Which Inhaled Corticosteroid For Asthma?

Journal of Family Practice, Sept, 1999 by Stephen A. Wilson

Raphael GD, Lanier RQ, Baker J, Edwards L, Rickard K, Lincourt WR. A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma. J Allergy Clin Immunol 1999; 103:796-803.

Clinical question Which inhaled steroid -- fluticasone (Flovent) or beclomethasone (Beclovent, Vanceril) -- is more effective for treating persistent asthma?

Background The National Institutes of Health's treatment guidelines for persistent asthma recommend the use of inhaled corticosteroids. Although the guidelines recognize categories of inhaled steroids and provide guidance for the use of low, medium, and high dosages, none is recommended.

Population studied A total of 399 nonsmoking men and women aged 12 years and older with chronic asthma requiring daily inhaled steroids for at least 6 months were enrolled. Each person had taken 8 to 12 puffs per day of either beclomethasone or triamcinalone for at least 1 month before enrollment. Screening and baseline forced expiratory volume in 1 second ([FEV.sub.1]) values were between 45% and 80% of predicted normal. Subjects had reversible lung function ([is greater than or equal to] 12% increase in [FEV.sub.1] after 2 puffs of albuterol). Continuation of theophylline or salmeterol was allowed if taken at stable and approved doses and if the morning dose was withheld before all study visits. The only other permitted asthma medication was the albuterol metered-dose inhaler (Ventolin) for symptomatic relief. Exclusion criteria included the use of oral or intravenous steroids, leukotriene modifiers, or nedocromil sodium for 1 month before the study.

Study design and validity This randomized double-blind double-dummy parallel-group clinical trial was conducted at 23 specialty asthma and primary care study centers and occurred over 12 weeks. There were 4 treatment groups: low-dose fluticasone (44 [micro] g/puff, 2 puffs twice daily); medium-dose fluticasone (110 [micro] g/puff, 2 puffs twice daily); low-dose beclomethasone (42 [micro] g/puff, 4 puffs twice daily); and medium-dose beclomethasone (42 [micro] g/puff, 8 puffs twice daily).

Before the 12-week randomization, there was a 2-week single-blind run-in period. During this phase, subjects took beclomethasone (42 [micro] g/puff, 4 puffs twice daily) with a placebo instead of their usual inhaled steroid. Eligibility for the study was evaluated, compliance with medication use was assessed, and a baseline was established.

Spirometry was done at screening (before the run-in period), at baseline (after the run-in period), and after 1, 2, 4, 6, 8, 10, and 12 weeks. Subjects kept diary cards documenting supplemental albuterol use, morning and evening peak expiratory flow rates (PEFRs), night awakenings caused by asthma, and asthma symptoms on a scale of 0 to 3 (where 0 = none and 3 = severe).

This well-designed study with 4 demographically similar treatment groups took great care to ensure compliance and similar knowable patient baselines using the run-in phase. Spacers were not used and 8 puffs twice daily of 42 [micro] g/puff beclomethasone was used instead of 4 puffs twice daily of the 84 [micro] g/puff product.

Outcomes measured Outcomes measured included [FEV.sub.1], dally albuterol use, asthma symptoms, PEFRs, and nighttime awakenings due to asthma.

Results Fluticasone at both the low and medium dose improved [FEV.sub.1] by 0.31 L (14%) and 0.36 L (15%), respectively, compared with improvements of 0.18 L (8%) and 0.21 L (9%) with the low and medium doses of beclomethasone. In each outcome category, with the exception of night awakenings, fluticasone bested beclomethasone: morning PEFR (P [is less than] .001), evening PEFR (P = .06), puffs per day of albuterol (P = .004), percent days without albuterol use (P = .01), asthma symptom scores on a 0 to 3 scale (P = .024), and percent days without symptoms (P = .027). Overall, greater improvements in pulmonary function parameters occurred with fluticasone treatment (P [is less than] .034). Similar side effect and withdrawal rates were reported between the various groups.

Recommendations for clinical practice When treating persistent asthma, fluticasone is more effective than beclomethasone in equivalent doses. This is true for both disease-oriented outcomes (eg, spirometry) and for patient-oriented outcomes (eg, fewer asthma attacks). Fewer attacks means less rescue albuterol, which translates into lower patient expense. Flovent requires fewer puffs (1 puff of 220 [micro] g) than Vanceril DS (4 puffs of 84 [micro] g) to accomplish more. Flovent costs approximately $1.70 per day, while an equivalent dose of beclomethasone costs $4.15 per day. Fewer puffs will likely lead to greater compliance. Cheaper, more effective, and easier to use -- fluticasone is the better inhaled steroid for persistent asthma.

Stephen A. Wilson, MD University of Pittsburgh Medical Center St. Margaret Memorial Hospital Pennsylvania E-mail: Skwils@aol.com