Traditional and Patient-centered Outcomes with Three Classes of Asthma Medication - Article Example

Traditional and Patient-centered Outcomes with Three Classes of Asthma Medication Introduction The purpose of this research was to study the relationship between clinical and subjective variables in the assessment of response to treatment in asthma with three different classes of medication, including a leukotriene receptor antagonist, long-acting ß2-agonist and inhaled corticosteroid (ICS) in patients with mild-to-moderate persistent asthma. By ‘clinical variables’, the authors mean traditional end-points like symptoms, reliever use, forced expiratory volume in one second per cent predicted, morning peak expiratory flow and airway hyper responsiveness; ‘subjective variables’ mean patient-centred benefits like quality of life, patient global assessments and the feeling of improvement as determined by asthma control questionnaire. There are 2 hypotheses in this study which are: 1) Some traditional measurements (clinical variables) of improvement during asthma treatment may not reflect the estimation of benefit by the patient. 2) Patients may benefit (subjective variables) from a specific class of asthma medication in ways which were not captured by the measurement of lung function. Measures of asthma control are a much debated topic in the recent times. This is because there are various measures to determine the efficacy of treatment. Most researchers use lung function and clinical improvement as criteria for improvement; even the international guide lines are based on these. However, what the researchers perceive as improvement may not be the same in case of patients. Patients may have their own meaning of improvement and only if they feel that a particular class of medicine is effective will they adhere to treatment. This is the basis of the hypotheses in the article under study. The Study This study included 58 subjects from three sites in Sydney and Melbourne, Australia. Only those with mild to moderate asthma, who had previously used a short-acting ß2-agonist with/without an inhaled corticosteroids (ICS) 500 µg beclomethasone equivalent and in the age group 16 to 75 years, were included in the study. In all subjects, ICS treatment was ceased at entry to the study. Those with mild to moderate asthma were only considered because, in reality, these patients need only monotherapy and they are symptomatic enough to show a treatment response. The inclusion criteria were: Those with coexisting lung disease, recent asthma exacerbation or respiratory infection, and current smoking or smoking history 10 pack–yrs were excluded from the study. Two treatment sequences were used as a part of study design: 1. Comparison of leukotriene receptor antagonist (montelukast) versus long-acting ß2-agonist (eformoterol) with matching placebos: For this study, the subjects were allocated by a computer-generated randomisation procedure and comprised of double-blind, double-dummy crossover comparison. A total of 29 subjects were randomised to each order of treatment (one set of 29 patients received montelukast then eformoterol; and the other set received eformoterol then montelukast). 6-week treatment periods were used with 1-week washouts. 2. Single-blind ICS with placebo capsules. Reliever bronchodilator medication (salbutamol) was permitted as required throughout the study. The measures of outcome used were: 1. Primary outcome variables: morning peak expiratory flow (PEF; the best from three spirometric maneuvers), and median daytime and night-time symptom intensity scores (scale: 0–4, where 0 = none and 4 = severe). 2. Secondary outcome variables: standard spirometric lung function variables, quality of life (QoL) score, AHR (measured as PD20 methacholine) and asthma control questionnaire (ACQ) score (scale: 0–6). These end-of treatment values were statistically compared with baseline as a covariate. Cross-over comparison of mean morning PEF was done for montelukast and eformoterol. Peak flow comparisons between the final treatment (fluticasone) and each of the crossover treatments (eformoterol and montelukast) were by paired t-tests, ignoring sequence allocation. Secondary variables also were compared similarly. The results of the study implied that clinical variables are not similar to subjective variables, although there was some relation to this aspect with montelukast treatment. Thus the relationship between clinical variables and subjective variables differs with medication class. Analysis of the study The first study hypothesis was tested by: 1. Examining the statistical significance and direction of differences between treatments for the multiple individual end-points 2. By summing the derived scores for each principal factor for each treatment. The second hypothesis was tested by a general linear modelling approach, using the derived score for patient-based end-points as the dependent variable and individual lung function variables (FEV1 % pred, FEV1/FVC, % best PEF and mean morning PEF) as the independent variables. Mean morning PEF and pattern for ACQ was significantly higher with eformoterol and with fluticasone than with montelukast (pfluticasone for symptom/reliever use factor, fluticasone>eformoterol for lung function factor, eformoterol = fluticasone for patient-centred factor). Montelukast was ranked third for all three factors. For the individual end-points which were examined in this study, the authors reported that fluticasone was superior to eformoterol for clinic lung function and AHR. It was equivalent to eformoterol for symptoms, morning PEF, daytime reliever use, QoL, ACQ and patient assessments of asthma control; and inferior to eformoterol for night-time reliever use. For most individual variables, the magnitude of improvement with montelukast was small, with significantly less benefit compared with eformoterol or fluticasone. The limitations of this study were: 1) The study was not a fully randomised crossover comparison of the three medications. The researchers did not take this approach because of concerns of safety to avoid prolonged fluticasone washout. Hence there was complete confounding between period and treatment effects. 2) Those who received eformoterol first, did not have the benefits of anti-inflammatory effect carry over. 3) Study hypotheses were tested during monotherapy rather than with multiple combinations of add-on therapy. Of course, this was done due to practical reasons. Also, monotherapy with a long-acting ß2-agonist is not a recommended for maintenance treatment. 4) The study was not powered to detect differences in exacerbation rates between the three treatments. 5) Due to withholding of medications prior to study visits, the clinic lung function measures may be affected. However, this may be considered negligible because the withholding period was shorter than the medication's duration of action. In the present study, shorter periods of withholding treatment would have been expected to favour eformoterol and montelukast in lung function end-points. Conclusion It does make sense to give importance to patient centred outcome as references to judge the efficacy of a class of drug. The authors wanted to prove that traditional measurements of improvement during asthma treatment may not reflect the estimation of benefit by the patient and that patients may benefit from a specific class of asthma medication in ways which were not captured by the measurement of lung function. However, they failed to demonstrate a correlation between traditional endpoints and patient-centric measures. Their conclusion is that the traditional endpoints may not capture the patient-centric information. Reference Jenkiens CR, Thien FCK, Wheatley JR and Reddel HK.“Traditional and patient-centered outcomes with three classes of asthma medication.” European Respiratory Journal (2005), 26. 21 Aug 2007 Read More