额外获益。特泽鲁单抗与AIT联合应用时，与单独AIT相比，在1年随访期内显著增强了减少猫毛诱发AR患者鼻部过敏原激发反应的疗效。最近，司普奇拜——一种新型抗IL-4Rα抗体——已在花粉季节SoC难治的中-重度SAR患者的PHECDA和MERAK试验中验证了其临床疗效，并已在中国获批用于SAR治疗。 生物制剂的快速开发和临床评估进展代表着AR治疗领域的变革前沿。然而，将其纳入临床实践需要坚实的证据支撑和以共识为驱动的策略。为此，中华医学会变态反应学分会鼻眼变态反应学组、中华医学会耳鼻咽喉头颈外科学分会鼻科学组、中国医师协会耳鼻咽喉头颈外科医师分会过敏学组以及耳鼻咽喉科国家医疗质量控制中心鼻科学组联合召集了具有丰富AR生物制剂临床试验经验的专家小组，就生物制剂在AR治疗中的应用展开讨论。经广泛深入的研讨，本立场文件就关键内容达成共识，包括患者选择标准、治疗方案和疗效评估方法，旨在为优化生物制剂在AR中的应用提供可操作的建议，最终推进AR的精准治疗。二、AR中2型炎症的机制及生物制剂治疗2.1 AR中的2型炎症机制 AR涉及IgE介导的Ⅰ型超敏反应：由肥大细胞脱颗粒触发急性期反应（APR；表现为流涕、喷嚏、鼻痒），随后出现迟发型T2炎症反应（LPR）。过敏原或污染物破坏上皮屏障，释放警报素（如IL-25、IL-33），进而激活固有淋巴细胞2（ILC2）和树突状细胞（DC），驱动Th2细胞分化。这些细胞产生细胞因子（IL-4、IL-5、IL-13），通过IgE类别转换、嗜酸性粒细胞募集、黏液高分泌以及经FcεRI结合使肥大细胞致敏等方式持续炎症反应。2.2 生物制剂治疗AR的靶点及其机制 基于T2炎症机制，AR的生物制剂主要靶向IgE介导的炎症和T2免疫反应。关键靶点包括IgE及Th2相关细胞因子（IL-4、IL-13、IL-5）及其受体。阻断IgE通过干扰IgE/FcεRI结合来抑制APR。IL-4和IL-13是T2炎症反应中的关键细胞因子，共享受体亚基IL-4Rα。因此，靶向IL-4Rα可同时抑制IL-4和IL-13信号传导，从而抑制LPR并缓解或消除AR的持续症状。 奥马珠单抗（Omalizumab） 是一种人源化抗IgE单克隆抗体（IgG1κ型），可选择性结合IgE Cε3结构域的FcεRI结合位点，从而阻止游离IgE与肥大细胞和嗜碱性粒细胞上的FcεRI受体结合。此外，奥马珠单抗还可直接解离预先结合在肥大细胞和嗜碱性粒细胞上的IgE，导致肥大细胞脱颗粒减少和白三烯合成降低。在AR患者中，奥马珠单抗可降低DC、肥大细胞和嗜碱性粒细胞上FcεRI的表达，从而减少过敏原呈递、Th2细胞活化和增殖。同时，奥马珠单抗可抑制IgE诱导的嗜酸性粒细胞迁移，并显著降低鼻腔分泌物中嗜酸性粒细胞阳离子蛋白水平。此外，奥马珠单抗还可通过特异性靶向膜结合IgE的B细胞并诱导其无能状态，从而降低IgE合成。综上，奥马珠单抗可能通过靶向IgE的源头合成、阻断IgE介导的过敏反应、调节免疫细胞活性和抑制炎症反应等多种机制发挥治疗效果。 司普奇拜（Stapokibart） 与 度普利尤单抗（Dupilumab） 均已在SAR患者中进行了研究。在接受司普奇拜治疗的患者中，炎症趋化因子（包括胸腺活化调节趋化因子TARC、嗜酸性粒细胞趋化因子和IgE水平）均有所降低。此外，鼻腔刷取样本的RNA测序分析也表明，司普奇拜组T2炎症生物标志物出现了下调。度普利尤单抗已获美国FDA批准用于哮喘、AD和CRSwNP的治疗，研究表明其可显著减少人外周血单核细胞中TARC的释放，并降低B细胞激活标志物CD23的水平。此外，度普利尤单抗还可在体外阻止IL-4引起的鼻腔上皮功能改变，包括恢复上皮屏障蛋白的表达、纤毛摆动效率和伤口修复速率。因此，靶向IL-4Rα的单克隆抗体可通过减轻T2炎症和恢复上皮屏障功能来发挥治疗效果。三、生物制剂治疗AR的临床研究设计、疗效和安全性数据3.1 已发表的评估AR生物制剂治疗临床试验的研究设计 由于生物制剂对T2炎症实现了精准调节，已有越来越多的临床研究探讨了其在AR患者中的应用价值。然而，已发表的临床试验在设计方面仍存在显著差异，特别是在生物制剂的治疗定位、患者人群选择、花粉暴露时期以及疗效终点设置等方面（详见表1）。 表1：已发表的不同给药方案生物制剂治疗AR的临床试验 作者及年份 注册号 受试者特征 研究分组（例数） 给药方案 临床终点 Casale et al. 2006 [67] NA 159 例 SAR，18–50 岁 奥马珠单抗 + IT（39）；奥马珠单抗（40）；IT（40）；安慰剂（40） 剂量：0.016 mg/kg/ 月 IgE（IU/mL）/Q2W/Q4W；时间：季前 + 共季节 主要终点：每日过敏严重程度评分比较；次要终点：AE 发生率 Okubo et al. 2020 [27] NCT03369704 337 例控制不佳 / 重度日本雪松花粉症，12–75 岁 奥马珠单抗 + SoC（162）；安慰剂 + SoC（175） 剂量：75–600 mg Q2W（根据血清总 IgE 水平和体重确定）；时间：共季节 主要终点：平均鼻部症状评分；次要终点：平均眼部症状评分、鼻和眼急救用药评分、日本 RQLQ 评分 Zhang et al. 2022 [68] NCT04489121 31 例中重度 SAR，18–60 岁 奥马珠单抗（16）；药物治疗（15） 剂量：单次 300 mg；时间：季前 主要终点：鼻部每日 CSMS 评分；次要终点：眼部 CSMS 评分、平均每日无药天数、过敏症状缓解天数、TNSS、TESS、RQLQ 和 PGIC Corren et al. 2021 [31] NCT03558997 103 例 SAR，18–55 岁 Dupilumab+SCIT（26）；Dupilumab（26）；SCIT（26）；安慰剂（25） 剂量：300 mg Q2W；时间：季前 主要终点：TNSS 较基线变化百分比（0–1h 峰值 AUC）；次要终点：TNSS 较基线百分比变化、TNSS AUC（0–1h）、sIgG4、log [sIgG4/sIgE]、TEAE 和严重 TEAE Zhang et al. 2024 [33] NCT05470647 92 例中重度 SAR，18–65 岁 Stapokibart QW+SoC（31）；Stapokibart Q2W+SoC（30）；安慰剂 + SoC（31） 剂量：Stapokibart 600 mg 负荷剂量（第 1 天），之后 300 mg QW/Q2W；时间：共季节 主要终点：rTNSS 较基线平均变化（第 2 周）；次要终点：每日 rTNSS 较基线平均变化、iTNSS、rTOSS、AM iTNSS、AM ITOSS、2 周和 4 周治疗期间无药天数、RQLQ 评分较基线变化、起效时间和总体疗效评价 Zhang et al. 2025 [34] NCT05908032 108 例中重度 SAR，基线血 EOS≥300/μL，18–65 岁 Stapokibart+SoC（50）；安慰剂 + SoC（58） 剂量：Stapokibart 600 mg 负荷剂量（第 1 天），之后 300 mg Q2W；时间：共季节 主要终点：2 周治疗后每日 rTNSS 较基线变化；次要终点：4 周治疗后 rTNSS 较基线平均变化、iTNSS、rTOSS、个体鼻和眼症状评分 2 周和 4 周较基线百分比变化、每日 rTNSS、iTOSS、总眼症状评分 Chaker et al. 2016 [69] NCT01010186 66 例 SAR，18–60 岁 VAK694+SCIT（12）；安慰剂 + SCIT（12）；Tezepelumab+SCIT（13） 剂量：3 mg/kg Q4W；时间：季前 主要终点：皮内迟发相反应（过敏原直径）；次要终点：IgE/IgG、Th1/Th2 细胞因子表达、Treg 诱导、迷你呼吸生活质量问卷、VAS、局部和全身免疫反应频率及严重程度 Corren et al. 2023 [32] NCT02237196 121 例猫毛 AR，18–65 岁 Tezepelumab（30）；SCIT（31）；Tezepelumab+SCIT（32）；安慰剂（28） 剂量：700 mg Q4W；时间：NA 主要终点：第 104 周 TNSS AUC₀₋₁₆h 峰值；次要终点：挑战后早期和晚期鼻吸气流量变化、IDST 和 SPT 早期反应 SAR：季节性过敏性鼻炎；IT：免疫治疗；SoC：标准治疗；IgE：免疫球蛋白 E；RQLQ：鼻结膜炎生活质量问卷；CSMS：鼻部 / 眼部综合症状评分；TNSS：总鼻部症状评分；rTNSS：反射性总鼻部症状评分；iTNSS：即时总鼻部症状评分；TESS：总眼部症状评分；PGIC：患者整体印象变化；AUC：曲线下面积；sIgE：特异性 IgE；sIgG4：特异性 IgG4；TEAE：治疗后出现的不良事件；EOS：嗜酸性粒细胞；IDST：鼻内过敏原挑战试验；SPT：皮肤点刺试验；VAS：视觉模拟评分；Treg：调节性 T 细胞。3.1.1 奥马珠单抗 五项临床试验评估了奥马珠单抗作为单药治疗或与SoC、免疫治疗联合应用的疗效和安全性。Casale等探索了SAR成人患者在加速脱敏AIT基础上联合花粉季前和季中奥马珠单抗治疗的安全性和疗效，主要结局为每日平均过敏症状评分。Kuehr等在SAR青少年中评估了奥马珠单抗与AIT联合应用，主要疗效终点为症状负荷（每日症状严重程度评分+急救药物使用量的综合评分）。Kopp等探讨了奥马珠单抗联合AIT对合并季节性变应性哮喘（SAA）的SAR青少年和成人患者的效果，以每日症状负荷作为主要终点。 对于PAR青少年和成人患者，奥马珠单抗在一项Ⅲ期试验中进行了评估，主要疗效终点为每日平均鼻部严重程度评分。在日本开展的一项Ⅲ期试验确定了奥马珠单抗在SoC基础上附加治疗SoC控制不佳的重度日本柳杉花粉症成人和青少年患者的疗效，奥马珠单抗剂量为75～600 mg（每2周或每4周一次），根据血清总IgE水平和体重确定。主要终点为严重症状期的平均鼻部症状评分。 国内一项研究者发起试验评估了在花粉期开始前2周单次给予奥马珠单抗300 mg对SAR成人患者的疗效，主要终点为鼻部每日平均CSMS。需要指出的是，该研究中奥马珠单抗仅在花粉期前给药一次，用于SAR症状的预防，因此无法验证受试者的难治性疾病状态，这是研究预设目标和试验设计的固有局限性。3.1.2 司普奇拜 司普奇拜在Ⅱ期MERAK试验和Ⅲ期PHECDA试验中对SAR患者进行了评估。MERAK试验中，受试者按1:1:1随机分配接受司普奇拜QW、司普奇拜Q2W或安慰剂，均联合SoC。治疗方案包括600 mg负荷剂量，随后每周或每2周给予300 mg。主要结局为第2周每日rTNSS自基线的平均变化。 由于MERAK试验在基线血嗜酸性粒细胞计数≥300个/μL的亚组中显示出良好疗效，而研究也报告血液中活化和致病性嗜酸性粒细胞水平与AR患者TNSS呈正相关。具体而言，一项中国横断面研究发现，合并高血嗜酸性粒细胞水平（≥300个/μL）的慢性鼻炎患者鼻部和眼部症状更为严重。因此，后续的Ⅲ期PHECDA试验专门纳入了这一患者群体，包含司普奇拜组（600 mg负荷剂量+300 mg Q2W）和安慰剂组两个研究臂，均联合SoC。主要和次要疗效终点与MERAK试验一致。 值得特别关注的是，司普奇拜是目前唯一在临床试验中专门纳入在自然花粉暴露期间经SoC诱导后仍持续出现中-重度鼻部症状的难治性SAR患者的生物制剂，填补了一项重要的研究空白。