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

Abstract

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.

Treatment of atopic dermatitis with dupilumab: experience from a tertiary referral centre

“…The finding that 18.4% of the patients developed conjunctivitis during the first 3 months of treatment is in accordance with data from clinical trials demonstrating conjunctivitis to be one of the most frequent adverse events related to dupilumab treatment (combined incidence 8% in phase 2B and 3 clinical trials) . In addition, the proportion of patients who discontinued treatment with dupilumab due to side‐effects was comparable with findings in phase 3 clinical trials (2% vs. 1–2%) …”

Keeping an eye on the ocular problems in dupilumab clinical trials

“…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 …”

“…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 . 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 . An increase in eosinophil counts after dupilumab administration might be another mechanism, as eosinophilic factors are elevated in the tears of patients with allergic conjunctivitis . IL‐13 inhibition might be another possible mechanism because it has been implicated in ocular mucus production and the regulation of conjunctival goblet cells and, therefore, the quality of tears .…”

“…Although one study found that antihistamine eye drops and artificial tears did not alleviate conjunctivitis, a small case series of 10 patients found that using artificial tears as a preventive method 1 week before starting dupilumab treatment may have reduced the incidence of conjunctivitis . Close collaboration with ophthalmologists for early and proper diagnosis and management of ocular complications in patients receiving dupilumab is also recommended …”