Fluticasone propionate powder and lack of clinically significant effects on hypothalamic-pituitary-adrenal axis and bone mineral density over 2 yearsin adults with mild asthma

Background: Although inhaled corticosteroids are widely used for the treatm ent of inflammation in asthma, prospective, long-term, placebo-controlled t rials characterizing their systemic safety with chronic use are lacking. Objective: This study was designed to prospectively evaluate the long-term safety of inhaled fluticasone propionate therapy. Methods: Fluticasone propionate powder, 500 mu g, or placebo was administer ed twice daily by means of the Diskhaler for 104 weeks to 64 adults with mi ld persistent asthma in a randomized, double-blind, parallel-groop study. P rimary safety variables were measured at baseline and every 6 months therea fter Although evaluation of efficacy was not an objective of this study, pu lmonary function testing was performed at monthly intervals. Results: Two years of treatment with fluticasone propionate had no signific ant effects on the skeletal system. No clinically significant changes were observed in ophthalmic parameters (glaucoma and posterior subcapsular catar acts). Mean change from baseline in lumbar spine (L-1 to L-4) bone density at week 104 was not significantly different between fluticasone propionate (-0.006 +/- 0.008 g/cm(2)) and placebo (-0.007 +/- 0.010 g/cm(2)). Markers of bone formation (serum osteocalcin) and resorption (urinary N-telopeptide ) did not differ significantly between treatment groups. The effects of flu ticasone propionate treatment on the hypothalamic-pituitary-adrenal axis we re minimal, with no alterations in morning plasma cortisol concentrations a nd minor but statistically significant decreases in poststimulation mean pe ak plasma cortisol concentrations (P = .021) and 8-hour plasma cortisol are a under the curve values (P = .020) at week 104. Drug-related adverse event s were primarily topical effects of inhaled corticosteroids. Pulmonary func tion improved significantly during 2 years of fluticasone propionate treatm ent. Conclusion: Fluticasone propionate powder, 500 mu g twice daily for up to 2 years, was efficacious and well tolerated, with no clinically relevant eff ects on the hypothalamic-pituitary-adrenal axis, bone density, or ophthalmi c parameters in adults with mild asthma.