Could conjunctivitis in patients with atopic dermatitis treated with dupilumab be caused by colonization with <i>Demodex</i>
 and increased interleukin-17 levels?: reply from the authors

Bruin‐Weller, Marjolein de; Graham, Neil M.H.; Pirozzi, Gianluca; Shumel, Brad

doi:10.1111/bjd.16348

Cited by 29 publications

(31 citation statements)

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“…However, an increased incidence of conjunctivitis has been detected in patients who received dupilumab compared with those who received placebo. Ocular surface disorders, including conjunctivitis, blepharitis, keratitis, eye pruritus and dry eye, are commonly reported adverse events in dupilumab‐treated patients with AD, with conjunctivitis being the most dominant one …”

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confidence: 99%

“…Currently, the pathogenesis of conjunctivitis in patients receiving dupilumab remains unknown . One suggestion is that Demodex mites may thrive due to the decreased IL‐4 and IL‐13 levels of ocular cytokines, leading to IL‐17‐mediated inflammation and a disease similar to ocular rosacea .…”

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confidence: 99%

“…One suggestion is that Demodex mites may thrive due to the decreased IL‐4 and IL‐13 levels of ocular cytokines, leading to IL‐17‐mediated inflammation and a disease similar to ocular rosacea . However, IL‐17 is decreased in dupilumab‐treated patients and the disease course of conjunctivitis is too short in comparison with ocular rosacea . Dupilumab may increase OX40 ligand activity, which is involved in atopic keratoconjunctivitis .…”

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confidence: 99%

“…Ocular surface disorders, including conjunctivitis, blepharitis, keratitis, eye pruritus and dry eye, are commonly reported adverse events in dupilumab-treated patients with AD, with conjunctivitis being the most dominant one. [2][3][4][5] In this issue of the BJD, Akinlade et al 2 reviewed the results of published clinical trials and synthesized the available data on the incidence rates, disease course and associated baseline characteristics of patients who developed conjunctivitis in clinical trials of dupilumab in AD, asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic esophagitis (EoE).…”

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confidence: 99%

“…Patients with AD have a greater risk of conjunctivitis than the general population, and patients with more severe AD have a greater risk than those with mild disease. 4 Allergic conjunctivitis and other ocular surface disorders are also common comorbidities of other atopic disorders such as asthma and allergic rhinitis. 2 However, the incidence rates of conjunctivitis in all asthma trials were lower than those in the AD trials.…”

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Keeping an eye on the ocular problems in dupilumab clinical trials

Chu

2019

Br J Dermatol

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Keeping an eye on the ocular problems in dupilumab clinical trials

Chu

2019

Br J Dermatol

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Risk Factors for Dupilumab-Associated Conjunctivitis in Patients With Atopic Dermatitis

2018

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IMPORTANCE Clinical trials of dupilumab for atopic dermatitis (AD) have reported an increased incidence of conjunctivitis in patients who received dupilumab compared with those who received placebo.OBJECTIVE To describe the characteristics of patients who develop conjunctivitis secondary to dupilumab treatment for AD. DESIGN, SETTING, AND PARTICIPANTS Case series of 12 patients who reported development of conjunctivitis from a cohort of 142 patients treated with dupilumab for AD at a secondary care center from March 14, 2017, to March 29, 2018.EXPOSURES Patients received a 600-mg injection of dupilumab as a loading dose and a 300-mg injection every 2 weeks thereafter.MAIN OUTCOMES AND MEASURES Primary outcome measures were severity of AD as measured by the Investigator Global Assessment (IGA) score, a 5-point scale from 0 (clear) to 4 (severe), at the time of dupilumab initiation and at conjunctivitis onset. RESULTSOf the 12 patients included in this series, 7 (58%) were male. The mean (SD) age of patients was 30 (8.1) years at the time conjunctivitis developed. All patients showed improvement of their AD at the time of conjunctivitis diagnosis, with a mean (SD) 1.9 (0.8)-point decrease in IGA score and 47.8% (11.2%) decrease in body surface area affected. Nine of the 12 patients (75%) had severe baseline AD with an IGA score of 4. All patients who discontinued treatment had severe AD at the time of initial dupilumab administration and had at least 1 atopic condition in addition to AD.CONCLUSIONS AND RELEVANCE Conjunctivitis that develops after administration of dupilumab to treat AD may be severe enough to necessitate stopping therapy. Severe conjunctivitis was more likely to develop in patients with more severe baseline AD who had a good response to dupilumab and an increased atopic phenotype. Studies are needed to confirm risk factors associated with development of conjunctivitis and to determine effective treatment.

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Ocular Surface Adverse Events are not Associated with Dupilumab use in Nasal Polyp Treatment

Swisher,

Kshirsagar,

et al. 2023

The Laryngoscope

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ObjectivesOcular surface reactions (OSR) have been associated with dupilumab for atopic dermatitis (AD) treatment. However, the association of dupilumab‐associated OSR (DA‐OSR) for nasal polyps (CRSwNP) treatment has not been studied. We evaluated DA‐OSR for CRSwNP treatment using the FDA Adverse Event Reporting System (FAERS).MethodsFAERS was queried for any general ocular reactions (DA‐GOR) from 2019Q1 to 2022Q4. DA‐OSR were subcategorized from DA‐GOR and compared between treatment groups (CRSwNP, asthma, AD). Logistic regression was used to predict DA‐OSR. Disproportionality analysis (DPA) of DA‐OSR was performed using OpenVigil.ResultsThere were 60,198 total observations, of which 5344 were treated for CRSwNP. The prevalence of DA‐GOR and DA‐OSR was greatest for AD (15.3%, 7.8%), followed by CRSwNP (12.2%, 6.7%) and asthma (9.2%, 3.5%). The most commonly reported OSRs were dry eyes (35.9%), conjunctivitis (15.7%), and increased lacrimation (11.0%). The reported odds ratio (ROR) of CRSwNP‐treated DA‐OSR was 0.84 (0.73–0.97; p = 0.015), compared to 1.29 (1.20–1.40; p < 0.001) for AD and 0.66 (0.59–0.73; p < 0.001) for asthma. For CRSwNP treatment, the DA‐OSR ROR was 0.97 (0.90–1.03; p = 0.3) for men and 0.78 (0.73–0.83, p < 0.001) for older adults (age > 50). ROR in the DPA for DA‐OSR was 12.5 (12.2–12.8; p < 0.001) for any indication and 0.58 (0.53–0.64; p < 0.001) for CRSwNP treatment only.ConclusionsWhile there are limitations to FAERS, this study confirms the association between dupilumab and OSR for AD treatment, and does not support an association between dupilumab and OSR for CRSwNP treatment. Younger adults experience more DA‐OSR in CRSwNP treatment without a specific predilection for sex.Level of EvidenceIV Laryngoscope, 2023

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Could conjunctivitis in patients with atopic dermatitis treated with dupilumab be caused by colonization with Demodex and increased interleukin-17 levels?: reply from the authors

Abstract: Linked Article: de Bruin‐Weller et al. Br J Dermatol 2018; 178:1083–1101.

Cited by 29 publications

References 4 publications

Keeping an eye on the ocular problems in dupilumab clinical trials

Keeping an eye on the ocular problems in dupilumab clinical trials

Risk Factors for Dupilumab-Associated Conjunctivitis in Patients With Atopic Dermatitis

Ocular Surface Adverse Events are not Associated with Dupilumab use in Nasal Polyp Treatment

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