Anti-interleukin-5 treatment for patients with severe asthma
| Administration | Dose | Patients | Study design | Subjects n | Primary end-point | Secondary end-point | Safety | Ref. | |
| Reslizumab | Intravenously once every 4 weeks over 52 weeks | 3 mg·kg−1 | Hypereosinophilic (induced sputum eosinophils >3%), high-dose ICS, ACQ >1.5, no OCS use | Phase III, double-blind RCT | 106 | Change in ACQ score from baseline to week 15: reslizumab, 0.7; placebo, 0.3 (p=0.054) | Number of exacerbations: OR 0.33 (95% CI 0.10–1.15; p=0.0833) | [91] | |
| Mepolizumab | Intravenously once every 4 weeks over 12 weeks | 250 or 750 mg | ICS <1000 μg per day BDP equivalent | Double-blind RCT | 362 | Change from baseline in morning PEF: no significant differences | Rate of exacerbations: no significant differences | SAEs: No significant differences with placebo | [92] |
| Intravenously once every 4 weeks over 52 weeks | 750 mg | Hypereosinophilic, recurrent severe exacerbations | Double-blind RCT, 2-week course of prednisolone | 61 | Relative risk of severe exacerbations during 50 weeks: 0.57 (95% CI 0.32–0.92; p=0.02) | Change in AQLQ: mean difference between groups +0.35 (95% CI 0.08–0.62; p=0.02) in mepolizumab versus placebo group | [93] | ||
| Intravenously once every 4 weeks over 52 weeks | 75, 250 or 750 mg | Hypereosinophilic, recurrent severe exacerbations | Double-blind RCT | 621 | Reduction of severe exacerbations during 52 weeks: 75 mg, 48% (95% CI 31–61%; p<0.0001); 250 mg, 39% (95% CI 19–54%; p=0.0005); 750 mg, 52% (95% CI 36–64%; p<0.0001) | Difference from placebo in change in ACQ from baseline: 75 mg, −0.16 (95% CI −0.39–0.07); 250 mg, −0.27 (95% CI −0.51–0·04); 750 mg, −0.20 (95% CI −0.43–0.03) | SAEs: no significant differences with placebo | [94] | |
| Intravenously or subcutaneously once every 4 weeks over 32 weeks | 75 mg i.v. or 100 mg s.c. | Hypereosinophilic, recurrent exacerbations; high-dose ICS for one group | Double-blind, double-dummy RCT | 576 | Reduction of exacerbations during 32 weeks: 75 mg i.v., 47% (95% CI 29–61%; p<0.001); 100 mg s.c., 53% (95% CI 37–65%; p<0.001) | Improvement from baseline in SGRQ: 75 mg i.v., +6.4; 100 mg s.c., 7.0 (p<0.001) Improvement from baseline in ACQ-5: 75 mg i.v., 0.42; 100 mg s.c., 0.44 (p<0.001) | SAEs: no significant differences with placebo | [95] | |
| Subcutaneously once every 4 weeks over 24 weeks | 100 mg | Hypereosinophilic (>300 per mm3), OCS use >6 months | Double-blind RCT; phase of optimisation of OCS regimen | 135 | Reduction in daily OCS dose: OR 2.39 (95% CI 1.25–4.56; p=0.008) | Proportion of patients with >50% reduction of OCS dose: OR 2.26 (95% CI 1.10–4.65; p=0.03) | SAEs: no significant differences with placebo | [96] | |
| Benralizumab | Subcutaneously once every 4 weeks then every 8 weeks over 52 weeks | 2, 20 or 100 mg | Medium/high-dose ICS use, 2–6 exacerbations per year, stratification by eosinophilic status | Phase IIb, double-blind, dose-ranging study; placebo controlled | 324 eosinophilic 285 noneosinophilic | Annual exacerbation rate in eosinophilic individuals: 100 mg, 41% (95% CI 11–60%; p=0.096; 95% CI 80%); no significant differences in 2- or 20-mg group | SAEs: no significant differences; AEs: significantly more nasopharyngitis and injection site reactions | [97] |
ICS: inhaled corticosteroids; ACQ: Asthma Control Questionnaire; OCS: oral corticosteroids; BDP: beclomethasone dipropionate; RCT: randomised controlled trial; PEF: peak expiratory flow; AQLQ: Asthma Quality of Life Questionnaire; SGRQ: St George's Respiratory Questionnaire; SAE: serious adverse event; AE: adverse event.