Patients with moderate to severe allergic rhinitis may benefit from subcutaneous immunotherapy (SCIT), despite the risk of systemic allergic reaction. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin (IL)-4 and IL-13, key drivers of the type 2 inflammation seen in allergic rhinitis, thereby inhibiting their signaling. In the LIBERTY Grass AID trial (NCT03558997), 16 weeks of treatment with 300 mg dupilumab every 2 weeks plus Timothy grass (TG) SCIT did not reduce TG allergen challenge nasal symptom scores compared with SCIT only but did improve tolerability of SCIT up-titration in patients with a history of grass pollen-induced seasonal allergic rhinitis. Here we present the pharmacokinetics of functional serum dupilumab and concentration–response relationships in 52 patients enrolled in this trial. Functional dupilumab concentrations and concentrations of TG-specific immunoglobulin E (IgE) and IgG4 were assessed in blood samples collected from dupilumab-only and SCIT+dupilumab-treated groups. Mean functional dupilumab concentrations were similar in both groups and reached a steady state of approximately 70–80 mg/L at week 5. One week after the end of treatment, TG-specific IgG4 concentrations were increased in the SCIT+dupilumab group, but not in the dupilumab-only group, over the range of dupilumab concentrations evaluated, whereas no changes were seen for TG-specific IgE concentrations. This study demonstrates that SCIT does not alter functional concentrations of serum dupilumab, and the impact of SCIT on TG-specific immunoglobulins is not affected by functional dupilumab concentrations over the range studied, indicating that maximum response was achieved in all patients.

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