Executive Summary

ASTRA's INHALED CORTICOSTEROID BUDESONIDE IS "SUPERIOR" FOR MILD ASTHMA to the beta-2 agonist terbutaline (Ciba-Geigy's Brethaire), according to a study published in the August 8 issue of The New England Journal of Medicine. The two-year study, conducted in Finland and Sweden by Haahtela et al., found that patients using budesonide had greater increases in peak expiratory flow (PEF) than those using terbutaline (32.8 liters per minute versus 4.8 liters). In addition, the study found that the use of supplemental medication was greater in the terbutaline group. The study authors concluded that "antiinflammatory therapy with inhaled budesonide is an effective first-line treatment for patients with newly detected, mild asthma and is superior to the use of terbutaline in such patients." The authors predicted that use of inhaled steroids to provide sustained control of airway inflammation "may allow a long-lasting remission" that could "reduce mortality due to asthma and lower treatment costs." The multicenter, double-blind study focused on patients who had developed asthma in the previous year. The 103 patients in the trial were instructed to take either two 600 mcg doses a day of budenoside or two 375 mcg doses a day of terbutaline. The patients' PEF values, daily records of asthma symptoms, and bronchial responsiveness were all assessed during evaluation periods held after 6, 12, 28, 44, 48, 72, 92, and 96 weeks of treatment. Bronchial responsiveness was tested by challenge with solutions of histamine diphosphate in six doubling concentrations (1,2,4,8,16, and 32 mg per ml). The concentration of histamine that produced a 15% drop in forced expiratory volume, measured in liters, was called the provocative concentration (PC). Budesonide- treated patients experienced an increase in PC of 1.6 histamine concentration levels, versus .5 levels for the terbutaline group. In addition, the use of supplemental medication (250 mcg puffs of terbutaline) in the first 12 weeks of the study decreased by 70% in the budesonide group, but increased by 21% in the terbutaline group. Ten patients receiving terbutaline were withdrawn from the study "because of insufficient efficacy of therapy," but only one patient withdrew from the budesonide group for that reason. In addition, five patients in the budesonide group and one patient in the terbutaline group stopped treatment because they were free of symptoms. Twelve terbutaline patients needed theophylline added to their treatment versus two patients in the budesonide group. Similarly, 36 courses of oral prednisolone were given to 17 patients in the terbutaline group, while 22 courses were needed by 13 patients in the budesonide group. The study findings support recommendations made by a panel convened by the National Heart, Lung and Blood Institute in February of this year ("The Pink Sheet" Feb. 11, p. 13). That panel stated that "even patients with mild-to-moderate asthma will often benefit from the regular administration and more aggressive use of anti-asthma medications, especially anti-inflammatory medicine." In an editorial in the same NEJM issue, Charles Reed, MD, Mayo Clinic, recommended that because asthma is an inflammatory disease "treatment should be directed at reversing the underlying inflammation, not simply at relieving bronchospasm." However, Reed also points out that the use of corticosteroids as a first-line treatment does have "some drawbacks," including the difficulty of teaching patients to use metered-dose inhalers correctly and that "suppression of the functions of the hypophysical-pituitary- adrenal axis by large doses can pose a serious risk in patients liable to respiratory arrest from acute severe attacks." Budesonide, marketed overseas under the brandname Pulmicort, is currently available in most of Western Europe and in Canada. In the U.S., budenoside is currently in Phase III clinical trials. In 1990, Astra began marketing budesonide with a Turbuhaler dry powder delivery system, which the company says is "superior to metered-dose inhalers" because it is easier for patients to use. A number of inhaled steroids are already on the market in the U.S. including beclomethasone diproprionate (Schering's Vanceril and Glaxo's Beclovent), triamcinolone acetonide (Rhone-Poulenc Rorer's Azmacort), and flunisolide (Forest Pharmaceuticals' Aerobid). Glaxo also has a second generation inhaled corticosteroid Flixotide (fluticasone propionate) under development in the U.S. The drug is currently undergoing Phase III study.