MADRID – In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.
This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to, a research fellow at the Medical Research Institute of New Zealand, Wellington.
Currently, theguidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.
In, the results of which were published just prior to the 2019 ERS Congress ( ), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.
For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.
The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV1) at any visit or at the end of the study.
Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in thein 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.
In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.
“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.
In the open-label Novel START trial, published in 2019 in the, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.
At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.
“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.
In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.
“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.
Dr. Hardy reports no potential conflicts of interest.