Study objective: To determine baseline characteristics predictive of response to omalizumab, an anti-IgE antibody, in patients with allergic asthma.
Design: Pooled analysis of two multicenter, double-blind, randomized, placebo-controlled phase III studies with omalizumab.
Patients: One thousand seventy allergic asthma patients symptomatic despite moderate-to-high doses (mean, 725 micro g/d) of inhaled beclomethasone dipropionate (BDP).
Interventions: Omalizumab (n = 542) or placebo (n = 528) were administered at a 4-weekly subcutaneous dose of at least 0.016 mg/kg/IgE (IU/mL) for 16 weeks in addition to stable BDP therapy.
Measurements and results: Univariate logistic regression was performed to explore baseline variables predictive of best response. Various aspects of response (reduced symptom scores, reduced usage of rescue medication, improved lung function, improved quality of life [QoL]) were explored as well as a composite definition of response (response in at least one of these four aspects with no asthma exacerbation during 16 weeks of treatment). Time to onset of response as well as the ability to predict eventual response were also determined for the composite definition of response. A consistent pattern of predictive covariates was seen over all definitions of response (except for QoL). For the composite definition, a history of emergency asthma treatment in the past year was the factor most predictive (p = 0.015) of best response on active treatment (response rate for those with such history was 67% for omalizumab and 42% for placebo; for those without a history the response rates were 63% and 54%, respectively). Another factor predictive of best response on active treatment was high BDP dose (p = 0.037; response rate for those treated with >or= 800 micro g/d was 65% for omalizumab and 40% for placebo; for those treated with < 800 micro g/d, the response rates were 63% and 55%, respectively). A low FEV(1) was also predictive (p = 0.072; response rates for those with FEV(1) <or= 65% predicted were 60% for omalizumab and 40% for placebo; for those with FEV(1) >or= 65% predicted, the response rates were 67% and 53%, respectively). Seventy-six percent of patients had at least one of these factors. This subgroup showed odds of being a responder (composite definition) 2.25 times higher (95% confidence interval, 1.68 to 3.01) than placebo. Some 38% of patients treated with omalizumab showed a response (composite definition) at the first evaluation time point at 4 weeks, increasing to 64% at week 16 (vs 48% for placebo; p < 0.001). Among omalizumab responders at 16 weeks, only 61% had responded at 4 weeks whereas 87% had responded at 12 weeks.
Conclusions: Patients who benefit most when omalizumab is administered as add-on therapy are those receiving high doses of BDP, those with a history of frequent emergency asthma treatment, and those with poor lung function. Patients should be treated with omalizumab for a minimum duration of 12 weeks.