Monoclonal Antibodies Targeting IL-5/IL-5R May Benefit Certain Patients With COPD

Individuals with chronic obstructive pulmonary disease (COPD) who use oral corticosteroids (OCS) for managing their symptoms may benefit from treatment with monoclonal antibodies targeting interleukin (IL)-5 and its receptor (IL-5R), according to one study. The findings, published in the International Journal of Chronic Obstructive Pulmonary Disease, suggest that anti–IL-5/IL-5R therapy could decrease COPD exacerbations and OCS dependency.

“The benefits seen in clinical practice seem better than what have been reported in clinical trials,” the study authors wrote. “We therefore aim to describe the characteristics and therapeutic response of COPD patients treated with anti–IL-5 monoclonal antibodies in the real-world setting of a tertiary care center.”

To the researcher’s knowledge, this retrospective, longitudinal study is the first to identify benefits of anti–IL-5/IL-5R therapies in patients with COPD.

Biologic therapies targeting immune cells responsible for eosinophil inflammation, such as IL-5 or IL-5R, have proven beneficial in asthma management but have not shown substantial benefits in studies of COPD. In clinical practice, however, physicians may use such biologics to treat patients with COPD and eosinophil inflammation. In these cases, monoclonal antibodies may reduce exacerbations and the need for chronic OCS use.

This study included patients with COPD treated with at least 3 doses of mepolizumab or benralizumab, both anti–IL-5 therapies. Additionally, patient demographics such as age, sex, BMI, and smoking history were recorded. Furthermore, disease and exacerbation-related data—such as airway comorbidities, lung function, and inflammatory profile—were reported at baseline and after 12 months of anti–IL-5 treatment between March 2017 and March 2021.

The researchers evaluated the annual exacerbation rate and/or OCS daily dose among patients with COPD, changes in forced expiratory volume per one second (FEV₁), and inflammatory biomarkers from baseline to the end of anti–IL-5 treatment.

A total of 7 patients with COPD received anti–IL-5 treatment. At baseline, all patients had evidence of emphysema, were OCS dependent, and had severely impaired lung function, with a mean FEV₁ of 34.6 ± 13.2%. Despite daily OCS use, 6 of the participants showed frequent exacerbations, with an exacerbation rate of 7.3 ± 3.9 in the previous year. Five of these 6 patients showed evidence of residual eosinophilic inflammation, with blood eosinophil levels of 237 ± 225×10⁶ cells/L.

Five patients completed 12 months of treatment with anti–IL-5/IL-5R biologics, and mean OCS use decreased by 78% from baseline, dropping from 12.0 ± 7.6 to 2.6 ± 4.3 mg/day. Additionally, the annual exacerbation rate decreased by 88%, from 8.2 ± 3.3 to 1.0 ± 1.2 per year.

The results of this study suggest that most of the patients’ exacerbations were eosinophilic, in which case anti–IL-5 therapy was able to significantly reduce these exacerbations. This is controversial, since most COPD patients have a heterogeneity in their exacerbations, leading the researchers to wonder if patients had been misidentified and had asthma. However, only one patient was found to have a previous diagnosis of asthma, defined has having an asthma-COPD overlap, while all other patients were only diagnosed with COPD.

Although the researchers acknowledge that the study was retrospective in nature and limited by a small population size, they believe the results of this study suggest that biologic therapies may be beneficial in reducing OCS use and exacerbations in patients with COPD.

“In conclusion, our case series suggests that monoclonal antibodies targeting IL-5 or its receptor may be effective in decreasing OCS exposure and exacerbation rate among eosinophilic COPD patients treated with chronic OCS,” wrote the researchers. “These findings need further validation but may serve to better select the population to be included in clinical trials studying biologic therapy in COPD.”

Reference

Laroche J, Pelletier G, Boulay M-È, Côté A, Godbout K. Anti-IL5/IL5R treatment in COPD: Should we target oral corticosteroid-dependent patients? International Journal of Chronic Obstructive Pulmonary Disease. 2023(18):755-763. doi:10.2147/copd.s370165