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Effective treatment with dupilumab in biologic-refractory severe asthma

Published online: September 24, 2020

Specific antibodies targeting key players in the pathophysiology of asthma, such as antibodies against Immunoglobulin E (IgE) and Interleukin 5 (IL-5) / Interleukin 5 receptor (IL5Rα),   have revolutionized the treatment of patients with severe asthma. However, a fraction of patients remains with high disease burden, persistent symptoms, and dependency on oral corticosteroids (OCS). It has been unclear whether a switch towards the new Interleukin 4-receptor (IL4Rα) - antibody dupilumab could be of benefit to patients who previously showed an insufficient response to another antibody therapy.

In a recent study published in The Journal of Allergy and Clinical Immunology: In Practice, Mümmler et al. performed a retrospective analysis on 38 patients who were poorly controlled during a previous antibody therapy and were subsequently switched to dupilumab. Inclusion criteria were a previous antibody therapy for a minimum duration of three months, a switch to dupilumab in less than 6 months after discontinuation of previous therapy, and a treatment duration with dupilumab for at least three months. Clinical parameters and lung function data were evaluated before antibody therapy, during previous therapy, and after 3 to 6 months of dupilumab treatment. Patients were classified into responder or non-responder categories according to changes in Asthma control test (ACT) score, forced expiratory volume in one second (FEV1), and oral corticosteroid (OCS) dose.

In the total cohort, patients experienced significant improvements in multiple lung function parameters, subjective asthma control as measured by ACT score, and a decrease in the asthma biomarkers fractional exhaled nitric oxide (FeNO) and serum IgE. When classified in responders and non-responders, the authors showed that around three quarters of the patients were categorized as responders. Further, it was found that responders more often showed elevated FeNO during previous antibody therapy.

This real-world study underlines the differential responses patients might exhibit to different asthma biologic treatments. It demonstrates that patients who were unresponsive to anti-IgE and/or anti-IL5/IL5Ra-therapies might still experience significant benefits from a switch towards an anti-IL4Rα-inhibiting strategy and that a therapeutic trial of an antibody switch might be a reasonable step.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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