NICE Endorses Dupilumab for Eosinophilic COPD Treatment
NICE Backs Dupilumab Eosinophilic COPD Option
Dupilumab eosinophilic COPD treatment gains momentum as the National Institute for Health and Care Excellence (NICE) final draft guidance recommends dupilumab as an add-on maintenance therapy for adults with uncontrolled chronic obstructive pulmonary disease (COPD) characterized by raised blood eosinophils (≥0.3 × 10^9 cells per litre or 300 cells per microlitre). Eligible patients are on triple therapy (inhaled corticosteroid, long-acting beta2-agonist [LABA], and long-acting muscarinic antagonist [LAMA]) or double therapy (LABA and LAMA) if inhaled corticosteroids are inappropriate.
Uncontrolled COPD means ≥1 severe exacerbation or ≥2 moderate exacerbations in the prior 12 months, with treatment response assessed at 12 months and discontinuation required if severe exacerbations increase or remain equal with higher moderate exacerbations compared to pre-treatment. Clinical evidence from the BOREAS and NOTUS phase 3 trials, detailed in NICE’s announcement, demonstrates reduced exacerbations and improved lung function, while economic modeling yields a committee-preferred incremental cost-effectiveness ratio (ICER) of £23,113 per quality-adjusted life year (QALY) gained, deemed acceptable within NICE’s £20,000–£30,000 range, supported by a commercial access agreement.
Exacerbation Cuts Transform High-Risk Care
Pooled data from the BOREAS and NOTUS trials, involving 938 dupilumab and 936 placebo patients on background therapy, reveal a 31% reduction in annualized moderate or severe exacerbations (rate ratio 0.69, 95% confidence interval [CI] 0.60–0.79; dupilumab 0.79 vs. placebo 1.16 events per year). This supports dupilumab eosinophilic COPD efficacy in high-risk patients with post-bronchodilator forced expiratory volume in the first second (FEV1) 30–70% predicted. Lung function improvements include least squares mean differences in pre-bronchodilator FEV1 of +83 ml (95% CI 53–112 ml) at week 12 and +73 ml (95% CI 40–107 ml) at week 52, alongside a -3.4-point (95% CI -5.0 to -1.8) improvement in Saint George’s Respiratory Questionnaire (SGRQ) total score at week 52. These outcomes, deemed clinically meaningful despite some minimal clinically important difference thresholds not fully met (e.g., SGRQ <4 points mean difference but 51.4% vs. 44.6% achieving ≥4-point improvement), address unmet needs in the eosinophilic COPD phenotype.
Trials Drive Evidence-Based Endorsement
BOREAS and NOTUS employed double-blind, randomized designs in moderate-to-severe COPD patients (FEV1/forced vital capacity ≤0.7, ppFEV1 >30% to ≤70%, ≥2 moderate or ≥1 severe exacerbation history), administering 300 mg subcutaneous dupilumab every 2 weeks versus placebo atop triple or double therapy, with pooled 52-week primary endpoint analysis despite NOTUS early termination. The economic model integrates a 52-week decision tree into a lifetime Markov structure with 12 health states by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages (1–4) and exacerbation status, using Fenwick et al. (2021) FEV1 decline rates adjusted by a 1.52 multiplier for raised eosinophils (yielding 62.17 ml/year without and 108.68 ml/year with recent exacerbation), combined moderate/severe exacerbation rate ratios, 3-year dupilumab treatment effect maintenance from TRAVERSE asthma data, standardized mortality ratios from Whittaker et al. (2024) plus a 14.2% case fatality rate from National Respiratory Audit Programme (NRAP) 2021–2023 data, and non-treatment-specific EQ-5D utilities mapped from SGRQ. This de novo synthesis, critiqued by the external assessment group (EAG), balances trial limitations (e.g., COVID-19 impacts, low severe events) with real-world applicability.
Funding Fast-Track Reshapes COPD Landscape
NICE’s endorsement mandates National Health Service (NHS) funding within 90 days of final publication for eligible patients, leveraging a confidential commercial arrangement discounting the £1,264.89 list price (300 mg/2 ml 2-pack, excluding VAT). It positions dupilumab eosinophilic COPD therapy as the first eosinophil-targeted biologic for COPD, expanding options beyond limited-use roflumilast or azithromycin. The £23,113/QALY ICER—factoring uncertainties in severe exacerbation reductions (32.6%, 95% CI -56.2% to +3.7%), long-term effects, and mortality—exemplifies value demonstration via responder stopping rules and equity considerations, as COPD disproportionately burdens lower socioeconomic groups (5-fold higher mortality in deprived areas).
This approval signals market access acceleration for phenotype-specific biologics, potentially influencing pricing negotiations and reimbursement precedents in single-payer systems by validating extrapolated benefits (e.g., lifetime FEV1 gains delaying GOLD progression) against innovation premiums, while highlighting needs for post-approval real-world evidence to refine ICER certainty and address implementation barriers like 12-month assessments. Overall, it reinforces biologic integration into COPD care, promising reduced exacerbations, hospitalizations, and health inequalities without exceeding resource thresholds.