3.1.3 其他生物制剂和益生菌 LIBERTY Grass AID Ⅱa期试验在SAR成人患者中评估了花粉季前度普利尤单抗联合或不联合皮下免疫治疗（SCIT）的效果，通过鼻腔过敏原激发（NAC）激发模型评估度普利尤单抗的疗效，其发现可能无法完全反映自然花粉暴露诱发的SAR临床反应。一项Ⅱa期试验研究了VAK694（抗IL-4）联合SCIT对皮内迟发相过敏原激发反应的影响。来瑞珠单抗（Lebrikizumab，抗IL-13）正在一项全球Ⅲ期试验（NCT06339008）中针对PAR成人患者进行评估。其他针对SAR的抗IL-4Rα抗体包括GR1802（Ⅱ期，NCT06315426、NCT06028490）、TQH2722（Ⅱ期，CTR20244837）和MG-K10（Ⅱ/Ⅲ期无缝设计，NCT06846385），目前均无数据披露。一项Ⅰ/Ⅱ期试验评估了特泽鲁单抗（抗TSLP）联合或不联合SCIT在AR成人患者中的效果。针对猫毛过敏AR患者开展的REGN1908-1909（抗Felis domesticus allergen 1，猫主要过敏原1）Ⅲ期试验（NCT04981717）因疗效不足而提前终止。益生菌研究（NCT03290248、NCT00746226）显示出改善症状的适度获益，但研究设计和益生菌菌株的异质性妨碍了明确临床建议的形成。3.2 生物制剂治疗AR的疗效数据3.2.1 随机对照临床试验中的疗效数据 在涉及SoC控制不佳的重度柳杉花粉症患者的日本Ⅲ期试验中，在SoC基础上附加奥马珠单抗显著改善了鼻部（最小二乘均数差：−1.03）和眼部（−0.87）症状评分，并提高了生活质量。在中国AR人群中，花粉季前奥马珠单抗预处理（花粉期开始前2周单次给予300 mg）在整个花粉季与标准药物治疗相比降低了CSMS。 司普奇拜作为SAR患者SoC控制不佳后的附加治疗在两项临床试验中进行了评估。MERAK试验揭示了在基线血嗜酸性粒细胞计数≥300个/μL患者中rTNSS的显著改善，这为随后专门针对该亚组开展的Ⅲ期PHECDA试验提供了依据。在PHECDA试验中，司普奇拜显著改善了rTNSS（最小二乘均数差：2周期间−1.3，4周期间−1.7），同时改善了眼部症状和RQLQ评分。 表2：RCT中生物制剂联合或不联合AIT治疗PAR和SAR的主要疗效结果汇总 靶点 生物制剂 / AIT 年份 注册号 国家 分期 样本量 研究人群 主要发现 IgE Omalizumab 1999 Unknown US Phase 3 289 青少年及成人 PAR（12–75 岁） 治疗 16 周期间，每日鼻部严重程度评分均值显著低于安慰剂组（p<0.001）[28] IgE Omalizumab 2017 NCT03369704 Japan Phase 3 337 重度日本雪松花粉症（尽管接受 SoC，12–75 岁） 与安慰剂相比，奥马珠单抗显著改善鼻和眼部症状，对标准治疗无应答的重度日本雪松花粉症患者有效 [27] IgE Omalizumab 2020 NCT04489121 China NA (IIT) 31 成人 SAR（18–60 岁） 花粉季开始前 2 周单次注射 300 mg 奥马珠单抗，在 SAR 患者中实现了优于标准药物治疗的整体症状控制和生活质量改善 [68] IgE Quilizumab 2010 NCT01160861 Canada Phase 1 36 成人 SAR 或 PAR 靶向膜 IgE 的 Quilizumab 显著降低总 IgE 和变应原特异性 IgE 水平，抑制新 IgE 产生，减轻变应原诱导的气道反应和嗜酸性粒细胞炎症，在 AR 和轻度哮喘中疗效持续至少 6 个月 [74] IgE MEDI4212 2012 NCT01544348 US Phase 1 295 特应性受试者 / 基线 IgE≥30 IU/mL（18–60 岁） MEDI4212 效力高于奥马珠单抗，在抑制 IgE 和减少 FcεRI 表达方面更优，且 IgE 抑制持续时间更短，但给药方案更灵活，耐受性良好 [75] IL-4Rα Stapokibart 2022 NCT05470647 China Phase 2 92 成人不受控 SAR（尽管接受标准治疗，18–65 岁） Stapokibart 安全性良好，Q2W 方案在减轻鼻部症状和改善晨间鼻部充血方面显示出整体获益 [33] IL-4Rα Stapokibart 2023 NCT05908032 China Phase 3 108 成人中重度 SAR（基线血 EOS≥300/μL，18–65 岁） Stapokibart 显著改善鼻和眼部症状及生活质量，治疗 4 周后观察到基线血嗜酸性粒细胞计数≥300/μL 患者的获益，伴随 2 型炎症减少，安全性良好 [34] IgE Omalizumab + RIT 2003 NCT00078195 US Phase 2 159 成人 SAR（18–50 岁） 预治疗可显著改善艾蒿 AR 的安全性和疗效，降低过敏反应风险，增强症状控制 [67] IgE Omalizumab + SIT Unknown Unknown Germany Unknown 225 青少年 SAR（6–17 岁） 联合治疗（奥马珠单抗 + SIT）在 2 个花粉季中使症状负荷降低 48%（p<0.001），耐受性良好 [70] IgE Omalizumab + SIT 2006 EUDRACT 2005-003860-47 Germany Unknown 140 青少年及成人 SAR（12–45 岁） 奥马珠单抗联合 SIT 可显著减轻症状负荷 [71] IL-4Rα Dupilumab + SCIT 2018 NCT03558997 US Phase 2a 103 成人禾草诱导 SAR（18–55 岁） SAR 患者中，Dupilumab 联合 SCIT 可改善治疗耐受性，减少停药和肾上腺素使用，但与单独 SCIT 相比，症状缓解未显著增强 [31] TSLP Tezepelumab + SCIT 2015 NCT02237196 US Phase 1/2 121 成人猫毛过敏 AR（18–65 岁） Tezepelumab 增强了 SCIT 的疗效，诱导持续 2 型炎症抑制，提示潜在促进长期耐受的作用 [32] PAR：常年性过敏性鼻炎；AIT：变应原特异性免疫治疗；RIT：冲击免疫治疗；SIT：皮下免疫治疗；SCIT：皮下变应原免疫治疗；IIT：研究者发起试验；QoL：生活质量；SoC：标准治疗；EOS：嗜酸性粒细胞；TSLP：胸腺基质淋巴细胞生成素。3.2.2 真实世界研究中的疗效数据 真实世界证据支持奥马珠单抗在SAR和PAR管理中的强效疗效，在症状严重程度、生活质量和合并哮喘控制方面均表现出持续的改善。长期治疗在合并哮喘的严重持续性AR患者中展示了持久的疗效，改善了鼻部症状和肺功能，同时降低了血嗜酸性粒细胞和总IgE等生物标志物水平。SAR中观察到迅速的症状缓解，在花粉峰季4周内，视觉模拟评分从64.4±20.8降至12.7±9.4。奥马珠单抗还改善了生活质量，RQLQ总分和日本RQLQ评分均有显著下降。在一项前瞻性观察研究中，1个月奥马珠单抗治疗显著改善了日本柳杉花粉诱发SAR患者的主观症状。一项回顾性队列研究发现，花粉季前奥马珠单抗治疗无论剂量或注射频率如何，均能带来显著的症状缓解和药物使用减少（CSMS：0.67 vs 4.00）。3.2.3 生物制剂与AIT联合应用的疗效数据 奥马珠单抗与AIT的联合方案在三项随机临床试验中进行了研究（见表2）。在一项Ⅱ期试验中，奥马珠单抗预处理增强了SAR成人患者加速脱敏AIT的安全性和疗效。另外两项临床试验表明，奥马珠单抗联合AIT显著降低了伴或不伴SAA的SAR患者的症状负荷。此外，一项网络Meta分析表明，抗IL-4Rα疗法和抗IgE疗法在鼻部症状改善方面优于AIT。综合上述发现，生物制剂与AIT联合应用可为AR患者提供临床获益。3.2.4 生物制剂对合并其他2型共病AR的疗效数据 度普利尤单抗对合并PAR的哮喘患者疗效在一项Ⅱb期哮喘试验的事后分析中有所报道。度普利尤单抗300 mg Q2W与安慰剂相比显著改善了SNOT-22总分和AR相关鼻部症状，但200 mg Q2W的改善效果未能达到统计学显著性。3.3 临床试验和真实世界研究的安全性数据 所有生物制剂在PAR和SAR患者中均展示出良好的安全性（见表3）。奥马珠单抗在儿科和成人AR人群中耐受性良好，临床试验中单药或联合方案均未报告安全性问题。真实世界研究报告了奥马珠单抗良好的安全性，不良事件罕见、轻微且短暂。司普奇拜的治疗期间不良事件（TEAE）发生率与安慰剂相当，均为轻至中度，未发现意外安全信号。Quilizumab、MEDI4212、度普利尤单抗和特泽鲁单抗的耐受性也良好，TEAE发生率与安慰剂组相似。各研究中均未报告严重或限制性治疗不良事件，支持上述生物制剂在AR治疗中的总体安全性。 表3：RCT中生物制剂治疗AR的主要安全性信号 生物制剂 临床试验文献 常见不良事件（发生率≥5%） 奥马珠单抗（抗 IgE） Okubo 等 [27]、Zhang 等 [68] 鼻咽炎、局部反应、头痛 奥马珠单抗 + AIT Casale 等 [67]、Kuehr 等 [70]、Kopp 等（DUAL 研究）[71] 潮红、瘙痒、荨麻疹、咳嗽、头痛、上呼吸道感染 Quilizumab（抗 IgE） Gauvreau 等 [74] 上呼吸道感染 MEDI4212（抗 IgE） Sheldon 等 [75] 非日本受试者：上呼吸道感染、荨麻疹；日本受试者：背痛 Dupilumab（抗 IL-4Rα） Corren 等 [31] 注射部位反应、鼻咽炎、上呼吸道感染 Dupilumab+AIT — 注射部位反应、鼻咽炎、超敏反应 Stapokibart（抗 IL-4Rα） Zhang 等（MERAK 研究）[33]、Zhang 等（PHECDA 研究）[34] 窦性心动过缓、高脂血症、血尿酸升高、上呼吸道感染、尿路感染 Tezepelumab（抗 TSLP） Corren 等（CATNIP 研究）[32] 鼻咽炎 Tezepelumab+AIT — 鼻咽炎、注射部位超敏反应AIT，过敏原特异性免疫治疗；IL-4Rα，白细胞介素 4 受体 α 亚基；TSLP，胸腺基质淋巴细胞生成四、变应性鼻炎生物制剂治疗建议4.1 AR生物制剂治疗的适应证 专家组建议对经SoC治疗（特别是INCS和抗组胺药联合方案，这是证据最充分的传统药物治疗方案）后仍未控制的SAR患者考虑生物制剂治疗。对于难治性疾病，翼管神经切除等手术干预也可作为可行的治疗替代方案，但其长期临床疗效有待进一步研究。 就本建议而言，未控制SAR定义为： 在当季花粉暴露期间，经SoC治疗至少1周后，仍存在控制不佳的鼻部症状，具体标准为TNSS≥6分（来自单个鼻部症状，如鼻塞/流涕/鼻痒/喷嚏，各项3分满分）。 目前，奥马珠单抗和司普奇拜分别在日本和中国获得了SAR治疗的监管批准：奥马珠单抗在日本获批用于SoC难治的重度花粉症，司普奇拜在中国获批用于SoC控制不佳的中-重度SAR。年龄适应症应遵照各生物制剂说明书。 关于生物制剂治疗的启动时机： 奥马珠单抗推荐在症状出现的早期阶段使用；司普奇拜则可在出现严重鼻部症状时考虑给药。此外，在使用生物制剂期间，可按需使用对症药物。 关于生物制剂与AIT的选择， 应以综合比较疗效、临床优先级、治疗可及性和卫生经济学考量的个体化临床决策为指导。生物制剂优先用于疾病急性加重期的快速症状控制，而AIT具有疾病修饰效果，在适当筛选的患者中有实现持久长期缓解的潜力。 