Treatment with Dupilumab in Severe Corticosteroid-Dependent Bronchial Asthma – A Case Study
We present the case of a 36-year-old woman with severe corticosteroid-dependent asthma with numerous comorbidities and complications due to long-term systemic corticosteroid therapy. Significant improvements in quality of life, asthma control, regression of skin changes in atopic dermatitis, and reduction in methylprednisolone consumption for this patient were only achieved after the initiation of biological treatment. Dupilumab, a monoclonal antibody against the α subunit of the receptor for interleukins IL-4 and IL-13, which is approved for the treatment of severe refractory eosinophilic bronchial asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyposis, was indicated in her treatment.
History, Clinical Picture, and Comorbidities
The patient (born 1986) had been treated from preschool age for bronchial asthma, seasonal allergic rhinitis, atopic dermatitis (AD), and recurring respiratory tract infections. Due to repeated exacerbations of asthma, she had been on long-term systemic corticosteroid therapy (SCS) since 2001 with a minimum dose of methylprednisolone 4 mg/day. In 2003, she developed hypersensitivity to non-steroidal anti-inflammatory drugs. Despite long-term SCS, she suffered from recurring severe asthma exacerbations (4–5 times a year), leading to repeated hospitalizations. Her condition only improved during two pregnancies when the maintenance dose of SCS was temporarily reduced. In recent years, she had been on a maintenance dose of methylprednisolone up to 20 mg/day, which was intermittently increased during asthma exacerbations, and discontinuation was not possible due to gradually worsening condition. Long-term SCS therapy over the years led to numerous complications.
The patient suffered from multiple comorbidities and underwent several surgical procedures: osteopenia, bilateral hip joint necrosis requiring total right hip arthroplasty, hyperglycemia, grade 3 obesity (weight 140 kg, BMI 50.2), hiatal hernia with gastroesophageal reflux disease, knee joint arthritis after repeated arthroscopic surgeries on the right knee, surgeries for umbilical and inguinal hernia.
The patient is a non-smoker, works part-time as an administrative worker, and has been granted a second-degree disability pension.
Previous Course of Therapy at the Severe Asthma Treatment Center
Between 2008 and 2020, she was monitored at a severe asthma treatment center where a comprehensive re-examination was conducted. Biological therapy for severe asthma (anti-IgE, anti-IL-5) was considered, but criteria for this treatment were not met. Due to long-term SCS, eosinophilia in peripheral blood was not demonstrable. The patient had borderline elevated FENO values (fraction of exhaled nitric oxide) – 26 ppb. No hypersensitivity to perennial inhalant allergens was detected.
In March 2021, she was referred to the severe asthma treatment center at the Department of Allergology and Clinical Immunology of University Hospital Olomouc. In the last 12 months before the examination, the patient had experienced 4 severe asthma exacerbations and 2 respiratory tract infections. In addition, she remained significantly symptomatic between exacerbations. She reported persistent dry irritating cough, rest and exercise-induced dyspnea, chest wheezing, nocturnal symptoms, low physical activity tolerance, erythematous dry lesions around the skin of elbow, knee joints and ankles, and watery rhinitis with nasal obstruction in May/June. The asthma control test (ACT) scored 10 points. She regularly took at least 20 mg/day of methylprednisolone, high doses of inhaled corticosteroids, long-acting beta2-agonists and anticholinergics, antileukotrienes, ketotifen, proton pump inhibitors, extended-release theophyllines, antihistamines, diuretics, and short-acting beta2-agonists 3-5 times daily for relief.
Indication of Biological Treatment and its Results
Spirometry showed mild obstructive ventilatory disorder with full reversibility in a highly positive bronchodilation test. FENO values were within normal limits. Laboratory tests revealed only mildly elevated eosinophilic cationic protein (ECP 24.4 μg/l) and specific IgE antibodies to spring tree, grass and weed pollen. Total IgE and peripheral blood eosinophil values were within normal limits. Mild depletion of CD3+ T lymphocytes was also noted.
The condition was concluded as severe refractory bronchial asthma with an allergic eosinophilic phenotype and a Type 2 inflammation endotype based on the clinical picture and findings. Since the disease remained uncontrolled despite maximum conventional therapy, complicated by significant SCS side effects, biological treatment with dupilumab targeting the IL-4 and IL-13 receptor was indicated. The treatment was approved by the insurance company's revision physician under §16 of the Public Health Insurance Act and initiated in June 2021.
After 9 months of dupilumab treatment, the patient's condition improved, with subjective reports of only exertional dyspnea. No asthma exacerbations occurred during the dupilumab therapy. There was complete regression of skin changes related to AD. The patient better tolerated physical activity, engaged in sports, and is trying to lose weight. Spirometric measurements showed normal ventilatory parameters. The maintenance dose of methylprednisolone was gradually reduced to 8 mg/day. The patient reports a significant improvement in quality of life, not experienced for many years.
prim. MUDr. Beáta Hutyrová, Ph.D.
Department of Allergology and Clinical Immunology, University Hospital Olomouc
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