Oral Corticosteroid Use In Patients Research Articles

Inhaled mometasone furoate reduces oral prednisone usage and improves lung function in severe persistent asthma

The reduction of oral prednisone use by mometasone furoate (MF) delivered by HFA-227 metered dose inhaler (MDI) was examined in oral corticosteroid (OCS)-dependent patients with severe persistent asthma. A 3-month, double-blind, placebo-controlled clinical trial (n=123), followed by a 9-month open-label phase (n=120). The study was conducted at 26 medical centers in the United States. Patients were randomized to treatment with MF-MDI 400 or 800 microg twice-daily (bid) doses, or placebo in the double-blind trial. All patients received MF in the open-label phase. At the endpoint of the double-blind trial, MF-MDI 400 and 800 microg bid reduced the daily OCS dose by 39.4% and 31.1%, respectively, while placebo increased the OCS dose by 107.2% (P<0.01). The OCS requirement was reduced by 50% or more in 63% and 60% of patients treated with MF-MDI 400 and 800 microg bid, respectively, compared with 14% of patients receiving placebo. After 12 weeks, despite prednisone reductions, pulmonary function, asthma symptoms, albuterol use, nocturnal awakenings, and physician-evaluated response to therapy also showed significant improvement with MF-MDI treatment compared with placebo. Further reductions in OCS requirements were achieved with long-term MF-MDI treatment in the open-label phase, with an overall 67% reduction in prednisone usage and 51% of patients completely eliminating prednisone usage by the 1-year time point. MF delivered by HFA-227 MDI significantly reduces daily OCS use compared with placebo and facilitates elimination of OCS use in patients with severe persistent asthma.

Pharmacologic management of asthma

Therapy for asthma has largely been focused on the end-organ effect of bronchoconstriction on airway smooth muscle. Xanthine derivatives such as theophylline were the initial oral bronchodilators used to manage asthma. Recent therapies directed at airway smooth muscle relaxation promote bronchodilation through stimulation of the b-adrenoreceptor. 1 The pharmacologic evolution of b-adrenergic agonists has led to the development of airway smooth muscle receptor‐specific agents, agents that can be administered topically through aerosol inhalation, and agents that are long lasting. Epidemiologic studies have validated the safety of the long-acting b-adrenoreceptor drugs and established that tachyphylaxis, as measured by the direct bronchodilating effect of these agents after repeated use, is inconsequential. More recently, the focus of asthma therapy development has been on modification of the inflammatory component of this disorder. 2 Oral corticosteroids cause substantial improvement in objective measures of lung function, but these agents are associated with considerable toxicity. 3, 4 The development of potent, highly lipidsoluble agents permits twice-daily dosage and may lead to a reduction in oral corticosteroid use in patients with corticosteroid-dependent asthma. Furthermore, inhaled corticosteroids provide an effective means of managing the pathology of inflammation with minimal adverse effects. With the enhanced understanding of asthma pathophysiology, drugs now are being designed to act against different steps in the inflammatory process. Newer agents include those directed at antagonizing the effects of leukotrienes that are secreted from inflammatory cells. These include two classes: 5-lipoxygenase inhibitors and leukotriene receptor antagonists. A number of other therapies are currently in development. Some of these interventions (e.g., monoclonal antibodies) prevent adhesion of inflammatory cells to vascular endothelium in conducting airways. Other mechanisms of action of investigational agents include modification of Thelper (TH2) cell interactions that trigger inflammatory activation, suppression of eosinophil development, and induction of eosinophil apoptosis in the bone marrow. PATHOPHYSIOLOGY