Dupilumab leads to sustained improvements in asthma exacerbations, lung function
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NASHVILLE, Tenn. — Patients with type 2 inflammatory asthma experienced sustained, long-term reductions in exacerbations and improvements in FEV1 with dupilumab, according to a presentation at the CHEST Annual Meeting.
“What’s important with our new biologics is we’re just now starting to learn what their long-term effects are,” Mario Castro, MD, MPH, adjunct research professor at the University of Missouri-Kansas City School of Medicine, told Healio.
Building on the phase 3 LIBERTY ASTHMA QUEST study, the open-label LIBERTY ASTHMA TRAVERSE extension study examined patients aged 12 years and older taking dupilumab (Dupixent, Sanofi/Regeneron) for their uncontrolled, moderate to severe asthma.
“The TRAVERSE study is a critical study that now provides us for the first time information on efficacy and safety out to 3 years with the biologic dupilumab, which is blocking the IL-4 alpha receptor,” Castro said.
The current analysis includes patients from TRAVERSE with blood eosinophil counts of 150 cells/µL or higher or fractional exhaled nitric oxide levels of 20 ppb or higher at QUEST baseline, as indicated by Global Initiative for Asthma Guidelines.
All patients had one or more, two or more, or three or more exacerbations during the year before they entered QUEST.
“Exacerbation history is important because we had seen in previous studies that some biologics work better if you’ve had two or more exacerbations,” Castro said. “So, the question was then if this biologic still works well if you have one or more exacerbations, compared to the frequent exacerbator.”
Whether they received placebo or dupilumab during QUEST, the patients in TRAVERSE received 300 mg of dupilumab every 2 weeks for up to 48 or 96 weeks. The researchers then assessed the patients’ unadjusted annualized severe asthma exacerbation rate (AER) and mean change from parent study baseline in FEV1.
“This information is important because what we’ve seen with other biologics sometimes is a waning of the effect of the biologic over time, where patients start to see exacerbations reoccur and start to kind of regress to the baseline,” Castro said.
During QUEST, dupilumab reduced AER compared with placebo among patients with one or more (0.458 vs. 1.107), two or more (0.528 vs. 1.483) and three or more (0.617 vs. 1.915) prior exacerbations.
During weeks 0 to 48 of TRAVERSE, AER fell further for patients in the dupilumab/dupilumab group compared with the patients in the placebo/dupilumab group for those with one or more (0.314 vs. 0.368), two or more (0.403 vs. 0.453) and three or more (0.445 vs. 0.545) prior exacerbations.
The researchers noted a continuation of this trend during weeks 48 to 96 of TRAVERSE among patients with one or more (0.229 vs. 0.25), two or more (0.285 vs. 0.235) and three or more (0.268 vs. 0.186) prior exacerbations.
Compared with QUEST baseline, the dupilumab/dupilumab group also saw greater mean changes in FEV1 than the placebo/dupilumab group at week 2 ( 1 prior exacerbations, 0.37 vs. 0.34; 2 prior exacerbations, 0.42 vs. 0.36; 3 prior exacerbations, 0.47 vs. 0.41) and at week 96 ( 1 prior exacerbations, 0.37 vs. 0.34; 2 prior exacerbations, 0.44 vs. 0.37; 3 prior exacerbations, 0.49 vs. 0.45) of TRAVERSE.
“There was a reduction in exacerbations and corresponding improvements in lung function and in asthma control. The fact that these were sustained over 3 years is very important, because again we didn’t see any waning of the effect,” Castro said.
Also, patients with three or more exacerbations reported greater use of inhaled corticosteroids as well as higher blood eosinophil counts.
“On average, counts were around 420 cells/µL in the three-or-more group and only 340 cells/µL in the one-or-more group, indicating that patients who have more exacerbations have more eosinophilic-driven, T2-driven disease process that one would expect would respond even better to a biologic,” Castro said.
Based on these results, the researchers concluded that dupilumab provided sustained efficacy among patients with uncontrolled, moderate to severe asthma and a type 2 inflammatory phenotype regardless of their total number of prior exacerbations.
“The take-home message here is reassuring those clinicians who are treating these patients that we see sustained efficacy and safety out to 3 years,” Castro said.
The researchers also are examining the impact that dupilumab is having on airway remodeling and disease modification.
“We’re very interested in how we can get to the stage of disease modification like our rheumatology colleagues have. They start patients and can modify the disease process,” Castro said. “We believe that these biologics are going to get us there.”