Researchers have found that there is a treatment in existence which could help patients with a particular kind of Chronic Obstructive Pulmonary Disease (COPD). This antibody treatment is said to reduce the rate of flare-ups by close to 20 percent in patients with a sub group of treatment-resistant COPD, according to the results of two large international trials presented at the European Respiratory Society International Congress in Milan, Italy and simultaneously published in the New England Journal of Medicine.
“The goal of precision medicine is to give the patient the right treatment,” said lead author Frank Sciurba, the director of the Center for COPD and Emphysema and University of Pittsburgh Medical Center’s Pulmonary Function Exercise Physiology Laboratory, and a visiting professor in the Division of Pulmonary, Allergy and Critical Care Medicine at the university’s School of Medicine. “These findings are the first example of a precision therapy that is uniquely effective in a sub group of patients with treatment-resistant COPD.”
COPD is a progressive lung disease that causes breathlessness as a result of airway obstruction and chronic inflammation that is believed to affect 30 million Americans. More than 12 million Americans are believed to have undiagnosed COPD and have no idea that they do. COPD is the third leading cause of death in America claiming approximately 120,000 lives every year.
There are a number of signs you can look out for should you suspect that you have COPD and these include; having a chronic cough, production of a lot of mucus, blueness of your fingernail beds and lips, fatigue, lack of energy and chest tightness among a number of other signs. Should you experience any of these signs while going about your day to day activities, you are advised to visit your health provider so that they can perform a spirometry test to check whether you do have COPD.
“There is significant variation between patients in the cells and other proteins responsible for lung inflammation, so there are actually many different subtypes of COPD”, Sciurba said.
One subgroup called eosinophilic predominant COPD is present in as many as 40 percent of patients and is characterized by elevated levels of a type of white blood cells known as eosinophils, he said.
The new study reports the outcomes of two Phase III clinical trials assessing the effectiveness of mepolizumab, an antibody treatments that brings down the number of eosinophils in the blood, in moderate to severe treatment-resistant eosinophilic COPD by blocking the pro-inflammatory results of interleukin-5. Despite a year of standard treatment known as “triple inhaled therapy” which includes the use of bronchodilators and glucocorticoids, patients included in the trials were still experiencing flare-ups.
Sciurba said that these patients already have been given every treatment that they have to offer them and are still having flare-ups that significantly interfere with their quality of life and can lead to deterioration in lung function and higher mortality. He added that they hoped to be able to offer them an option.
The Food and Drug Administration (FDA) have already approved mepolizumab to help reduce symptom flare-ups and improve life quality in eosinophilic asthma.
The first trial which was conducted from the year 2014 to the year 2017 was conducted at 117 sites in 15 countries and was termed METREX. It involved a total number of 837 patients diagnosed with COPD, who were stratified by blood eosinophil counts and randomized to receive either placebo or 100 milligrams of mepolizumab which was delivered under the skin on a monthly basis for a year.
The patients with high eosinophil counts that were receiving doses of mepolizumab had a statistically significant 18 percent lower rate of moderate or severe flare-ups (1.4 per year compared to 1.7 per year) than those that were in the group receiving doses of placebo. The exacerbation rate of the patients with low eosinophil counts treated with the biologic did not differ from the placebo. The time to the first exacerbation also was lower with placebo than mepolizumab, but only in the group with the high eosinophil count.
In a second trial that was done concurrently, the team made an assessment of the effect of a higher dose of mepolizumab in 675 patients with elevated eosinophil levels. This second trial was termed METREO. Patients were selected at random in the trial to receive 100 to 300 milligrams of mepolizumab or placebo with the same schedule and delivery method as that of METREX.
Similar to the first trial, METREX, the findings of the second trial showed that the rate of the flare-ups was reduced by 20 percent in the group with a high eosinophil count after 100 milligrams of mepolizumab. The METREO outcome narrowly missed statistical significance. There was however no advantage showed of the 300 milligram dose over the lower dose.
Through analyzing data from both the METREO and METREX trials, it was found that as baseline blood eosinophil counts increased, it also had the same effect on mepolizumab’s reduction in the annual exacerbation rate. Sciurba said that these findings indicated that patients with a higher initial eosinophil count benefited more than those with lower eosinophil counts. There was no difference in the safety profile between placebo and mepolizumab in either trial.
“In addition to providing a new treatment option for patients with treatment-resistant moderate to severe COPD, the results are also important because they identify a potential biomarker for the disease and demonstrate that eosinophilic inflammation plays a role in flare-ups in COPD,” Sciurba said.
The division chief of the Division of Pulmonary, Allergy, and Critical Care Medicine Dr. Rama K. Mallampalli said, “The findings in these trials exemplify what we hope to achieve not only in COPD but across all lung diseases with regards to a precision approach to treatment.”
GlaxoSmithKline, a British pharmaceutical company established in 2000 through the merging of two companies, Glaxo Wellcome and Smithkline Beecham provided the funding for both the first and the second trials that were conducted. They plan to seek approval from the FDA for the use of mepolizumab in eosinophilic COPD.