Ingrid Hein

November 01, 2017

TORONTO — For patients with uncontrolled asthma, the more exacerbations they experience, the more responsive they are to dupilumab, according to an ad hoc analysis of data from a phase 2b trial.

"If we look strictly at the real effect of dupilumab, we see a higher magnification of benefit in patients with a higher exacerbation rate in the previous year," said Jonathan Corren, MD, from the UCLA David Geffen School of Medicine in Los Angeles.

Dupilumab, a human monoclonal antibody that inhibits the actions of both interleukin (IL)-4 and IL-13, was shown to reduce asthma exacerbations in patients with moderate to severe asthma and elevated eosinophil levels in a placebo-controlled phase 2a study (Lancet. 2016;388:31-44).

And in a 24-week phase 2b study of dupilumab in patients with uncontrolled asthma who were using medium- or high-dose inhaled corticosteroids and a long-acting beta agonist, the drug was shown to be effective in patients with eosinophil counts above 300 cells/µL and below 300 cells/µL, as reported by Medscape Medical News.

In their analysis of the data, Dr Corren and his colleagues assessed the effectiveness of dupilumab in patients with severe asthma.

"When using a new drug, there's always a question of whether or not it will be effective in the patients who need it most," Dr Corren explained here at CHEST 2017.

All patients enrolled in the phase 2b study had experienced at least one exacerbation in the previous year. They were randomized to dupilumab 200 mg, dupilumab 300 mg, or placebo every two weeks.

In the intention-to-treat population, 465 patients had experienced at least one exacerbation, 227 had experienced at least two, 122 had had experienced at least three, and 62 had experienced at least four.

When the study participants were stratified by history of exacerbation frequency, the researchers found the higher the exacerbation rate before treatment, the higher it was afterward.

"This shows that there's a phenotype of asthma severity that seems to be stable over a 2-year period," Dr Corren explained. "This is an observation that's important."

However, the benefit of dupilumab was greatest in patients who experienced the most exacerbations before treatment.

Table. Adjusted Annualized Severe Exacerbation Event Rate

Exacerbations Dupilumab 200 mg Group Dupilumab 300 mg Group Placebo Group
≥4 0.338 0.297 1.67
≥3 0.628 0.421 1.382
≥2 0.321 0.320 0.938
≥1 0.269 0.265 0.897


"What it means is that the more exacerbations a patient had historically, the better we can expect this IL-4 and IL-13 inhibitor to improve their asthma," said Dr Corren. Overall, the reduction in exacerbations was 70% higher in the dupilumab groups than in the placebo group.

In addition, lung function — as indicated by FEV₁ scores, Asthma Control Questionnaire (ACQ) scores, and patient-reported Asthma Quality of Life Questionnaire (AQLQ) scores — improved in all patients in the dupilumab groups, regardless of previous exacerbations.

We all know it's going to work, but how we target it is the most important factor.

The study results were received with excitement in the packed house, but many audience members said they are waiting for data from the phase 3 trial.

"This is impressive. It shows that no matter how severe the asthma is, even if you're having exacerbations six times a year, it's still going to be a helpful drug," said Drew Harris, MD, from the University of Virginia in Charlottesville.

"It's really an exciting new therapy," he told Medscape Medical News. However, he pointed out, there is still no biomarker to accurately determine which patients would benefit most.

"We all know it's going to work, but how we target it is the most important factor," he explained. "We're looking forward to seeing the results from the phase 3 trials to find out."

Dr Corren reports receiving grant funding from Sanofi. Dr Harris has disclosed no relevant financial relationships.

CHEST 2017: American College of Chest Physicians Annual Meeting. Presented October 30, 2017.

Follow Medscape on Twitter @Medscape and Ingrid Hein @ingridhein


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