Table 8– Placebo-controlled studies of potential new treatments in severe asthma
First author [ref.]SeveritySubjects nDesignTreatmentOutcomesSummary results
Wenzel [99]Severe309R, db, pc, pGolimumab, anti TNF-α, 24 weeksFEV1, exacerbations AQLQ, PEFRFEV1 unchanged, no reduction in exacerbations, AQLQ, PEFR Adverse profile side-effects
Pavord [56]Severe, with ≥2 exacerbations in past year621R, db, pc, pMepolizumab (75, 250 or 750 mg infusions at 4 weeks), anti-IL-5, 52 weeksRate of exacerbationsAll doses reduced exacerbations by 39–52% No effect on ACQ, AQLQ or FEV1
Haldar [157]Severe61R, db, pc, pMepolizumab, anti-IL5, 50 weeksExacerbations, symptoms, FEV1, AQLQ, AHR, sputum and blood eosinophilsReduced exacerbations Improved AQLQ Reduced eosinophils
Nair [58]Severe20R, db, pc, pMepolizumab, anti-IL5, 50 weeksExacerbations, oral steroid reductionReduced exacerbations, eosinophils and OCS dose
Kips [159]Severe26R, db, pc, pSCH55700, anti-IL-5, 12 weeksSputum and blood eosinophils, symptoms, FEV1Reduced blood sputum eosinophils No other significant outcomes
Castro [57]Poorly controlled on high-dose inhaled CS53R, db, pc, pReslimuzab, anti-IL-5, 12 weeksACQ, FEV1, Sputum eosinophilsImproved ACQ score Reduction in sputum eosinophils Improved FEV1
Corren [160]Moderate-severe294R, db, pc, pAMG317, anti-IL-4Rα antibody, blocks IL-4 and IL-13, 12 weeksACQ scores, exacerbationsNo effect on ACQ or exacerbations
Corren [59]Moderate-severe219R, db, pc, pLebrikizumab, anti-IL13 antibody, 24 weeksChange in pre-bronchodilator FEV1Improved FEV1, compared with placebo, with greatest changes in high levels of periostin or FeNO 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-severe194R, db, pc, pTralokinumab (150, 300, or 600 mg), IL-13 neutralising monoclonal antibody, 3 monthsChange from baseline in ACQ-6 at week 13No 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-dependent44R, db, pc, pMasitinib (3, 4.5 and 6 mg·kg−1·day−1), c-kit and PDGFR tyrosine kinase inhibitor, 16 weeksOCS dose ACQ, FEV1No difference in OCS dose
ACQ improved, no difference in FEV1
Busse [162]Moderate-to-severeR, db, pc, pDaclizumab, IL-2Rα chain antibody, 20 weeksChange 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 asthma34R, db, pc, pSCH527123, CXCR2 receptor antagonist, 4 weeksChanges in sputum and neutrophil activation markersReduction 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; FeNO: 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.