Table 8– Placebo-controlled studies of potential new treatments in severe asthma

First author [ref.]	Severity	Subjects n	Design	Treatment	Outcomes	Summary results
Wenzel [99]	Severe	309	R, db, pc, p	Golimumab, anti TNF-α, 24 weeks	FEV₁, exacerbations AQLQ, PEFR	FEV₁ unchanged, no reduction in exacerbations, AQLQ, PEFR Adverse profile side-effects
Pavord [56]	Severe, with ≥2 exacerbations in past year	621	R, db, pc, p	Mepolizumab (75, 250 or 750 mg infusions at 4 weeks), anti-IL-5, 52 weeks	Rate of exacerbations	All doses reduced exacerbations by 39–52% No effect on ACQ, AQLQ or FEV₁
Haldar [157]	Severe	61	R, db, pc, p	Mepolizumab, anti-IL5, 50 weeks	Exacerbations, symptoms, FEV_₁, AQLQ, AHR, sputum and blood eosinophils	Reduced exacerbations Improved AQLQ Reduced eosinophils
Nair [58]	Severe	20	R, db, pc, p	Mepolizumab, anti-IL5, 50 weeks	Exacerbations, oral steroid reduction	Reduced exacerbations, eosinophils and OCS dose
Kips [159]	Severe	26	R, db, pc, p	SCH55700, anti-IL-5, 12 weeks	Sputum and blood eosinophils, symptoms, FEV₁	Reduced blood sputum eosinophils No other significant outcomes
Castro [57]	Poorly controlled on high-dose inhaled CS	53	R, db, pc, p	Reslimuzab, anti-IL-5, 12 weeks	ACQ, FEV₁, Sputum eosinophils	Improved ACQ score Reduction in sputum eosinophils Improved FEV₁
Corren [160]	Moderate-severe	294	R, db, pc, p	AMG317, anti-IL-4Rα antibody, blocks IL-4 and IL-13, 12 weeks	ACQ scores, exacerbations	No effect on ACQ or exacerbations
Corren [59]	Moderate-severe	219	R, db, pc, p	Lebrikizumab, anti-IL13 antibody, 24 weeks	Change in pre-bronchodilator FEV₁	Improved FEV₁, compared with placebo, with greatest changes in high levels of periostin or F_eNO group (post hoc analyses) No effect on ACQ-5 or diary measures Exacerbations were 60% lower in treated group with high Th2
Piper [60]	Moderate-to-severe	194	R, db, pc, p	Tralokinumab (150, 300, or 600 mg), IL-13 neutralising monoclonal antibody, 3 months	Change from baseline in ACQ-6 at week 13	No change in ACQ-6 at 13 weeks FEV₁ increase of 0.21 L versus 0.06 L with placebo (p=0.072) β₂-agonist use decrease of -0.68 versus -0.10 with placebo (p=0.020) Better response in those with higher IL-13 levels in sputum
Humbert [161]	Severe, CS-dependent	44	R, db, pc, p	Masitinib (3, 4.5 and 6 mg·kg⁻¹·day⁻¹), c-kit and PDGFR tyrosine kinase inhibitor, 16 weeks	OCS dose ACQ, FEV₁	No difference in OCS dose ACQ improved, no difference in FEV₁
Busse [162]	Moderate-to-severe		R, db, pc, p	Daclizumab, IL-2Rα chain antibody, 20 weeks	Change in FEV₁ (%) Asthma exacerbations	Improved FEV₁ Reduction in day-time asthma scores, use of SABA Prolonged time to severe exacerbations Reduction in blood eosinophils
Nair [163]	Severe asthma	34	R, db, pc, p	SCH527123, CXCR2 receptor antagonist, 4 weeks	Changes in sputum and neutrophil activation markers	Reduction in blood and sputum neutrophil Reduction in mild exacerbations No reduction in ACQ score (p=0.053)

R: Randomised; db: double-blind; pc: placebo-controlled; p: parallel; TNF-α: tumour necrosis factor-α; FEV₁: forced expiratory volume in 1 s; AQLQ: Asthma Quality of Life Questionnaire; PEFR: peak expiratory flow rate; IL: interleukin; ACQ: Asthma Control Questionnaire; AHR: airway hyperresponsiveness; OCS: oral corticosteroids; CS: corticosteroids; F_eNO: exhaled nitric oxide fraction; Th2: T-helper cell type 2; c-kit: stem cell factor receptor; PDGFR: platelet-derived growth factor receptor; IL-2Rα: IL-2 receptor-α; SABA: short-acting β-agonist.