麻豆传媒

NASHVILLE, Tenn. -- Treatment with the biologic dupilumab (Dupixent) was associated with sustained reductions in oral corticosteroid (OCS) use in asthma patients who required both low and high daily OCS doses at baseline, according to post hoc findings from the open-label, extension trial.

Further follow-up of patients in the study also showed sustained reductions in exacerbations from baseline with improvements in lung function maintained after close to 2 years of treatment.

The updated findings from the trial were presented here at , the annual meeting of the American College of Chest Physicians.

Among adult patients with severe OCS-dependent asthma prior to starting dupilumab, treatment with the biologic was associated with sustained reductions in OCS use.

In the parent LIBERTY ASTHMA VENTURE trial, OCS use from baseline was reduced by 70% in patients taking the fully human monoclonal antibody over 24 weeks, with patients in the placebo arm of the study reducing OCS use by 42%.

The annualized severe asthma exacerbation rate was also reduced by 59% in VENTURE, and lung function, as measured by pre-bronchodilator forced expiratory volume in one second (FEV₁), was improved by 0.22 L compared with placebo.

Roughly half of patients taking the biologic in VENTURE no longer required OCS after 24 weeks on treatment.

The TRAVERSE extension trial analysis included 187 patients with OCS-dependent asthma who continued to receive 300 mg of dupilumab every 2 weeks for almost 2 years. Patients taking placebo in VENTURE were also switched to dupilumab in the TRAVERSE trial.

In patients requiring daily OCS doses of 10 mg or less and in those requiring more than 10 mg a day before starting the biologic, treatment with dupilumab was associated with sustained reductions in OCS use.

Among patients in VENTURE on more than 10 mg of OCS a day at baseline, those who switched from placebo to dupilumab (n=36) reduced their OCS use from a mean of 17.57 mg per day at baseline to 3.63 mg per day at 96 weeks, representing a 76% reduction. While patients in the study's active-treatment arm (n=30) reduced their daily OCS use from 18.08 mg to 4.17 mg per day at week 98, representing an 83% reduction.

"What we are seeing is continued improvement and continued reductions in oral corticosteroid use in patients who have been on this drug for close to 2 years," Xavier Soler, MD, of GSK and the University of San Diego, told 麻豆传媒.

Soler presented the post hoc TRAVERSE findings in a poster session at the meeting.

In a separate poster, Mario Castro, MD, of the University of Kansas Medical Center in Kansas City, presented data on asthma exacerbation and lung function in the TRAVERSE patients originally enrolled in the LIBERTY ASTHMA QUEST study, which included patients with and without an allergic phenotype.

"The message here is that we built on the earlier studies -- QUEST and VENTURE -- showing sustained efficacy in terms of exacerbation declines, lung function, and oral corticosteroid dependence," Castro told 麻豆传媒.

In TRAVERSE at weeks 48-96, patients with at least one, two, or three exacerbations per year at baseline and type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb) all showed sustained reductions in exacerbations and maintained lung function.

Among patients in the placebo arm of QUEST with at least three exacerbations a year at study entry, the annualized exacerbation rate declined from 4.68 at baseline to 0.19 at weeks 48-96. Among patients in the active-treatment arm, the annualized exacerbation rate declined from 4.53 at baseline to 0.27 at weeks 48-96.

In another related study, Njira Lugogo, MD, of the University of Michigan in Ann Arbor, presented very early patient recruitment data from the global, real-world use RAPID registry of asthma patients prescribed dupilumab.

Lugogo told 麻豆传媒 that most patients enrolled in the registry to date live in the U.S., but global data are expected as early as 2023.

"The very early data show us that the population taking this drug is similar to patients recruited for the clinical trials in terms of demographics," she said. "What is different is that the real-world patients tend to be sicker, with an average of more than four exacerbations a year, compared to an average of 2.5 exacerbations in the study population."

During the first 6 months, the registry enrolled 205 patients (mean age 50 years, 65% female, 74% white, and 13% Black).