Mepolizumab Showing Promise for High-Risk Eosinophilic COPD

Ingrid Hein

September 13, 2017

MILAN — Patients with chronic obstructive pulmonary disease (COPD) who have high blood eosinophil counts might benefit from treatment with mepolizumab, according to results from the METREO and METREX trials.

"In the overall population, the effects were modest, but when we stratified the population for blood type, we were able to identify a particularly responsive population," said Ian Pavord, DM, from the University of Oxford in the United Kingdom, who is lead investigator on the METREO trial.

In fact, mepolizumab reduced exacerbations by about 20% overall in patients with high-risk eosinophilic COPD who were receiving optimal standard-of-care treatment.

However, in patients with blood counts of at least 300 eosinophils/mm³ — which are levels seen in those with severe asthma — exacerbations were decreased by at least 38%. This reduction is comparable to that seen in patients with asthma treated with the humanized anti-interleukin (IL)-5 monoclonal antibody.

Mepolizumab is already approved for the treatment of severe asthma.

Dr Pavord discussed the METREX trial, which looked at the efficacy and safety of mepolizumab in patients with eosinophilic COPD, and the METREO trial, which looked at dosing, here at the European Respiratory Society International Congress 2017. Study results were published online Tuesday in the New England Journal of Medicine.

Interest in the studies was strong. During his poster presentation, Dr Pavord took questions from the gathered crowd for more than 2 hours. And during an oral presentation on the studies, Frank Sciurba, MD, from the University of Pittsburgh, who is lead investigator on the METREO trial, addressed a standing-room-only crowd.

"These were patients with recurrent exacerbations despite high-intensity treatment already on dual and triple therapies and steroids," Dr Pavord explained.

In both trials, results were moderate. Mepolizumab 100 mg consistently lowered the annual rate of moderate or severe exacerbations by 18% in the METREX trial and 20% in the METREO trial.

In the METREO dosing trial, there were no significant differences in effect between 100 mg and 300 mg doses.

However, when data from both trials were combined, numbers for patients with higher blood eosinophil counts became clinically significant.

Patients who presented with higher baseline eosinophil counts were "a particularly responsive population," Dr Pavord reported. "Those patients' elevated risk can be reduced substantially; we saw a 38% reduction. That's the main finding here that is clinically significant."

The METREX and METREO Trials

In their analysis of data from the two trials, Dr Pavord and his colleagues assessed patients classified as having an eosinophilic phenotype (≥150 eosinophils/mm³ at screening or ≥300 eosinophils/mm³ during the previous year).

The METREX efficacy and safety trial assessed mepolizumab 100 mg every 4 weeks for 52 weeks in 462 patients. The mean rate of moderate or severe exacerbations per year was lower in the mepolizumab group than in the placebo by about 18% (1.40 vs 1.71; rate ratio, 0.82; 95% confidence interval [CI], 0.68 - 0.98; adjusted P = .04).

In the METREO dosing trial, the mean rate of moderate or severe exacerbations per year was lower in the mepolizumab 100 mg and 300 mg groups than in the placebo group (1.19 vs 1.27 vs 1.49). Exacerbations were about 20% lower in the 100 mg group than in the placebo group.

When the mepolizumab 100 mg group was compared with the placebo group, the results were clinically insignificant (rate ratio, 0.80; 95% CI, 0.65 - 0.98; adjusted P = .07). The same was true when the 300 mg group was compared with the placebo group (rate ratio, 0.86; 95% CI, 0.70 - 1.05; adjusted P = .14).

With results at clinically moderate levels, anti-IL-5 agents "aren't going to work in everyone," Dr Pavord explained. But by identifying who is going to get the most benefit, we can use this drug effectively.

"I would like to see this drug available to treat patients with severe COPD who have a strong eosinophil signal and have recurrent exacerbations," he added. Although neither trial was designed to find this end point, these numbers are clinically significant.

"Higher eosinophil counts are the biomarker of COPD; that is clear," Dr Sciurba told Medscape Medical News after his presentation.

"I think we need to rethink what we mean by an exacerbation," said Jorgen Vestbo, DrMedSci, from the University of Manchester in the United Kingdom.

"We have to have biomarkers," he explained. "What is actually an exacerbation? What is caused by colder weather? And so on."

When a patient reports an exacerbation, it gets recorded as one, but there is no actual evidence. "We need to do tests for COPD, just as cardiologists do for ischemic heart disease," he told Medscape Medical News.

But advances in biologics need to be put in perspective, said Fernando Martinez, MD, from the University of Arizona in Tucson.

"Sure, there's been very significant advancement in the treatment of asthma, but there's one significant problem: it's very expensive. The worst medicine for anyone is one they cannot afford," he said.

The METREO and METREX trials were supported by grants from GlaxoSmithKline. Dr Pavord reports financial relationships with Boehringer Ingelheim, Aerocrine, Almirall, Novartis, GlaxoSmithKline, Genentech, Regeneron, Merck & Co., Schering-Plough, Mylan Speciality, Dey Pharma, Napp Pharmaceuticals, and Respivert. Dr Sciurba reports financial relationships with the COPD Foundation, the US Department of Defense, Astellas, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Phillips Respironics, PulmonX, PneumRx, and Spiration. Dr Vestbo and Dr Martinez have disclosed no relevant financial relationships.

European Respiratory Society (ERS) International Congress 2017: Poster PA1366, presented September 10, 2017; Late-breaking abstract OA3194, presented September 12, 2017.

Follow Medscape Pulmonary Medicine on Twitter @MedscapeLung and Ingrid Hein @ingridhein

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