Table 1.
Agents targeting IL-5 in COPD
| Agent/Trials | Dose, frequency | Study design, duration, number of subjects | Outcomes |
|---|---|---|---|
| Mepolizumab (Anti-IL5) | |||
| Dasgupta et al,29 NCT01463644 A pilot phase II |
750 mg monthly IV | Single center, Randomized, double blind, placebo controlled 24 weeks 18 patients |
Primary: Mepolizumab reduced sputum eosinophil counts from 11% to 0.5% at 6 months vs placebo 7% to 2%(p<0.05). Blood eosinophils decreased from 0.7+0.5 cells.mm−3 to 0.03+0.05 cells mm−3(p<0.05). Secondary: No significant difference in the lung function parameters, exacerbation rates, sputum markers of remodeling, health-related quality of life scores. |
| Pavord et al,28 NCT02105948 (METREX), Phase III NCT02105961 (METREO), Phase III |
100 mg subcutaneous q 4 weeks 300 mg subcutaneous q 4 weeks |
Multicenter Randomized, double blind, placebo controlled 52 weeks 1,510 patients |
Primary: Significantly reduction in the annual exacerbation rate vs placebo for patients with eosinophilic phenotype (patients with blood eosinophil counts 150 cells/μL at screening or ≥300 cell/μL within the previous (1.40 versus 1.71; n=462; p=0.04); difference was not significant in the overall population Secondary: Significant reduction in time to first moderate/severe exacerbation in the eosinophilic population (192 versus 141 days; p=0.04); no statistically significant differences in any other endpoints between groups Primary: Rate ratios for exacerbations were 0.80 (p=0.07) and 0.86 (p=0.14) versus placebo for 100-mg and 300-mg dosages of mepolizumab, respectively Secondary: No statistical significance in any endpoints versus placebo in either group. |
| Benralizumab IL-(IL5Rα receptor antagonist) | |||
| Brightling et al,33 NCT01227278 Phase IIa |
100 mg subcutaneous q 4 weeks | Single center randomized, double blind, placebo controlled 56 weeks 101 patients |
Primary: Annualized rate of acute exacerbations of COPD: benralizumab 0.95, placebo 0.92 (no significant difference) Secondary: Significant increase in pre-bronchodilator FEV1 versus placebo (0.13 L versus −0.06 L; p=0.014); no significant differences between groups in change from baseline for mean SGRQ-C, CRQ-SAS, BODE scores; no difference in treatment- emergent adverse events between treatment groups. |
| Criner et al, GALATHEA34 Phase III Celli et al, TERRANOVA35 Phase III |
Undisclosed dosage | Multicenter Randomized, double blind, placebo controlled 56–60 weeks |
Results are not yet released, preliminary data revealed no difference in primary outcome in decreasing exacerbations in patients with COPD. |
Abbreviations: BODE, BMI, Airway Obstruction, Dyspnea, Exercise tolerance; CRQ-SAS, Chronic respiratory Questionnaire-Standardized dyspnea domain; IV, Intravenous; Q, every; SGRQ-C, St. George’s Respiratory Questionnaire-COPD.