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

Abstract

Regulatory T (Treg) cells are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2_LD) activates Treg cells. Our aim was to assess IL-2_LD efficacy for controlling clinical responses to allergen exposures. 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. 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. 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.