Leukotriene antagonists in asthma

Abstract

This recent article published in The New England Journal of Medicine describes a new style of clinical trial, a pragmatic trial. The purpose of the pragmatic design is to take into account the vagaries of clinical practice and simulate ‘real life’. This trial highlights the difficulties in the performance, reporting and interpretation of such trials. The paper includes two parallel, multicentre pragmatic trials that compare leukotriene antagonists and inhaled corticosteroids as first line (n = 306) and add on (n = 352) asthma controller therapy in a primary care setting in the UK. The primary outcome measure was the Mini Asthma Quality of Life Questionnaire. In both trials, there was no difference between groups in the mini AQLQ score [−0.11(CI −0.35 to 0.13) and −0.11 (95% CI, −0.32 to 0.11)] or secondary outcome measures at two months or at two years (see Fig. 1). However, there are many factors producing bias towards equivalence in this study, including enrolment of patients without disease, poor adherence, open label design, use of concomitant therapy, lack of placebo and lack of objective outcome measures. We are concerned that this trial, published in such a high-impact journal, will be misinterpreted by busy clinicians as proof of equivalence between the two therapies in question. Although this paper provides a useful focus for discussion of pragmatic trials, we strongly believe that its results should not influence clinical practice. Time Course of Improvements in ACQ and MiniAQLQ Scores and Peak Expiratory Flow over a Two-Year Period in Patients with Asthma. Panel A shows outcomes over a two-year period for patients receiving a leukotriene-receptor antagonist (LTRa) or an inhaled glucocorticoid as first-line asthma-controller therapy. Panel B shows outcomes over a two-year period for patients receiving an LTRa or a long-acting beta2-agonist (LaBa) as an add-on to an inhaled glucocorticoid. ACQ denotes Asthma Control Questionnaire (on which scores (shown as means ± SD) range from 0 to 6, with higher scores representing worse control and a minimal clinically important difference (MID) of 0.5). Mini Asthma Quality of Life Questionnaire (Minia QLQ) (on which scores (shown as means ± SD) range from 1 to 7, with higher scores representing better quality of life and an MID of 0.5), and PEF peak expiratory flow (shown as medians with I bars representing the interquartile ranges). Reviewers: John Widger and John Massie, Royal Children's Hospital, Melbourne ([email protected])