Biologic therapies for chronic obstructive pulmonary disease

ABSTRACT

Introduction

Chronic obstructive pulmonary disease (COPD) is a disorder characterized by a complicated chronic inflammatory response that is resistant to corticosteroid therapy. As a result, there is a critical need for effective anti-inflammatory medications to treat people with COPD. Using monoclonal antibodies (mAbs) to inhibit cytokines and chemokines or their receptors could be a potential approach to treating the inflammatory component of COPD.

Areas covered

The therapeutic potential that some of these mAbs might have in COPD is reviewed.

Expert opinion

No mAb directed against cytokines or chemokines has shown any therapeutic impact in COPD patients, apart from mAbs targeting the IL-5 pathway that appear to have statistically significant, albeit weak, effect in patients with eosinophilic COPD. This may reflect the complexity of COPD, in which no single cytokine or chemokine has a dominant role. Because the umbrella term COPD encompasses several endotypes with diverse underlying processes, mAbs targeting specific cytokines or chemokines should most likely be evaluated in limited and focused populations.

KEYWORDS:

• COPD
• chronic inflammation
• cytokines
• chemokines
• monoclonal antibodies

Article highlights

• Several mAbs have either undergone clinical testing or are currently being evaluated for treating COPD.

• MAbs can be subdivided into those that aim to block specific pro-inflammatory and pro-neutrophilic cytokines and chemokines (TNF-α, CXCL8, and IL-1β) and those that act on T2-mediated inflammation, (anti-IL-5 and/or its receptor, anti-IL-4/anti-IL-13, anti-IL-33, and anti-TSLP).

• The various mAbs tested in different RCTs generally have little or no effect on COPD.

• Likely, the failure observed while evaluating various biological agents in COPD reflects the disorder’s complexity, which includes numerous endo/phenotypic pathways.

• However, mAbs targeting the IL-5 pathway appear to have a statistically significant, albeit weak, effect in patients with eosinophilic COPD.

• MAbs to cytokines and chemokines should be tested in specific, restricted populations.

• MAbs may be the future of personalized COPD treatment, but new studies focusing on key outcomes other than AECOPDs, such as pulmonary function, are needed.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in, or financial conflict with, the subject matter or materials discussed in the manuscript, including employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.