Table 2.
Comparison of Biologics by Seminal Studies
| BIOLOGIC AGENT | POPULATION | EXACERBATION RATES |
LUNG FUNCTION |
SYMPTOM SCORES |
REF. |
|---|---|---|---|---|---|
| OMALIZUMAB | Severe, allergic asthma Size: 525 Age, mean: 39.0–39.3; range: 12–74 Pre-treatment FEV1: 67.7–68.2% Time: 28 weeks |
Exacerbations per patient (during trial) SSP: −48.1% SRP: −40.9% |
Pre-BDR FEV1 (% predicted) +2.93% |
N/A |
Busse et al Phase III[31] |
| OMALIZUMAB | Stable, moderate-severe allergic asthma Size: 546 Age, mean: 39.0–40.0;range: 12–76 Pre-treatment FEV1: 69.8–69.9% Time: 28 weeks |
Exacerbations per patient (during trial) SSP: −57.6% SRP: −52.0% |
N/A | N/A | Solèr et al. [44] |
| OMALIZUMAB | Severe, poorly controlled asthma Size: 419 Age, mean: 43.3–43.4:range: 12–75 Pre-treatment FEV1:61.0–61.6% Time: 28 weeks |
Rate of exacerbations (during trial) −26%* Rate of severe exacerbations (during trial) −50% |
Pre-BDR FEV1 +0.094 FEV1 % predicted +2.8% |
AQLQ +0.45 |
INNOVATE Phase III [49] |
| OMALIZUMAB | Severe, poorly controlled, allergic asthma Size: 850 Age, mean: 43.7–45.3; range: 12–75 Pre-treatment FEV1: 64.4–65.4% Time: 48 weeks |
Rate of exacerbations (during trial) −25% |
N/A |
AQLQ(S) +0.29 Asthma Symptom Score −0.26 |
EXTRA [50] |
| MEPOLIZUMAB | Severe, uncontrolled, eosinophilic asthma Size: 616 Age, mean: 46.4–50.2, range: 12–74 Initial FEV1: 59–61% Time: 52 weeks |
Exacerbations (per patient per year) 75mg: −48% 250mg: −39% 750mg:−52% |
Pre-BDR FEV1 75mg: +0.061L 250mg: +0.081L 750mg: +0.056L |
ACQ-6 75mg: −0.16 250mg: −0.27 750mg: −0.20 AQLQ 75mg: +0.08 250mg: +0.05 750mg: +0.22 |
DREAM Phase II [53] |
| MEPOLIZUMAB | Severe, uncontrolled, eosinophilic asthma Size: 576 Age, mean: 49–51 years, range: 12–82 years Initial FEV1: 59–62% Time: 32 weeks |
Exacerbations (per patient per year) IV: −47% SC: −53% |
Pre-BDR FEV1 IV: +0.100L SC: +0.098L Post-BDR FEV1 IV: +0.146L SC: +0.138L |
ACQ-5 IV: −0.42 SC: −0.44 SGRQ IV: −6.4 SC: −7.0 |
MENSA Phase III[54] |
| RESLIZUMAB | Moderate-severe, uncontrolled, eosinophilic asthma Size: 953 Age: median: 48–49, range: 12–75 Pre-treatment FEV1: 63.6–70.4% Time: 52 weeks |
Exacerbations (per patient per year) Study 1: −50% Study 2: −59% Pooled Data: −54% |
Pre-BDR FEV1** Study 1: +0.126L Study 2: +0.090L Pooled Data: +0.11L |
AQLQ +0.23 ACQ-7 −0.25 ASUI +0.05 Pooled Data** |
Castro et al. Phase III [57] |
| BENRALIZUMAB+ | Severe, uncontrolled, eosinophilic asthma Size: 1306 Age, mean: 48.8–50.0; range 12–75 Pre-treatment FEV1: 57.7–58.9% Time: 56 weeks |
Annual Rate Ratio Q4w: −36% Q8w: −28% |
Pre-BDR FEV1** Q4w: +0.125L Q8w: +0.116L |
Total Asthma Symptom Score
Q4w: −0.12 Q8w: −0.23 ACQ-6 Scores** Q4w: −0.19 Q8w: −0.25 AQLQ(S) +12 Scores** Q4w: +0.16 Q8w: +0.24 |