关于生物制剂的选择，还可结合共病情况和生物标志物加以指导： 合并哮喘的AR患者：建议使用靶向IL-4Rα（司普奇拜）或IgE（奥马珠单抗）的单克隆抗体 合并AD或CRS时：优先考虑抗IL-4Rα抗体 生物标志物方面：血嗜酸性粒细胞计数升高（≥300个/μL）支持使用抗IL-4Rα抗体；血清总IgE水平升高（30～1500 IU/mL）提示适合抗IgE抗体 对于嗜酸性粒细胞<300个/μL的患者， 生物制剂治疗的证据仍然匮乏。现有奥马珠单抗治疗SAR的RCT通常未依据基线嗜酸性粒细胞计数分层，因此难以将研究结论直接应用于这一特定人群。考虑到奥马珠单抗以IgE为靶点的作用机制及其在不同嗜酸性粒细胞水平患者中均有效的证据，奥马珠单抗可作为SoC治疗失败患者的可行附加治疗方案，即使嗜酸性粒细胞<300个/μL亦可考虑。迫切需要针对这一低嗜酸性粒细胞AR队列进行前瞻性对照研究，专门评估生物制剂治疗的效果。4.2 疗效评估、随访与监测 目前，缺乏有效的客观生物标志物来预测或监测AR患者生物制剂治疗的反应，因此患者报告结局是临床评估的基石。最广泛使用的疗效终点是TNSS评分（0～12分，由鼻塞、流涕、鼻痒和喷嚏四项症状评分之和构成，每项0～3分）。其他重要评估指标包括眼部症状总评分（TOSS）、RQLQ和急救药物使用情况。 对于SAR（目前批准的生物制剂的适应证），治疗通常与花粉季节同步。疗效应在相关花粉暴露的背景下进行评估。有意义的评估需要观察目标花粉季期间患者的症状控制和生活质量改善情况。研究表明，跨越连续两个花粉季的治疗和评估可提供持久疗效的充分证据。应在1～2个目标花粉季后进行重新评估，以决定是否继续后续季节的治疗。对于PAR，应在充分的初始治疗期后进行重新评估，以使生物制剂充分发挥效果。 从安全性角度，可考虑监测外周血嗜酸性粒细胞计数，因为某些生物制剂在其他T2炎症疾病中已被报告与短暂、无症状性嗜酸性粒细胞升高相关，尽管其在AR中的临床意义有待进一步阐明。五、结论与展望 现有证据表明，靶向T2炎症关键通路（如IgE和IL-4Rα）的生物制剂在难治性SAR患者中具有明确疗效。司普奇拜在中国获批用于SAR治疗，已引发AR生物制剂领域临床试验数量的显著增加（详见表4）。关键在于，生物制剂通过支持内型导向的患者筛选（如嗜酸性粒细胞高表型），解决了疾病异质性的问题，有望优化临床结局。 表4：已完成的 AR 生物制剂临床试验汇总 靶点 生物制剂 启动年份 注册号 国家 分期 样本量 研究人群 主要结局指标 IgE Omalizumab 2003 NCT00078195 US Phase 2 168 季节性过敏成人 平均每日过敏严重程度评分 IgE Omalizumab 2007 NCT00604786 US NA 18 猫毛过敏成人 嗜碱性粒细胞表面 IgE 变化 IgE Omalizumab 2017 NCT03369704 Japan Phase 3 337 雪松花粉症（≥12 岁，控制不佳） 严重症状期鼻部症状评分 IgE Omalizumab 2019 NCT06806826 Turkey Phase 4 50 AR 成人 鼻和眼部症状 VAS 评分 IgE XmAb7195 2020 NCT04489121 China NA 32 SAR 成人 每日 CSMS 评分 IgE XmAb7195 2014 NCT02148744 US Phase 1a 72 健康成人伴 IgE 升高 / 特应性疾病 生物利用度（SC）、XmAb7195 AUC 测量 IgE XmAb7195 2016 NCT02881853 US Phase 1b 57 健康成人 不良事件 IgE LP-003 2023 NCT06046391 China Phase 2 180 SAR/PAR 成人（尽管接受 SoC 仍控制不佳） 花粉高峰期鼻部症状评分、安全性与耐受性 IgE Quilizumab 2010 NCT01160861 Canada/Sweden/US Phase 1b 36 草诱导 SAR 成人 TNSS 中 CFB 百分比变化（AUC₀₋₁₆h，第 17 周） IL-4Rα Dupilumab 2018 NCT03558997 Canada Phase 2a 103 中重度 SAR 成人 2 周治疗后每日 rTNSS 中 CFB 均值 IL-4Rα Stapokibart 2022 NCT05470647 China Phase 2 92 中重度 SAR 成人 2 周治疗后每日 rTNSS 中 CFB 均值 IL-4Rα Stapokibart 2023 NCT05908032 China Phase 3 108 中重度 SAR（EOS≥300/μL，尽管接受 SoC） 2 周治疗后每日 rTNSS 中 CFB 均值 IL-4 VAK694 2009 NCT01018693 UK Phase 2a 37 SAR 成人 皮内迟发相反应面积、第 104 周 TNSS AUC₀₋₁₆h TSLP Tezepelumab 2015 NCT02237196 US Phase 1/2 121 猫毛过敏成人 第 8 天过敏性症状评分变化 Fel d 1 REGN1908-1909 2014 NCT02127801 US/Global Phase 1b 74 猫毛过敏诱导 AR 成人 每日 CSMS 评分（过去 12 周均值） Fel d 1 REGN1908-1909 2021 NCT04981717 Global Phase 3 446 与猫生活的 AR 儿童（≥12 岁）（因疗效不足终止） — 值得关注的是，支持生物制剂治疗PAR的证据仍然有限，主要依赖事后分析和观察性研究，迫切需要开展更严谨全面的临床试验。未来仍需高质量的临床试验来确立确切的疗效和安全性。生物制剂与AIT的联合方案也可能提供有前景的协同和持久的免疫调节效果，有望在更安全的条件下实现持续耐受。生物制剂的长期安全性和有效性，尤其是在儿科和老年人群中以及长期使用时，需要持续进行严格评估。 AR治疗的“一刀切”时代正让位于精准医学时代。 靶向生物制剂正在补充传统治疗方案，并为适合的患者亚群重新定义治疗成功的标准。这一转变需要对每位患者的表型和内型特征以及个人偏好进行全面评估，以制定具有成本效益的个体化诊疗路径。随着生物制剂相关证据的持续积累，本立场文件将定期更新，纳入过敏和免疫学领域的最新进展。 图 2 | “五位一体” 诊疗方案INCS：鼻用糖皮质激素；AIT：变应原特异性免疫治疗；SCIT：皮下免疫治疗；SLIT：舌下免疫治疗；SAR：季节性过敏性鼻炎；IL-4Rα：白细胞介素 4 受体 α 亚基；PAR：常年性过敏性鼻炎；AR：过敏性鼻炎；SoC：标准治疗；TNSS：总鼻部症状评分。 本文为学术文献中文译文，仅供专业医疗人员学习参考，不构成临床诊疗依据。如需引用，请参阅原文：Zhang Y, Li J, Li X, et al. Chinese Position Paper on Biologic Therapy for Allergic Rhinitis. Allergy. 2026. DOI: 10.1111/all.70312 欢迎关注微信公众号，关注后回复【AR单抗共识】，即可获得原文。 推荐阅读： 方寸藏山海｜耳鼻咽喉头颈外科的常见病、多发病与罕见病 登顶 JAMA！2026年头颈癌最新综述 26年前韩德民院士与许庚教授对鼻内镜外科技术的理解&26年来鼻内镜外科技术迭代与理念演进 AI时代来临：未来5–10年，耳鼻咽喉头颈外科哪些疾病最可能被AI"替代"？ 耳鼻咽喉头颈外科特色疾病名称大全 更多资讯欢迎点击下方关注本公众号 如果这篇文章对您有用，欢迎「点赞」「转发」「评论」❤️🔥❤️🔥❤️🔥 您的鼓励就是对我成长最大的帮助！

36 abstracts to be presented across Regeneron-invented therapies, including first-time Phase 3 presentations for two distinct investigational allergen-blocking antibodies for cat and birch allergies New Dupixent ® (dupilumab) data highlight its clinical and real-world impact across dermatological, respiratory and gastrointestinal diseases, including analyses of food allergy sensitization in children with atopic dermatitis TARRYTOWN, N.Y., Feb. 10, 2026 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced 36 abstracts across its immunology and inflammation portfolio and pipeline will be presented at the 2026 American Academy of Allergy, Asthma and Immunology (AAAAI) Annual Meeting being held February 27 to March 2 in Philadelphia, Pennsylvania. Highlights include the first presentations from the novel Phase 3 allergen-specific programs demonstrating the potential of a first-in-class approach to addressing burdensome ocular symptoms in adults with cat and birch allergies. New Dupixent ® (dupilumab) analyses across dermatological, respiratory and gastrointestinal diseases will also be presented in collaboration with Sanofi. “At Regeneron, we are pioneering new approaches to treating allergic diseases, and at AAAAI we will present for the first time Phase 3 data from two potentially first-in-class treatments for cat and birch allergies invented by Regeneron scientists that have the potential to change the paradigm for treatment of allergic diseases. Based on these data, we will embark on additional registration-enabling trials this year,” said Boaz Hirshberg, M.D., Senior Vice President, Clinical