Standard teaching of health care professionals for decades in the United States has been that those individuals who have more than rare instances of asthma need one medicine to use daily to prevent symptoms and a second medicine in the form of a bronchodilator inhaler to be available to stop, or rescue from, symptoms. The daily medicine to use routinely has been either an inhaled steroid since the early 1990s, or the class of medication to which Singulair (a.k.a. Montelukast) belongs since the late 1990s. The bronchodilator inhaler starts to work in approximately 5 to 10 minutes but only affects the smooth muscle for about 4 to 6 hours to stop the narrowing of the lung’s airways.
In 2001, the inhaled steroid became available in the same cannister with a bronchodilator inhaler that could work for approximately 12 hours. This would be prescribed for those with symptoms occurring more than a couple of days per week. However, the first of these combination inhalers was Advair (a.k.a ‘the purple disc’) which contained a bronchodilator inhaler called salmeterol that wouldn’t begin to affect the smooth muscle of the airways for at least 30 minutes, so it wasn’t safe to use to stop symptoms quickly.
Several years after Advair, another combination inhaler was approved in the United States in 2006 called Symbicort that contained a different bronchodilator called formoterol. This inhaler could both begin to work in 5-10 minutes, and continue to work for approximately 12 hours. However, Symbicort was approved here only to prevent asthma symptoms…not to reverse symptoms that had already started…because the clinical trials did not test how well Symbicort could stop symptoms that began abruptly.
However, absence of proof does not mean proof of absence. For more than the past 15 years, medical scientists and clinicians have proceeded to test the hypothesis that Symbicort should work to both prevent and stop asthma symptoms. They called the concept ‘single maintenance and reliever therapy or SMART. While there is also a second combination inhaler with formoterol called Dulera, the published clinical outcomes of SMART have focused on Symbicort.
The results of initial studies were mixed. A 2010 review article published in the journal Thorax analyzed the results of eight clinical trials using Symbicort with varying experimental designs. While there was an approximate 50% reduction in exacerbations, patients who used Symbicort as SMART, on average, (a) needed the reliever effect once per day, (b) awoke from sleep with asthma symptoms once every 7-10 days, (c) were only asthma-free on less than 50% of days and (d) had increased numbers of a white blood cell associated with inflammation from asthma called an eosinophil that were seen on biopsies of the airway walls.
Over the past 10 years, there has been increasing acceptance of SMART’s utility. A pivotal 2018 set of clinical studies—the SYGMA 1 and SYGMA 2 trials– published in the New England Journal of Medicine showed that the rate of severe exacerbations in adolescents and adults with mild asthma was reduced by 64% while using Symbicort as needed, compared with using only a bronchodilator as needed. The rates of exacerbation were the same with 17-25% less use of the inhaled steroid, by those using Symbicort as needed compared with those using a daily steroid inhaler. Two subsequent 2019 studies—the ‘Novel SMART’ study in the New England Journal and the ‘PRACTICAL’ study in the Lancet—provided similar findings.
For those adolescents and adults with moderately severe asthma, studies before and after 2010 that compared SMART with the same dose of Advair and a different as-needed rescue inhaler showed a 32% reduction in exacerbations and some significant improvement of aspects of daily asthma control in a couple of these studies. Compared with a daily higher dose of Advair plus the different as-needed rescue inhaler, daily plus rescue use of Symbicort led to a 25% reduction in severe exacerbations; however, there was no difference in control of daily symptoms.
If one wishes to use Symbicort ‘smartly’ for asthma control, one obstacle exists—insurers. Our FDA still has not approved Symbicort for both daily maintenance therapy and for rescue therapy. Yet, Canada, the United Kingdom and Australia all have approved Symbicort for those 12 years and older. A 2008 review of the medical literature published in the Journal of Medical Economics concluded that SMART reduces direct and indirect costs compared to fixed therapy with either Symbicort or Advair. A specific monetary amount was determined in a 2008 study published in the Canadian Journal of Clinical Pharmacology. The average Canadian cost per patient per 6 months from the health care perspective was $545 for those on SMART use of Symbicort, compared to $690 for those on fixed higher dose Symbicort with a different rescue inhaler and $842 for those on Advair with a different rescue inhaler.
A hopeful sign for insurer coverage in the near future is that asthma guidelines from the National Heart Lung and Blood Institute of NIH were updated in December 2020 for the first time since 2007. These guidelines include a new recommendation that SMART use of Symbicort, or Dulera, is appropriate for those age 5 and older with moderate to severe asthma. As we have learned over the past year, expert consensus is important for decisions in public health policy. Let’s hope that we all are open-minded and learn from the experiences of other similarly situated countries.