Differential response to biologics in a patient with severe asthma and ABPA: a role for dupilumab?

Abstract

Background Allergic bronchopulmonary aspergillosis (ABPA) is a severe hypersensitivity reaction to aspergillus species colonizing the airways of patients with asthma or cystic fibrosis. Biologics including anti-IgE and anti-IL5 antibodies have strongly changed the treatment of severe asthmatics and have partly been reported to be effective in the treatment of ABPA. Recently, dupilumab, an anti-IL4-Rα antibody which inhibits signaling by the Th2-cytokines IL4 and IL13, has been approved for the treatment of severe asthma. Case presentation Here, we report the case of a 49-year-old woman with severe asthma and ABPA, who was uncontrolled despite maximum inhalative therapy, anti-IL5-Rα antibody and continuous oral steroid therapy. Moreover, trials of itraconazole as well as omalizumab showed insufficient efficacy. Lung function revealed peripheral obstruction. FeNO and IgE were increased, eosinophils were suppressed under treatment while marked increases had been documented previously. Switching to dupilumab led to a complete resolution of pulmonary symptoms, resolution of exacerbations and complete withdrawal of oral steroids. A drastic improvement in lung function was noted, with an increase in FEV1 of almost 1 l. FeNO was normalized and IgE strongly reduced. Conclusion Our case highlights that a patient may exhibit differential treatment responses to the currently available asthma biologics and suggests switching treatment if outcome is insufficient. A potential role for dupilumab in the treatment of ABPA warrants future studies.

Complete withdrawal of glucocorticoids after dupilumab therapy in allergic bronchopulmonary aspergillosis: A case report

“…The administration of dupilumab decreases the peripheral blood count of eosinophils and the serum levels of IgE in patients with severe bronchial asthma[ 9 ]. Several reports have also demonstrated the efficacy of dupilumab in ABPA (Table 1 )[ 5 , 9 - 11 ]. For example, Mümmler et al [ 5 ] reported a case of bronchial asthma associated with ABPA in which the administration of omalizumab or dupilumab reduced the dose of oral glucocorticoids.…”

“…Several reports have also demonstrated the efficacy of dupilumab in ABPA (Table 1 )[ 5 , 9 - 11 ]. For example, Mümmler et al [ 5 ] reported a case of bronchial asthma associated with ABPA in which the administration of omalizumab or dupilumab reduced the dose of oral glucocorticoids. Also, Mikura et al [ 9 ] and Ramonell et al [ 10 ] reported cases of ABPA in which the administration of dupilumab, but not that of mepolizumab, made possible a reduction in the dose of oral glucocorticoids.…”

“…However, most cases of ABPA require therapy with oral glucocorticoids to control clinical exacerbations of bronchial asthma. The oral glucocorticoid-sparing effect of anti-IL-4/IL-13 antibody (dupilumab) has been previously reported[ 5 ]. However, there is no report on the complete withdrawal of glucocorticoids following dupilumab therapy.…”

Successful treatment with mepolizumab for allergic bronchopulmonary mycosis complicated with bilateral septic arthritis of the knee joints caused by Methicillin-resistant Staphylococcus aureus

“…The level of serum IgE was over 6000 IU/mL (out of range) in this case, calling for doses above the nomogram-based upper limit. Indeed, some case reports describe an insufficient efficacy of omalizumab for ABPM [ 13 ]. We thus doubted the efficacy of omalizumab in this case and decided not to use it.…”

“…Dupilumab, a humanized monoclonal antibody against IL-4 receptor, also has potential for treatment of ABPM [ 13 , 22 ]. We had no idea whether mepolizumab or dupilumab was preferable for this case from the perspective of biological effects.…”