G. Ayre

Safety of anti-immunoglobulin E therapy with omalizumab in allergic patients at risk of geohelminth infection

Background Although the role of immunoglobulin E (IgE) in immunity against helminth parasites is unclear, there is concern that therapeutic antibodies that neutralize IgE (anti‐IgE) may be unsafe in subjects at risk of helminth infection.

Effectiveness of omalizumab in patients with inadequately controlled severe persistent allergic asthma: An open-label study

BACKGROUND In a 1-year, randomized, open-label study in patients with moderate-to-severe allergic (immunoglobulin E (IgE)-mediated) asthma, adding omalizumab to best standard care (BSC) significantly improved efficacy outcomes compared with BSC alone (control). We assessed the efficacy of omalizumab in the subgroup of patients with inadequately controlled severe persistent allergic asthma despite high-dose inhaled corticosteroids (ICS) plus a long-acting beta(2)-agonist (LABA), which reflects the European Union (EU) label population. METHODS Efficacy outcomes included annual asthma exacerbation rate, annual asthma deterioration-related incident (ADRI) rate, % predicted forced expiratory volume in 1 s (FEV(1)), asthma symptoms (Wasserfallen score) and quality of life (Mini Asthma Quality of Life Questionnaire (Mini-AQLQ)), which were compared in the omalizumab and control groups. Outcomes were also determined for omalizumab-treated patients judged to have responded to therapy (> or = 0.5-point improvement in Mini-AQLQ overall score at 27 weeks). RESULTS In total, 164 patients (omalizumab, n=115; control, n=49) were receiving high-dose ICS plus a LABA. Annual asthma exacerbation rate was significantly reduced by 59% in the omalizumab group vs. control (1.26 vs. 3.06; P<0.001). ADRI rate was significantly reduced by 40% in the omalizumab group compared with control (5.61 vs. 9.40; P<0.05). Significant improvements were also seen in % predicted FEV(1) (71% vs. 60%; P<0.001), change from baseline in asthma symptom scores (-6.7 vs. 0.5; P<0.05) and Mini-AQLQ overall score (1.32 vs. 0.17; P<0.001). In omalizumab-treated patients, 71/102 (70%) were judged to have responded to therapy. In these Mini-AQLQ-assessed responders, exacerbation rate was reduced by 64% vs. control (1.12 vs. 3.06; P<0.001), ADRI rate was reduced by 50% vs. control (4.71 vs. 9.40; P<0.01). Percent predicted FEV(1) (73% vs. 60%; P<0.001), change from baseline in asthma symptom scores (-8.1 vs. 0.5; P<0.001) and Mini-AQLQ overall score (1.81 vs. 0.17; P<0.001) were also further significantly improved vs. control. CONCLUSIONS Adding omalizumab to BSC is efficacious in patients with inadequately controlled severe persistent allergic asthma despite high-dose ICS plus a LABA (EU label population), with further efficacy observed in patients judged to have responded to therapy which may more accurately illustrate the actual benefit of omalizumab therapy in clinical practice. The naturalistic setting of this study confirms the benefits observed in double-blind randomized clinical trials.

Omalizumab reduces the rate of asthma deterioration-related incidents in patients with poorly controlled allergic asthma*

34 Omalizumab Reduces the Rate of Asthma Deterioration-Related Incidents in Patients with Poorly Controlled Allergic Asthma J. G. Ayres ], R. Niven 2, G. Ayre 3, M. Blogg 3, H. Fox3; ]Chest Research Unit, Heartlands Hospital, Birmingham, UNITED KINGDOM, 2North West Lung Research Centre, Manchester, UNITED KINGDOM, 3Novartis Horsham Research Centre, Horsham, UNITED KINGDOM. RATIONALE: To evaluate the efficacy of omalizumab (Xolair| a monoclonal anti-immunoglobulin E antibody, for reducing the rate of asthmadeterioration related incidents (ADRIs) in patients with poorly controlled allergic asthma. METHODS: In a 52-week, open-label study, 312 patients (aged 12-75 yrs) receiving _>400 mcg/d (pediatric) or _>800 mcg/d (adult) inhaled beclomethasone dipropionate or equivalent for poorly controlled, moderate-to-severe allergic asthma were randomized (2:1) to current asthma therapy (CAT) with or without subcutaneous omalizumab (at least 0.016 mg/kg/IgE [IU/mL) per 4 wks). The primary efficacy variable was the annualized rate of ADRIs, ie, >1 of the following events due to asthma: course of oral steroids or antibiotics, missed school/work attendance, unscheduled physician visit, or emergency room visit/hospitalization. RESULTS: Baseline characteristics were comparable for the two groups (omalizumab, n=206; CAT alone, n=106), with 99% of patients being treated according to GINA step 3/4. Among evaluable patients, treatment with omalizumab significantly reduced the mean rate of ADRIs vs CAT alone (4.92 and 9.76 per patient-year, respectively; p<0.001). The percentage of patients who remained ADRl-free was increased for omalizumab-treated patients vs CAT alone (36% [69/191] and 20% [18/89], respectively; p=0.008). These results were paralleled by significantly improved lung function and fewer exacerbations for those treated with omalizumab, which proved safe and well tolerated. CONCLUSIONS: The findings of this naturalistic study indicate that add-on therapy with omalizumab is effective in reducing the rate of ADRIs in patients with moderate-to-severe allergic asthma who remain poorly controlled despite conventional treatment. Funding: Novartis Pharma AG and Genentech lnc 535 Fluticasone Propionute (FP) CFC Delivered via Valved Holding Chamber with Facemask for 12 Weeks Improved Asthma Control in Children Aged 24-47 Months with Asthma