Research finds little difference in outcomes among strategies to adjust asthma therapy in adults

Among adults with asthma controlled with low-dose inhaled corticosteroid therapy, the time to treatment failure was not significantly different among patients who received corticosteroid dose adjustment based on physician assessment, a biomarker, or symptom occurrence, according to a study in the September 12 issue of JAMA. Asthma disease activity varies daily, seasonally, and episodically, presumably related to airway inflammation. "Accordingly, asthma management requires periodic dose adjustments of controller medications, particularly inhaled corticosteroids. Adjustments have been based on (1) physician assessment of symptoms, activity limitation, rescue albuterol use (a bronchodilator used for treating asthma), lung function, and exacerbations at usual office or clinic visits, (2) a biomarker of disease activity (e.g., exhaled nitric oxide), or (3) the occurrence of symptoms on a day-to-day basis," according to background information in the article. "No consensus exists for adjusting inhaled corticosteroid therapy in patients with asthma."

William J. Calhoun, M.D., of the University of Texas Medical Branch, Galveston, and colleagues hypothesized that adjustment of inhaled corticosteroids based on symptoms or measurement of exhaled nitric oxide would be superior to adjustment based on physician assessment. The researchers conducted a randomized, placebo-controlled trial that included 342 adults with mild to moderate asthma controlled by low-dose inhaled corticosteroid therapy (n = 114 assigned to physician assessment-based adjustment [101 completed], n = 115 to biomarker-based [exhaled nitric oxide] adjustment [92 completed], and n = 113 to symptom-based adjustment [97 completed]). The Best Adjustment Strategy for Asthma in the Long Term (BASALT) trial was conducted by the Asthma Clinical Research Network at 10 academic medical centers in the United States for 9 months between June 2007 and July 2010. For physician assessment-based adjustment and biomarker-based adjustment, the dose of inhaled corticosteroids was adjusted every 6 weeks; for symptom-based adjustment, inhaled corticosteroids were taken with each albuterol rescue use.

The researchers found that the time to treatment failure, the primary study outcome, did not differ significantly among the 3 treatment strategies. The 9-month Kaplan-Meier failure rates were 22 percent (24 events) for physician assessment-based adjustment (PABA), 20 percent (21 events) for biomarker-based adjustment (BBA), and 15 percent (16 events) for symptom-based adjustment (SBA).

Treatment failure rates were not different among groups when multiple episodes of treatment failure were included. There were not significant differences among the treatment groups for asthma exacerbation (including multiple episodes) rates; and the average proportion of treatment failures that progressed to exacerbations. The authors also found that measures of lung function and asthma symptoms were not significantly different among the groups.

"In summary, among adult participants with mild to moderate persistent asthma, neither the SBA nor the BBA strategy for inhaled corticosteroid therapy was superior to the standard PABA strategy for the outcome of treatment failure."

Editorial: Inhaled Corticosteroid Dose Adjustment in Mild Persistent Asthma

In an accompanying editorial, George T. O'Connor, M.D., M.S., of the Boston University School of Medicine, (and Contributing Editor, JAMA), and Joan Reibman, M.D., of New York University, New York, comment on the findings of this study.

"This report adds to prior randomized trials that have compared the typical physician-prescribed dosing of inhaled corticosteroids (ICS) with intermittent dosing guided by symptoms for patients with relatively mild asthma. A prior Asthma Clinical Research Network (ACRN) study of adults with mild persistent asthma indicated that a strategy of initiating a course of inhaled or oral corticosteroid only when asthma symptoms became bothersome (according to a written action plan), led to a similar peak expiratory flow rate and asthma exacerbation rate as the everyday physician-prescribed dosing of controller medications (ICS or leukotriene antagonist), although some outcomes such as bronchial reactivity and symptom-free days were improved by regular twice daily use of ICS. Like the BASALT trial, the prior ACRN study was designed to show superiority of one strategy over another, rather than to test equivalence, and the lack of superiority of any strategy over the others must be interpreted accordingly."

Source: American Medical Association (AMA)