Targeting IL-5 in COPD

Figures & data

Figure 1 T2 inflammatory pathway and the target site for anti-IL-5 agents.

Abbreviations: CRTh2, chemoattractant receptor homolog from Th2 cells; ILC2, innate lymphoid cells; TSLP, thymic stromal lymphopoietin; IL, Interleukin.

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,^Citation29 NCT1463644 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,^Citation28 NCT2105948 (METREX), Phase III NCT2105961 (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,^Citation33 NCT1227278 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, GALATHEA^Citation34 Phase III Celli et al, TERRANOVA^Citation35 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.

Dasgupta A, Kjarsgaard M, Capaldi D, et al. A pilot randomised clinical trial of mepolizumab in COPD with eosinophilic bronchitis. Eur Respir J. 2017;49:3. doi:10.1183/13993003.02486-2016

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Pavord ID, Chanez P, Criner GJ, et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med. 2017;377(17):1613–1629. doi:10.1056/NEJMoa170820828893134

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Brightling CE, Bleecker ER, Panettieri RA Jr., et al. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med. 2014;2(11):891–901. doi:10.1016/S2213-2600(14)70187-025208464

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Benralizumab Efficacy in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History (GALATHEA) NCT2138916; 2018.

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Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History (TERRANOVA) NCT2155660; 2018.

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