. 2021 Sep 16;77(3):778–797. doi: 10.1111/all.15056

TABLE 1.

Phase III ^a mepolizumab clinical trials, primary endpoints, and key inclusion/exclusion criteria across eosinophilic‐driven diseases

Eosinophilic‐driven disease and studies	ITT/mITT/treated population, n	Key criteria for patient population (full details are in the publications)	Treatment dosages	Primary and secondary endpoint results
*Severe eosinophilic asthma*
DREAM ¹³ Pavord, et al. 2012	616	Aged 12–74 years with asthma Receiving high‐dose ICS with a second controller ≥2 exacerbations requiring systemic corticosteroid treatment in the previous year Eosinophilic inflammation	Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV Placebo Every 4 weeks for 52 weeks Treatment was plus SoC	Primary Rate of clinically significant exacerbations/patient/year ^b : reduced vs. placebo by: 48% (95% CI 31, 61; p < .001), mepolizumab 75 mg IV 39% (19, 54; p < .001), mepolizumab 250 mg IV 52% (36, 64; p < .001), mepolizumab 750 mg IV Secondary Mean pre‐bronchodilator FEV₁: improved vs. placebo by: 61 ml (95% CI −39, 161), mepolizumab 75 mg IV 81 ml (−19, 180), mepolizumab 250 mg IV 56 ml (−43, 155), mepolizumab 750 mg IV Mean ACQ score: improved vs. placebo by: −0.16 (95% CI −0.39, 0.07), mepolizumab 75 mg IV −0.27 (−0.51, 0.04), mepolizumab 250 mg IV −0.20 (−0.43, 0.03), mepolizumab 750 mg IV Mean AQLQ score: improved vs. placebo by: 0.08 (95% CI −0.16, 0.32), mepolizumab 75 mg IV 0.05 (−0.19, 0.29), mepolizumab 250 mg IV 0.22 (−0.02, 0.46), mepolizumab 750 mg IV Geometric mean FeNO: ratio to placebo: 0.97 (95% CI 0.82, 1.15), mepolizumab 75 mg IV 0.90 (0.76, 1.06), mepolizumab 250 mg IV 0.96 (0.81, 1.13), mepolizumab 750 mg IV
MENSA ¹⁴ Ortega, et al. 2014	576	Aged 12–82 years with asthma Receiving high‐dose ICS with a second controller ≥2 exacerbations requiring systemic corticosteroid treatment in the previous year Blood eosinophil count ≥150 cells/µl at screening or ≥300 cells/µl during the previous year	Mepolizumab 75 mg IV Mepolizumab 100 mg SC Placebo Every 4 weeks for 32 weeks Treatment was plus SoC	Primary Rate of clinically significant exacerbations/patient/year ^b : reduced vs. placebo by: 47% (95% CI 28, 60; p < .001), mepolizumab 75 mg IV 53% (95% CI 36, 65; p < .001), mepolizumab 100 mg SC Secondary Mean pre‐bronchodilator FEV₁: improved vs. placebo by: 100 ml (95% CI 13, 187; p = .02), mepolizumab 75 mg IV 98 ml (95% CI 11, 184; p = .03), mepolizumab 100 mg SC Mean ACQ score: improved vs. placebo by: −0.42 (95% CI −0.61, −0.23; p < .001), mepolizumab 75 mg IV −0.44 (95% CI −0.63, −0.25; p < .001), mepolizumab 100 mg SC Mean SGRQ score: improved vs. placebo by: −6.4 (95% CI −9.7, −3.2; p < .001), mepolizumab 75 mg IV −7.0 (−10.2, −3.8; p < .001), mepolizumab 100 mg SC
SIRIUS ⁴⁴ Bel, et al. 2014	135	Aged ≥12 years with asthma Receiving high‐dose ICS with a second controller 6‐month history of maintenance treatment with systemic corticosteroids before study entry Blood eosinophil count ≥150 cells/µl during the optimization phase or ≥300 cells/µl during the previous year	Mepolizumab 100 mg SC Placebo Every 4 weeks for 20 weeks Treatment was plus SoC	Primary Daily OCS dose reduction category (90–100%; 75–<90%; 50–<75%; >0–<50%): mepolizumab vs. placebo: overall OR of 2.39 (95% CI 1.25, 4.56; p = .008) Other Clinically significant exacerbations/patient/year ^b : reduced by 32% vs. placebo (RR 0.68 [95% CI 0.47, 0.99]; p = .04) Mean ACQ‐5 score: improved vs. placebo by −0.52 (95% CI −0.87, −0.17; p = .004) Mean SGRQ score: improved vs. placebo by −5.8 (95% CI −10.6, −1.0; p = .02) Mean pre‐bronchodilator FEV₁: improved vs. placebo by 114 ml (p = .15)
MUSCA ⁴³ Chupp, et al. 2017	551	Aged ≥12 years with asthma Receiving high‐dose ICS with a second controller ≥2 exacerbations requiring SCS treatment in the previous year Blood eosinophil count ≥150 cells/µl at screening or ≥300 cells/µl during the previous year	Mepolizumab 100 mg SC Placebo Every 4 weeks for 24 weeks Treatment was plus SoC	Primary Mean SGRQ total score: improved vs. placebo by −7.7 (95% CI −10.5, −4.9; p < .0001) ^c Secondary Mean ACQ‐5 score: improved vs placebo by −0.4 (95% CI −0.6, −0.2; p < .0001) Mean pre‐bronchodilator FEV₁ : improved vs placebo by 120 ml (95% CI 47, 192; p = .001) Rate of clinically significant exacerbations/patient/year: 58% reduction vs. placebo (RR 0.42 [95% CI 0.31, 0.56; p < .0001])
