PURPOSE OF THE STUDY.
To determine if omalizumab (anti-IgE) above the standard dosing ranges can be beneficial in severe asthmatics and compare responses to patients who are within normal dosing ranges.
In Australia, most patients receiving government-funded omalizumab are enrolled in the Australian Xolair Registry. This registry includes 21 sites, with patients ≥12 years old who have severe, uncontrolled asthma; patients with serum IgE levels ≥76 IU/mL; and patients who have failed to achieve adequate control with optimized asthma therapy.
Registry data were obtained (including demographics, medical history, disease status and control, current treatment, lung function, medical resource use, and patient-reported outcomes) by using the Asthma Control Questionnaire (ACQ-5) and the Asthma Quality of Life Questionnaire (AQLQ). Patients were assessed at 6, 12, 18, and 24 months after starting omalizumab. Participants were classified according to their baseline weight and/or IgE level and whether these variables were above or within the standard dosing table (Australia and the US use the same dosing tables). The primary outcome measured was the change in symptom control as measured by the ACQ-5. Secondary outcomes measured were changes in the AQLQ mean score and pre- and postbronchodilator forced expiratory volume in 1 second (FEV1). In a small portion of patients, changes in hospital admissions and exacerbations were also evaluated.
A total of 179 participants were included, with 55 (31%) dosing above the standard dosing and 124 (69%) within standard dosing. Above-range participants had higher baseline IgE levels (812 IU/mL; range 632–1747) compared with in-range participants (209 IU/mL; range 134–306). Baseline AQLQ scores were significantly lower for above-range asthmatics versus in-range patients (3.21 [SD 1.14] vs 4.01 [SD 1.21, P = .02]). Above-range participants received a median dose of omalizumab of 750 mg (IQR 650–750) compared with in-range participants who received a median dose of 450 mg (IQR 300–600). After 6 months of therapy, there was a statistically significant improvement in ACQ-5 scores for both the above-range group (3.61 to 2.10, P < .0001) and the in-range group (3.47 to 1.93, P < .0001). AQLQ also reflected statistical improvement for both groups (above-range group: 3.22 to 4.41; in-range group: 3.71 to 4.88, P < .0001). Above-range participants demonstrated statistically significant improvements in pre- and postbronchodilator FEV1 that were similar to the changes seen for the in-range participants. There was no difference in the exacerbation rate for either group.
Omalizumab dosing (750 mg monthly) in severe asthmatic patients who are above established criteria because of weight or baseline IgE levels demonstrate significantly improved symptom control, quality of life measures, and lung function, and these improvements are similar to changes seen in individuals treated with in-range doses.
These results provide literature support for above-range dosing of omalizumab (Xolair) for severe asthmatic patients. According to EPR-3 for asthma management, severe allergic asthmatic patients who are poorly controlled on combination therapy are good candidates for targeted therapy with this monoclonal antibody. Dose and frequency of omalizumab in the US are based on weight and total IgE level, leading to a higher calculated dose for patients with either a higher starting IgE level or elevated body weight. Patients with severe persistent asthma who are highly atopic experience significant costs and morbidity, with decreased options for asthma treatment if their IgE level is too high. Additional studies of omalizumab dosing for this group of patients are needed to further support its benefit.
- Copyright © 2017 by the American Academy of Pediatrics