Mepolizumab Lessens Exacerbations, Improves Quality of Life

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Treatment with mepolizumab, an antibody designed to lower the levels of eosinophils — immune cells linked with worse chronic obstructive pulmonary disease (COPD) — was found to reduce the annual rate of exacerbations and improve health-related quality of life in people with eosinophil-associated COPD.

The findings, from a meta-analysis of two clinical trials, support the potential benefits of mepolizumab for COPD patients with high levels of eosinophils.

“Mepolizumab works in patients with COPD who have flares despite taking their usual inhalers,” these results suggest, according to the researchers.

“This analysis showed that mepolizumab reduced the number of COPD flares that needed antibiotics or steroid tablets. The number of patients who went to hospital was also reduced by about one fifth,” the team wrote.

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The study, “Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO,” was published in the International Journal of Chronic Obstructive Pulmonary Disease.

Up to 40% of COPD patients have an increased number, in their blood, of a type of immune cell called eosinophils. These cells are associated with an increased risk of COPD worsening episodes known as disease exacerbations, which can each last for several days and impair breathing.

Mepolizumab, marketed by GlaxoSmithKline (GSK) and sold as Nucala (among other brand names), is approved as an add-on treatment for people with severe eosinophilic asthma, a form of asthma caused by elevated numbers of eosinophils.

The antibody works by blocking interleukin-5 (IL-5) — a key eosinophil signaling molecule — and thus lowering the levels of these immune cells in the blood.

Clinical data from patients with severe eosinophilic asthma showed that mepolizumab reduced their frequency of exacerbations and lessened disease burden. Based on those findings, a team of scientists from the U.K., the U.S., Italy, and Canada hypothesized that treatment with mepolizumab similarly might help people with COPD who have elevated levels of eosinophils.

To test this hypothesis, two Phase 3 trials were conducted: METREX (NCT02105948) and METREO (NCT02105961). Both were sponsored by GSK.

The trials enrolled COPD patients with a history of moderate or severe exacerbations despite undergoing standard COPD treatment with maximal inhaled corticosteroid-based triple maintenance therapy for at least 12 months. Participants were randomly assigned to receive either mepolizumab subcutaneously (under-the-skin) at 100 milligrams (mg) in METREX, 100 or 300 mg in METREO, or a placebo every four weeks for one year (52 weeks).

In both trials, 100 mg of mepolizumab given as an add-on treatment reduced the mean annual exacerbation rate when compared with the placebo. However, only the reductions in the METREX trial were statistically significant.

Now, the scientists, along with GSK researchers, conducted a meta-analysis of the clinical data from the METREX and METREO trials.

Their goal was “to provide more robust estimates of the effect of mepolizumab compared with placebo on COPD outcomes including exacerbation rates and quality of life, and to fully explore the relationship between blood eosinophil count and treatment responses,” the researchers wrote.

Specifically, the team compared the outcomes of the 100 mg dose of mepolizumab versus a placebo in COPD patients with a blood eosinophil count of at least 150 cells per microliter at screening or at least 300 cells per microliter in the previous year.

Overall, from the 1,510 patients who participated in the two trials, 1,136 matched the high eosinophils count criteria and were included in the analysis. Specifically, the analysis evaluated data from 456 patients in the 100 mg dose group, 225 in the 300 mg group, and 455 in the placebo group.

The majority (94%) had a high disease burden, as shown by their classification in group D of the Global Initiative for Chronic Obstructive Disease, or GOLD. The mean annual exacerbation rate in the previous year was 2.6 events per year.

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Health-related quality of life was measured using the St. George’s Respiratory Questionnaire (SGRQ) and the COPD Assessment Test (CAT). SGRQ scores range from zero to 100 points and the CAT from zero to 40, and in both cases higher scores indicate worse health status.

At the start of the trials (baseline), patients in the 100 mg dose of mepolizumab had a mean score of 53 in SGRQ and 18.6 in CAT; those in the placebo group had 54.7 in SGRQ and 19.5 in CAT.

Following treatment with mepolizumab, the mean annual exacerbation rate was reduced from 2.6 to 1.32 events/year versus 1.61 events/year in the placebo – an 18% reduction with mepolizumab versus the placebo.

In total, 18% of patients treated with 100 mg of mepolizumab experienced one or more exacerbation that required hospitalization, compared with 22% of patients in the placebo group.

Also, placebo-treated patients experienced a first moderate or severe exacerbation significantly earlier that those given mepolizumab. The difference was 155 days for those in the placebo group versus 218 days for those receiving mepolizumab.

While the SGRQ scores were initially lower — meaning an improvement — after mepolizumab treatment as compared with the placebo, by the end of the trial (week 52) no significant differences were seen between groups.

Regarding CAT scores, mepolizumab was better than the placebo at reducing these scores and they remained significantly lower by the end of the trials.

At the end of week 52, 56% of patients treated with mepolizumab and 50% given the placebo self-reported as having improved, a difference that was not statistically significant. However, clinician-rate response to therapy suggested that significantly more patients (53%) in the mepolizumab group improved, compared with 44% given a placebo.

Researchers then conducted an additional analysis to assess patients’ outcomes when stratified by the number of eosinophils. For this, they included patients with levels of eosinophils that fell outside the initial criteria.

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These results showed that the benefits of mepolizumab at a dose of 100 mg improved as the number of eosinophils increased. Specifically, the exacerbation rates were reduced by 14% in patients with 300 cells per microliter, by 23% in those with 500 cells per microliter, and by 30% for patients with 750 cells per microliter.

“Mepolizumab worked better in patients who had higher numbers of eosinophils in the blood before they were given mepolizumab,” the researchers wrote.

This suggests that the number of eosinophils might help clinicians predict which patients are more likely to benefit from treatment with mepolizumab.

Overall, “data from this meta-analysis show that the use of blood eosinophil counts allows for the identification of patients with COPD who continue to experience exacerbations while treated with maximal ICS [inhaled corticosteroid]-based triple maintenance therapy who are responsive to anti–IL-5 treatment,” the researchers wrote.

“Mepolizumab treatment benefits on reducing exacerbations and decreasing aspects of disease burden were clearest in patients with blood eosinophil counts [equal or higher than] 300 cells [per microliter], suggesting that this population requires further investigation,” the team concluded.