Anti-interleukin-13 treatment for patients with severe asthma
| Drug | Administration | Dose | Patients | Study design | Subjects n | Primary end-point | Secondary end-point | Safety | Ref. |
| Lebrikizumab | Subcutaneously, once-monthly over 6 months | 250 mg | Severe asthma, ICS dose between 200 and 1000 μg fluticasone propionate equivalent | Phase III, double-blind RCT; placebo controlled, dose ranging | 219 | Mean±sem change in FEV1 from baseline at week 12: lebrikizumab +9.8±1.9% versus placebo +4.3±1.5% (p=0.02); relative increase higher in high-periostin subgroup (14±3.1% versus 5.8±2.1%) | No significant results concerning rates of exacerbations and change in ACQ-5 from baseline at week 12 | SAEs: no significant differences; more musculoskeletal events in lebrikizumab group (13.2% versus 5.4%, p=0.045) | [105] |
| Tralokinumab | Subcutaneously, once every 2 weeks over 13 weeks | 150, 300 or 600 mg | Moderate to severe asthma | Phase II, double-blind RCT; placebo controlled | 194 | Mean±sd change in ACQ-6 score from baseline at week 13: tralokinumab −0.76±1.04, placebo −0.61±0.90 (p=0.375) | Mean±sd change from baseline in FEV1 tralokinumab 0.21±0.38 L versus placebo 0.06±0.48 L (p=0.072) Decrease in β2-agonist use (puffs per day): tralokinumab 0.68±1.45 versus placebo 0.10±1.49 (p=0.020) | SAEs: no significant differences with placebo | [102] |
| Lebrikizumab | Subcutaneously once-monthly over 12 weeks | 125, 250 or 500 mg | Stable asthma with no ICS use | Phase II, double-blind RCT; placebo-controlled | 212 | Median (range) relative change in FEV1 from baseline at week 12: 125 mg, +3.5 (−1.1–8.1) (p=0.13); −250 mg, +4.8% (−0.1–9.7) (p=0.05); −500 mg, 2.3% (−2.6–7.3) (p=0.35) | No significant relative change in FEV1 in high-periostin subgroup Time to treatment failure: all groups, HR 0.21 (95% CI 0.09–0.47, p<0.001) No significant change in morning PEF or rescue medication use | SAEs: no significant differences with placebo | [103] |
| GSK67958 | Intravenously once-monthly over 12 weeks | 10 mg·kg−1 | Severe asthma, high-dose ICS | Phase III, double-blind RCT; placebo controlled | 198 | Adjusted least squares mean change in ACQ-7 score from baseline at week 12 (values): GSK67958, −0.31; placebo, −0.17 (p=0.058) | Adjusted least squares mean change from baseline in FEV1: GSK67958 −0.01 versus placebo 0.03 (p=0.276); similar results in patients with increased serum IgE levels or blood eosinophil counts | SAEs: no significant differences with placebo | [104] |
ICS: inhaled corticosteroids; RCT: randomised control trial; FEV1: forced expiratory volume in 1 s; ACQ: Asthma Control Questionnaire; HR: hazard ratio; PEF: peak expiratory flow; SAE: serious adverse event.