Asthma Knowledge Centre
Alvesco
Clinical efficacy
The Global Initiative for Asthma (GINA) 2007 guidelines1 state that the goals for successful asthma management are to:
- Achieve and maintain control of symptoms
- Maintain pulmonary function as close to normal as possible
- Maintain normal activity levels, including exercise
- Prevent asthma exacerbations
- Avoid adverse effects from asthma medications
- Prevent asthma mortality
Asthma management involves a combination of patient education, control of the patient’s environment and pharmacotherapy. Several therapeutic agents are available; ICS are currently the most effective.1 ICS can reduce asthma symptoms, reduce airway inflammation and hyperresponsiveness, improve lung function, improve quality of life, decrease acute episodes requiring urgent care, reduce the need for rescue medication and prevent asthma mortality.1, 2, 3 Current treatment guidelines recommend ICS as first-line therapy for persistent asthma of all severities in both adults and children.1
However, concerns over the use of ICS remain due to the potential side effects. Furthermore, experience with, and concern about, side effects are among patients’ primary reasons for poor adherence to treatment.4 In turn, non-compliance can result in an increase in symptoms, nocturnal awakenings, exacerbations and rescue medication use.4 Ideally, an ICS will:5
- Maximize efficacy
- Minimize local oropharyngeal and systemic adverse events
Alvesco has demonstrated safe and effective asthma control in randomized clinical studies6–8, 9, 10, 11, 12 and has an efficacy profile comparable with, or better than, that of the currently available ICS.13, 14, 15, 10, 12, 15, 17, 18, 19 In addition, Alvesco can reduce the need for oral corticosteroids20,21 and has proven long-term safety and efficacy.22, 23 Alvesco has also shown excellent efficacy and safety in adolescents and children.24, 25, 26, 27 Throughout this section, key clinical studies have been used to demonstrate the benefits Alvesco can provide physicians and patients in the management of asthma.
Clinical study design
The efficacy of Alvesco has been determined in dose range finding studies and comparator studies with other ICS and oral corticosteroids. Most studies followed a protocol similar to that shown in Figure 1.
Figure 1. The general protocol for Alvesco clinical trials.
*Depending on the study, patients were allowed: Rescue medication only; Continued use of their ICS; Specified ICS at a specified dose ICS=inhaled corticosteroid
Efficacy variables
Standard measures of pulmonary function and asthma control were used to assess the clinical effectiveness of Alvesco. These included measurements of FEV1, FVC and PEF as well as patient diary recordings of morning and evening PEF, daytime and nighttime asthma symptom scores and daily use of rescue medication. Symptom scores were rated using a 5-point scale from 0 (no symptoms, good asthma control) to 4 (poor symptom control, asthma symptoms that may significantly interfere with daily activities). In some studies, efficacy was measured by predefined lack of efficacy (LOE) criteria. To assess quality of life, the standardized Asthma Quality of Life Questionnaire28 (AQLQ) was used. In children, quality of life was assessed using the pediatric AQLQ.29
Morning peak expiratory flow
Morning PEF provides a daily measure of lung function at a time point when lung function is at its lowest.
Doses
Corresponding ex-actuator and ex-valve doses are shown in Table 1.
| Ex-actuator dose | Ex-valve dose |
|---|---|
| 80 μg | 100 μg |
| 160 μg | 200 μg |
| 320 μg | 400 μg |
| 640 μg | 800 μg |
| 1280 μg | 1600 μg |
Lack of efficacy criteria
LOE is determined when a high dropout rate is expected (for example, asthma patients randomized to placebo groups). The increase in patient dropouts related to LOE provides an additional means of determining efficacy, together with changes in pulmonary function. LOE criteria integrate several efficacy variables, including lung function, symptoms and exacerbations. For the following Alvesco efficacy studies, LOE was defined as:
- A clinical exacerbation or decrease in FEV1 ≥20% of the pre-study value or <50% of predicted,
OR - A nighttime symptom score of ≥2 or ≥3 in at least 4 or 2 (depending on the study) of the 7 nights immediately preceding a clinic visit, OR
- A daytime symptom score ≥3 for at least 4 of the 7 days immediately preceding a clinic visit, OR
- Another deterioration in pulmonary function that the investigator deemed may compromise the patient’s health
Patient asthma severity
Patients of all asthma severity classifications were included in the Alvesco trials. The GINA guidelines and FEV1 (% predicted) ranges were used to assess asthma severity.
Tolerability and safety
All studies recorded adverse events. Standard laboratory tests were performed and vital signs were measured during clinic visits. In addition, some studies measured markers of HPA-axis function. The safety and tolerability of Alvesco is described in detail in the Safety and Tolerability sections.
Statistical analyses
The statistical analyses used were dependent on the study. The intention-to-treat (ITT) population was used for the primary analysis in superiority studies (for example, Alvesco versus placebo and between doses in dose-range finding studies), whereas the per-protocol (PP) analysis was used for non-inferiority studies (for example, Alvesco versus an active comparator). However, if non-inferiority was shown, then superiority was subsequently tested. In the following studies, ITT data are reported unless otherwise stated.
For Alvesco prescribing information please refer to full Summary of Product Characteristics
Disclaimer: For exclusive use at EPG Asthma Knowledge Centre, July 2008. Local regulation may apply. Please check your local SmPC.
References:
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