Evaluation of Budesonide-Formoterol for Maintenance and Reliever Therapy Among Patients With Poorly Controlled Asthma A Systematic Review and Meta-analysis

IMPORTANCE The Global Initiative for Asthma (GINA) recommends 2 alternative treatments for patients receiving treatment at steps 3 to 5: single inhaler combination inhaled corticosteroid-formoterol as both maintenance and reliever (SMART) or inhaled corticosteroid-long-acting beta(2)-agonist as maintenance plus short-acting beta(2)-agonist as reliever. OBJECTIVE To assess whether switching to SMART is associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA treatment step with maintenance inhaled corticosteroid-long-acting beta(2)-agonist plus short-acting beta(2)-agonist reliever among patients with poorly controlled asthma. DATA SOURCES For this systematic review and meta-analysis, the literature, internal study databases at AstraZeneca and the Medical Research Institute of New Zealand, and references from a previous systematic review and meta-analysis on SMART were searched to identify randomized clinical trials published from January 1990 to February 2018, that compared budesonide-formoterol by SMART with maintenance inhaled corticosteroid-long-acting beta(2)-agonist plus short-acting beta(2)-agonist reliever. STUDY SELECTION Trials of at least 24 weeks' duration were included if they reported baseline data on GINA treatment step, asthma control status, and efficacy measures of severe exacerbations. Included patients were adults and adolescents with asthma and baseline Asthma Control Questionnaire 5-item version scores of 1.5 or higher. DATA EXTRACTION AND SYNTHESIS Patient-level data were identified by independent extraction, and analyses were performed using a fixed-effect model. Data analysis was performed from August 2018 to November 2021. MAIN OUTCOMES AND MEASURES The primary outcome was time to first severe asthma exacerbation associated with each treatment, analyzed by Cox proportional hazards regression. RESULTS Overall, 4863 patients were included (3034 [62.4%] female; mean [SD] age, 39.8 [16.3] years). Switching patients with uncontrolled asthma at GINA step 3 (n = 1950) to SMART at either step 3 or 4 was associated with a prolonged time to first severe asthma exacerbation, with a 29% reduced risk compared with stepping up to step 4 inhaled corticosteroid-long-acting beta(2)-agonist maintenance plus short-acting beta(2)-agonist reliever (hazard ratio, 0.71; 95% CI, 0.52-0.97). For patients with uncontrolled asthma at step 3 and step 4 (n = 2913), switching to SMART was associated with a prolonged time to first severe asthma exacerbation and a 30% reduced risk compared with remaining at the same treatment step (hazard ratio, 0.70; 95% CI, 0.58-0.85). CONCLUSIONS AND RELEVANCE In this systematic review and meta-analysis, for patients with poorly controlled asthma, SMART was associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA step with maintenance inhaled corticosteroid-long-acting beta(2)-agonist plus short-acting beta(2)-agonist reliever. These findings suggest that if an adult or adolescent receiving treatment at GINA step 3 or 4 has poorly controlled asthma, it is preferable to switch to the SMART regimen rather than to step up or continue the GINA treatment step with maintenance inhaled corticosteroid-long-acting beta(2)-agonist plus short-acting beta(2)-agonist reliever therapy.

Automated summary

This study found that switching to SMART treatment was associated with a longer time to the first severe asthma exacerbation for patients with poorly controlled asthma. Compared to escalating or continuing GINA treatment with inhaled corticosteroid-long-acting beta(2)-agonist plus short-acting beta(2)-agonist reliever, the SMART regimen was preferred.