Development, Internal Medicine at Regeneron. “We are also sharing new insights on Dupixent, another drug invented by Regeneron scientists and currently the most widely used innovative branded antibody medicine. These results highlight the potential of Dupixent to further evolve the treatment paradigms of several chronic diseases, including asthma, certain allergic fungal diseases and allergies in children with atopic dermatitis. Together, these data represent our continued commitment to translate scientific insights into therapeutic breakthroughs across immunology and inflammation.” First-in-class potential for targeted antibody treatments in cat and birch allergies in “ocular challenge” a trials Presented for the first time will be results from separate Phase 3 cat and birch allergen-challenge trials, which evaluated antibody cocktails that target the most dominant allergens—FelD1 for cat allergy and BetV1 for birch allergy. The trials assessed the ability of these therapies to reduce ocular allergic symptoms, such as ocular itch and conjunctival redness, in response to antigen challenge, as well as skin prick reactivity one week after treatment, compared to placebo. The results add to data from earlier trials demonstrating the effects of these cocktails on nasal, respiratory and skin endpoints in these patients. Additional registration-enabling trials for both programs that evaluate similar endpoints but after longer follow-up are initiating this year. The cat and birch allergy programs are part of a broader allergy pipeline, which include innovative strategies with the goal of eliminating all IgE-mediated allergies. The safety and efficacy of these investigational medicines have not been evaluated by any regulatory authority. New Dupixent insights on allergy sensitization, asthma treatment escalation and potential in AFRS The impact of early and sustained Dupixent treatment on allergy sensitization in children will be shared in two new long-term analyses from a Phase 3 open-label extension trial in children with moderate-to-severe atopic dermatitis. In the separate analyses, IgE levels for common food and environmental allergies were measured throughout the course of Dupixent treatment for up to 1.5 years. These included IgE levels for egg white, peanut, cow’s milk, wheat, dust mite, plant or fungal/bacterial allergens. In adults and adolescents with asthma, two real-world analyses will also be shared evaluating the potential of moving Dupixent earlier in the treatment paradigm. The analyses measured reduction of exacerbations and systemic corticosteroid use in patients uncontrolled on medium-dose inhaled corticosteroids (ICS), comparing the addition of Dupixent with escalating to high-dose inhaled corticosteroids or the addition of other biologics. Additionally, late-breaking data from the Phase 3 AIMS trial in adults and children aged 6 years and older with allergic fungal rhinosinusitis (AFRS) will be presented. These data formed the basis for a supplemental Biologics License Application (sBLA) in the U.S., which is currently under Priority Review with a target action date of February 28, 2026. The safety and efficacy of Dupixent in AFRS have not been fully evaluated by any regulatory authority. The full list of Regeneron allergy presentations at AAAAI includes: Abstract Title Presentation Number Presenting Author Presentation Date and Time (ET) B cells accumulate in lung during allergic inflammation and play a role in tissue remodeling 899 Oral Abstract Session Maloney, A. Tuesday, Mar 2 12:45 - 2:00 pm Immunological evaluation of cat allergic individuals living with or without a cat 278 Atanasio, A. Friday, Feb 27 2:45 - 3:45 pm Prediction of symptomatic relief in allergic individuals using a preclinical mouse model of allergic anaphylaxis 279 Atanasio, A. Friday, Feb 27 2:45 - 3:45 pm IL4Ra blockade reduces Oral Immunotherapy outcome-related adverse events through inhibition of Mast cell activity in a murine model of oral immunotherapy 463 Atanasio, A. Saturday, Feb 28 9:45 - 10:45 am A Single Prophylactic Dose of REGN1908-1909 Significantly Suppressed Cat-Allergen Induced Allergic Conjunctivitis Signs and Symptoms and Skin Test Reactivity 746 Gagnon, R. Sunday, Mar 1 9:45 - 10:45 am Utilizing an Indirect Basophil Activation Test to Interrogate the Potency of Bet v 1 and Related Allergens 743 Maloney, K. Sunday, Mar 1 9:45 - 10:45 am Multidimensional Burden In Cat Allergic Individuals Despite Allergen Avoidance Efforts 677 Schneider, S. Sunday, Mar 1 9:45 - 10:45 am Antibody Cocktail Targeting Bet v1 Reduces Signs and Symptoms of Allergic Conjunctivitis in Birch Allergic Individuals Undergoing Conjunctival Allergen Challenge 742 Torkildsen, G. Sunday, Mar 1 9:45 - 10:45 am The full list of Regeneron and Sanofi Dupixent presentations at AAAAI includes: Abstract Title Presentation Number Presenting Author Presentation Date and