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

Michelle Rosenzwajg; Alina Gherasim; Franck Dietsch; Marine Beck; Nathalie Domis; Roberta Lorenzon; Yannick Chantran; Bertrand Bellier; E Vicaut; Angele Soria; Frederic De Blay; David Klatzmann

doi:10.1016/j.jaci.2024.10.033

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

J Allergy Clin Immunol. 2024 Nov 10:S0091-6749(24)01181-3. doi: 10.1016/j.jaci.2024.10.033. Online ahead of print.

Authors

Affiliations

¹ AP-HP, Pitié-Salpêtrière Hospital, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (i2B), F-75651, Paris, France; Sorbonne Université, INSERM, UMR_S 959, Immunology-Immunopathology- Immunotherapy (i3); F-75651, Paris, France.
² Centre de recherche clinique ALYATEC, 1 Place de l'Hôpital, Strasbourg, France.
³ AP-HP, Saint Antoine Hospital, Immunology department, F-75012, Paris, France.
⁴ Sorbonne Université, INSERM, UMR_S 959, Immunology-Immunopathology- Immunotherapy (i3); F-75651, Paris, France.
⁵ AP-HP, Saint Louis/Lariboisière Hospitals, Unité de recherche clinique and Université Paris 7, F-75010, Paris, France.
⁶ AP-HP, Tenon Hospital, Dermatology and Allergy Department, Paris, France.
⁷ AP-HP, Pitié-Salpêtrière Hospital, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (i2B), F-75651, Paris, France; Sorbonne Université, INSERM, UMR_S 959, Immunology-Immunopathology- Immunotherapy (i3); F-75651, Paris, France. Electronic address: [email protected].

PMID: 39532189
DOI: 10.1016/j.jaci.2024.10.033

Abstract

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

Objective: To assess IL-2_LD efficacy for controlling clinical responses to allergen exposures.

Methods: RHINIL-2 was a phase-2a, randomised, double-blind, placebo-controlled trial. Patients with allergic rhinitis to birch pollen (BP) were included, 66% having concomitant asthma. All had a total nasal symptom score (TNSS) ≥5 following nasal exposure to BP in an environmental-exposure-chamber (EEC). Patients received 1 MUI/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 EEC were evaluated using TNSS, the rhinitis visual analogue scale (VAS) and spirometry. The primary efficacy endpoint was the difference in TNSS area under the curve between inclusion and day 40 (TNSSΔAUC).

Results: IL-2_LD treatment induced a significant expansion of Tregs. The TNSSΔAUC in the IL-2 and Placebo groups was non significantly different. TNSS and VAS AUCs were significantly reduced from baseline to day 40 in the IL-2_LD group only (p=0.04 and p=0.01, respectively). The ratio of forced expiratory volume in 1 second/forced vital capacity (FEV_1P) and the forced mid-expiratory flow (FEF_25-75%) showed improvement in the IL-2_LD vs Placebo groups at day 40 (p=0.04 and 0.04, respectively). However, the short treatment duration used in this study cannot have effects on specific IgE or IgG4 levels given their half-life. There was no severe treatment-related adverse events.

Conclusion: IL-2_LD is well-tolerated in allergic patients, even with asthma, clearing the path for further therapeutic development. Our work suggests that Treg 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.

Keywords: Immunopathologies; Immunotherapy; Tolerance; biotherapy.