Photo Credit: DouglasOlivares

The following is a summary of “Effects of dupilumab on mannitol airway hyperresponsiveness in uncontrolled severe asthma,” published in the November 2024 issue of Allergy and Immunology by Stewart et al. 

Airway hyper-responsiveness (AHR) is key in persistent asthma, but the impact of IL-4/13 blockade with dupilumab (Dupi) remains unclear. 

Researchers conducted a retrospective study to investigate the effect of 12 weeks of dupi on AHR, asthma control, and QoL.  

They conducted a study with participants having uncontrolled type-2 high severe asthma after a 4-week run-in on beclomethasone/formoterol (BDP/FM) MART. Participants received open-label Dupi (300 mg, 2-weekly) for 12 weeks. Mannitol challenges were performed at baseline, 2, 4, and 12 weeks, with a 12-week washout. The study had 90% power to detect a 1 doubling difference (dd) in the mannitol PD₁₀ FEV₁ threshold at week 12. 

The results showed that 23 out of 24 patients completed mannitol AHR in 12 weeks. Mean baseline values were age 52 years, FEV₁ 82%, ACQ 2.53, mini-AQLQ 3.84, ICS dose 1,300 μg, FeNO 50 ppb, and eosinophils 552 cells/μl. Mannitol sensitivity (PD₁₀) significantly decreased by week 4 and reactivity as response dose ratio (RDR) by week 2. After 12 weeks of Dupi, PD₁₀ improved by 1.78 (95% CI 1.23, 2.33) P<0.001, and RDR by 3.40 (95% CI 2.25, 4.55) P<0.001. ACQ improved by 1.73 (1.11,2.36), mini-AQLQ by 2.31 (1.57,3.05), FEV₁ by 0.39L (0.11,0.67), and PEF by 61L/min (24,98) (all P<0.01). BDP/FM MART use decreased by 1.7 puffs/day (0.7,2.7) P<0.01. After washout, the dd change was 0.96 (0.02,1.91) P<0.05. 

Investigators found that Dupi significantly reduced mannitol AHR, despite a decrease in ICS use, while improving lung function, asthma control, and QoL. 

Source: jacionline.org/article/S0091-6749(24)01275-2/fulltext