Time (ET) Atopic Dermatitis Dupilumab Treatment up to 1 Year Reduces Allergen-Specific IgE in Young Children With Moderate-to-Severe Atopic Dermatitis 016 Beck, L.A. Friday, Feb 27 2:45 - 3:45 pm Progressive Reduction of Allergen-Specific IgE in Children Aged 6 to 11 Years With Moderate-to-Severe Atopic Dermatitis Treated With Dupilumab 015 Beck, L.A. Friday, Feb 27 2:45 - 3:45 pm Minimally Invasive Skin Tape Strip Proteomic Analysis Demonstrates Significant Inhibition of Epidermal Hyperplasia Protein Cluster in Pediatric Atopic Dermatitis Patients Treated With Dupilumab 053 Goleva, E. Friday, Feb 27 2:45 - 3:45 pm Systemic Treatments Outcomes for Moderate-to-Severe Atopic Dermatitis in Children Aged Less Than 12 Years: PEDISTAD 5-Year Results 052 Leung, D.Y.M. Friday, Feb 27 2:45 - 3:45 pm Asthma Dupilumab With Medium-Dose Inhaled Corticosteroids Versus Omalizumab With High-Dose Inhaled Corticosteroids Improves Clinical Outcomes In Patients With Coexisting Chronic Rhinosinusitis With Nasal Polyps And Uncontrolled Asthma L03 Wagenmann, M. Saturday, Feb 28 9:45-10:45am Baseline Predictors of Clinical Remission in Children With Uncontrolled, Moderate-To-Severe Asthma Treated With Dupilumab: A Post Hoc Analysis of the VOYAGE Study 130 Bacharier, L.B. Friday, Feb 27 2:45 - 3:45 pm Dupilumab Improves Lung Function and Reduces Total and Specific IgE Levels in Patients With Asthma and Allergic Bronchopulmonary Aspergillosis: The Phase 2 LIBERTY ABPA AIRED Study 828 Corren, J. Sunday, Mar 1 3:30 - 5:00 pm Systemic Corticosteroid Use Before Biologic Initiation Among Pediatric Patients With Asthma in the United States 138 Guilbert, T.W. Friday, Feb 27 2:45 - 3:45 pm Systemic Corticosteroid Use Among Pediatric Patients With Uncontrolled Moderate-to-Severe Asthma in the United States 119 Jackson, D.J. Friday, Feb 27 2:45 - 3:45 pm Escalation to High-Dose ICS Versus Dupilumab Initiation in Uncontrolled Asthma Patients on Medium-Dose ICS: A Matched Analysis of Administrative Claims 125 Katial, R. Friday, Feb 27 2:45 - 3:45 pm Utility of Spirometry-Derived Ratios to Detect Changes in Large and Small Airways With Dupilumab in Moderate-to-Severe Asthma 643 Lipworth, B. Sunday, Mar 1 9:45 - 10:45 am Real-World Outcomes Following Asthma Treatment Escalation From Medium-Dose ICS to high-Dose ICS or Biologics 133 Lugogo, N.L. Friday, Feb 27 2:45 - 3:45 pm Patient-Reported Burden of Coexisting Type 2 Inflammatory Conditions in Patients Initiating Dupilumab for Asthma: Baseline Data From the REVEAL Registry 634 Maspero, J.F. Sunday, Mar 1 9:45 - 10:45 am Improved Quality of Life Over 1 Year in Patients With Asthma who Initiate Dupilumab in a Real-World Clinical Setting: The RAPID Registry 143 Peters, A.T. Friday, Feb 27 2:45 - 3:45 pm Children With Asthma Receiving Dupilumab had Reduced Exacerbations and Improved Asthma Control Versus Placebo, Regardless of Asthma Duration 118 Phipatanakul, W. Friday, Feb 27 2:45 - 3:45 pm CRSwNP Dupilumab for Treatment of Allergic Fungal Rhinosinusitis in Adults and Children Aged 6 and Over: Results From LIBERTY-AIMS Study L40 Late Breaking Poster Presentation Han, J. Sunday, Mar 1 9:45 - 10:45 am Comparative Efficacy of Dupilumab and Tezepelumab in Patients With Chronic Rhinosinusitis With Nasal Polyps: An Anchored Matching-adjusted Indirect Comparison L78 Late Breaking Poster Presentation Lipworth, B. Sunday, Mar 1 9:45 - 10:45 am Dupilumab Led to Rapid Improvements in Nasal Congestion and Loss of Smell in Patients With Chronic Rhinosinusitis With Nasal Polyps: Results from the Global AROMA Registry 244 Buchheit, K. Friday, Feb 27 2:45 - 3:45 pm Efficacy of Dupilumab vs Omalizumab in Patients With Severe Chronic Rhinosinusitis With Nasal Polyps Coexisting With Asthma and Allergic Rhinitis: Results From the Head-to-Head, Prospective, Randomized EVEREST study 241 Oppenheimer, J. Friday, Feb 27 2:45 - 3:45 pm Dupilumab Improved Work Productivity in Patients With CRSwNP: Results From the Global AROMA Registry 237 Peters, A.T. Friday, Feb 27 2:45 - 3:45 pm Concurrent Improvement in Nasal Polyp Score and Forced Expiratory Volume in One Second With Dupilumab vs Omalizumab in Patients With Severe CRSwNP and Coexisting Asthma: Results From the EVEREST Study 238 Peters, A.T. Friday, Feb 27 2:45 - 3:45 pm Real-World Dupilumab Effectiveness Through 18 Months in Patients With CRSwNP and Coexisting Allergic Rhinitis: Results From the Global AROMA Registry 245 White, A. Friday, Feb 27 2:45 - 3:45 pm COPD Evaluating Fractional Exhaled Nitric Oxide as a Predictor of Clinical Outcomes in Patients With Chronic Obstructive Pulmonary Disease With Type 2 Inflammation 652 Soliman, M. Sunday, Mar 1 9:45 - 10:45 am EoE Dupilumab Leads to Sustained Treatment Response up to 52 Weeks in Dysphagia and Odynophagia Associated With Eosinophilic Esophagitis in Adults and Adolescents: Post-Hoc Analysis of the LIBERTY EoE TREET Study 180 