© 2007 American Thoracic Society
Montelukast and Theophylline: No Use or Some Use in Persistent Asthma?From the Authors:We thank Currie and colleagues for their interest in our article (1). They suggest caution extrapolating these results into everyday practice; however, the intention of our study is to provide information relevant to everyday asthma care. Effectiveness trials test the utility of treatments in real-world situations with broad inclusion criteria and clinically meaningful outcomes, whereas efficacy trials test the utility of treatments in controlled situations with selected patients and often use surrogate outcomes. Our trial was designed as an effectiveness trial rather than an efficacy trial. It is not surprising that one-fourth of our participants with poorly controlled asthma were not prescribed inhaled corticosteroids (ICS) when nearly one-third of patients with severe or fatal asthma are not prescribed ICS (2, 3). The results of our trial can be generalized to patients with asthma needing additional treatment because our trial population was representative of inadequately controlled patients with asthma in the community. The suggestion that all patients should be treated with ICS prior to adding montelukast or theophylline is a valid approach. However, our trial supports meta-analyses suggesting that addition of montelukast adds a modest benefit to ICS (4, 5). Contrary to our hypothesis, there was a greater effect of both theophylline and montelukast on asthma control in those patients not on ICS. Thus, these agents would be of greatest benefit as monotherapy in patients who cannot or will not take ICS. The correspondents suggest that the study is invalid because of the substantial rate of nonadherence that we reported based on blood concentrations. Adherence with chronic therapies are often in the range of 50%, and this reflects the reality of clinical practice (6). Because nonadherent patients represent a biased sample, subgroup analysis of adherent patients is often suspect. Nonetheless, exploratory analyses of our results did not show that adherent patients were benefited more than nonadherent patients. Accordingly, we cannot ascribe our results entirely to nonadherence. We did not report airway inflammation measures. Because we wanted to focus on clinically relevant outcomes, we measured asthma control as an indicator of patient symptoms rather than biological outcomes that have been previously studied. Both theophylline and montelukast have antiinflammatory and bronchodilating effects and improve asthma control in short-term studies of selected patients (7). The important question, though, is whether this translates into treatments that are effective and sustained in ways that are meaningful to patients in a realistic clinical setting.
for the American Lung Association Asthma Clinical Research Centers FOOTNOTES Conflict of Interest Statement: C.G.I. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. D.A.K. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. N.R.A. has served on advisory boards for GlaxoSmithKline (GSK) and Altana, receiving approximately $2,000 per year for 5 years, and has given two to three talks over the past 5 years for GSK, with an honorarium of $2,500 for each. M.C. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. N.A.H. has received grant support from GSK, Sepracor, Boehringer-Ingelheim, and Dey; honoraria from GSK and Boehringer-Ingelheim; and has served on advisory boards for GSK, Sepracor, and Dey. J.T.H. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.J.L. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.A.W. received consulting fees from GSK, Pfizer, Sanofi-Aventis, Emphasys, Spiration, and Forest in the past 3 years for research oversight and review committees. He has served on advisory boards or as a consultant for Boehringer-Ingelheim, Pfizer, GSK, Hill-Rom, Merck Manual and Otsuka. He has also received research grants from Boehringer-Ingelheim, and GSK. REFERENCES
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