Dupilumab: local formulary information
Clinical effectiveness
Evidence for the effectiveness of dupilumab in COPD comes from 2 double-blind, placebo controlled, randomised phase 3 trials: BOREAS (n=939) and NOTUS (n=935). The studies had similar designs and the same primary outcome (annualised rate of moderate or severe exacerbations of COPD). Moderate exacerbations were defined as those that resulted in treatment with a systemic glucocorticoid, an antibiotic agent, or both. Severe exacerbations were defined as those that led to hospitalisation or an emergency medical care visit or that resulted in death.
Secondary endpoints were assessed at up to 52 weeks. St. George's Respiratory Questionnaire (SGRQ) scores range from 0 to 100, with lower scores indicating a better quality of life, with the minimum clinically important difference being 4 points. Evaluating Respiratory Symptoms in COPD (E-RS-COPD) scores range from 0 to 40, with lower scores representing less severe respiratory symptoms.
BOREAS included an additional 12-week safety follow-up period. NOTUS was stopped early because it met its primary end point at a planned interim analysis.
The intervention in both studies was dupilumab (as add-on) 300 mg given subcutaneously once every 2 weeks, compared with matched placebo. The populations of the studies were very similar, that is, people with moderate to severe COPD with an eosinophil count of at least 0.3 x 10^9 cells per litre who had at least 2 moderate exacerbations, or 1 severe exacerbation, within the past year. People had to have been taking an inhaled corticosteroid plus a LABA and a LAMA (triple therapy), or a LABA and a LAMA if inhaled corticosteroids were not appropriate. Enrolment of people who currently smoke was capped at 30% in both studies.
For TA1142, data from the trials was pooled to increase statistical power. The results of the analysis are summarised in table 1. Dupilumab reduced the adjusted annualised exacerbation rate compared with placebo by a mean 0.37 events per year (37 events per 100 patients), from 116 events to 79 events per 100 patients.
| Outcome compared with placebo | BOREAS | NOTUS | Pooled analysis |
|---|---|---|---|
|
Primary outcome |
– |
– |
– |
|
Adjusted annualised rate of moderate or severe exacerbations per year (Rate ratio [95% CI]) |
0.70 (0.58 to 0.86, p=0.0005) |
0.66 (0.54 to 0.82, p=0.0002) |
0.69 (0.60 to 0.79, p<0.0001) |
|
Secondary outcomes |
– |
– |
– |
|
Change from baseline in prebronchodilator FEV1 at week 12. (Least-Squares mean difference [95% CI]) |
+83 ml (42 to 125, p<0.0001) |
+82 ml (40 to 124, p=0.0001) |
+83 ml (53 to 112, p<0.0001) |
|
Change from baseline in prebronchodilator FEV1 at week 52. (Least-Squares mean difference [95% CI]) |
+83 ml (38 to 128, p=0.0003) |
+62 ml (11 to 113, p=0.0182) |
+73 ml (40 to 107, p<0.0001) |
|
Change from baseline to week 52 in SGRQ total score. (Least-Squares mean difference [95% CI]) |
−3.4 (-5.5 to −1.3, p=0.0017) |
−3.4 (-5.8 to -0.9, p=0.0068) |
−3.4 (−5.0 to −1.8, p<0.0001) |
|
Percentage of patients with a change of at least 4 points in the SGRQ total score at week 52. (OR [95% CI]) |
51.5 with dupilumab; 43.1 with placebo (OR 1.4 [1.1 to 1.9, p=0.0089]) |
51.4 with dupilumab; 46.5 with placebo (OR 1.2 [0.9 to 1.6, p=0.3329]) |
51.4 with dupilumab; 44.6 with placebo (OR 1.3 [1.1 to 1.6, p=0.0089]) |
|
Change in Evaluating Respiratory Symptoms in COPD (E-RS–COPD) total score from baseline to week 52. (Least-squares mean difference [95% CI]) |
−1.1 (−1.8 to −0.4, p=0.001) |
−0.6 (−1.4 to 0.2, no p value reported) |
−0.9 (−1.4 to −0.4, p=0.0006) |
Abbreviations: CI, confidence interval; E-RS–COPD, evaluating respiratory symptoms in chronic obstructive pulmonary disease; FEV1,forced expiratory volume in 1 second; OR, odds ratio; SGRQ, St. George's Respiratory Questionnaire.
This page was last updated: