Oral steroid-sparing effect of two doses of nebulized fluticasone propionate and placebo in patients with severe chronic asthma

Inhaled steroids, delivered by metered dose aerosol and dry powder inhalers , have proved effective in reducing the need for oral steroids in patients with oral steroid-dependant asthma. This randomized, double-blind study, co mpared the efficacy and tolerability of nebulized fluticasone propionate (F P Nebules(TM)), 2 mg b.d. (FP 4 mg) and 0.5 mg b.d. (FP 1 mg) with placebo, on the reduction of oral steroid requirement in 301 adult patients with or al steroid-dependent asthma. Primary efficacy was assessed by the reduction in daily oral steroid dose. Secondary efficacy parameters included daily diary card peak expiratory flo w (PEF), day and night-time symptoms and clinic lung function measurements. Safety was assessed by adverse event monitoring and serum cortisol levels. After 12 weeks of treatment the adjusted mean +/- SEM reduction in oral pre dnisolone was significantly greater in the FP 4 mg group (4.44 +/- 0.98 mg day(-1)) compared with FP 1 mg (2.16 +/- 1.00 mg day(-1), P = 0.039) and pl acebo (1.20 +/- 1.02 mg day(-1), P= 0.004). A higher percentage of patients discontinued the use of oral steroids with FP 4 mg (37%) compared with FP 1 mg (26%,P=0.038) and placebo (18%, P<0.001). Following treatment, the adj usted mean morning PEF showed a trend in favour of FP 4 mg (280 +/- 4 l min (-1)) compared with placebo (270 +/- 5 1 min(-1), P = 0.053) and the evenin g PEF was significantly higher with FP 4 mg (305 +/- 4 1 min(-1)) compared with FP 1 mg (292 +/- 4 1 min(-1), P = 0.010). FP 4 mg resulted in a signif icantly higher percentage of days when the patients were free from daytime (P=0.036) and night-time (P=0.021) wheeze, compared with placebo. Significa ntly fewer patients withdrew from the FP 4 mg group compared with the other two groups (vs. FP 1 mg, P = 0.003; vs, placebo, P = 0.032). All three tre atments were well tolerated and the incidence of adverse events was similar between the groups. FP Nebules at a daily dose of between 1 and 4 mg are a safe and effective m eans of reducing the oral steroid requirement of patients with chronic oral steroid dependent asthma. (C) 1999 HARCOURT PUBLISHERS LTD.