Dupilumab's Ocular AEs Higher in AD Patients Than Asthma

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Atopic dermatitis (AD) and asthma, chronic inflammatory diseases that often coexist, greatly impact the quality of life of patients. Both conditions are often characterized by type 2 (T2) dominated inflammation. Dupilumab, a fully human monoclonal antibody that blocks the interleukin-4 receptor alpha chain, inhibiting the binding of IL-4 and IL-13, was the first biological agent registered for the treatment of both AD and severe asthma (SA).¹ For both conditions, dupilumab has been shown to improve signs and symptoms, as well as quality of life in patients.²

While dupilumab’s adverse events (AEs) are generally low, the incidence of dupilumab-associated ocular surface disease (DAOSD) —including conjunctivitis and blepharoconjunctivitis—is notably higher in AD patients, with rates up to 34.2%. This contrasts with lower DAOSD rates in asthma patients, suggesting a higher susceptibility in AD patients.^3-4 A recent study aimedto explore AEs of dupilumab in real-life settings, comparing AD and asthma patients, with a focus on ocular AEs, including their prevalence, onset, management, and impact on treatment continuation.⁵

Methods

This study compared the safety and efficacy of dupilumab in patients with moderate to severe AD and SA using data from 2 registries: the Immune-Mediated Inflammatory Disorder registry at Erasmus MC University Medical Center for AD patients and the RelyOnDupi registry at Franciscus Gasthuis and Vlietland for SA patients. Eligible participants were adults (≥18 years) with moderate to severe AD or uncontrolled SA who initiated dupilumab treatment, excluding those who did not consent, used dupilumab for conditions other than AD or SA, or discontinued treatment within 4 weeks. Ocular AEs were categorized by symptoms and diagnoses, with treatments and referrals documented, as well as reasons for treatment discontinuation. The primary endpoint was the comparison of AE proportions between AD and SA patients, and secondary objectives included the prevalence, onset, and treatment of ocular AEs and reasons for discontinuation.

Results

The study analyzed 470 patients (322 with AD and 148 with SA) treated with dupilumab, with a median follow-up of 24 months. AD patients had a higher prevalence of allergic conjunctivitis and a notable proportion had concurrent mild to moderate asthma, while SA patients had a higher rate of concomitant mild to severe AD and frequently used maintenance oral corticosteroids (OCS).

Researchers reported that AEs occurred in 62.8% of patients, with AD patients experiencing a higher rate (70.5%) compared to SA patients (45.9%). Headaches, head and neck dermatitis, and influenza-like symptoms were common, with SA patients reporting more headaches and injection site reactions. Notably, the study found 39.2% of SA patients used maintenance OCS, and a small percentage had eosinophilia, with no therapeutic intervention needed as eosinophil levels decreased over time.

The study found ocular AEs were significantly more common in AD patients (95.8% of ocular AEs) than in SA patients (4.2%), with 92.2% of AD patients experiencing at least 1 ocular AE. Common symptoms included irritation, redness, and itching. Researchers found AD patients had a higher prevalence of ocular surface disease diagnoses, such as conjunctivitis and blepharitis. The onset of ocular AEs in AD patients typically occurred within the first12 weeks of treatment, and many received ophthalmic treatments, with a significant portion referred to ophthalmologists. In contrast, the study stated that SA patients had fewer ocular AEs and were less likely to be referred to ophthalmologists.

Dupilumab was discontinued by 32.1% of patients, with a higher rate in AD patients (36.0%), often due to ocular AEs. Among those who discontinued, researchers found many switched to other treatments with improvement in ocular AEs. SA patients discontinued less frequently (23.6%), with fewer cases linked to ocular AEs and without significant ophthalmological referrals.

Conclusion

The study found a significantly higher incidence of ocular AEs in AD patients, particularly those with severe disease and a history of allergic conjunctivitis. Researchers stated that ocular AEs improved after discontinuation of dupilumab in both groups, highlighting the need for better collaboration among specialists to manage these events effectively.

In addition to ocular AEs, SA patients experienced more headaches, influenza-like symptoms, and injection site reactions. Researchers hypothesized this could potentially be due to the stress of in-hospital administration and higher prevalence of upper respiratory comorbidities. Limitations of the study include potential inconsistencies in AE reporting between hospitals and the lack of comprehensive pre-treatment ophthalmic assessments. Despite these limitations, the study’s findings emphasize the need for vigilance regarding ocular AEs in AD patients and suggest that multidisciplinary collaboration is crucial for managing these AEs and improving patient outcomes. Researchers suggested further research should work to better understand the mechanisms behind ocular AEs and identify patients at higher risk.

References

1. Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387(10023):1109-1122. doi:10.1016/S0140-6736(15)00149-X
2. Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378(26):2486-2496. doi:10.1056/NEJMoa1804092
3. Akinlade B, Guttman-Yassky E, de Bruin-Weller M, et al. Conjunctivitis in dupilumab clinical trials. Br J Dermatol. 2019;181(3):459-473. doi:10.1111/bjd.17869
4. Bosma AL, de Wijs LEM, Hof MH, et al. Long-term effectiveness and safety of treatment with dupilumab in patients with atopic dermatitis: Results of the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry. J Am Acad Dermatol. 2020;83(5):1375-1384. doi:10.1016/j.jaad.2020.05.128
5. Schlösser AR, Bult L, Thelen JC, et al. Higher prevalence of dupilumab-induced ocular adverse events in atopic dermatitis compared to asthma: A daily practice analysis. Clin Transl Allergy. 2024;14(8):e12386. doi:10.1002/clt2.12386