Cianferoni, A. Friday, Feb 27 2:45 - 3:45 pm Dupilumab Maintains Histologic and Endoscopic Improvements Across Age Subgroups in Pediatric Patients With Eosinophilic Esophagitis (EoE) Over 52 Weeks: Pooled Analysis From Two Phase 3 Studies (EoE KIDS and LIBERTY EoE TREET) 172 McGown, E. Friday, Feb 27 2:45 - 3:45 pm CSU Dupilumab Reduced Itch and Urticaria Activity in Chronic Spontaneous Urticaria Patient Subpopulations 001 Casale, T.B. Friday, Feb 27 2:45 - 3:45 pm Dupilumab Efficacy in Pooled LIBERTY-CSU CUPID Study A and Study C Regardless of Baseline Serum Total IgE Levels 023 Saini, S.S. Friday, Feb 27 2:45 - 3:45 pm Cross-Franchise Serum Total IgE Reductions With Dupilumab Treatment in Pediatric Patients With Atopic Dermatitis, Asthma or Eosinophilic Esophagitis and their Relationship to Clinical Improvement 014 Beck, L.A. Friday, Feb 27 2:45 - 3:45 pm About Regeneron's VelocImmune Technology Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite ® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved fully human monoclonal antibodies. This includes Dupixent ® (dupilumab), Libtayo ® (cemiplimab-rwlc), Praluent ® (alirocumab), Kevzara ® (sarilumab), Evkeeza ® (evinacumab-dgnb), Inmazeb ® (atoltivimab, maftivimab and odesivimab-ebgn) and Veopoz ® (pozelimab-bbfg). In addition, REGEN-COV ® (casirivimab and imdevimab) had been authorized by the FDA during the COVID-19 pandemic until 2024. U.S. INDICATIONS DUPIXENT is a prescription medicine used: to treat adults and children 6 months of age and older with moderate-to-severe eczema (atopic dermatitis or AD) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children with AD under 6 months of age. with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in adults and children 6 years of age and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. It is not known if DUPIXENT is safe and effective in children with asthma under 6 years of age. with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adults and children 12 years of age and older whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with CRSwNP under 12 years of age. to treat adults and children 1 year of age and older with eosinophilic esophagitis (EoE), who weigh at least 33 pounds (15 kg). It is not known if DUPIXENT is safe and effective in children with EoE under 1 year of age, or who weigh less than 33 pounds (15 kg). to treat adults with prurigo nodularis (PN). It is not known if DUPIXENT is safe and effective in children with PN under 18 years of age. with other medicines for the maintenance treatment of adults with inadequately controlled chronic obstructive pulmonary disease (COPD) and a high number of blood eosinophils (a type of white blood cell that may contribute to your COPD). DUPIXENT is used to reduce the number of flare-ups (the worsening of your COPD symptoms for several days) and can improve your breathing. It is not known if DUPIXENT is safe and effective in children with COPD under 18 years of age. to treat adults and children 12 years of age and older with chronic spontaneous urticaria (CSU) who continue to have hives that are not controlled with H1 antihistamine treatment. It is not known if DUPIXENT is safe and effective in children with CSU under 12 years of age, or who weigh less than 66 pounds (30 kg). to treat adults with bullous pemphigoid (BP). It is not known if DUPIXENT is safe and effective in children with BP under 18 years of age. DUPIXENT is not used to relieve sudden breathing problems and will not replace an inhaled rescue medicine or to treat any other forms of hives (urticaria). IMPORTANT SAFETY INFORMATION Do not use if you are allergic to dupilumab or to any of the ingredients in DUPIXENT ® . Before using DUPIXENT, tell your healthcare provider about all your medical conditions, including if you: have eye problems. have a parasitic (helminth) infection. are scheduled to receive any vaccinations. You should not receive a “live vaccine” right before and during treatment with DUPIXENT. are pregnant or plan to become pregnant. It is not known whether DUPIXENT will harm your unborn baby. A pregnancy registry for women who take DUPIXENT during pregnancy collects information about the health of you and your baby. To enroll or get more information call 1-877-311-8972 or go to . are breastfeeding or plan to breastfeed. It is not known whether DUPIXENT passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you are taking oral, topical, or inhaled corticosteroid medicines; have asthma and use an asthma medicine; or have AD, CRSwNP, EoE, PN, COPD, CSU, or BP and also have asthma. Do not change or stop your other medicines, including corticosteroid medicine or other asthma medicine, without talking to your healthcare provider. This may cause other symptoms that were controlled by those medicines to come back. DUPIXENT can cause serious side effects, including: Allergic reactions. DUPIXENT can