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Table 2 Anti-IL5 trials in eosinophilic lung disorders

From: Anti-IL5 therapy for asthma and beyond

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)

  1. Index: eos= eosinophils; db= double-blind; pc= placebo-controlled; mc= multi-center; sc= single-centre; FEV1= peak expiratory flow i.v.= intravenous; s.c.= sub-cutaneous; wk= week; ns= non-significant; FIP1L1–PDGFRA :Fip1-like 1/platelet-derived growth factor receptor a fusion; ACQ= Asthma Control Questionnaire; Birmingham Vasculitis Activity score= BVAS.