Published online: March 25, 2017
Following several phase III efficacy trials, omalizumab (Xolair®) was approved in the US in 2003 and in the EU in 2005 as add-on treatment for severe allergic asthma. Phase III trials typically include a relatively homogeneous group of patients recruited from carefully selected centers and who are treated according to a strict clinical protocol. However, once a drug is approved, it is used across a broad (and much more heterogeneous) spectrum of patients, clinics, and clinicians. Effectiveness studies evaluate the extent to which the promise of a newly approved drug translates into “real-life” (or “real-world”; the terms are used interchangeably) outcomes in daily clinical practice.
In a recent report published in The Journal of Allergy and Clinical Immunology: In Practice. Alhossan and colleagues followed up on a prior qualitative review with a meta-analysis to provide quantitative evidence of the “real-life” effectiveness of omalizumab. The meta-analysis included the original 24 studies as well as one study published since, and focused on the following outcomes at 4-6, 12, and 24 months: treatment response (GETE; Global Evaluation of Treatment Effectiveness [GETE]); lung function (FEV1; forced expiratory volume in 1 second); quality of life (AQLQ; Asthma-related Quality-of-Life Questionnaire); asthma control (ACT; Asthma Control Test); oral and inhaled corticosteroid use; asthma exacerbations; and hospitalizations.
The investigators extracted three effect sizes for analysis: proportions of patients; means (± standard deviations) relative to baseline as raw numbers and standardized as Cohen’s d; and changes in proportions of patients expressed as relative risk (RR). Note that a Cohen’s d of ~0.20 is considered a small, ~0.50 a medium, and ~0.80 a large effect; these are reference points, not absolute markers.
In this meta-analysis, 77.2% of patients achieved a good or excellent GETE rating at 4-6 months and 73.0% at 12 months, indicating a strong response to omalizumab treatment in about 3 out of 4 patients. There were significant improvements in FEV1 at 4-6 (Cohen’s d = 0.47; 9.4% predicted FEV1), at 12 (Cohen’s d = 0.51; 10.6% predicted FEV1), and at 24 months (Cohen’s d = 0.50; 9.6% predicted FEV1), suggesting a sustained medium treatment effect over time compared to lung function at the start of omalizumab treatment. Asthma-related quality of life improved by 1.29 AQLQ points from baseline to 4-6 months (Cohen’s d = 1.05) and by 1.51 AQLQ points from baseline to 12 months (Cohen’s d = 1.20), indicating a large effect of omalizumab treatment on quality of life. Likely, this is related to the improvements in asthma control, which improved by 3.71 ACT points over baseline at 4-6 (Cohen’s d = 0.77), by 4.88 ACT points at 12 (Cohen’s d = 1.01), and by 5.60 ACT points at 24 months (Cohen’s d = 1.22), indicating a large treatment effect. In the process, patients were less likely to require oral corticosteroids after 4-6 (RR = 0.70) and 12 months (RR = 0.46). A small-to-moderate reduction in inhaled corticosteroids was observed over the first 12 months of treatment (Cohen’s d = 0.38; 264.5 beclomethasone equivalents). Asthma exacerbations declined by 2.64 per year in the first year of treatment (Cohen’s d = 0.71), a significant reduction over the year before treatment. There was a small reduction by 0.53 (Cohen’s d = 0.36) in hospitalizations over the first 12 and by 0.52 (Cohen’s d = 0.48) over the first 24 months compared to the 12 months prior to the start of omalizumab therapy.
Physicians consistently observed positive treatment responses in a large majority (~75%) of patients across the time points for which data were available. This was accompanied by moderate improvements in lung function. Importantly, patients reported pronounced improvements in their quality of life in parallel with marked increases in asthma control and less need for oral and inhaled corticosteroids and experienced fewer asthma exacerbations and hospitalizations. This meta-analysis of “real-life” effectiveness studies provides strong support for improvement in subjective outcomes that directly affect patients, outcomes that may be less likely to be included in .efficacy trials.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.