Efficacy of Omalizumab, an Anti-immunoglobulin E Antibody, in Patients with Allergic Asthma at High Risk of Serious Asthma-related Morbidity and Mortality*

Summary Aim: Add-on therapy with omalizumab, an anti-immunoglobulin E antibody, is effective in improving disease control in patients with allergic asthma of varying severity. The aim of the present study was to determine the efficacy of omalizumab in a subgroup of patients at high risk of serious asthma-related morbidity and mortality. Methods: A meta-analysis was performed of three randomised, double-blind, placebo-controlled studies (studies 1, 2 and 3) that enrolled 1412 patients with moderate or severe allergic asthma, all requiring daily treatment with inhaled corticosteroids (ICS). Omalizumab was administered subcutaneously every 2 or 4 weeks at a total 4-weekly dose of at least 0.016mg/kg/IgE [IU/ml]. Each study consisted of a 16-week steroid-stable phase and a 12-16-week steroid-reduction phase, followed by a 24-week extension phase (studies 1 and 2 only). The primary outcome measure was the annualised rate of significant asthma exacerbation episodes (sAEEs) during the steroid-stable phase for the pooled subgroup of 254 high-risk patients (omalizumab, n = 135; placebo, n = 119). sAEEs were those requiring a doubling of baseline ICS dose (studies 1 and 2 only) or use of systemic steroids (all three studies). Results: Overall, the number of patients with at least one sAEE during the steroid-stable phase was reduced from 35% (42/119) with placebo to 18% (24/135) with omalizumab. Mean sAEE rates were 1.56 and 0.69 per patient-year, respectively, a reduction of 56% with omalizumab (p = 0.007). Similar reductions in exacerbations in favour of omalizumab were observed for the whole study period and for all AEEs. In those with a history of hospitalisation in the last year, 6/49 (12%) on placebo vs. 2/44 (4.5%) on omalizumab were re-hospitalised during the study period. Patients treated with omalizumab also showed significantly greater improvements from baseline in PEFR (p = 0.026), overall AQoL (p = 0.042) and mean nocturnal (p = 0.007) and mean total (p = 0.011) asthma symptom scores compared with placebo. Conclusions: In patients at high risk of serious asthma-related morbidity and mortality, treatment with omalizumab offers the potential to halve the rate of asthma exacerbations and improve disease control.