Researchers Rethink "SMART" Regimen for Asthma

Diana Sobieraj, PharmD

A recent meta-analysis found 1 inhaler product can serve as a single maintenance and reliever therapy (SMART) with lower risk of asthma exacerbation than different regimens for symptom control and acute symptom relief.

Diana Sobieraj, PharmD, Department of Pharmacy Practice, University of Connecticut School of Pharmacy, and colleagues conducted a systematic review and meta-analysis of trials to compare SMART to the more commonly used regimens of inhaled corticosteroid (ICS) with or without long-acting beta-agonist (LABA) to control symptoms, and higher dose ICS with or without LABA or a short-acting beta-agonist (SABA) to relieve acute symptoms.

Researchers were working with the hypothesis the combined use of inhaled corticosteroid and formoterol in lieu of SABAs would provide quick symptom relief while delivering steroid sooner during the course of symptom deterioration. This would thereby help with “effectively managing asthma symptoms and reducing exacerbation risk,” they wrote.

The investigators identified 16 randomized controlled trials of SMART involving 22,748 patients, 15 of which evaluated a budesonide/formoterol combination dry-powder inhaler (Symbicort) which is a different formulation than the metered-dose inhaler available in the US.

The trials assessed at least 1 of the following outcomes: asthma exacerbation (reflected in such requirements as systemic corticosteroid, emergency department visits or hospitalization); all-cause or asthma-specific mortality; reduced pulmonary function (determined my such measures as spirometry or forced expiratory volume in one second [FEV₁] ); and worsened asthma-related quality of life (quantified with either the Asthma Control Test or the Asthma Control Questionnaire).

Sobieraj and colleagues reported that, in patients aged 12 years or older (n = 22,524, mean age 42 years, 65% female), SMART was associated with a reduced risk of asthma exacerbation compared with the same ICS dose (Risk Ratio = 0.68) or higher ICS dose (RR 0.77) with LABA as control therapy. Results were similar for ICS without LABA for symptom control.

SMART was associated with reduced RRs regardless of the comparator, researchers wrote. They noted that the efficacy associated with SMART was primarily based on a composite outcome including asthma exacerbations requiring systemic corticosteroids,

ER visits or hospitalization.

"Although it is recommended that trials report the individual components of a composite outcome, this was rarely done," researchers wrote.

In an editorial accompanying the meta-analysis, Jerry Krishnan, MD, PhD, Division of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois; and David Au, MD, MS, Health Services Research and Development Service, Veterans Affairs Puget Sound Health Care System, noted that since the dry-powder inhaler has not been approved by the FDA, "the applicability to a US population of SMART studies based on the use of a dry-powder is less clear."

Although they agreed that the favorable findings with SMART compared to scheduled doses of ICS and LABA could be attributed to the faster onset of action from formoterol, Krishnan and Au also considered the possibility that there may be benefit from the specific inhaler device.

"Dry-powder and metered-dose inhaler devices require different techniques that could contribute to different types of errors in inhaler use, difference in drug deposition in the airways, and different clinical outcomes," Krishnan and Au wrote.

The study, "Association of Inhaled Corticosteroids and Long-Acting β-Agonists as Controller and Quick Relief Therapy With Exacerbations and Symptom Control in Persistent Asthma," was published online in JAMA last month.