Single-inhaler asthma therapy reduces exacerbation frequency, severity
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Key takeaways:
- Global Initiative for Asthma (GINA) guidelines recommend single maintenance and reliever therapy (SMART) for steps 3, 4 and 5 of treatment.
- Compared with standard therapy, SMART reduced asthma exacerbations and prolonged time to first exacerbation in multiple trials.
- Also compared with standard therapy, SMART was not inferior in improving daily asthma symptoms and quality of life.
Single maintenance and reliever therapy, also known as SMART or single-inhaler therapy, significantly reduces asthma exacerbation frequency and severity, according to a review published in Annals of Allergy, Asthma & Immunology.
However, the studies included in this review were not unanimous in these findings, John Oppenheimer, MD, clinical professor in the division of allergy/immunology, rheumatology and pulmonology, department of medicine, Rutgers New Jersey Medical School, and colleagues wrote in the review.
By combining inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) in a single device, SMART is designed to improve adherence to therapy for asthma management. GINA and National Heart, Lung, and Blood Institute recommend its use for both maintenance and reliever therapy.
“Clinicians are beginning to adopt this approach,” Oppenheimer, who also is an allergist at Pulmonary and Allergy Associates NJ and a Healio Allergy/Asthma Peer Perspective Board Member, told Healio.
“As noted from prior research, when patients are faced with an asthma exacerbation, most taper or discontinue their controller therapy and escalate their reliever meds. Studies have demonstrated that escalation of ICS can be helpful in averting further lack of control. By marrying the ICS with their rescue therapy, further exacerbation can be reduced,” he said.
The authors reviewed four controlled trials, two open-label studies, an observational study, a systemic review and two studies they categorized as “negative.”
Results of the controlled trials
In the first controlled trial of patients with asthma aged 16 years and older, those in a SMART maintenance and reliever group using SMART experienced significantly longer times to first exacerbation than patients receiving standard care (P = .0007). The SMART group also had a 30% reduced risk for severe exacerbations (HR = 0.7; 95% CI, 0.57-0.85), among other positive results.
A second controlled trial of patients with asthma aged 12 years and older also found a prolonged time to first exacerbation among a group using SMART compared with a fixed-dose group. Additionally, the patients using SMART had 28% to 39% fewer flareups compared with the fixed-dose group.
In the third controlled trial, involving patients aged 4 to 80 years, participants using SMART experienced significantly longer times to first exacerbation compared with other therapies (P < .001) with a 45% to 47% reduced risk for severe asthma exacerbation. The SMART group had improved daily daytime asthma and other symptoms as well.
With patients aged 12 years and older, the fourth controlled trial also found prolonged time to first severe exacerbation with SMART compared with two other approaches. The trial further found a 27% risk reduction for severe exacerbation compared with formoterol and a 45% reduction compared with terbutaline.
Additional positive findings
In the first open-label study, involving patients aged 16 to 65 years, patients using SMART had significantly fewer “high-use” days (P = .01) and severe exacerbations (P = .004) as well as longer time to first exacerbation (P = .008) than a group on standard care. However, the groups did have similar likelihoods for seeking medical attention after a high-use episode.
The second open-label study, with patients aged 12 years and older, also found prolonged time to first severe exacerbation with SMART and a 25% (95% CI, 7%-39%) lower risk for severe exacerbation compared with an approach using two different. The SMART group additionally experienced reductions in days with exacerbations, oral corticosteroid use, hospital visits and other benefits.
Patients in a SMART group in the multicenter observation study had significantly improved asthma control questionnaire scores compared with a standard therapy group (P = .027) along with more patients reporting well-controlled asthma (56.1% vs. 43.6%; P = .004) and a lower mean daily ICS dose (563.3 ± 1.3 µg per day vs. 1,013.8 ± 1.4 µg per day; P < .001).
Finally, the authors cited a systemic review that found patients with poorly controlled asthma at step 3 of the GINA treatment guidelines would have less risk and longer times to first severe exacerbation with a combination of budesonide and formoterol at step 3 or 4 compared with fixed doses with an ICS-LABA controller and short-acting beta-agonist (SABA) reliever at step 4 of the guidelines.
Results of the negative studies
In the first of the two studies the authors classified as negative, researchers found no significant extension of the time to first exacerbation in a group of patients using SMART compared with a group on standard care, nor any significant difference in asthma control days and other measures. However, the SMART users did experience a 21% reduction in annual exacerbation rates and a 31% reduction in annual hospitalizations and ED visits.
The second negative study, which comprised patients aged 12 years and older, reported exacerbation rates of 2.7% in a group using SMART and 4.1% in a group using conventional best practices, which the authors called similar. These groups also had no statistically significant differences in time to first severe exacerbation or differences in other measures such as overall mean as needed rescue inhalation use.
Conclusions
The findings of these studies indicate SMART’s value in reducing asthma exacerbations and improving asthma control with lower doses of ICS compared with fixed doses of ICS-LABA for maintenance or higher doses of ICS, both with SABA as needed, while potentially decreasing requirements for oral corticosteroids as well.
“The review stresses a very robust literature regarding the utility of the SMART approach,” Oppenheimer said. “Some of the practical impediments of SMART are reinforced, including the fact that insurers have not yet adopted this approach in their pharmacy benefits. As an example, docs continue to get letters noting overuse of combination therapy in those using SMART.”
Also, the use of multiple inhalers has been associated with poor adherence, increased exacerbations and asthma that is difficult to control, the researchers said. But the single inhaler used in SMART, the authors continued, possibly improves adherence and provides increased doses of ICS to prevent inflammation from getting worse.
By continuing the implementation of this approach in treating patients with asthma, Oppenheimer said, doctors can improve the care they provide.
But despite these positive findings, the researchers cautioned that conclusions were not unanimous. Also, pharmaceutical companies provide funding for these trials, prompting the authors to call for further research by other organizations to consolidate SMART’s efficacy. The authors further cited a need for insurance companies to discuss policy changes to help patients better comply with SMART recommendations.
For more information:
John Oppenheimer, MD, can be reached at nallopp22@gmail.com.
Perspective
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Andrew M. Namen, MD, FCCP, FAASM
This review supports the knowledge that SMART for asthma care provides better outcomes than the traditional ICS and rescue inhaler approach.
It is significant because it represents a cultural shift away from a multi-inhaler approach using ICS and SABA to a single-inhaler approach as well as increased use of ICS/LABA during times of worsening symptoms.
Safety with additional ICS/LABA use (as opposed to standard dosing) during increased asthma symptoms was as safe as escalating SABA use, which is a reversal of a previous concept where increased ICS/LABA use was associated with increased adverse events.
These findings also are consistent with my experience, including the effect of reduced asthma exacerbations, longer time to next exacerbation and reduced hospitalizations, typically defined in the RCTs included in this review as use of oral systemic steroids for three days, hospitalizations or ER visits. The improved asthma control and symptoms are consistent with my experience as well and support SMART as the preferred approach for step 3 and 4 asthma care.
However, this model has been difficult to sustain in practice. Insurers only allow one inhaler per month, and asthmatics who use the SMART approach would run out before their next prescription.
Overall, these findings should reassure providers that when coupled with ICS, additional LABA use is safe among patients who use the SMART approach. Future research should be designed to incentivize insurers to ensure the availability of multiple ICS/LABA inhalers in a single month for patients who practice SMART.
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