<p>Updated Evaluation of Dupilumab in the Treatment of Asthma: Patient Selection and Reported Outcomes</p>

Abstract

Uncontrolled asthma continues to be a problem for many patients with moderateto-severe allergic asthma. Dupilumab, which blocks the receptors for interleukin-4 and interleukin-13, has been effective in reducing asthma exacerbations, improving forced expiratory volume in one second (FEV 1), and reducing oral corticosteroid use. When selecting patients for dupilumab, it is important to consider entry criteria for the original studies, subgroups that have responded best, and the presence of comorbid diseases that may also respond to dupilumab. Factors that were considered when selecting patients likely to respond to dupilumab in asthma studies include: failure of moderate or high dose inhaled steroids in combination with an additional controller medication, baseline FEV 1 reversibility of 12% or greater, and Asthma Control Questionnaire > 1.5. The baseline characteristics that predicted a better response to dupilumab included blood eosinophils > 150 cells/mm 3 and fractional exhaled nitric oxide > 25 parts per billion. Comorbidities that may also respond to treatment with dupilumab include atopic dermatitis, chronic rhinosinusitis, and allergic rhinitis. A combination of these factors should be considered when selecting the patients most likely to benefit from dupilumab.

Anti-alarmins in asthma: targeting the airway epithelium with next-generation biologics

“…In the clinic, it may be observed that Fe NO remains high in these patients during anti-IL-5 treatment, despite the reduction in eosinophils [28,29]. Similarly, anti-IL-4Rα treatment can reduce Fe NO , but transient eosinophilia may be observed [8]; caution should therefore be taken when considering anti-IL-4Rα for patients with a history of hypereosinophilic conditions [30]. Alternatively, mixed granulocytic asthma may be present, in which there are elevated levels of both eosinophils and neutrophils [24].…”

Dupilumab-induced erythema nodosum

“…Some investigators have suggested that the occurrence of EN is a contraindication to further use of dupilumab, but a correlation between the drug and the adverse event cannot be confirmed without re-exposure. 11 In consultation with the Allergy Department, it was decided to restart dupilumab, given the remarkable improvement in asthma symptoms. The temporal relationship between the initiation of dupilumab treatment and onset of the EN eruption, improvement after discontinuation, and recurrence after rechallenge, suggests a potential correlation between dupilumab and EN.…”

Use of Dupilumab in Glucocorticoid-Dependent Asthma

“…Transient eosinophilia in patients treated with dupilumab was observed in a few studies as compared with placebo. This is believed to be caused by the reduction in the dose of glucocorticoids and blocking eosinophil migration into the tissue through the inhibition of IL-4- and IL-13-mediated eotaxins and vascular adhesions 39 . It is important to note that dupilumab does not directly affect the eosinophil synthesis; hence, no long-term effects on eosinophil counts are expected 19 .…”