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- Material and methods
Background: Omalizumab is efficacious in the treatment of moderate-to-severe and severe persistent allergic (immunoglobulin E-mediated) asthma, reducing exacerbations, emergency visits and improving quality of life (QoL). However, as exacerbations are relatively infrequent, assessment of efficacy on day-to-day symptoms is warranted.
Aims: To investigate the effect of add-on omalizumab on day-to-day symptoms, and how they correlate with QoL in severe persistent asthma.
Methods: The correlation between asthma symptom scores and QoL [Asthma Quality of Life Questionnaire (AQLQ)] was assessed. Symptom-free days (total symptom score = 0) and symptom-controlled days (definition 1: total symptom score ≤1; and definition 2: morning peak expiratory flow ≥90% of baseline, daytime asthma score ≤1 and night-time asthma score = 0) were compared between the omalizumab-treated group, omalizumab responders and placebo.
Results: Four hundred and nineteen patients (omalizumab, n = 209; placebo, n = 210) were included in the efficacy analyses, and 61% (118/195) of patients with response data were classified as responders. Total symptom score strongly correlated with AQLQ overall and symptom scores and individual domains. AQLQ overall score correlated well with symptom scores. Responders had significantly more symptom-free days than the omalizumab-treated and placebo groups (45.8%, 37.2% and 22.6% respectively), and more symptom-controlled days (definition 1: 56.1%, 47.9% and 35.3%, respectively, and definition 2: 50.8%, 43.9% and 28.0%, respectively).
Conclusions: In patients with inadequately controlled severe persistent asthma, day-to-day symptoms correlate well with QoL. Add-on omalizumab significantly improves day-to-day symptoms compared with placebo. Further improvement in responders confirms the physician’s assessment as a response measure.
Severe asthma is associated with a high risk of asthma-related hospitalization and mortality (1, 2) and significantly impairs patients’ quality of life (QoL) (3). The economic burden of asthma is the greatest in patients with inadequately controlled severe persistent asthma (4). Although treatments are available for severe persistent asthma, many patients remain inadequately controlled. For example, the INSPIRE study reported that 52% of patients were classified by the Asthma Control Questionnaire as having uncontrolled asthma and 74% of patients used short-acting β2-agonists daily despite regular maintenance therapy with inhaled corticosteroids (ICS) or ICS plus a long-acting β2-agonist (LABA) (5).
Adding omalizumab, an anti-immunoglobulin (Ig) E antibody, to standard asthma therapies (ICS with or without an LABA and additional controller medications as needed) has proven efficacy in the treatment of severe persistent allergic (IgE-mediated) asthma, reducing exacerbations, emergency visits for asthma and improving QoL (6).
Analyses of clinical trial data (6) and pooled data (7–11) have found the physician’s overall assessment – a composite measure including patient interview, review of medical notes, spirometry and symptom diaries, rescue medication use and peak expiratory flow (PEF) – to be the most meaningful measure of response to omalizumab therapy (12). Graded in a five-level evaluation of asthma control (complete control; marked improvement in control; discernible but limited control; no appreciable change; worsening in control), those with marked improvement or complete control are defined as responders (12). In this responder group, clinical outcomes were further improved compared with the overall omalizumab-treated population (12). In order to target those patients who will benefit most from omalizumab, thereby minimizing unnecessary drug exposure and healthcare costs, the omalizumab European Union (EU) label states that treatment response should be assessed at 16 weeks by the physician and treatment discontinued in those judged not to respond.
Asthma exacerbations and exacerbation-related healthcare resource use are strong indicators of lack of asthma control, but can occur relatively infrequently in many patients. Day-to-day asthma symptoms are also of major relevance to patients, and therefore may be useful in demonstrating the efficacy of a given treatment.
The aims of this study were to investigate the correlation between day-to-day asthma symptoms and asthma-related QoL, and to evaluate the effect of add-on omalizumab on day-to-day control of asthma symptoms in patients with severe persistent asthma. Results in omalizumab responders were also examined.
- Top of page
- Material and methods
Our results show a correlation between day-to-day asthma symptom scores (morning, day, night and total) and the AQLQ across all domains in patients with inadequately controlled severe persistent allergic asthma despite GINA 2002 step 4 therapy. Day, night and total asthma symptom scores were strongly correlated with AQLQ overall and symptoms domains, particularly daytime symptoms. This confirms that day-to-day asthma symptom scores provide a measure of asthma control that is highly relevant to patients, and are an important component of assessments of asthma control in addition to asthma exacerbations (14). Indeed, the characteristics listed in the GINA 2006 guidelines indicating controlled asthma include the absence of daytime and nocturnal symptoms (15).
Baseline clinical characteristics, AQLQ score and additional controller medication usage were similar in all groups. All patients had inadequately controlled severe persistent asthma, high medication use and healthcare utilization, and had experienced continuing uncontrolled asthma symptoms despite GINA 2002 step 4 therapy (13). The similar baseline clinical characteristics between the omalizumab-treated group and the omalizumab-responder subgroup provide further evidence of the difficulty in predicting which patients might achieve the greatest benefit with omalizumab, and the value of assessing response after 16 weeks of treatment.
Our results show that add-on omalizumab significantly increases the number of symptom-free days, symptom-controlled days and improves day-to-day symptoms compared with add-on placebo in patients with inadequately controlled severe persistent allergic asthma despite GINA 2002 step 4 therapy. The assessment of the effectiveness of omalizumab in patients who respond to omalizumab therapy was an important feature of this study. In the omalizumab-responder population, further improvements were seen over the omalizumab-treated population in all outcomes. Assessment of this subgroup may reflect treatment outcomes seen in clinical practice after omalizumab therapy is continued only in those judged by a physician to have responded to omalizumab after 16 weeks of treatment, as stated in the EU label.
In conclusion, day-to-day asthma symptoms correlate well with improved QoL and provide an important additional simple measure of asthma control. Add-on omalizumab improves day-to-day symptoms in patients with inadequately controlled severe persistent allergic asthma. This study also illustrates the value of assessing treatment response to omalizumab after 16 weeks.