Dupilumab in a patient with severe asthma and glucocorticoid hypersensitivity: a case report

Abstract

Recently, several biologics have been approved for the treatment of severe asthma. Dupilumab, a biologic used to treat severe asthma, is a monoclonal antibody targeting interleukin-4 and interleukin-13. In the present case, inhaled corticosteroid-induced glucocorticoid hypersensitivity was suspected, and the administration of omalizumab and mepolizumab had no beneficial effects. Subsequently, we switched to dupilumab therapy, which produced better effectiveness. Therefore, when a biologic agent proves ineffective, changing to another suitable biologic agent should be considered.

Introduction

Although the treatment and management of asthma have improved with advances in inhalation therapy, severe asthma accounts for an estimated 5% to 10% of the global asthma population. Severe asthma is generally defined as asthma requiring medium- or high-dose inhaled corticosteroid (ICS)/long-acting beta-2 agonist (LABA) therapy combined with other longer-acting medications. Biologics targeting immunoglobulin E (IgE), interleukin (IL)-5, IL-4, IL-13, and thymic stromal lymphopoietin are available for severe asthma, and their efficacy and safety are being clarified. ¹ Dupilumab, a monoclonal antibody targeting IL-4/13, is indicated for atopic dermatitis, chronic rhinitis with nasal polyposis, and asthma. Dupilumab was approved for severe asthma in Japan in March 2019. Switching to dupilumab has been reported to be useful for patients with severe asthma. ² Although glucocorticoid hypersensitivity (GH) attributable to ICS therapy is considered rare, we suspected this in our patient, and consequently, switching the biologic agent to dupilumab resulted in a better treatment outcome. Biologics might be more beneficial than oral corticosteroid (OCS) therapies in patients with asthma and suspected GH.

Case report

A woman in her early 50s presented with a 10-year history of bronchial asthma. She was started on ICS, LABA, and long-acting muscarinic antagonist (LAMA) therapy, which was discontinued after an ICS/LABA-induced exacerbation. Subsequently, her symptoms resolved spontaneously without further treatment. However, 3 years before presentation, she developed an upper airway infection, and her asthma symptoms such as wheezing and dyspnea became uncontrollable. She was then referred to our hospital.

This patient was an ex-smoker (1.5 pack-years) with known allergies to alcohol, non-steroidal anti-inflammatory drugs, and various steroids. Her medical history included sudden hearing loss and sinusitis. Other respiratory diseases were excluded by chest computed tomography. She also had histories of erythema and fever following ICS administration and intravenous infusions of prednisone, and she was considered steroid-hypersensitive. Therefore, she was administered 10 mg of cortisone. The biomarker test for type 2 inflammation revealed IgE, eosinophil, and fractional exhaled nitric oxide (FeNO) levels of 580 IU/mL, 928.2/μL, and 126 ppb, respectively. She was considered a good candidate for biologics. In accordance with the Japan Asthma Prevention and Management Guidelines, omalizumab therapy was initiated in June 2017. The patient was hospitalized in October 2017 after four doses of omalizumab because of an asthma exacerbation. She was administered hydrocortisone. Subsequently, mepolizumab 100 mg was selected, and the cortisone dose was reduced to 2.5 mg. However, the patient complained of dyspnea while trying to sleep at least once a week. Therefore, we again switched her treatment to dupilumab 300 mg in June 2019.

Over 2 weeks of dupilumab administration, her wheezing disappeared, and her nocturnal symptoms dramatically improved. One year later, cortisone was discontinued, and improvements in her symptoms were noted. Because her symptoms had stabilized, LAMA therapy was also discontinued. Her eosinophil count was temporarily elevated, but it subsequently settled into the normal range (Figure 1). During the COVID-19 pandemic, she did not experience any asthma exacerbations or require any emergency visits.

Figure 1.

Timeline of the patient’s clinical course.

Witten informed consent for this case report was obtained from the patient. All details of this patient were de-identified for this case report. The reporting of this case report conforms to the CARE guidelines. ³

Discussion

In this case, dupilumab was the most effective of the three administered biologics, and this patient was successfully weaned off oral cortisone. There are few case reports of ICS-induced GH, and its pathogenesis is unknown.^4–6 GH is characterized by cushingoid features. In this case, the patient experienced repeated exacerbations attributable to ICS therapy, but she was not tested for Cushing's syndrome. For ICS-induced asthma exacerbations, cortisone and biologics such as mepolizumab and dupilumab can be used. In this case, dupilumab treatment was effective for the patient’s asthma symptoms.

Biologics that inhibit IgE, IL-5, IL-4/13, and thymic stromal lymphopoietin are available for the treatment of severe asthma. In this case, omalizumab, mepolizumab, and benralizumab were available at hospital admission. Omalizumab, a monoclonal antibody against IgE, is also indicated for seasonal allergic rhinitis and idiopathic chronic urticaria. Mepolizumab is an anti-IL-5 monoclonal antibody indicated for eosinophilic granulomatosis with polyangiitis, whereas benralizumab is an IL-5Rα–directed monoclonal antibody. The eosinophil count is a biomarker predictive of the response to mepolizumab and benralizumab. Unfortunately, omalizumab and mepolizumab were not beneficial in this case. The patient was subsequently administered dupilumab after it was approved in 2019. Dupilumab, which inhibits IL-4 and IL-13 signaling, is indicated for severe asthma, atopic dermatitis, and nasal polyps.^7–9 FeNO is a biomarker predictive of the response to dupilumab. A change in biologics to dupilumab has been reported to be effective in patients who previously received anti-IgE, IL-5, and IL-5α therapies. ¹⁰ In addition, although it is important to monitor eosinophil counts, dupilumab was reported to be useful in patients with severe asthma in a real-world setting. ² In this case, dupilumab stabilized asthma in our patient without ICS and OCS administration.

Therefore, when omalizumab and mepolizumab are ineffective, a switch to dupilumab could prove beneficial. Because ICS-induced GH was suspected in this patient, her asthma symptoms improved after a switch to dupilumab. Furthermore, she was successfully weaned off OCS and LAMA treatment.

Supplemental Material

sj-pdf-1-imr-10.1177_03000605231193922 - Supplemental material for Dupilumab in a patient with severe asthma and glucocorticoid hypersensitivity: a case report

Supplemental material, sj-pdf-1-imr-10.1177_03000605231193922 for Dupilumab in a patient with severe asthma and glucocorticoid hypersensitivity: a case report by Hiroshi Handa, Hajime Tsuruoka, Kohei Kinoshita and Masamichi Mineshita in Journal of International Medical Research