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Ocular Safety of Dupilumab Compared With IL-5 Inhibitors in Asthma
Hsiao-Mei Tsao1, Pei-Lun Wu2, Ya-Hui Wang3
1Data Science Center, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
Background:
Ocular adverse events (OAEs) are a clinical concern among patients with asthma receiving biologic therapy. Although dupilumab is associated with OAEs in atopic dermatitis (AD), its comparative ocular safety versus interleukin-5 (IL-5) inhibitors in asthma remains unclear.
Objective:
To compare the risk of OAEs between dupilumab and IL-5 inhibitors in adults with asthma using a target trial emulation framework.
Methods:
This retrospective cohort study utilized the TriNetX US Collaborative Network (2018-2025) to identify adults with asthma initiating dupilumab or IL-5 inhibitors (mepolizumab or benralizumab), excluding those with OAEs within the 12 months before treatment initiation. After 1:1 propensity score matching, the composite outcome of OAEs was assessed. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards regression over a 6-month follow-up.
Results:
After matching, 7,073 pairs were identified, with few having AD (0.9%) but substantial chronic obstructive pulmonary disease (COPD) comorbidity (∼30%). Unlike prior studies in AD populations, overall OAE incidence was low in both groups, though risk was higher with dupilumab than IL-5 inhibitors (2.6% vs 2.1%; aHR, 1.25; 95% CI, 1.01-1.55). Conjunctivitis risk was also higher (1.5% vs 1.1%; aHR, 1.38; 95% CI, 1.03-1.86), whereas no significant difference was observed for dry eye syndrome (aHR, 1.15; 95% CI, 0.80-1.66). Subgroup analyses showed no evidence of effect modification by age, sex, allergic rhinitis, or COPD status (all P for interaction >.05), although risk was higher among younger adults for OAEs and among younger and male adults for conjunctivitis. Findings were generally consistent, though significance was not retained after excluding patients with AD, hypereosinophilic syndrome or Sjögren's syndrome (aHR, 1.23; 95% CI, 0.98-1.54) or among persistent biologic use (aHR, 1.29; 95% CI, 0.87-1.93).
Conclusion:
Dupilumab was associated with a modestly higher, but overall infrequent, risk of OAEs than IL-5 inhibitors in asthma over 6 months (2.6% vs 2.1%), a rate substantially lower than the 8-28% previously reported in AD populations. This risk, driven primarily by conjunctivitis, was most pronounced among younger adults, men, and patients with comorbid AD, suggesting that AD may also contribute to this adverse effect. Continued ocular monitoring is warranted, particularly in these subgroups.
