Biomarkers that predicted treatment response in phase III RCTs of biologic therapies in severe obstructive lung disease
| Cut-off (greater response versus lesser/no response) | Outcome(s) | Trial (treatment) |
| Phase III RCTs in patients with severe asthma | ||
| IgE | ||
| ≥274 IU·mL−1, 148–273 IU·mL−1 and 76–147 IU·mL−1 versus 0–75 IU·mL−1 | Exacerbation rate | INNOVATE [117] (omalizumab) |
| Emergency visits | ||
| FEV1 | ||
| AQLQ score | ||
| Blood eosinophil count | ||
| ≥260 cells per μL versus <260 cells per μL | Exacerbation rate | EXTRA [82] (omalizumab) |
| Continuous modelling (higher blood eosinophil count = greater response) | Exacerbation rate | DREAM [100] (mepolizumab) |
| Continuous modelling (higher blood eosinophil count = greater response); identified a cut-off of ≥150 cells per μL versus <150 cells per μL | Exacerbation rate | DREAM/MENSA [118] (mepolizumab) |
| Trends also noted for: FEV1 SGRQ score ACQ-5 score | ||
| Continuous modelling (higher blood eosinophil count = greater response) | Exacerbation rate | MUSCA [102] (mepolizumab) |
| FEV1 | ||
| ACQ-5 score | ||
| ≥400 cells per μL versus <400 cells per μL | FEV1 | Corren et al. [105] (reslizumab) |
| ≥300 cells per μL versus <300 cells per μL | Exacerbation rate | LAVOLTA I and LAVOLTA II [108] (lebrikizumab) |
| ≥300 cells per μL versus <300 cells per μL | FEV1 | CALIMA [106] (benralizumab) |
| ≥300 cells per μL versus <300 cells per μL | Exacerbation rate | SIROCCO [107] (benralizumab) |
| FEV1 | ||
| ≥300 cells per μL and ≥150–<300 cells per μL versus <150 cells per μL | FEV1 | LIBERTY ASTHMA QUEST [109] (dupilumab) |
| ≥300 cells per μL versus <300 cells per μL | OCS dose | LIBERTY ASTHMA VENTURE [64] (dupilumab) |
| Exacerbation rate | ||
| FEV1 | ||
| FeNO | ||
| ≥19.5 ppb versus <19.5 ppb | Exacerbation rate | EXTRA [82] (omalizumab) |
| ≥50 ppb and ≥25–<50 ppb versus <25 ppb | FEV1 | LIBERTY ASTHMA QUEST [109] (dupilumab) |
| ≥50 ppb and ≥25–50 ppb versus <25 ppb | OCS dose | LIBERTY ASTHMA VENTURE [64] (dupilumab) |
| Exacerbation rate | ||
| FEV1 | ||
| ≥37 ppb versus <37 ppb or all patients | Exacerbation rate | STRATOS 1 [110] (tralokinumab) |
| FEV1 | ||
| AQLQ score | ||
| ACQ-6 score | ||
| Total asthma symptom score | ||
| Periostin | ||
| ≥50 ng·mL−1 versus <50 ng·mL−1 | Exacerbation rate | EXTRA [82] (omalizumab) |
| Combined blood eosinophil count+periostin | ||
| ≥300 cells per μL or ≥50 ng·mL−1 versus <300 cells per μL or <50 ng·mL−1 | Exacerbation rate | LAVOLTA I and LAVOLTA II [108] (lebrikizumab) |
| Phase III RCTs in patients with severe COPD | ||
| Blood eosinophil count | ||
| ≥500 cells per μL, ≥300–<500 cells per μL and ≥150–<300 cells per μL versus >150 cells per μL | Exacerbation rate | METREX/ METREO [33] (mepolizumab) |
RCT: randomised controlled trial; FEV1: forced expiratory volume in 1 s; AQLQ: Asthma Quality of Life Questionnaire; FeNO: exhaled nitric oxide fraction; COPD: chronic obstructive pulmonary disease; SGRQ: St George's Respiratory Questionnaire; ACQ-n: n-item Asthma Control Questionnaire; OCS: oral corticosteroid.