What is the role of biologics in pulmonary diseases?

From the Guidelines

Biologics are not recommended as a first-line treatment for lung diseases, but may be considered in specific cases, such as severe asthma or COPD with eosinophilic phenotypes, where they have shown promise in reducing exacerbations 1.

Current Treatment Options

The current treatment options for lung diseases, such as COPD, include:

• Inhaled corticosteroids (ICS) combined with long-acting beta-agonists (LABA) or long-acting muscarinic antagonists (LAMA) to improve lung function and reduce exacerbations 1
• Phosphodiesterase-4 inhibitors, such as roflumilast, to reduce moderate and severe exacerbations in patients with chronic bronchitis and severe to very severe COPD 1
• Antibiotics, such as azithromycin, to reduce the risk of exacerbations in patients prone to exacerbations 1
• Mucolytic agents, such as N-acetylcysteine, to reduce exacerbations and improve health status in patients not receiving ICSs 1

Biologics in Lung Diseases

Biologics, such as monoclonal antibodies, are being increasingly used to treat severe lung diseases, particularly asthma and COPD. These medications target specific inflammatory pathways and may be effective in reducing exacerbations and improving symptoms. However, their use is still emerging and more research is needed to fully understand their benefits and risks.

Key Considerations

When considering the use of biologics in lung diseases, the following key considerations should be taken into account:

• Patient selection: Biologics should only be considered in patients with severe disease who have not responded to conventional treatments 1
• Biomarkers: Biomarkers, such as blood eosinophil counts and FeNO levels, should be used to guide treatment selection and monitoring 1
• Safety: Biologics can have potential adverse effects, such as injection site reactions and hypersensitivity reactions, and should be monitored regularly 1

From the FDA Drug Label

Dupilumab is a human monoclonal IgG4 antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling by specifically binding to the IL-4Rα subunit shared by the IL-4 and IL-13 receptor complexes. Inflammation driven by IL-4 and IL-13 is an important component in the pathogenesis of asthma, AD, CRSwNP, EoE, PN, and COPD.

Biologics in Lung Diseases: Dupilumab, a biologic, is used to treat lung diseases such as asthma and COPD by inhibiting IL-4 and IL-13 signaling, which are key components in the pathogenesis of these diseases.

• The mechanism of action of dupilumab involves binding to the IL-4Rα subunit, which inhibits IL-4 and IL-13 cytokine-induced inflammatory responses.
• Dupilumab treatment has been shown to decrease certain biomarkers of inflammation, such as fractional exhaled nitric oxide (FeNO) and circulating concentrations of eotaxin-3, total IgE, and periostin 2.

From the Research

Biologics in Lung Diseases

• Biologics have been proven safe and effective for patients with uncontrolled severe asthma, leading to the Global Initiative for Asthma (GINA) recommending their use instead of maintenance oral corticosteroids (OCS) in patients with severe asthma 3.
• Examples of biologics used in severe asthma include omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab, which target different pathways such as immunoglobulin E (IgE), interleukin-5 (IL-5), and IL-4 receptor α-unit (IL-4R α) 3.
• Switching from omalizumab to mepolizumab has been shown to improve asthma control, health status, and exacerbation rate in patients with uncontrolled severe eosinophilic asthma 4.

Efficacy and Safety of Biologics

• A systematic review of five biologics (benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab) found that all reduce exacerbation rates with high certainty of evidence 5.
• Benralizumab, dupilumab, and mepolizumab also reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence 5.
• The biologics probably improve asthma control, quality of life (QoL), and forced expiratory volume in one second (FEV1), although the certainty of evidence is moderate 5.

Biologics in COPD

• Mepolizumab has been shown to reduce the annualized rate of moderate or severe exacerbations in patients with chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype 6.
• The use of biologics in COPD is a relatively new area of research, and more studies are needed to fully understand their efficacy and safety in this population.

Asthma-COPD Overlap Syndrome

• Asthma and COPD are highly prevalent chronic diseases with overlapping pathologic and functional features, particularly among the elderly 7.
• The presence of different phenotypes or components of obstructive airway diseases needs to be addressed to individualize and optimize treatment 7.