CALIMA Phase III[59] |
| BENRALIZUMAB+ | Severe, uncontrolled, eosinophilic asthma Size: 1205 Age, mean: 47.6–50.1; range: 12–75 Pre-treatment FEV1: 56.1–57.4% Time: 48 weeks |
Annual Rate Ratio
Q4w: −45% Q8w: −51% |
Pre-BDR FEV1** Q4w: +0.106L Q8w: +0.159L |
Total Asthma Symptom Score**
Q4w: −0.08 Q8w: −0.25 ACQ-6** Q4w: −0.15 Q8w: −0.29 AQLQ[S]+12** Q4w: +0.18 Q8w: +0.30 |
SIROCCO Phase III [60] |
| BENRALIZUMAB | Severe, uncontrolled, eosinophilic and oral glucocorticoid- dependent asthma Size: 220 Age, mean 49.9–52.9; range: n/a Pre-treatment FEV1: 57.4–62.0% Time: 28 weeks |
Annual Exacerbation Rate Q4w: −55% Q8w: −70% |
Pre-BDR FEV1*** (week 20) Q4w: +0.256L Q8w: +0.222L |
ACQ-6
Q4w: −0.24 Q8w: −0.55 AQLQ(S)+12 Q4w: +0.23 Q8w: +0.45 |
ZONDA [61] |
| DUPILUMAB | Persistent, moderate-severe, eosinophilic asthma Size: 104 Age: mean: 37.8–41.6, range: 18–65 Pre-treatment FEV1: 72.0% Time: 12 weeks |
Occurrence of asthma exacerbation (during trial) −87% |
Pre-BDR FEV1 +0.270L |
ACQ-5 −0.73 Asthma symptom scores −0.7 SNOT-22 −8.49 |
Wenzel et al. Phase IIA [63] |
| DUPILUMAB | Uncontrolled,moderate-to-severe asthma Size: 1902 Age: mean: 47.9, range: 12+ Pre-treatment FEV1: 58.43% Time: 52 weeks |
Adjusted annualized rate of severe exacerbations Overall: 200mg: −47.7% 300mg: −46.0% Eos-high: 200mg: −65.8% 300mg: −67.4% |
Pre-BDR FEV1 Overall: 200mg: +0.14L 300mg: +0.13L Eos-high: 200mg: +0.21L 300mg: +0.24L |
AQLQ
200mg: +1.28 300mg: +1.29 ACQ-5 200mg: −0.15 300mg: −0.16 |
Castro et al. Phase 3[64] |
| DUPILUMAB | Severe, oral glucocorticoid-dependent asthma Size: 210 Age: mean: 50.7–51.9, range: >12 Pre-treatment FEV1: 51.64–52.69% Time: 24 weeks |
Annualized rate of severe exacerbation events Overall: −59% Eos-high: −71% Eos-low: −60% |
Pre-BDR FEV1** Overall: +0.22L Eos-high: +0.32L Eos-low: +0.24L |
ACQ-5** Overall: −0.47 |
Rabe et al.[65]. |
Index
Abbreviations: SSP: steroid-stable phase, SRP: steroid-reduction phase, IV: intravenous, SC: subcutaneous, Exac.: exacerbation, Sx: symptoms, Dx: diagnosis, OGCs: oral glucocorticoids, FOE: fluticasone or equivalent, BPD: beclomethasone dipropionate, HD: high dose, mo: months, adoles: adolescents, maint: maintenance, Q4w: Q4 weeks, Q8w: Q8 weeks. Eosinophil-high: ≥300 cells/μL. Eosinophil-low: <150 cells/μL. Exacerbation rate column: values are reported as “rate reduction versus placebo”, unless otherwise noted. Lung function and symptom column: values are reported as “difference from placebo”, unless otherwise noted. Un-bolded values demarcate results that did not meet statistical significance.
Key:
*
Post-hoc analysis
**
LS mean ∂ vs placebo
***
No significant difference by week 28 (end of study)