cause allergic reactions, including skin reactions, that can sometimes be severe. Stop using DUPIXENT and tell your healthcare provider or get emergency help right away if you get any of the following signs or symptoms: breathing problems or wheezing, swelling of the face, lips, mouth, tongue or throat, fainting, dizziness, feeling lightheaded, fast pulse, fever, hives, skin rash, including rash that looks like a bullseye, painful red or blue bumps under the skin, or red pus-filled spots on the skin, general ill feeling, itching, swollen lymph nodes, nausea or vomiting, joint pain, or cramps in your stomach area. Eye pr ob l e m s. Tell your healthcare provider if you have any new or worsening eye problems, including eye pain or changes in vision, such as blurred vision. Your healthcare provider may send you to an ophthalmologist for an exam if needed. I n fl a mm a t i o n o f y ou r b l oo d v e ss e l s. Rarely, this can happen in people with asthma who receive DUPIXENT. This may happen in people who also take a steroid medicine by mouth that is being stopped or the dose is being lowered. Tell your healthcare provider right away if you get: rash, chest pain, worsening shortness of breath, brown or dark colored urine, persistent fever, or a feeling of pins and needles or numbness of your arms or legs. Psoriasis. This can happen in people with atopic dermatitis and asthma who receive DUPIXENT. Tell your healthcare provider about any new skin symptoms. Your healthcare provider may send you to a dermatologist for an examination if needed. Joint aches and pain. Some people who use DUPIXENT have had trouble walking or moving due to their joint symptoms, and in some cases needed to be hospitalized. Tell your healthcare provider about any new or worsening joint symptoms. Your healthcare provider may stop DUPIXENT if you develop joint symptoms. The most common side effects include: Eczema: injection site reactions, eye problems, including eye and eyelid inflammation, redness, swelling, itching, eye infection, dry eye, and blurred vision, cold sores in your mouth or on your lips, and high count of a certain white blood cell (eosinophilia). A s t h ma: injection site reactions, high count of a certain white blood cell (eosinophilia), pain in the throat (oropharyngeal pain), and parasitic (helminth) infections. Chronic Rhinosinusitis with Nasal Polyps: injection site reactions, eye problems, including eye and eyelid inflammation, redness, swelling, itching, eye infection, and blurred vision, high count of a certain white blood cell (eosinophilia), stomach problems (gastritis), joint pain (arthralgia), trouble sleeping (insomnia), and toothache. Eosinophilic Esophagitis: injection site reactions, upper respiratory tract infections, cold sores in your mouth or on your lips, and joint pain (arthralgia). Prurigo Nodularis: eye problems, including eye and eyelid inflammation, redness, swelling, itching, and blurred vision, herpes virus infections, common cold symptoms (nasopharyngitis), dizziness, muscle pain, and diarrhea. Chronic Obstructive Pulmonary Disease: injection site reactions, common cold symptoms (nasopharyngitis), high count of a certain white blood cell (eosinophilia), viral infection, back pain, inflammation inside the nose (rhinitis), diarrhea, stomach problems (gastritis), joint pain (arthralgia), toothache, headache, and urinary tract infection. Chronic Spontaneous Urticaria: injection site reactions. Bullous Pemphigoid: joint pain (arthralgia), eye problems, including eye and eyelid inflammation, redness, swelling, itching, and blurred vision, and herpes virus infections. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of DUPIXENT. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. Use DUPIXENT exactly as prescribed by your healthcare provider. It’s an injection given under the skin (subcutaneous injection). Your healthcare provider will decide if you or your caregiver can inject DUPIXENT. Do not try to prepare and inject DUPIXENT until you or your caregiver have been trained by your healthcare provider. In children 12 years of age and older, it’s recommended DUPIXENT be administered by or under supervision of an adult. In children 6 months to less than 12 years of age, DUPIXENT should be given by a caregiver. P l ea se s e e a cc o mp any i n g f u l l P r e s cri b i n g I n f o r ma t i o n i nc l ud i n g P a t i en t I n f o r ma t i o n. About Regeneron Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases. Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center ® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases. For more information, please visit or follow Regeneron on LinkedIn , Instagram , Facebook or X . Regeneron Forward-Looking Statements and Use of Digital Media This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. (“Regeneron” or the “Company”), and actual events or results may differ materially from these forward-looking statements. