By Will Boggs MD
NEW YORK (Reuters Health) - 11/9/2019
As-needed use of a budesonide-formoterol inhaler is more effective than maintenance budesonide plus terbutaline reliever therapy for reducing severe exacerbations in adults with mild to moderate asthma, according to results from the randomized PRACTICAL trial.
"These findings suggest that budesonide-formoterol reliever therapy is not only an alternative regimen to daily maintenance inhaled corticosteroids plus a short-acting beta2-agonist in adults with mild to moderate asthma, as recommended in the recent international (GINA) guidelines, but may be the preferred option for prevention of severe exacerbations in this population," Dr. Richard Beasley of the Medical Research Institute of New Zealand, in Wellington, told Reuters Health by email.
People whose asthma symptoms are intermittent or mild are often poorly adherent to regular maintenance regimens, and this can contribute to exacerbations.
Dr. Beasley and colleagues from 15 sites across New Zealand tested as-needed budesonide-formoterol reliever therapy versus maintenance budesonide plus as-needed terbutaline in an open-label clinical trial of 885 adults with mild-to-moderate asthma.
At study entry, 12% of patients reported having had a severe exacerbation in the previous 12 months.
The annual rate of severe asthma exacerbations, the primary endpoint, was significantly lower with as-needed budesonide-formoterol than with budesonide maintenance plus as-needed terbutaline therapy (0.119 vs. 0.172 per patient per year; P=0.049), the researchers report in The Lancet, online August 23.
The combined moderate and severe asthma-exacerbation rate was also significantly lower with as-needed budesonide-formoterol than with budesonide maintenance plus as-needed terbutaline (0.165 vs. 0.237 per patient per year; P=0.024).
The times to first severe exacerbation and first moderate or severe exacerbation were longer with as-needed therapy than with maintenance therapy.
Asthma Control Questionnaire (ACQ)-5 scores and FEV1 did not differ between the treatment groups across all time points.
Mean adherence with twice-daily maintenance budesonide was 76%, and the mean daily dose of budesonide was 126.5 ug lower with as-needed therapy than with maintenance therapy.
Similar proportions of participants in the as-needed group (88%) and maintenance group (83%) experienced at least one adverse event.
"The greater benefit with this regimen is likely to be due to the titration of the inhaled corticosteroid through the vehicle of co-administered bronchodilator taken as-needed to relieve symptoms," Dr. Beasley said. "In this way, the symptom-driven increase in the dose of inhaled corticosteroid in worsening asthma has the potential to lead to the resolution of the exacerbation before it becomes severe enough for the patient to seek medical review."
Dr. Sally E. Wenzel of the University of Pittsburgh Graduate School of Public Health, in Pennsylvania, who co-authored an accompanying editorial, told Reuters Health by email that physicians "should move treatment of mild asthma into a paradigm that is, in fact, already followed by many patients, prn albuterol/salbutamol, but adding the prn controller as well. This approach, just with a different drug, is likely the way many if not most milder asthma patients treat themselves."
Physicians "have options for the care of milder asthma patients beyond daily inhaled corticosteroid therapy, which also gets away from having to address adherence to meds every time a patient is seen - something that likely makes patients somewhat uncomfortable in the first place," she said.
"There are patients who are too severe/poorly controlled with this type of approach," Dr. Wenzel said. "If patients have 2 exacerbations per year, they are likely not candidates for this approach."
"A better understanding of the biology behind frequently exacerbating asthma (including biomarkers) might help to identify which patients are most likely to benefit or which warrant maintenance therapy," the editorial concludes.
The trial did not have commercial funding. Several authors of the study and both authors of the editorial reported ties to AstraZeneca, which manufactures both of the medicines used.
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