NEJM Journal Watch
David J. Amrol, MD
New studies show that inhaled steroids plus albuterol can be used as a rescue therapy for patients with moderate-to-severe asthma.
Use of intermittent inhaled corticosteroids (ICS) for asthma now is recommended widely, but its uptake in the U.S. has been slow. According to both international and U.S. guidelines, ICS/formoterol is recommended as both maintenance and reliever therapy (MART) in patients with moderate-to-severe asthma; the long-acting β-agonist (LABA) formoterol is suitable for both roles because it is both long-acting and has quick onset of action. Two studies published this year offer further support for using as-needed ICS for adolescents and adults with moderate-to-severe asthma — but both used albuterol plus ICS as the reliever combination.
In one trial, 3100 adolescents and adults with uncontrolled moderate-to-severe asthma received either budesonide/albuterol or albuterol alone as a rescue inhaler (while continuing their maintenance therapy with daily ICS or ICS/LABA). During 24 weeks, the budesonide/albuterol group had significantly fewer severe asthma exacerbations than did the albuterol-alone group (NEJM JW Gen Med Jul 1 2022 and N Engl J Med 2022; 386:2071).
In another trial, 1200 U.S. Black and Latinx adults — considered to be at high risk for fatal asthma exacerbations — were randomized to use inhaled beclomethasone or placebo every time they used their albuterol rescue inhaler; they also continued their daily maintenance inhalers. During 15 months, annualized rates of severe asthma exacerbations were significantly lower in the beclomethasone/albuterol group than the placebo group (NEJM JW Gen Med Apr 1 2022 and N Engl J Med 2022; 386:1505).
Despite patients’ and clinicians’ best intentions, most people with asthma do not use daily maintenance ICS consistently. These studies show that additional intermittent ICS — given every time a patient uses a β-agonist rescue inhaler and before a full-blown exacerbation becomes apparent — is beneficial. I recommend ICS/formoterol as a single maintenance and rescue inhaler for patients with moderate-to-severe asthma, in line with the Global Initiative for Asthma (GINA) and the U.S. National Asthma Education and Prevention Program (NAEPP) guidelines; however, this is not always a viable option, as generic budesonide/formoterol costs US$200 to $300 per canister. (Note: In the U.S., formoterol is available in combination with budesonide or mometasone.) Based on these 2022 studies, a good second choice is 2 to 4 puffs of albuterol followed by 80 to 250 µg of beclomethasone equivalent every 4 hours as needed for asthma symptoms (in addition to a baseline controller). Unfortunately, this requires two inhalers in the U.S., but clinical trials are underway for combined ICS/albuterol products.