Pharmacokinetics and Concentration-Response of Dupilumab in Patients With Seasonal Allergic Rhinitis.
J Clin Pharmacol
; 62(5): 689-695, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-34791679
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.
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Base de dados:
MEDLINE
Assunto principal:
Rinite Alérgica Sazonal
/
Rinite Alérgica
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article