Asthma drug dupilumab may ease symptoms in EGPA: Small study
Medication reduced biomarkers of inflammation, disease activity
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Dupilumab, an approved medication for diseases marked by high levels of the immune cell eosinophils, may help ease symptoms in people with eosinophilic granulomatosis with polyangiitis (EGPA), according to a study reporting on three patients.
The therapy, sold as Dupixent, helped control asthma and atopic dermatitis — two conditions commonly associated with elevated eosinophil counts — and reduced markers of inflammation and disease activity, data showed.
“Dupilumab may help control the eosinophilic [manifestations] of EGPA, thereby contributing to overall disease activity control without exacerbating” manifestations related to blood vessel inflammation,” researchers wrote. “However, given the small sample size and retrospective nature of this study, larger … trials [following patients over time] are required to confirm its efficacy in EGPA.”
The study, “Clinical Effectiveness of Dupilumab in Eosinophilic Granulomatosis With Polyangiitis: A Retrospective Observational Study,” was published in the International Journal of Clinical Practice.
Dupilumab targets protein that contributes to eosinophil activation
EGPA is a rare type of ANCA-associated vasculitis, a group of autoimmune diseases characterized by inflammation and damage of small blood vessels. It is characterized by the formation of immune cell clumps rich in eosinophils, which normally help fight infections, and typically affects the respiratory system, with asthma being a common symptom.
Dupilumab is an antibody-based therapy that works by targeting the interleukin-4 receptor alpha subunit, a protein that contributes to eosinophil activation. It is approved for conditions marked by high eosinophil counts (eosinophilia), including certain forms of asthma, atopic dermatitis, and chronic obstructive pulmonary disease. Atopic dermatitis is a skin condition characterized by red, dry, itchy, and inflamed patches.
“However, the role of dupilumab in EGPA remains controversial,” the researchers wrote.
In this study, a team of researchers in South Korea retrospectively analyzed data from 65 EGPA patients (67.7% women) with a mean age of 52 years, who were seen at a single center in the country.
About half tested negative for ANCAs, the self-reactive antibodies that drive most cases of AAV, while 44.6% had ANCAs targeting the myeloperoxidase protein, and 9.2% had ANCAs targeting the proteinase 3 protein.
The most common disease manifestation was ear, nose, and throat involvement (83.1%), followed by lung (70.8%) and neurologic manifestations (60%).
Rate of asthma worsening episodes reduced, unchanged in all 3 patients
The team then compared data from two women and one man (age range, 25 to 40 years) who received dupilumab in addition to conventional therapies with those of six age- and sex-matched controls who received conventional treatment alone. All had high eosinophil counts in the blood.
In terms of eosinophil-related, or eosinophilic, manifestations at diagnosis, all dupilumab-treated patients presented with asthma, inflammation of the air-filled cavities around the nose and eyes (sinusitis), and non-malignant growths in the nasal cavities.
Two of these patients also showed involvement of the skin and peripheral nervous system — the part of the nervous system outside the brain and spinal cord — while the remaining patient had peripheral nervous system and kidney involvement.
Dupilumab was used to manage treatment-resistant asthma in two people and treatment-resistant atopic dermatitis in the remaining person. The therapy was administered via under-the-skin (subcutaneous) injections at an initial dose of 600 mg, followed by 300 mg every two weeks. Treatment duration ranged from four months to nearly four years.
Among age- and sex-matched control patients who did not receive dupilumab, some experienced worsening eosinophilic [manifestations], underscoring the potential therapeutic value of dupilumab.
In all three patients, the rate of asthma worsening episodes was reduced or unchanged, and lung function measures improved after dupilumab. Atopic dermatitis also eased after treatment. There was no worsening of disease manifestations not related to eosinophils.
Dupilumab treatment also resulted in lower levels of eosinophils and inflammation markers, as well as reduced disease activity, as assessed by the validated Birmingham Vasculitis Activity Score.
Among the six patients treated with conventional therapy alone, two experienced worsening of eosinophilic and non-eosinophilic disease manifestations, two continued to experience persistent sinusitis, and another experienced an episode of worsening sinusitis.
“Among age- and sex-matched control patients who did not receive dupilumab, some experienced worsening eosinophilic [manifestations], underscoring the potential therapeutic value of dupilumab,” the team wrote. “These findings suggest that dupilumab may provide therapeutic benefits in EGPA by stabilising disease activity through eosinophilic manifestation control while maintaining” stability of manifestations related to blood vessel inflammation.
