Elevated inflammatory type 2 biomarkers at baseline predict multicomponent clinical remission following dupilumab treatment in patients with moderate-to-severe asthma

Abstract

Prérequis/contexte

Clinical remission is an emerging treatment goal in asthma. Dupilumab, a fully human monoclonal antibody that blocks signalling of IL-4/13, key and central drivers of type 2 inflammation, is efficacious in patients with moderate-to-severe asthma.

Objectifs

This post hoc analysis evaluated the association between baseline blood eosinophil (Eos) and fractional exhaled nitric oxide (FeNO) levels and the likelihood of achieving clinical remission during QUEST (NCT02414854) in patients with moderate-to-severe asthma.

Méthodes

Patients who completed QUEST and subsequently enrolled in TRAVERSE (NCT02134028) were included. In QUEST, patients received either add-on dupilumab 200/300 mg or placebo q2w for 52 weeks. Remission was defined as meeting the following criteria at QUEST week 52: no exacerbations or oral corticosteroid use during QUEST, stable (decrease in pre-/post-bronchodilator forced expiratory volume in 1 second < 5% from baseline) or improved lung function, and 5-item Asthma Control Questionnaire score <1.5.

Résultats/discussions

At week 52, 38.3% (n = 387) of dupilumab and 26.2% (n = 136) of placebo recipients achieved remission. The likelihood of achieving remission was significantly higher for dupilumab vs placebo when baseline Eos was ≥ 150, ≥ 300, or ≥ 500 cells/μL (OR [95% CI] 2.17 [1.64, 2.86], 2.74 [1.92, 3.92], 4.04 [2.45, 6.68], respectively; all P < 0.0001) but not <150 cells/μL; and when baseline FeNO was ≥ 20 (2.35 [1.74, 3.16]; P < 0.0001) and ≥50 ppb (2.26 [1.38, 3.70]; P < 0.01) but not < 20 ppb. Remission rates were significantly higher with dupilumab vs placebo in patients with the following baseline biomarker combinations: Eos ≥ 150 cells/μL and FeNO ≥ 20 ppb (2.63 [1.88, 3.66]; P < 0.0001), Eos ≥ 300 cells/μL and FeNO < 35 ppb (2.37 [1.41, 3.98]; P < 0.01), and Eos ≥ 300 cells/μL and FeNO ≥ 35 ppb (3.28 [1.98, 5.44]; P < 0.0001), but not Eos ≥ 150 cells/μL and FeNO < 20 ppb, Eos < 150 cells/μL and FeNO ≥ 20/< 20 ppb, or Eos < 300 cells/μL and FeNO ≥ 35/< 35 ppb.

Conclusion

In patients with moderate-to-severe asthma, baseline elevated Eos and FeNO levels, both alone and in combination, were associated with a higher likelihood of achieving remission after dupilumab treatment.