Published online: January 17, 2018
Asthma and perennial allergic rhinitis (PAR) often coexist. Patients with asthma and comorbid PAR typically have more severe disease and poorer control of symptoms, resulting in worse health outcomes. Numerous clinical studies strongly suggest a link between PAR and asthma, and support the concept of a “united airway disease” in which the two conditions are unified by a systemic type 2 immunologic response to common perennial allergens such as house dust mites and animal dander. Despite its high prevalence, PAR is often inadequately managed, and patients commonly have persistent nasal symptoms. The link between the upper and lower airways has important implications for both the diagnosis and management of these common comorbidities. Systemic therapy with a drug that is targeted against the shared underlying pathophysiology of type 2 immune diseases such as asthma and allergic rhinitis may improve symptom control in patients with both conditions. Dupilumab, a human monoclonal antibody, is a novel immunomodulatory drug that is currently approved for the systemic treatment of patients with moderate-to-severe atopic dermatitis; clinical studies have also reported promising results for dupilumab in the treatment of patients with uncontrolled persistent asthma.
In a study published recently in The Journal of Allergy and Clinical Immunology (JACI), Weinstein and colleagues examined the efficacy and safety of dupilumab in patients with moderate-to-severe, uncontrolled persistent asthma and comorbid PAR. The authors retrospectively analyzed data from 241 patients with asthma and comorbid PAR (defined as positive IgE antibody response to several known PAR-causing antigens above a threshold at study entry, including cat and dog dander and dust mites) who had received treatment with either dupilumab or placebo in addition to their existing asthma medication, as part of a previously published asthma phase 2b pivotal clinical trial. All patients in this trial received treatment with medium-to-high-dose inhaled corticosteroids and a long-acting β2-agonist and were randomized to additional treatment with a dupilumab dose of either 200 or 300 mg every 2 or 4 weeks or placebo for 24 weeks. This post hoc analysis was performed on the patients who received treatment every 2 weeks, as these were the regimens selected for ongoing phase 3 study. The effect of dupilumab on nasal symptoms associated with PAR was evaluated using some of the components of the 22-item Sino-Nasal Outcome Test (SNOT-22) score, which assessed the presence and severity of nasal symptoms and their impact on patient quality of life. Patient responses were used to derive an overall nasal symptom score, as well as scores for the severity of 4 different nasal symptoms associated with PAR.
The researchers found that in patients with asthma and comorbid PAR, add-on treatment with dupilumab 300 mg every 2 weeks significantly improved patient-reported overall SNOT-22 score. Moreover, when researchers examined the scores for a variety of nasal symptoms associated with PAR, they found that the addition of dupilumab improved post-nasal discharge, nasal blockage, runny nose, and sneezing when compared to placebo. Dupilumab 200 mg every 2 weeks was associated with numerical improvements in SNOT-22 and individual nasal symptom scores compared with placebo, but these improvements were not statistically significant.
The authors of the study concluded that systemic therapy with dupilumab, at a dose of 300 mg every 2 weeks, when added to existing treatment for moderate-to-severe asthma with inhaled corticosteroids and a long-acting β2-agonist not only reduces severe asthma exacerbations and improves lung function and asthma control, but has the potential to improve nasal symptoms in patients with asthma and comorbid PAR. This is an important clinical finding because PAR and asthma are unified by a systemic type 2 immunologic response to common perennial allergens, and inadequately treated PAR can worsen asthma control in patients who are suffering from both conditions. Future studies are required to confirm the benefit of dupilumab in this important group of patients with uncontrolled persistent asthma and comorbid PAR.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most cited journal in the field of allergy and clinical immunology.