COPD, COPD (Chronic Obstructive Pulmonary Disease), Eosinophilia
Conditions
Keywords
dupilumab, biologic therapy, eosinophilic COPD, Type 2 Inflammation, Eosinophils, FEV1, compassionate use, Real-World Evidence
Brief summary
This multicentre retrospective cohort study describes lung function and patient-reported outcomes in adults with chronic obstructive pulmonary disease (COPD) and type 2 inflammation who received add-on dupilumab in routine clinical care at six Italian centres. During the study period dupilumab was not reimbursed for COPD in Italy and was provided exclusively through the manufacturer's named-patient compassionate-use programme. Access to that programme required a documented blood eosinophil count of at least 300 cells/microliter, at least two moderate or one severe exacerbation in the preceding 12 months, and persistent symptoms despite maximal inhaled therapy, but set no upper or lower limit on the degree of airflow limitation. As a consequence, the cohort includes participants whose airflow limitation falls outside the post-bronchodilator forced expiratory volume in 1 second (FEV1) window of 30 to 70 percent predicted that was required for entry into the BOREAS and NOTUS registration trials. Post-bronchodilator spirometry, COPD Assessment Test (CAT) score, modified Medical Research Council (mMRC) dyspnoea grade and, where locally available, fractional exhaled nitric oxide (FeNO) were recorded at treatment initiation and at approximately 12 weeks. The variable of primary interest is the change from baseline in post-bronchodilator FEV1 at 12 weeks, the timepoint pre-specified for the lung function endpoint of the registration trials. A pre-specified analysis compares the change in FEV1 between participants whose baseline FEV1 falls inside the 30 to 70 percent predicted window and those whose baseline FEV1 falls outside it. The study is observational and non-interventional. Dupilumab was prescribed independently of the study, according to clinical judgement and the rules of the compassionate-use programme, and no study-specific procedure was performed. Data were abstracted from routine clinical records.
Detailed description
Design and setting. Retrospective, observational, multicentre cohort study conducted at six Italian respiratory and internal medicine centres: San Carlo di Nancy Hospital (GVM Care & Research, Rome), Fondazione Policlinico Universitario Campus Bio-Medico (Rome), Azienda Ospedaliero-Universitaria Sant'Andrea (Sapienza University of Rome), Ospedale Cristo Re (Rome), Azienda Ospedaliera San Camillo-Forlanini (Rome) and Ospedale Isola Tiberina - Gemelli Isola (Rome). The study protocol (code PN002) was approved by the Comitato Etico Regionale Umbria on 20 May 2026. The study was conducted in accordance with the Declaration of Helsinki and is reported following the STROBE recommendations for observational research. Rationale. The BOREAS and NOTUS phase 3 trials established the efficacy of dupilumab in COPD with type 2 inflammation but restricted enrolment to a post-bronchodilator FEV1 between 30 and 70 percent predicted. Whether the functional response extends to patients outside that window has not been examined in a multicentre real-world cohort, and no published observational series has reported the response at the 12-week timepoint pre-specified in the registration trials. Participants and treatment. Consecutive adults with a physician diagnosis of COPD who commenced dupilumab between October 2024 and April 2026 were considered. All received dupilumab 300 mg subcutaneously every two weeks as add-on therapy through the manufacturer's named-patient compassionate-use programme; background inhaled therapy was continued unchanged. Because compassionate-use access is typically requested for refractory disease and applies no ceiling on disease severity, the cohort is expected to be weighted towards the severe end of the type 2-inflamed COPD spectrum and should not be read as a representative sample of all candidates for biologic therapy. Measurements. Spirometry was performed at each centre according to the American Thoracic Society and European Respiratory Society technical standards. All reported spirometric values are post-bronchodilator. Percent predicted values, z-scores and lower limits of normal were computed from the Global Lung Function Initiative 2012 equations for the Caucasian population. Airflow limitation was graded on post-bronchodilator FEV1 percent predicted using the Global Initiative for Chronic Obstructive Lung Disease thresholds. Symptom burden was quantified with the CAT and the mMRC dyspnoea scale. FeNO was measured before spirometry where locally available. Blood eosinophil counts were obtained from routine laboratory testing at the screening visit. Assessments were scheduled at baseline and at approximately 12 weeks, following local standard of care. Analysis. Continuous variables are summarised as mean with standard deviation and as median with interquartile range; categorical variables as counts and percentages. Paired comparisons between baseline and 12 weeks were performed with the Wilcoxon signed-rank test, with the paired t-test reported alongside; 95 percent confidence intervals for mean differences were derived