© 2005 American Thoracic Society
GOAL—Asthma Control, but at What Cost?From the Authors:Dr. Todd's letter focuses on suppression of the HPA axis caused by high doses of inhaled corticosteroids. His concerns, summarized in the last paragraph of his letter, are of limited relevance to the GOAL study (1). They suggest that patients ended up on fluticasone propionate at "double the probable maximum effective dose," and cite evidence from dose–response studies in which single measures (usually FEV1) serve as the endpoint (2). In GOAL, the dose was individualized (increased at intervals) to obtain the maximal clinical response, and a composite measure, which is more discriminating of control, was used (3). The dose was not excessive as it was increased according to clinical need. The results confirm that some patients only achieve control with the highest dose, at times only after 3 to 6 months. These results raise questions about conventional methods of assessing dose–response relationships of corticosteroids in chronic uncontrolled asthma. GOAL examined a fundamental question—whether asthma control can be achieved. Practical limitations of design prevented inclusion of dose-minimization strategies (e.g., step-down routines). However, the highest dose of corticosteroids employed was one approved and widely used in adults. The results provide useful evidence on the superiority and steroid-sparing effects of combination treatment. We recognize that the question of how hard to try in individual patients to achieve control (with respect to dose and duration of treatment) remains a challenge. The decision is based upon patient needs and expectations, cost, and potential adverse effects. A second concern of Dr. Todd is the "insensitive and unreliable" tests of HPA axis function. We accept that 24-hour urinary cortisols are less sensitive than the ACTH stimulation test, but the latter was not a practical option in a large scale outpatient study, and is not without risk. The 24-hour urinary cortisol method is superior to single point measurement of blood cortisol, widely used and accepted by regulatory authorities (4, 5). The references on adrenal suppression and crisis cited by Dr. Todd are not relevant to GOAL. The second is of unusual design, two involved use of a pressurized metered dose inhaler (MDI) that results in higher systemic exposure to corticosteroid than the Diskus device, and one concerned mainly children. Of the four adults with adrenal crisis, all were on doses higher than used in GOAL. The clinical relevance of the reductions in urinary cortisols in some patients in the GOAL study remains controversial, and must be weighed against the risk of exacerbations, and the "cost" of continued uncontrolled asthma.
for GOAL Study Steering Committee, University of Cape Town Lung Institute, Cape Town, South Africa FOOTNOTES Conflict of Interest Statement: E.D.B. received honoraria for speaking at scientific meetings and courses organized and financed by AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline and served on Advisory Boards for the following companies: AstraZeneca, Boehringer Ingelheim, Hoffman le Roche and GlaxoSmithKline. He performed consultancy services for AstraZeneca, Aventis, Altana, Hoffman le Roche and Kyowa Hakko. REFERENCES
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