Mepolizumab in the treatment of eosinophilic chronic obstructive pulmonary disease

Figures & data

Figure 1 Mechanism of Action for monoclonal antibodies targeting IL-5. Mepolizumab and reslizumab bind and neutralize circulating IL-5 preventing interaction of IL5 with IL-5Rα. Benralizumab directly binds IL-5Rα activating NK cells and macrophage to induce antibody-mediated cytotoxicity of eosinophils and basophils. Republished with permission of Dove Medical Press Ltd, from Benralizumab: a unique IL-5 inhibitor for severe asthma, Tan LD, Bratt JM, Godor D, et al, 9, 2016; permission conveyed through Copyright Clearance Center, Inc.⁴⁷

Abbreviations: ADCC, antibody-dependent cell-mediated cytotoxicity; IL, interleukin; mAB, monoclonal antibody; NK, natural killer.

Table 1 Baseline characteristics, efficacy end points, and randomization

Study	Treatment arms	Subjects randomized	Study endpoints	Study population
METREX	Overall^a Mepo 100 mg Placebo High Stratum^b Mepo 100 mg Placebo Low Stratum^c Mepo 100 mg Placebo	417 419 233 229 184 190	Primary: -Rate of moderate to severe AECOPD Secondary: -Time to first moderate to severe AECOPD -Rate of AECOPD requiring ED visit or hospitalization -Rate of severe AECOPD -Change from baseline SGRQ-C score -Change from baseline CAT score	COPD patients with exacerbation risk despite ICS+LABA+LAMA maintenance therapy (two or more moderate AECOPD or one severe AECOPD)
METREO^d	Mepo 100 mg Mepo 300 mg Placebo	223 225 226

Notes: ^aAll subjects regardless of peripheral blood eosinophil count. ^bHigh Stratum: subjects with blood eosinophil counts ≥150 cells/μL at screening or ≥300 cells/μL within last 12 months. ^cLow Stratum: subjects with blood eosinophil counts <150 cells/μL at screening with no count ≥300 cells/μL within last 12 months. ^dAll subjects (in METREO): blood eosinophil counts ≥150 cells/μL at screening or ≥300 cells/μL within the last 12 months.

Abbreviations: AECOPD, acute exacerbation of COPD; CAT, COPD Assessment Test; ED, emergency department; ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; LAMA, long-acting anti-muscarinic; SGRQ, Saint George’s Respiratory Questionnaire.

Table 2 Primary and secondary efficacy end points

Endpoint	METREX High Stratum^a	METREO^b
	Mepolizumab 100 mg vs Placebo	Mepolizumab 100 mg vs Placebo	Mepolizumab 300 mg vs Placebo
Primary endpoint
Frequency of moderate/severe AECOPD (Rate ratio)	0.82 (0.68 to 0.98) Adjusted p=0.04 ✓	0.80 (0.65 to 0.98) Adjusted p=0.07 x	0.86 (0.70 to 1.05) Adjusted p=0.14 x
Secondary endpoints
Time to first moderate/severe AECOPD (Hazard ratio)	0.75 (0.60 to 0.94) Adjusted p=0.04 ✓	0.82 (0.64 to 1.04) Adjusted p=0.14 x	0.77 (0.60 to 0.97) Adjusted p=0.14 x
Exacerbations leading to ED visit or hospitalization (Rate ratio)	1.16 (0.77 to 1.75) Adjusted p=0.60 x	0.59 (0.35 to 0.98) Adjusted p=0.14 x	0.83 (0.51 to 1.34) Adjusted p=0.45 x
SGRQ C total score change from baseline (Mean Difference)	0.2 (−2.8 to 3.2) Adjusted p>0.99 x	−1.8 (−4.5 to 0.8) Adjusted p=0.45 x	−0.1 (−2.8 to 2.6) Adjusted p=0.93 x
CAT score changes from baseline (Mean Difference)	−0.8 (−2.0 to 0.5) Adjusted p>0.99 x	−1.1 (−2.3 to 0.0) Adjusted p=0.93 x	−0.4 (−1.5 to 0.8) Adjusted p=0.93 x

Notes: ^aMETREX High Stratum: subjects with blood eosinophil counts ≥150 cells/μL at screening or ≥300 cells/μL within last 12 months. ^bMETREO (all subjects): blood eosinophil counts ≥150 cells/μL at screening or ≥300 cells/μL within last 12 months. ✓Indicates result was statistically significant (level of 0.05) after adjustment for multiple testing. x Indicates result was not statistically significant (level of 0.05) after adjustment for multiple testing.

Abbreviations: AECOPD, acute exacerbation of COPD; CAT, COPD Assessment Test ED, emergency department; SGRQ, Saint George’s Respiratory Questionnaire.

Figure 2 Exacerbations (moderate or severe) by screening eosinophil count. The rate of moderate or severe exacerbations quantified based on peripheral blood eosinophil count. At the time of screening, data are from a pre-specified meta-analysis from METREO and METREX. From The New England Journal of Medicine, Pavord ID, Chanez P, Criner GJ, et al, Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease, 377, 1613-1629. Copyright © (2017) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.⁵⁵

Tan LD, Bratt JM, Godor D, Louie S, Kenyon NJ. Benralizumab: a unique IL-5 inhibitor for severe asthma. J Asthma Allergy. 2016;9:71–81. doi:10.2147/JAA.S7804927110133

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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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