dupilumab dupixent is used to treat oral corticosteroid dependent asthma

  • allergic eosinophilic asthma, with elevated eos > 150
  • atopic dermatitis and chronic rhinosinusitis with nasal polyps
  • oral corticosteroid dependent asthma, regardless of types

Dupilumab is indicated as an add-on maintenance treatment for adults and adolescents with oral corticosteroid (OCS)-dependent asthma, regardless of inflammatory endotype. Management guidelines for patients with poor symptom control and severe asthma recommend considering add-on treatments with a long-acting antimuscarinic or low-dose azithromycin, and/or a biologic agent. The selection of the specific biologic therapy depends on the patient’s inflammatory endotype and dependence on OCSs, with consideration for the mode of delivery, other allergic comorbidities, patient preference, and patient prescription plan coverage (Figure 1).

Dupilumab is a monoclonal antibody that inhibits type-2 inflammation more broadly than targeting eosinophils alone. Dupilumab is directed at the α-subunit of the interleukin (IL)-4 receptor, which can modulate signaling for IL-4 and IL-13, both of which play important roles in IgE synthesis, mucus secretion, and eosinophil recruitment, among other effects central to the airway inflammation that characterizes asthma. Dupilumab inhibits signaling of IL-4 and IL-13, both drivers of type 2 (T2) inflammation. Although most patients with asthma have a T2-driven allergic and nonallergic eosinophilic inflammatory response, some patients have low or absent signs of T2 inflammation as in the patient presented here, whereas others have multiple upregulated inflammatory pathways. This biologic agent is indicated both for allergic eosinophilic asthma in patients with elevated eosinophil and/or fractional exhaled nitric oxide levels and for patients who have a nonallergic response and are OCS dependent. Patients with OCS-dependent asthma, including those with a low blood eosinophil count, demonstrated a reduced rate of severe exacerbations, increased lung function, and a reduced mean OCS dose when dupilumab was added to maintenance therapy, irrespective of baseline OCS dose. The size of the response, however, is more robust in patients with eosinophilic inflammation.

Dupilumab is a monoclonal antibody that binds to the α subunit of the IL-4 receptor, resulting in reduced IL-4 and IL-13 signaling. Among other targets, this leads to the inhibition of vascular cell adhesion molecule-1 (VCAM-1) expression. Movement of circulating eosinophils into tissues is regulated by VCAM-1, so the reduction in eosinophil tissue migration gives rise to the transient increase in blood eosinophil counts. In contrast, dupilumab leads to a significant reduction in blood levels of total and allergen-specific IgE. Other biologic agents indicated for asthma with an eosinophilic phenotype cause a reduction in blood eosinophils after several weeks of treatment, with a variable response to IgE levels.

This patient has uncontrolled asthma despite appropriate treatment, according to the Global Initiative for Asthma (GINA). Consideration of add-on treatment is warranted to control symptoms and minimize future risk and, in this case, may include a biologic agent or bronchial thermoplasty. Of the biologic agents listed, only dupilumab is effective as an add-on maintenance therapy for oral corticosteroid-dependent asthma, regardless of phenotype. While not the case here, any patient with persisting symptoms despite several months of controller medications should be assessed for the following before stepping up treatment: inhaler technique, adherence, risk factors and comorbidities, as well as determining if the diagnosis is correct.

Dupilumab is indicated as an add-on maintenance treatment for patients aged 6 years or older with moderate to severe asthma with an eosinophilic phenotype, poorly controlled with a mediumto high-dose inhaled corticosteroid in combination with an additional controller medication, with a pretreatment blood eosinophil count greater than 150/μL (0.15 × 109/L). It is also indicated for those with oral corticosteroid-dependent asthma, as well as for patients with atopic dermatitis and chronic rhinosinusitis with nasal polyps, all present in this patient, which contributed to the selection of this particular biologic agent. Adult dosing in patients with asthma is with a 600-mg loading dose followed by a subcutaneous injection of 300 mg every 2 weeks. Although there is no higher dosage, a lower dosage is recommended in patients weighing less than 132.28 lb (60 kg).

Add-on treatment with dupilumab can reduce asthma exacerbations and improve lung function and asthma control. Results from clinical studies have shown improvement in lung function after 2 weeks that was statistically significant at week 12, with greater benefits seen in patients with higher baseline levels of eosinophils and a fractional exhaled nitric oxide level greater than 25 parts per billion.1

Footnotes

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