Dupilumab for maintenance treatment of uncontrolled chronic obstructive pulmonary disease (COPD) with raised blood eosinophils

Dupilumab is a fully human monoclonal antibody that specifically targets the type 2 inflammatory pathway by blocking the alpha subunit of the nterleukin-4 (IL-4) receptor, thereby inhibiting the signaling network activated by both IL-4 and interleukin-13 (IL-13), which are key drivers of type 2 inflammation (1):

• by interrupting this proinflammatory cascade, dupilumab has the potential to prevent multiple downstream effects of IL-4 and IL-13, including eosinophil recruitment, mucus hypersecretion, and airway remodeling, which contribute to the pathophysiology of eosinophilic chronic obstructive pulmonary disease (COPD)
• evidence has shown that, when added to standard triple inhaled therapy in patients with COPD and evidence of type 2 inflammation, dupilumab significantly reduced the annual rate of moderate-to-severe exacerbations and led to clinically meaningful improvements in lung function and health-related quality of life

Pathophysiology of eosinophilic COPD (1):

• while traditionally viewed as a neutrophil-dominant inflammatory disease driven by exposure to noxious particles like cigarette smoke, our understanding has evolved to recognize distinct inflammatory endotypes
• in a relevant subset of COPD patients, evidence highlights the crucial role of type 2 inflammation, characterized by the presence of eosinophils associated with high levels of type 2 cytokines such as interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13)
• this eosinophilic phenotype, estimated to be present in approximately 20–40% of the COPD population, is linked to a higher frequency of exacerbations and a more rapid disease progression

NICE state (2):

Dupilumab can be used as an add-on maintenance treatment option for uncontrolled chronic obstructive pulmonary disease (COPD)* with raised blood eosinophils** in adults if:

• they are having:
  • triple therapy including an inhaled corticosteroid, a long-acting beta2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), or
  • double therapy including a LABA and a LAMA if inhaled corticosteroids are not appropriate, and
• the company provides dupilumab according to the commercial arrangement

*Uncontrolled COPD is defined as 1 or more severe exacerbations or 2 or more moderate exacerbations in the previous 12 months

**Raised blood eosinophils is defined as having a blood eosinophil count of 0.3 x 10^9 cells per litre or more (300 cells per microlitre or more)

Assessment of response to dupilumab at 12 months

Stop dupilumab if, compared with the 12 months before starting it, the number of severe exacerbations:

• is higher, or
• is the same, and the number of moderate exacerbations is higher

The NICE committee concluded:

“…Clinical trial evidence shows that dupilumab plus triple therapy, or double therapy if an inhaled corticosteroid is not appropriate, reduces the number of exacerbations and improves lung function and quality of life compared with double or triple therapy alone for uncontrolled COPD…”

Reference:

1. Lupia C et al. Short-Term Effects of Dupilumab in Eosinophilic COPD. J Clin Med. 2026 Jan 18;15(2):775.
2. NICE (March 2026). Dupilumab for maintenance treatment of uncontrolled chronic obstructive pulmonary disease with raised blood eosinophils