REALITI‐A ^a Harrison, et al. 2020 ⁴⁵	368	Aged ≥18 years with asthma Newly prescribed mepolizumab treatment in the real world (physician decision) Relevant medical records for ≥12 months pre‐enrollment	Mepolizumab 100 mg SC as prescribed in clinical practice (every 4 weeks) Treatment was plus SoC	Rate of clinically significant asthma exacerbations/patient/year ^b during the 12‐month mepolizumab follow‐up period vs. the pre‐mepolizumab treatment period: relative reduction of 69% (RR 0.31 [95% CI 0.27, 0.35]; p < .001) Other Median daily maintenance OCS dose: the median percent reduction during treatment up to Weeks 53–56 was 52% (95% CI 50.0, 75.0)
*EGPA*
MIRRA ⁶⁴ Wechsler, et al. 2017	136	Aged ≥18 years with a diagnosis of relapsing or refractory EGPA ^d for ≥6 months prior to the study EGPA was defined as a history or presence of asthma, a blood eosinophil count of 10% or absolute eosinophil count ≥1000 cells/µl and ≥2 criteria typical of EGPA ^d Receiving a stable dose of prednisolone or prednisone (≥7.5–≤50.0 mg/day, with or without additional immunosuppressive therapy) for ≥4 weeks before the baseline visit	Mepolizumab 300 mg SC Placebo Every 4 weeks for 52 weeks Treatment was plus SoC	Co‐primary Total accrued weeks of remission ^e : 28% of the patients in the mepolizumab group vs. 3% in the placebo group had remission for ≥24 weeks Proportion of patients who had remission: 32% patients in the mepolizumab group vs. 3% patients in the placebo group had remission at both Week 36 and week 48 (OR 16.74 [95% CI 3.61, 77.56]; p < .001).
HES
200622 ⁸² Roufosse, et al. 2020	108	Aged ≥12 years with a diagnosis of FIP1L1‐PDGFRA–negative HES ^f for ≥6 months History of ≥2 flares within the last 12 months and a blood eosinophil count ≥1000 cells/µl Stable background HES therapy for ≥4 weeks	Mepolizumab 300 mg SC Placebo Every 4 weeks for 32 weeks Treatment was in addition to existing background HES therapy (whether chronic or episodic)	Primary Proportion of patients who experienced an HES flare ^g : was 50% lower for patients receiving mepolizumab vs. placebo (n = 15/54 [28%] vs. n = 30/54 [56%]; p = .002).
*CRSwNP*
SYNAPSE ¹⁰¹ Han, et al. 2021	407	Aged ≥18 years with recurrent, refractory severe bilateral NP symptoms Eligible for repeat nasal surgery Had ≥1 nasal surgery in the last 10 years Received stable maintenance therapy for ≥8 weeks before screening, with symptoms of CRS for ≥12 weeks before screening	Mepolizumab 100 mg SC Placebo Every 4 weeks (by safety syringe) for 52 weeks Treatment was plus SoC, including intranasal corticosteroids	Co‐primary Median change from baseline in total endoscopic NP score ^h : Improved vs. placebo −0.73 (95% CI −1.11, −0.34; p < .0001) Median change from baseline in nasal obstruction VAS score ^h : Improved vs placebo: −3.14 (−4.09, −2.18; p < .0001) Key secondary Time to first nasal surgery up to Week 52: Lower risk vs. placebo: Hazard ratio 0.43 (95% CI: 0.25, 0.76; p = .0032)
*COPD*
METREX/METREO ¹²¹ Pavord, et al. 2017	836/674	Aged ≥40 years and diagnosed with COPD for ≥1 year History of COPD exacerbations in the last year (≥2 moderate or ≥1 severe exacerbations) Receiving background ICS‐based therapy in the year before screening Receiving triple inhaled therapy comprising a high‐dose ICS, LABA, and LAMA for ≥3 months before screening METREO: Eosinophilic phenotype METREX: Eosinophilic and non‐eosinophilic phenotype	METREX: mepolizumab 100 mg SC or placebo METREO: mepolizumab 100 mg SC, mepolizumab 300 mg SC or placebo In both trials, treatment was administered every 4 weeks, for 52 weeks Treatment was plus SoC	Primary Rate of moderate/severe exacerbations reduced vs. placebo by: METREX (eosinophilic phenotype): 18% (RR 0.82; [95% CI 0.68, 0.98]; p = .04), mepolizumab 100 mg SC METREO: 20% (RR 0.80 [95% CI 0.65, 0.98]; p = .07), mepolizumab 100 mg SC METREO: 14% (RR 0.86 [95% CI 0.70, 1.05]; p = .14), mepolizumab 300 mg SC
MATINEE ¹²⁴ ClinicalTrials.gov, 2020. https://clinicaltrials.gov/ct2/show/NCT04133909	Target: 800	Aged ≥40 years History of COPD exacerbations in the last year (≥2 moderate or ≥1 severe exacerbations) Patients with COPD with an eosinophilic phenotype (blood eosinophil count ≥300 cells/µl at screening and ≥150 cells/µl during the previous year)	Mepolizumab 100 mg SC Placebo Every 4 weeks for 52 weeks Treatment s plus SoC (ICS plus 2 additional COPD medications [ie, ICS‐based triple therapy])	Primary Annualized rate of moderate/severe exacerbations Primary endpoint: rate of moderate or severe exacerbations Study not yet completed

