Chronic bronchitis symptoms hint at benefits of mepolizumab in COPD with T2 inflammation

The presence of chronic bronchitis (CB) symptoms in chronic obstructive pulmonary disease (COPD) with type 2 (T2) inflammation drives a more pronounced and significant benefit from mepolizumab in terms of reducing COPD Assessment Test (CAT) scores, a measure of disease impact on patients, as shown in a post hoc analysis pooling data from two phase III trials — METREX and METREO.

Within the subset of patients with T2 inflammation (eosinophil count ≥300 cells/μL at screening), mepolizumab reduced the CAT scores from baseline to week 52 to a greater extent than placebo (least-squares [LS] mean, −3.1 vs −1.2) and exceeded the clinically important threshold of a 2-point decrease in patients with symptoms of CB. The between-group difference of −1.9 was statistically significant (95 percent confidence interval [CI], −3.7 to −0.1). [ERS 2024, poster PA4783]

In patients without symptoms of CB, the worsening in the CAT scores at week 52 was numerically smaller with mepolizumab than with placebo (LS mean difference, −0.5, 95 percent CI, −2.8 to 1.7).

While METREX and METREO were not originally designed to enrol patients based on their T2 inflammation status, this analysis indicated that treatment with mepolizumab among those meeting the eosinophil cutoff resulted in the same numerical 24-percent reduction in the annualized rate of moderate or severe exacerbations vs placebo, regardless of the presence or absence of CB symptoms (rate ratio, 0.76, 95 percent CI, 0.56–1.03; and 0.76, 95 percent CI, 0.51–1.14, respectively).

"This post hoc analysis shows that mepolizumab may be of clinical benefit in patients with COPD exhibiting an eosinophilic phenotype, regardless of the presence of CB symptoms,” said Professor Claus Vogelmeier from the Department of Pulmonary Medicine, Philipps-Universität Marburg in Marburg, Germany.

Focus on T2 inflammation

The current analysis further dissected the subset of pooled patients with a screening blood eosinophil count ≥300 cells/μL (regarded as exhibiting T2 inflammation) into two groups: those with CB and those without, based on cough and sputum symptoms recorded in St George's Respiratory Questionnaire.

CB symptoms were present in 61.5 percent of patients randomized to mepolizumab 100 mg and 65.7 percent of those to placebo, among all who met the T2 inflammation criterion with available data on CB symptoms (n=336).

The presence of CB symptoms also tended to predict a higher CAT responder rate at week 52 with mepolizumab vs placebo (53 percent vs 40 percent; odds ratio, 1.71, 95 percent CI, 0.97–3.01), defined as those achieving a ≥2-point reduction from baseline.

MATINEE: the definitive success?

However, the overall results from METREX and METREO have been described as "discordant" and "difficult to interpret." [Am J Respir Crit Care Med 2019;199:110-112] Specifically, METREX found a significant reduction in moderate or severe exacerbations with mepolizumab in the primary analysis population characterized by an eosinophilic phenotype, whereas the reduction in METREO was not statistically significant, despite all participants being characterized as such. [N Engl J Med 2017;377:1613-1629]

Just a day before ERS 2024 commenced, it was announced that a third phase III trial of mepolizumab in COPD, MATINEE, had turned in positive results for the same primary endpoint. MATINEE included patients with and without symptoms of CB, allowing for the presentation of emphysema, based on blood eosinophil count criteria that differed from those used in the two prior trials. Patients were treated for up to 104 weeks. [ERS 2024, poster PA4789]

While the full results of MATINEE are eagerly awaited, the role of T2 inflammation in driving COPD exacerbations appears to be further solidified.