Low-dose IL-2 in birch pollen allergy: A phase-2 randomized double-blind placebo-controlled trial

IF 11.2 1区医学 Q1 ALLERGY Journal of Allergy and Clinical Immunology Pub Date : 2025-02-01 Epub Date: 2024-11-10 DOI:10.1016/j.jaci.2024.10.033

Michelle Rosenzwajg MD, PhD , Alina Gherasim MD , Franck Dietsch MD , Marine Beck PhD , Nathalie Domis PhD , Roberta Lorenzon MD, PhD , Yannick Chantran PharmD , Bertrand Bellier PhD , Eric Vicaut MD , Angele Soria MD , Frederic de Blay MD , David Klatzmann MD, PhD

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Abstract

Background

Regulatory T (Treg) cells are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2_LD) activates Treg cells.

Objective

Our aim was to assess IL-2_LD efficacy for controlling clinical responses to allergen exposures.

Methods

RHINIL-2 was a phase-2a, randomized, double-blind, placebo-controlled trial. Patients with allergic rhinitis to birch pollen (BP) were included; 66% of them had concomitant asthma. All had a total nasal symptom score (TNSS) of 5 or more following nasal exposure to BP in an environmental exposure chamber. Patients received 1 MUI per day of IL-2 (n = 12) or placebo (n = 12) for 5 days, followed by weekly injections for 4 weeks. Clinical responses to subsequent BP exposures in the environmental exposure chamber were evaluated by using TNSS, the rhinitis visual analog scale (VAS), and spirometry. The primary efficacy end point was the difference in TNSS area under the curve (AUC) between inclusion and day 40.

Results

IL-2_LD treatment induced a significant expansion of Treg cells. The difference in TNSS AUC between inclusion and day 40 AUC in the IL-2 and placebo groups was not significant. TNSS and visual analog scale AUCs were significantly reduced from baseline to day 40 in the IL-2_LD group only (P = .04 and P = .01, respectively). The ratio of FEV₁ to forced vital capacity (FEV_1P) and the forced midexpiratory flow (FEF_25%-75%) showed improvement in the IL-2_LD–treated versus in the groups given placebo at day 40 (P = .04 and P = .04, respectively). However, the short treatment duration used in this study could not have effects on specific IgE or IgG4 levels given their half-life. There were no severe treatment-related adverse events.

Conclusion

IL-2_LD is well tolerated in patients with allergy, even in those with asthma, thus clearing the path for further therapeutic development. Our work suggests that Treg cells can safely attenuate an ongoing allergic response. It paves the way for larger studies with longer treatment periods, which are needed to properly evaluate the therapeutic potential of IL-2 in allergy.

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治疗桦树花粉过敏的低剂量白细胞介素-2：第二阶段随机双盲安慰剂对照试验。

背景：调节性 T 细胞（Tregs）在对过敏原的免疫耐受中起着关键作用。低剂量 IL-2 (IL-2LD) 可激活 Tregs：评估 IL-2LD 对控制过敏原暴露临床反应的疗效：RHINIL-2是一项2a期随机、双盲、安慰剂对照试验。试验纳入了对桦树花粉（BP）过敏的鼻炎患者，其中66%的患者同时患有哮喘。在环境暴露室（EEC）中鼻腔暴露于桦树花粉后，所有患者的鼻部症状总分（TNSS）均≥5。患者每天注射 1 MUI IL-2（12 人）或安慰剂（12 人），共注射 5 天，然后每周注射一次，共注射 4 周。使用 TNSS、鼻炎视觉模拟量表（VAS）和肺活量测定法评估患者对随后在 EEC 中暴露血压的临床反应。主要疗效终点是入组与第40天之间TNSS曲线下面积的差异（TNSSΔAUC）：结果：IL-2LD治疗诱导Tregs显著扩增。IL-2组和安慰剂组的TNSSΔAUC无显著差异。只有IL-2LD组的TNSS和VAS AUC从基线到第40天显著降低（分别为p=0.04和p=0.01）。在第 40 天，IL-2LD 组与安慰剂组相比，1 秒钟用力呼气量/用力呼吸量比值（FEV1P）和用力中呼气流量（FEF25-75%）均有所改善（p=0.04 和 0.04）。不过，鉴于特异性 IgE 或 IgG4 的半衰期较短，本研究中使用的短疗程不会对其水平产生影响。没有出现与治疗相关的严重不良反应：IL-2LD在过敏性患者，甚至是哮喘患者中的耐受性良好，为进一步的治疗开发开辟了道路。我们的研究表明，Treg 可以安全地减轻正在发生的过敏反应。这为进行更大规模、更长治疗期的研究铺平了道路，而要正确评估IL-2在过敏症中的治疗潜力，就必须进行更大规模、更长治疗期的研究。

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来源期刊

Journal of Allergy and Clinical Immunology 医学-过敏

CiteScore

25.90

自引率

7.70%

发文量

1302

审稿时长

38 days

期刊介绍： The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.