Omalizumab for asthma and allergic bronchopulmonary aspergillosis in adults with cystic fibrosis

Abstract

Background: In cystic fibrosis (CF), omalizumab has been used for difficult-to-treat asthma and allergic bronchopulmonary aspergillosis (ABPA) but safety and efficacy data are limited for this population. Methods: We assessed patients receiving omalizumab for asthma or ABPA in the Toronto adult CF center between 2005 and 2017. We evaluated treatment safety and efficacy by analyzing changes in FEV 1 % predicted (FEV 1 pp) max value, slope and variability captured by the area under the curve (AUC), the cumulative dose of systemic corticosteroids (SCS), use of intravenous (IV) antibiotics and hospitalization days before omalizumab and up to 1 year after treatment initiation. Linear mixed effects model was used for FEV 1 pp slope and the trapezoidal rule for FEV 1 pp AUC. Results: Twenty-seven CF patients received omalizumab, 16 (59.3%) for asthma and 11 (40.7%) for ABPA. No significant omalizumab-related adverse effects were observed. In the asthmatic group, the max value of FEV 1 pp improved on omalizumab and the cumulative dose of SCS decreased. In the ABPA group, the rate of FEV 1 pp decline (slope) and the variability of FEV 1 pp (AUC) improved on omalizumab. In ABPA patients, the cumulative SCS dose was not significantly different but 4 (36%) patients decreased their SCS dose by > 50% compared to baseline. Days on IV antibiotics and hospital days did not differ significantly before and while on omalizumab therapy. Conclusions: In adult CF patients with difficult-to-treat asthma or ABPA, omalizumab should be considered. Larger studies are needed to identify patient characteristics that may predict response to omalizumab.

Use of monoclonal antibodies for allergic bronchopulmonary aspergillosis in patients with asthma and cystic fibrosis: literature review

“…At baseline the median for FEV1 (% predicted) was 58% (range 24.36–76.2), 9 – 11 , 14 – 22 , 34 , 36 – 38 and after 3 months to 3 years of follow-up FEV1 had a median of 62% of the predicted value (range 35.6–90). 9 , 10 , 14 , 16 – 19 , 21 , 22 , 34 , 36 , 38 Three studies reported the value in liters at baseline and after treatment with a median of 2.28 L (range 1.36–5.3) pre-treatment and a median of 2.4 L (range 1.5–5.5) post-treatment. 11 , 20 , 37 …”

“…We found a total of 17 studies which included 104 patients. 9 – 11 , 14 – 22 , 34 – 38 Seven were case series, defined as ⩾three patients, nine were case reports and one was a randomized double-blind cross-over study; 89 patients (85.5%) were on long-term systemic steroids at the time of initiation of Omalizumab, 14 patients were not receiving steroids (9.2%) and in one case it was not reported. Follow-up ranged from 3 months to 3 years.…”

“…We found 12 studies with baseline eosinophil count, including values for 83 patients (79.8%), with a median of 570 cells/µL (range 100–2200). 10 , 11 , 16 – 22 , 34 , 36 , 38 After treatment, the eosinophil count was reported for 10 patients (9.6%), with a median of 200 cells/µL (range 100–964); 85.7% of these patients had eosinophil counts below 500 cells/µL after treatment. 9 – 11 , 17 , 21 …”

“…Specifically, for patients treated with Omalizumab (in the asthmatic population), baseline values had a median of 1500 IU/mL. 10 , 11 , 14 – 22 , 34 – 38 It is important to note that an IgE value of ⩽700 IU/mL and a maximum dose of 750 mg/month have been determined as the upper limit for the use of Omalizumab in severe asthma. Furthermore, dosage is calculated according to the patient’s weight and IgE levels.…”

Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis: An Update on the Newest Diagnostic Tools and Therapeutic Approaches

“…Since IgE-mediated hypersensitivity is involved in ABPA pathogenesis, omalizumab (i.e., a humanized monoclonal antibody against IgE) use has been proposed for ABPA in CF patients [ 68 , 69 ]. Perisson et al retrospectively analysed 18 patients and observed a stabilization in lung function decline after the initiation of biological therapy with omalizumab along with a notable reduction in the corticosteroid daily dose needed and an improvement in the nutritional status [ 70 ].…”