SMART (Single inhaler Maintenance and Reliever Therapy) is a relatively new approach to asthma treatment, focusing exclusively on combination inhalers that contain an inhaled corticosteroid (ICS) and formoterol, a rapid-acting LABA.
This approach is supported in the Global Initiative for Asthma (GINA) guideline, which is updated yearly (and first incorporated SMART into their recommendations in 2006!), and also integrated into the National Asthma Education and Prevention Program’s (NAEPP) 2020 Focused Updates to the Asthma Management Guidelines.
In general, recommendations are divided into 2 groups: 1) adults and adolescents ≥12yo, and 2) children (GINA focuses on children aged 6-11yo while NAEPP says 4-11yo).
Adults & Adolescents
In adults and adolescents, use of as-needed combination low-dose ICS-formoterol for symptom relief (without maintenance treatment) has been shown to reduce the risk of severe asthma exacerbations requiring oral corticosteroids or requiring ED visit or hospitalization by 65% compared with SABA-only treatment, and reduce the risk of needing an ED visit or hospitalization by 37% compared with daily ICS plus as-needed SABA.
Multiple studies (e.g., JAMA 2018, Cochrane Review 2013) have shown that SMART with ICS-formoterol reduce the risk of severe exacerbations compared with the same or higher dose of ICS or ICS-LABA, with similar symptom control.
Per the above 2018 JAMA meta-analysis, the following figure shows the association of SMART with exacerbations requiring systemic corticosteroids, hospitalization, or ED visits among patients aged 12 years or older versus the same dose of inhaled corticosteroids and LABA controller therapy:
Similarly, again per the same JAMA meta-analysis, the following figure shows the association of SMART with exacerbations requiring systemic corticosteroids, hospitalization, or ED visits among patients aged 12 years or older versus a higher dose of inhaled corticosteroids and LABA controller therapy:
Based on the above evidence, GINA recommends SMART as the preferred approach to initial treatment of asthma in adults and adolescents (12 years of age and older).
In adults and adolescents, the above evidence studied budesonide-formoterol at a dose of 200/6 mcg (160/4.5 mcg delivered dose) by dry powder inhaler, a formulation that is not on the US market (see more details below). The maximum total recommended dose of budesonide-formoterol in a single day for adults and adolescents is 12 inhalations [total 72 mcg formoterol (54 mcg delivered dose)].
Children
Recommendations are limited for the use of ICS-formoterol in children owing simply to less available data. For instance, per GINA’s 2023 guideline, there have been no studies of as-needed ICS-formoterol in children aged 6-11 years.
Nevertheless, ICS-formoterol remains one of 3 preferred options for Step 3 treatment in children per GINA’s stepwise treatment approach. This recommendation is largely based on a single study of SMART with very low-dose budesonide-formoterol showed a large reduction in exacerbations, compared with the same dose of budesonide-formoterol plus SABA reliever, or compared with higher dose ICS. Additional evidence showed that another ICS-LABA, fluticasone-salmeterol, was non-inferior to ICS alone for severe exacerbations, with no difference in symptom control or reliever use.
Per GINA’s recommendation, the recommended dose of budesonide-formoterol in children <12yo is 100/6 mcg metered dose (80/4.5 delivered dose) by dry powder inhaler, which again is a formulation not currently on the US market (see more details below). The maximum total recommended dose of budesonide-formoterol in a single day for children <12yo is 8 inhalations [total 48 mcg formoterol (36 mcg delivered dose)].
Similar to GINA, the NAEPP’s 2020 update also comments on the relative lack of data for children under 12yo. Nevertheless, for 4-11yo patients with moderate to severe persistent asthma, citing similar evidence to that discussed above, the NAEPP’s Expert Panel recommends ICS-formoterol in a single inhaler used as both daily controller and reliever therapy compared to either a higher-dose ICS as daily controller therapy and SABA for quick-relief therapy or the same-dose ICS-LABA as daily controller therapy and SABA for quick-relief therapy (Strong recommendation, high certainty of evidence for ages 12 years and above, moderate certainty of evidence for ages 4 to 11 years).
SMART in the USA
Despite the above evidence and guidelines favoring the use of SMART, there has been little uptake thus far in the USA. Several barriers may be at play:
- Provider awareness and understanding of SMART may be lacking
- ICS-formoterol combinations on the US market (budesonide-formoterol and mometasone-formoterol) lack FDA approval for use as SMART, and no study has specifically evaluated mometasone-formoterol as SMART
- The majority of evidence supporting SMART evaluated budesonide-formoterol as a dry powder inhaler (DPI), but only the pressurized metered-dose inhaler (pMDI) is available on the US market; however the two forms are thought to be therapeutically equivalent
- Potential cost of SMART, particularly given the variability in insurance coverage