SMART Effective in Treatment of Moderate to Severe Asthma ? Quantitative Synthesis on Real-World Evidence
Introduction
The current Global Initiative for Asthma (GINA) recommendations are based on level A evidence originating from large randomized controlled trials (RCTs) and high-quality meta-analyses. Treatment of a significant proportion of asthmatic patients is done using protocols from data by RCTs for which they would not have been eligible. This discrepancy results in remarkable gaps in evidence between the selected cohorts in RCTs and non-selected asthmatic patients. The updated GINA guidelines prefer inhaled corticosteroid (ICS)/formoterol maintenance and reliever therapy (SMART) to maintenance ICS/long-acting ?-2 agonist (LABA) + as-needed short-acting ?-2 agonist (SABA) in the treatment of moderate to severe asthma.
Aim
This is a quantitative synthesis on real-world evidence comparing SMART and maintenance ICS/LABA + as-needed SABA in the treatment of moderate to severe asthma.
Method
Study Design
- Network meta-analysis of real-world observational and interventional studies that compared the efficacy and safety of SMART with ICS/LABA + as-needed SABA therapies in asthmatic patients.
- The effect estimates of the network meta-analysis were expressed as relative effect (RE) and 95% credible interval (95%CrI).
- Efficacy was ranked according to the surface under the cumulative ranking curve analysis (SUCRA).
- Quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS) and studies with NOS score >7 were considered of high quality and NOS score <6 were considered of low quality.
- Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence.
Endpoints
- Risk of severe exacerbations
- Changes from baseline in forced expiratory volume in 1 sec (FEV1)
- Asthma control questionnaire (ACQ) score
- Serious adverse events (SAEs)a
Results
- A total of 6 studies comprising 2 real-world observational studies and 4 interventional open-label randomized studies with 11,360 asthmatic patients were included for meta-analysis.
- The risk of severe asthma exacerbation was significantly reduced with SMART including an ICS at medium-dose (MD) than MD ICS/LABA FDC + as-needed SABA (RR 0.54; p < 0.001) and low-dose (LD) SMART (RR 0.82; p < 0.05).
- The risk of developing at least 1 AE was also significantly lower in patients treated with MD SMART as compared to MD ICS/LABA FDC +as-needed SABA (RR 0.57; p<0.001) and LD SMART (RR 0.82; p < 0.05).
- As per the SUCRA analysis, efficacy was ranked as follows:
- MD SMART > LD SMART > ICS + LABA free combination + as-needed SABA > ICS/LABA FDC + as-needed SABA > MD ICS/LABA FDC + as-needed SABA.
- There were no significant differences in changes in FEV1 across the treatment arms.
- The improvement in ACQ score was significantly more in MD ICS/LABA FDC + as-needed SABA (p < 0.05).
- There were no statistically significant differences in the risk of SAEs across the treatment arms; p>0.05.
Conclusions
- The results of this network meta-analysis of real-world evidence support the GINA recommendation that SMART should be considered as an ideal choice in the treatment of moderate to severe asthma, irrespective of the dose of ICS used in the formulation.
- SMART was associated with significant reduction in the risk of severe exacerbation in adults with moderate to severe asthma.
Respir Med. 2021 Nov;188; 106611.
