Safety and efficacy of eblasakimab, an interleukin 13 receptor α1 monoclonal antibody, in adults with moderate-to-severe atopic dermatitis: A phase 1b, multiple-ascending dose study.

BACKGROUND: Eblasakimab, an interleukin (IL)-13 receptor α1 antagonist, blocks IL-4 and IL-13 signaling through the type 2 receptor. OBJECTIVE: The safety and efficacy of eblasakimab was evaluated in adults with moderate-to-severe atopic dermatitis (AD). METHODS: In this phase 1b randomized, double-blinded study, 52 patients with moderate-to-severe AD received weekly subcutaneous injections of eblasakimab 200, 400, or 600 mg, or placebo for 8 weeks. Primary outcome was the incidence of treatment-emergent adverse events. Secondary outcomes included percentage change in the Eczema Area and Severity Index from baseline; Eczema Area and Severity Index improvement of at least 50%, 75%, or 90% from baseline; and percentage change in the peak-pruritus numeric rating scale score from baseline. RESULTS: Treatment-emergent adverse events were reported in 47% placebo and 71% eblasakimab patients; most were considered mild or moderate and did not lead to study discontinuation. At week 8 eblasakimab 600 mg showed statistically significant improvement in mean percentage change in Eczema Area and Severity Index versus placebo (-65% vs -27%, P = .014). Other key secondary physician- and patient-reported end points were met. LIMITATIONS: Longer studies are required to confirm eblasakimab safety and efficacy in AD patients. CONCLUSIONS: Treatment of adults with moderate-to-severe AD with eblasakimab was well-tolerated and associated with significant clinical improvements versus placebo.

Therapeutic efficacy of a co-blockade of IL-13 and IL-25 on airway inflammation and remodeling in a mouse model of asthma.

Repeated airway inflammation and unremitting remodeling provoke irreversible pulmonary dysfunction and resistance to current drugs in patients with chronic bronchial asthma. Interleukin (IL)-13 and IL-25 play an important role in airway inflammation and remodeling in asthma. We aimed to investigate whether co-inhibiting IL-13 and IL-25 can effectively down-regulate allergen-induced airway inflammation and remodeling in mice. Mice with asthma induced by chronic exposure to ovalbumin (OVA) were given soluble IL-13 receptor α2 (sIL-13R) or soluble IL-25 receptor (sIL-25R) protein alone and in combination to neutralize the bioactivity of IL-13 and IL-25, and relevant airway inflammation and remodeling experiments were performed. We found that the co-blockade of IL-13 and IL-25 with sIL-13R and sIL-25R was more effective than either agent alone at decreasing inflammatory cell infiltration, airway hyperresponsiveness (AhR) and airway remodeling including mucus production, extracellular collagen deposition, smooth muscle cell hyperplasia and angiogenesis in mice exposed to OVA. These results suggest that the combined inhibition of IL-13 and IL-25 may provide a novel therapeutic strategy for asthma, especially for patients who are resistant to current treatments.

[Effect of combined use of sIL-5Rα and sIL-13Rα2 on VCAM-1 and IFN-γ in allergic rhinitis rats].

OBJECTIVE: To investigate the effects of sIL-5Rα and sIL-13Rα2 on VCAM-1 and IFN-γ in allergic rhinitis rats. METHODS: A total of 50 Wistar rats were randomly divided into 5 groups: the normal group (group A), the allergic rhinitis model group (group B), the sIL-5Rα treatment group (group C), the sIL-13Rα2 treatment group (group D), the combination of sIL-5Rα and sIL-13Rα2 treatment group (group E or the combined treatment group). Rats in the latter 4 groups were sensitized with ovalbumin (OVA) and Al(OH)(3), and challenged with OVA to establish allergic rhinitis models, while rats in the normal group were treated with saline. Rats in the sIL-5Rα treatment group, the sIL-13Rα2 treatment group and the combined treatment group were absorbed on day 31 to day 38 once daily once nasal cavity with sIL-5Rα(100 µg), sIL-13Rα2 (100 µg) and the combination of sIL-5Rα (100 µg) and sIL-13Rα2 (100 µg) 30 min before challenged, while rats in the allergic rhinitis model group received PBS(50 µl). Then the levels of VCAM-1 and IFN-γ in serum and nasal lavage fluid (NLF) were measured by ELISA. RESULTS: Compared with the normal group, the levels of VCAM-1 in the allergic rhinitis model group were higher, while IFN-γ were lower (all P < 0.01). Compared with the allergic rhinitis model group, the sIL-5Rα treatment group, the sIL-13Rα2 treatment group and the combined treatment group could effectively reduced serum and NLF VCAM-1 level [group E: (283.5 ± 5.7) µg/L, (101.8 ± 4.8) µg/L; group C: (311.5 ± 12.6) µg/L, (133.9 ± 5.8) µg/L; group D: (304.7 ± 6.6) µg/L, (128.5 ± 7.7) µg/L], and increased IFN-γ level [group E: (874.7 ± 9.6) pg/ml, (349.2 ± 12.1) pg/ml; group C: (600.2 ± 16.1) pg/ml, (195.5 ± 16.1) pg/ml; group D: (577.9 ± 9.6) pg/ml, (196.7 ± 9.9) pg/ml ]; compared with single treatment, the combined treatment group also had significant differences(P < 0.01). CONCLUSIONS: Combined treatment with sIL-5Rα and sIL-13Rα2 to treat the allergic rhinitis rats can significantly reduce VCAM-1 levels in serum and NLF, and increase IFN-γ levels, thus, to achieve the purpose of mitigation and treatment of allergic rhinitis.