Increasing Inhaled Steroids Curbs Asthma in Adults

Maria Turner

March 16, 2018

For adults and adolescents with asthma being treated with inhaled glucocorticoids, with or without add-on therapy, the temporary quadrupling of the dose at the first sign of asthma control deterioration reduces the incidence of severe exacerbations by 19%, according to results from a new study.

Although the hoped-for 30% reduction was not reached, "in terms of the total number of exacerbations prevented, we actually probably saw a bigger effect," said investigator Timothy Harrison, MD, from the University of Nottingham in the United Kingdom.

"We were expecting an exacerbation rate of somewhere between 13% and 20%" in the control group, he told Medscape Medical News, "but in actual fact, we saw an exacerbation rate of approximately 50%."

In their open-label, randomized study — which was published online March 3 in the New England Journal of Medicine — Harrison and his colleagues recruited 1922 participants 16 years and older with a clinical diagnosis of asthma who experienced at least one asthma exacerbation in the previous year that was treated with systemic glucocorticoids. Mean age in the cohort was 57 years, 81% of the patients were recruited from primary care, and 68% were female.

 

The patients were randomized to one of two self-management plans: 965 were instructed to quadruple their dose of inhaled glucocorticoids at the first sign of asthma deterioration; and the 957 patients who were not served as the control group.

The primary outcome was time to the first severe exacerbation, indicated by treatment with systemic glucocorticoids or an unscheduled visit to a healthcare provider.

The primary analysis involved 938 patients in the quadruple group and 933 in the control group. Fewer patients in the quadruple group than in the control group reported a severe exacerbation in the year after randomization (45% vs 52%; adjusted hazard ratio for time to first exacerbation, 0.81; P = .002). In addition, fewer patients in the quadruple group required hospitalization because of an exacerbation, which was the most serious adverse event reported (3 vs 18).

On the basis of these results, Harrison said he would "definitely recommend" the quadruple-dose strategy for patients on low to moderate doses of inhaled glucocorticoids as part of their maintenance plan.

Recommend Increase for Patients on Low to Moderate Dose

"We have nothing else," Harrison told Medscape Medical News. "If we say, don't follow this, we're basically saying, wait until you get bad enough to need oral prednisolone."

In terms of benefits and safety, patients already on high doses of inhaled steroids do not necessarily have a lot to gain by increasing doses of inhaled steroids instead of switching to an oral steroid, However, Harrison pointed out, "data on the systemic effects of oral and inhaled steroids are not good," so we had to make a lot of assumptions.

He also pointed out that in real life, many patients don't take their inhaled steroids regularly. This could mean that patients adhering to this strategy are actually restarting their glucocorticoids at the quadruple dose.

The degree of benefit is debatable.

Not everyone agrees that the study results are solid enough to support the strategy in adults.

"The degree of benefit is debatable," Philip Bardin, PhD, from the Hudson Institute of Medical Research at Monash University and Medical Centre in Melbourne, Australia, writes in an accompanying editorial.

He calls the findings into question, particularly because a similar trial presented at the American Academy of Allergy, Asthma and Immunology and World Allergy Organization 2018 Joint Congress in Orlando showed that increasing the dose of inhaled steroids in children was not beneficial, as reported by Medscape Medical News.

Findings from the randomized, double-blind children's study mean that the case "is pretty much open and shut," said Bardin. "It's pretty clear that escalating glucocorticoids does not work."

In contrast, the adult study is not a "truly randomized controlled trial. The study was done in the community and the treatment wasn't blinded," he explained. It tried to mirror real life, which is both its strength and its weakness.

This does not make it less valid, he explained, but it does mean the results have to be taken with more caveats.

"Obviously, there is a potential for bias in an open-label study," Harrison acknowledged. However, he pointed out, in clinical practice, patients and physicians are not blinded, so the placebo effect is at work there, too.

And, he asked, "if the whole thing was a placebo effect, how would we have seen a difference in hospital admissions?"

Different Results in Children and Adults

The fact that the results were different in adults and children does not surprise Eric Macy, MD, from the Kaiser Permanente San Diego Medical Center.

"Adults are different than kids," he told Medscape Medical News. And the diminished growth trend seen in children on higher doses of inhaled steroids will not be a concern in adults.

For adults, the quadruple dose "might be a good thing," he said. "They basically avoided some emergency room visits and there was less systemic exposure to steroids."

Macy said he agrees with Harrison that higher doses of inhaled steroids might not be much different than oral prednisone, in terms of exposure.

"It's a very nice piece of work," he said of the adult study. "It's really nice to have these studies done in the community, and I have nothing but praise for the researchers who pulled this off."

Daniel Jackson, MD, from the University of Wisconsin School of Medicine and Public Health in Madison, who was involved with the children's study, said he agrees with Bardin that the lack of blinding in the study makes it difficult to be certain of the findings.

But "ultimately, both studies tell us that exacerbations are still occurring despite these strategies, so we need to develop new predictors of exacerbations in order to prevent them, he told Medscape Medical News.

Harrison reports financial relationships with AstraZeneca, GSK, and Vectura. Bardin reports financial relationships with GSK. Macy has disclosed no relevant financial relationships. Jackson reports financial relationships with Boehringer Ingelheim and Merck.

American Academy of Allergy, Asthma and Immunology (AAAAI) and World Allergy Organization (WAO) 2018 Joint Congress. Presented March 3, 2018.

Follow Medscape on Twitter @Medscape and Maria Turner @mednewseditorturner

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