Combined maintenance and rescue therapy in one inhaler appears effective in moderate to severe asthma

Combining maintenance and rescue therapy in one inhaler appears to be effective in patients with uncontrolled asthma, according to two new studies published last week in Lancet Respiratory Medicine. Both studies looked at different Single Maintenance and Reliever Therapy (SMART) regimens that combined a single inhaled corticosteroid with a long-acting β₂ agonist. This therapy has been approved in other countries but is not currently approved in the United States.

The first study, an industry-funded double-blind, randomized, controlled trial, randomly assigned 1,714 patients to receive beclometasone-formoterol as needed (n=857) or salbutamol as needed (n=859) in addition to maintenance therapy with beclometasone-formoterol. All patients underwent a two-week run-in period during which they received beclometasone and formoterol in one daily inhalation plus salbutamol via a pressurized metered-dose inhaler as required. Eight hundred fifty-two patients in the beclometasone-formoterol group and 849 in the salbutamol group were analyzed. The study's primary outcome was time to first severe exacerbation, defined as hospital admission or emergency department visit or systemic steroid use for at least three consecutive days.

Two hundred fifty-one patients reported 326 severe exacerbations during the 48-week study period. Patients who received beclometasone-formoterol for maintenance and rescue therapy had significantly greater time to the first exacerbation (209 days vs. 134 days) and a risk reduction of 36% (hazard ratio, 0.64; 95% CI, 0.49 to 0.82; P<0.0005) compared with the other group. The beclometasone-formoterol group also had fewer days with mild asthma exacerbations. Both therapies were well tolerated and few patients experienced serious adverse events.

“Our findings further support the notion of a single inhaled corticosteroid and a rapid-onset, long-acting β₂ agonist combination for maintenance and relief in patients with moderate to severe asthma,” the authors concluded.

The second trial looked at the efficacy and safety of SMART with budesonide-formoterol over 24 weeks in patients at risk for severe asthma. Patients were randomly assigned to receive budesonide-formoterol (n=151) or a standard fixed-dose regimen of budesonide-formoterol plus salbutamol (n=152). The primary outcome measure was the proportion of patients in each group who had at least one high-use β-agonist episode.

Overall, the two groups did not differ significantly in the primary outcome (56% vs. 45%, respectively; relative risk, 1.24; 95% CI, 0.99 to 1.56; P=0.058). However, patients in the SMART group had fewer days of high use (mean, 5.1 days vs. 8.9 days; P=0.01) and fewer severe asthma exacerbations (35 vs. 66; P=0.004). The authors concluded that SMART “has a favourable risk-to-benefit profile compared with standard maintenance treatment and can be recommended for use in adults at risk for severe asthma.”

The author of an accompanying commentary noted that although SMART has been considered controversial, these two studies provide convincing additional evidence to support its use. However, he cautioned that more research is needed because it is unclear which patients would benefit from each type of asthma treatment.