Pharmacokinetics and Concentration-Response of Dupilumab in Patients With Seasonal Allergic Rhinitis

Abstract

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-4 and interleukin-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 of 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 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 ≈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.

Keywords: concentration-response relationship; dupilumab; grass allergy; pharmacokinetics; seasonal allergic rhinitis; subcutaneous immunotherapy.