Chest
Volume 125, Issue 4, April 2004, Pages 1378-1386
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Clinical Investigations
ASTHMA
Predicting Response to Omalizumab, an Anti-IgE Antibody, in Patients With Allergic Asthma

https://doi.org/10.1378/chest.125.4.1378Get rights and content

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 μg/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 ≥ 800 μg/d was 65% for omalizumab and 40% for placebo; for those treated with < 800 μg/d, the response rates were 63% and 55%, respectively). A low FEV1 was also predictive (p = 0.072; response rates for those with FEV1 ≤ 65% predicted were 60% for omalizumab and 40% for placebo; for those with FEV1 ≥ 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.

Section snippets

Materials and Methods

The present analysis used data from adults and adolescents (aged ≥ 12 years) with allergic asthma, symptomatic despite moderate-to-high daily doses of ICS (beclomethasone dipropionate [BDP]), who were randomized to treatment in two phase III, double-blind, placebo-controlled, multicenter studies. The identical study design and similarities in patient populations and clinical findings justified pooling of the two studies, the protocol and main efficacy findings of which are reported in full

Results

The pooled patient population comprised 1,070 adults and adolescents with allergic asthma who were randomized to treatment with either omalizumab (n = 542) or placebo (n = 528) in addition to stable BDP therapy. Overall, the two treatment groups were comparable in terms of baseline characteristics (Table 1). Completer rates for the 16-week, steroid-stable phase were 95.2% (516 of 542 patients) for those treated with omalizumab and 90.7% (479 of 528 patients) for placebo recipients.

Discussion

Identification of those patients most likely to achieve the greatest benefit from omalizumab therapy has obvious implications for clinical decision making on the utility of this new treatment option for allergic asthma. In the present study, based on the findings of two large placebo-controlled phase III clinical trials,56 a pooled exploratory analysis was therefore performed in an attempt to characterize such patients. Various aspects of response to omalizumab (as add-on therapy to standard

Conclusion

Treatment with omalizumab significantly reduces the risk of asthma exacerbations in patients with allergic asthma. Asthma patients who benefit most from add-on treatment with omalizumab are those receiving high doses of ICS, those with a history of frequent emergency asthma treatment, and patients with poor lung function. A minimum treatment duration of 12 weeks appears necessary before deciding whether a satisfactory response will be achieved with omalizumab. Taken together, these findings

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This study was supported by Novartis Pharma AG, Basel, Switzerland, and Genentech Inc., South San Francisco, CA.

According to their statement, the authors and all study investigators have not made any financial arrangement whereby the value of the compensation could be influenced by the outcomes of the study, have not received significant payments of other sorts from the sponsors (excluding the costs of conducting the study), do not have a proprietary or financial interests in the test product such as patent, trademark, or licensing agreements, and do not hold a significant equity interest in the sponsor of the study (exceeding $50,000).

Drs. Freeman and Fox hold permanent positions with Novartis Pharma AG.

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