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Products”) and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Product Candidates”) and research and clinical programs now underway or planned, including without limitation Dupixent ® (dupilumab) for the treatment of allergic fungal rhinosinusitis and other potential indications, Regeneron’s investigational allergen-blocking antibody combination therapies for the treatment of cat and birch allergies, and Regeneron’s broader allergy pipeline discussed in this press release; the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron’s Product Candidates and new indications for Regeneron’s Products, including those referenced above; uncertainty of the utilization, market acceptance, and commercial success of Regeneron’s Products and Regeneron’s Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the studies discussed or referenced in this press release, on any of the foregoing or any potential regulatory approval of Regeneron’s Products and Regeneron’s Product Candidates (such as those referenced above ) ; the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees (including the research programs discussed or referenced in this press release, such as those evaluating Dupixent for food and environmental allergies and expanded use in asthma ) may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; the ability of Regeneron’s collaborators, licensees, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron’s Products and Regeneron’s Product Candidates; the ability of Regeneron to manage supply chains for multiple products and product candidates and risks associated with tariffs and other trade restrictions; safety issues resulting from the administration of Regeneron’s Products and Regeneron’s Product Candidates (such as those referenced above) in patients, including serious complications or side effects in connection with the use of Regeneron’s Products and Regeneron’s Product Candidates in clinical trials; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron’s ability to continue to develop or commercialize Regeneron’s Products and Regeneron’s Product Candidates; ongoing regulatory obligations and oversight impacting Regeneron’s Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement or copay assistance for Regeneron’s Products from third-party payors and other third parties, including private payor healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payors and other third parties and new policies and procedures adopted by such payors and other third parties; changes to drug pricing regulations and requirements and Regeneron’s pricing strategy; other changes in laws, regulations, and policies affecting the healthcare industry; competing products and product candidates (including biosimilar products) that may be superior to, or more cost effective than, Regeneron’s Products and Regeneron’s Product Candidates; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron’s agreements with Sanofi and Bayer (or their respective affiliated companies, as applicable), to be cancelled or terminated; the impact of public health outbreaks, epidemics, or pandemics on Regeneron's business; and risks associated with litigation and other proceedings and government investigations relating to the Company and/or its operations (including the pending civil proceedings initiated or joined by the U.S. Department of Justice and the U.S. Attorney's Office for the District of Massachusetts), risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA ® (aflibercept) Injection), the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron’s business, prospects, operating results, and financial condition. A more complete description of these and other material risks can be found in Regeneron’s filings with the U.S. Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2025. Any forward-looking statements are made based on management’s current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update (publicly or otherwise) any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise. Regeneron uses its media and investor relations website and social media outlets to publish important information about the Company, including information that may be deemed material to investors. Financial and other information about Regeneron is routinely posted and is accessible on Regeneron's media and investor relations website ( ) and its LinkedIn page ( ). Regeneron Contacts: Media Relations Hannah Kwagh Tel: +1 914-847-6314 Hannah.Kwagh@regeneron.com Ilana Yellen Tel: +1 914-330-9618 Ilana.Yellen@regeneron.com Kailey Kilmartin Tel: +1 914-652-0679 Kailey.Kilmartin@regeneron.com Investor Relations Mark Hudson Tel: +1 914-847-3482 Mark.Hudson@regeneron.com a The conjunctival allergen challenge was conducted with the Ora Conjunctival Challenge Model (Ora-CAC ® ) .