DOI: 10.2500/aap.2024.45.230072 ISSN: 1088-5412

Real-world effectiveness and predictors of super-responders to dupilumab in a Chinese uncontrolled asthma cohort

Xiaoying Chen, Huiting Luo, Wenbo Yan, Kailun Tang, Junfeng Huang, Shuojia Xie, Zhenxuan Lin, Zhenle Zhang, Xu Shi, Mo Xian, Wanjun Wang, Jing Li, Ruchong Chen
  • Pulmonary and Respiratory Medicine
  • General Medicine
  • Immunology and Allergy

Background: Dupilumab has been shown to be effective in clinical trials for moderate-to-severe uncontrolled asthma. However, the efficacy of dupilumab in the real world and the prediction of treatment response have not been well studied in patients with asthma. Objective: To investigate the efficacy of dupilumab and explore predictors of super-responders in a Chinese retrospective cohort. Methods: From January 2021 through December 2022, the patients with uncontrolled asthma who were treated with dupilumab for 4 months were included. Symptom control, type 2 inflammatory biomarkers, and lung function were collected at baseline and follow-up for efficacy assessment. Super-responders were defined as exacerbation-free, off maintenance of oral corticosteroids (mOCS), and with a score of the five-item Asthma Control Questionnaire (ACQ-5) of <0.5. The uni- and multivariable logistic regressions were used to construct predictive models for super-responders based on baseline features. Results: A total of 53 patients were included. After 4 months treatment, the median (interquartile range [IQR]) ACQ-5 score decreased from 1.8 (1.6‐2.4) to 0.4 (0.2‐0.8) (p < 0.001), the median (IQR) number of exacerbations, from 0.0 (0.0‐1.0) to 0.0 (0.0-0.0) (p = 0.005). The median (IQR) dose of mOCS (prednisone equivalent) decreased from 15.0 mg/day (8.8‐22.5 mg/day) to 2.5 mg/day (0.0‐10.0 mg/day) (p = 0.008) in nine patients who were receiving mOCS. All efficacy assessment parameters, including sputum eosinophil were significantly improved, while blood eosinophil count did not decline (530 cells/mm3 [300‐815 cells/mm3] versus 560 cells/mm3 [220‐938 cells/mm3], p = 0.710). After taking dupilumab, 25 of 53 patients (47.2%) achieved a super-response. The age of onset < 42 years (odds ratio [OR] 7.471 [95% confidence interval {CI}, 1.286‐43.394) and the baseline fractional exhaled nitric oxide (FeNO) of 25‐50 ppb (OR 35.038 [95% CI, 3.104‐395.553]) predicted super-responders, which showed a C-index of 0.822 (95% CI, 0.697‐0.947). Conclusion: Dupilumab significantly improved symptom control, type 2 inflammatory markers, and lung function in Chinese patients with uncontrolled asthma. Airway eosinophils, rather than blood eosinophils, can be a reliable indicator of therapeutic efficacy. The early-onset asthma as well as the medium-high level of baseline FeNO contributed to the prediction of super-responders.

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