Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA)

Objective To examine the benefits of adding salmeterol compared with increasing dose of inhaled corticosteroids. Design Systematic review of randomised, double blind clinical trials. Independent data extraction and validation with summary data from study reports and manuscripts. Fixed and random effects analyses. Setting EMBASE, Medline, and GlaxoWellcome internal clinical study registers. Main outcome measures Efficacy and exacerbations. Results Among 2055 trials of treatment with salmeterol, there were nine parallel group trials of greater than or equal to 12 weeks with 3685 symptomatic patients aged greater than or equal to 12 years taking inhaled steroid in primary or secondary care. Compared with response to increased steroids: in patients receiving salmeterol morning peak expiratory flow was greater at thr ee months (difference 22.4 (95% confidence interval 15.0 to 30.0) litre/min. P< 0.001) and six months (27.7 (19.0 to 36.4) litre/min, P< 0.001). Forced expiratory volume in one second (FEV1,) was also increased at three months (0.10 (0.04 to 0.16) litres, P < 0.001) and six months (0.08 (0.02 to 0.14) litres, P <0.01) as were mean percentage of days and nights without symptoms (three months: days-12% (9% to 15%), nights-5% (3% to 7%); six months: days-15%(12% to 18%), nights-5% (3% to 7%); all P < 0.001) and mean percentage of days and nights without need for rescue treatment (three months: days-17% (14% to 20%), nights-9% (7% to 11%); six months: days-20% (17 to 23%), nights-8% (6% to 11%); all P< 0.001). Fewer patients experienced any exacerbation with salmeterol (difference 2.73% (0.43% to 5.04%), P = 0.02), and the proportion of patients with moderate or severe exacerbations was also lower (2.42% (0.24% to 4.60%), P = 0.03. Conclusions Addition of salmeterol in symptomatic patients aged 12 and over on low to moderate doses of inhaled steroid gives improved lung function and increased number of days aid nights without symptoms or need for rescue treatment with no increase in exacerbations of any severity.