First author [ref]/year/drug | Disease (severity) | Study design | Dosage/ delivery | Baseline eosinophil count | Comments on eosinophilia | Outcome summary |
---|---|---|---|---|---|---|
Garrett [54]/ 2003 | HES | n= 4 open label | 3 doses 10 mg/kg or 750 mg (max) i.v. every 4 wk | • Blood eos > 750/μL after an 8 wk pre-treatment run in period | • Blood eos reduced in all patients, sustained in 12 wk follow-up span | • Symptoms and quality of life improved in all patients |
Mepolizumab | Severe, uncontrolled | |||||
• Progressive improvements in FEV1 | ||||||
Rothenberg [55]/2008 | HES | n= 85 db, pc,, mc, parallel group study | 750 mg i.v. at 4 wk interval 36 wk study | • Blood eos<1000/μL after a 6 week run-in period with prednisone therapy | • Blood eos<600/μl for 8 wks, achieved in 95% patients in drug group , 45% placebo, p< 0.0001 | • Primary end-point (reduction of prednisone to 10 mg or less without clinical severity) was reached 84% of patients in drug group, 43% placebo, p< 0.0001 |
Mepolizumab | (patients negative for FIP1L1-PDGFRA fusion gene) | |||||
Baseline (median all patients): | ||||||
• Blood eos (x 109/L): 0.447 ± 0.694 | • Sputum eos not measured | |||||
Roufosse [56]/ 2010 | L-HES | n=85 db, pc, international study | 750 mg i.v. at 4 wk interval 36 wk study | • Controlled eosinophil levels (<1000/μL)by OCS monotherapy at a daily dose of 20–60 mg. | • Blood eos were maintained ≤ 600/μL by L-HES (Mepolizumab group) for 8 wks and during the entire length of the study compared to placeb0 | • Significant lower mean daily prednisone dose of 4.64 mg in drug dosed group , compared to 28.3 mg in placebo (P=0.014) |
Mepolizumab | (T-lymphocytic variant) – recruitment based on T-cell phenotyping and profile negative for FIP1L1-PDGFRA gene | |||||
• Patients with low CCL17 levels were seen to significantly maintain blood eos ≤ 600 μl | ||||||
Kim [57]/2010 | EGPA | n= 7 | 4 monthly 750 mg (i.v) | • Mean eos count 3.4% | • Reduction in eos count from 2.9% (mean) to 0.4 at wk 16 (wash-out phase) | • Mean reduction in corticosteroid 18.8 mg to 4.6 mg, P< 0.001 |
Mepolizumab | Mean FEV1 76% predicted | open –label pilot study | 40 wk study | |||
Mean Prednisone dose 12.9 mg | • Eos mean 3.8% at wk 40 | • Significant improvement of ACQ during study and wash-out phase | ||||
• Patients clinically stable through study period, but EGPA manifestations on cessation of test drug | ||||||
Moosig [58] 2011 | Active refractory (n= 3) or relapsing (n= 7) active EGPA | sc, phase II, uncontrolled | 750 mg i.v. once every 4 weeks (9 infusions in total) | • BVAS does not include eos as a criteria | • 6 patients (≥120 cells/μl) showed reduction in eos from their respective baseline, maintained throughout. | • Disease extent dropped from 4at weel 0 to 0 at week 32 (p= 0.009) |
Mepolizumab | ||||||
OCS ≥ 12.5 mg/daily | • Variations in eos levels ranged from 13 – 4282 cells/μl | • Eight patients achieved remission at week 32 (primary end-point), BVAS score= 0, OCS<7.5 mg/day | ||||
BVAS ≥ 3 | ||||||
• No relapse occurred | ||||||
Brightling [59] 2014 | Moderate to severe | n= 101 | 100 mg s.c. every 4 weeks (three doses), then every 8 weeks (five doses) over 48 weeks | • Inclusion criteria Sputum eosinophils > 3% at screening or past year | • Significant reduction in both sputum and blood eosinophil levels at week 4, and maintained till week 56 | • No changes in acute exacerbation rates, lung function or symptom score between treatment and placebo arm at week 56 for overall population |
Benralizumab | COPD | Phase II | ||||
Exacerbations ≥ 1 in previous year | Mc, pb,db | |||||
• Sub-group analysis stratified results based on ≥ 150 or ≥ 200 or ≥ 300 eosinophils/μl | • Increase in blood and sputum eos after final dose | |||||
• non-significant decrease in exacerbation rate compared with placebo in patients with baseline eosinophil counts of ≥ 150 cells/ uL(p= 0°84), ≥ 200 cells/ uL (p= 0°26), or 300 cells/μl (p= 0°28) | ||||||
 |  |  |  |  |  | • Changes in FEV1 at week 56 was significant in patients with blood eosinophil counts ≥150 cells/ μL (p= 0°031) or ≥ 200 cells/ μL (p= 0°035), and non-significant in those with counts of ≥ 300 cells/μL (p= 0°22) |