from the t distribution and standardised effect sizes are expressed as Cohen's dz. Two pre-specified analyses addressed generalisability and robustness: participants were classified as trial-eligible or trial-ineligible according to whether baseline post-bronchodilator FEV1 fell within the 30 to 70 percent predicted window, with between-group comparison by the Mann-Whitney U test; and heterogeneity across recruiting centres was assessed with the Kruskal-Wallis test and with a leave-one-centre-out sensitivity analysis. No imputation was performed for missing data; analyses used all available paired observations and the denominator is reported for every estimate. Overlap with previous work. Twelve participants from one contributing centre were previously reported in a single-centre descriptive compassionate-use case series with a different analysis timepoint and a different set of endpoints. They are included here within the larger multicentre cohort, which addresses a distinct research question with a pre-specified primary variable. Registration timing. This study was registered retrospectively, after completion of data collection
Interventions
DRUGDupilumab
Dupilumab 300 mg administered subcutaneously every two weeks as add-on therapy to unchanged background inhaled treatment. Treatment was prescribed in routine clinical care, independently of this study, under a named-patient compassionate-use programme. No treatment was assigned by the investigators for the purposes of the study
Sponsors
Azienda Ospedaliera di Perugia
Ospedale San Carlo di Nancy, Roma
Campus Bio-Medico University
S. Andrea Hospital
Azienda Ospedaliera San Camillo Forlanini
Isola Tiberina - Gemelli Isola Hospital, Rome, Italy
Ospedale Cristo Re - Roma
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Physician diagnosis of COPD with post-bronchodilator FEV1/FVC ratio below 0.70 * Documented blood eosinophil count of at least 300 cells/microliter at screening * At least two moderate or one severe COPD exacerbation in the previous 12 months * Persistent symptoms despite maximal inhaled therapy * Started dupilumab 300 mg subcutaneously every two weeks as add-on therapy between October 2024 and April 2026 under the manufacturer's named-patient compassionate-use programme * Post-bronchodilator spirometry available at baseline and at approximately 12 weeks
Exclusion criteria
* Dupilumab started for a primary indication other than COPD * Post-bronchodilator spirometry not available at baseline or at the 12-week assessment * Pre-bronchodilator values only, with no post-bronchodilator measurement recorded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in post-bronchodilator FEV1 at 12 weeks | Baseline and 12 weeks after the first dose of dupilumab | Post-bronchodilator forced expiratory volume in 1 second (FEV1), measured in millilitres by spirometry performed according to ATS/ERS technical standards. Change is calculated as the value at 12 weeks minus the value at baseline. Positive values indicate a higher FEV1 at 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in post-bronchodilator FEV1 percent predicted at 12 weeks | Baseline and 12 weeks | Post-bronchodilator FEV1 expressed as a percentage of the predicted value derived from the Global Lung Function Initiative 2012 equations for the Caucasian population. Change is the value at 12 weeks minus the value at baseline. |
| Change from baseline in post-bronchodilator FEV1 z-score at 12 weeks | Baseline and 12 weeks | Post-bronchodilator FEV1 expressed as a z-score derived from the Global Lung Function Initiative 2012 equations. Change is the value at 12 weeks minus the value at baseline. |
| Change from baseline in post-bronchodilator forced vital capacity at 12 weeks | Baseline and 12 weeks | Post-bronchodilator forced vital capacity (FVC) measured in millilitres by spirometry. Change is the value at 12 weeks minus the value at baseline. |
| Change from baseline in COPD Assessment Test total score at 12 weeks | Baseline and 12 weeks | The COPD Assessment Test (CAT) is an eight-item patient-completed questionnaire; each item is scored from 0 to 5 and the total score ranges from 0 to 40, with higher scores indicating greater symptom burden. Change is the total score at 12 weeks minus the total score at baseline. |
| Number of participants with an increase in post-bronchodilator FEV1 of at least 100 mL at 12 weeks | Baseline and 12 weeks | Count of participants whose post-bronchodilator FEV1 at 12 weeks exceeds the baseline value by 100 mL or more. The threshold was defined a priori. |
| Number of participants with a decrease in COPD Assessment Test total score of at least 2 points at 12 weeks | Baseline and 12 weeks | Count of participants whose CAT total score at 12 weeks is at least 2 points lower than at baseline, corresponding to the established minimal clinically important difference. |
| Number of participants with a decrease in modified Medical Research Council dyspnoea grade of at least 1 grade at 12 weeks | Baseline and 12 weeks | Count of participants whose mMRC grade at 12 weeks is at least one grade lower than at baseline. |
Countries
Italy
Contacts
PRINCIPAL_INVESTIGATORLorenzo Carriera
Azienda Ospedaliera di Perugia
Outcome results
None listed