Abbreviations: BVAS, Birmingham Vasculitis Activity Score; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CRSwNP, chronic rhinosinusitis with nasal polyposis; ED, emergency department; EGPA, eosinophilic granulomatosis with polyangiitis; FeNO, an exhaled nitric oxide concentration; FEV₁, forced expiratory volume in 1 s; HES, hypereosinophilic syndrome; HRQOL, health‐related quality of life; ICS, inhaled corticosteroids; ITT, intent‐to‐treat; IV, intravenous; LABA, long‐acting β₂‐agonist; LAMA, long‐acting muscarinic‐receptor antagonist; MCID, minimal clinically important difference; mITT, modified intent‐to‐treat; NP, nasal polyposis; OCS, oral corticosteroids; OR, odds ratio; RR, rate ratio; SC, subcutaneous; SCS, systemic corticosteroid(s); SoC, standard of care; VAS, visual analog scale.

^{^a}

All trials are Phase III except for the REALITI‐A study, which was a real‐world study.

^{^b}

Clinically significant exacerbations were defined as the worsening of asthma requiring systemic corticosteroids for ≥3 days (or a doubling [or more] of the existing maintenance dose of OCS for ≥3 days if patients were on maintenance OCS) or an ED visit or hospital admission.

^{^c}

A reduction in SGRQ is indicative of improvement. The SGRQ is scored from 0 to 100, with higher scores indicating worse HRQOL. The MCID is a 4‐point reduction in score. ⁴³

^{^d}

Criteria typical of EGPA included histopathological evidence of eosinophilic vasculitis, perivascular eosinophilic infiltration, or eosinophil‐rich granulomatous inflammation; neuropathy; pulmonary infiltrates; sinonasal abnormality; cardiomyopathy; glomerulonephritis; alveolar hemorrhage; palpable purpura; or antineutrophil cytoplasmic antibody positivity.

^{^e}

Defined as a BVAS of 0 and the receipt of prednisolone or prednisone ≤4.0 mg/day during the 52‐week period. The BVAS version 3 has a scale of 0–63, with higher scores indicating greater disease activity.

^{^f}

HES diagnosis was based on organ system involvement and/or dysfunction that could be directly related to a blood eosinophil count more than 1500 cells/µl on ≥2 occasions, and/or tissue eosinophilia, without a discernible secondary cause.

^{^g}

HES flares during the treatment period were defined as either of the following: physician‐documented change in clinical signs or symptoms of a HES‐related clinical manifestation that required an increase in maintenance OCS dose by ≥10 mg prednisone equivalent/day for 5 days or an increase in/addition of any cytotoxic and/or immunosuppressive HES therapy; 2 receipt of ≥2 courses of blinded OCS during the treatment period, blinded OCS was administered for approx. Two weeks if the blood eosinophil count exceeded a predefined threshold (2 × baseline value [randomization] or baseline value +2500 cells/µl).

^{^h}

Co‐primary endpoints. Total endoscopic NP score was the sum of left and right nostril scores ranging from 0 (no polyps) to 4 (large polyps causing complete obstruction of the inferior meatus) giving a total score of up to 8. VAS scores ranged from 0.0 to 10.0.