番茄社区

Adding dupilumab (Dupixent) to triple therapy reduced exacerbations and improved lung function for chronic obstructive pulmonary disease (COPD) patients with blood eosinophil evidence of type 2 inflammation, according to a second phase III trial reported at the recent American Thoracic Society annual meeting.

In this exclusive 番茄社区 video, Surya Bhatt, MD, of the University of Alabama at Birmingham, discusses the background and results of the NOTUS study.

Following is a transcript of his remarks:

The NOTUS study is a randomized clinical trial comparing the efficacy and safety of dupilumab in patients with chronic obstructive pulmonary disease with a specific endo phenotype of frequent exacerbations and type 2 inflammation. The study was designed to see if dupilumab could reduce the frequency of exacerbations and the secondary outcomes also -- improved lung function and quality of life.

So the patients enrolled were people with COPD between the ages of 40 and 85 years with lung function between 30% to 70% predicted FEV₁ [forced expiratory volume in one second], and also with frequent exacerbations defined as at least two moderate or one severe exacerbation in the previous year. And they had to be on triple therapy in the form of inhaled corticosteroids, long-acting beta agonists and long-acting muscarinic antagonist and could be on dual therapy if inhaled corticosteroids were contraindicated and at least one of the exacerbations had to be on triple therapy. And they were randomized, one-to-one, and patients also had to have at least 300 eosinophils in the blood at the time of screening.

And they were randomized one-to-one to dupilumab with placebo, and followed for 52 weeks. And the primary outcome was a decrease in exacerbation frequency. And the important secondary outcomes were FEV₁ improvement over 12 weeks and then at 52 weeks. And also improvement in quality of life as measured by the St. George's Respiratory Questionnaire and also daily symptom burden as measured by the E-RS [Evaluating Respiratory Symptoms] COPD daily symptom score.

The study met its primary endpoint. There was a 34% reduction in exacerbation frequency. Several key secondary endpoints were also met. There was a significant improvement in FEV₁ of about 82 mL at week 12, and this was rapid at the first point of measurement and was sustained throughout the 52 weeks. There were also significant improvements in the St. George's Respiratory Questionnaire of 3.3 units and also significant improvements in the E-RS COPD daily symptom burden. The E-RS COPD score was not statistically significant, but was numerically significantly different.

The NOTUS study confirmed the findings of the previous phase III study examining the same issue in the form of the BOREAS trial, which also found a 30% reduction in exacerbation frequency and improvement in all the important secondary outcomes of lung function, quality of life, and daily symptom burden. So this study basically, after confirming the findings of the BOREAS study, serves as a replication study attesting to the validity of the results seen in the previous study. There were also no safety signals in both the trials, again, confirming that dupilumab is safe to use in this patient population.

So I think for the first time we have a biologic that works for exacerbation reduction and also importantly for improving lung function and quality of life. So both these trials together give us a strong body of evidence that this would be a very effective therapy in patients with type 2 inflammation as indicated by blood eosinophil counts.

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