LAUSR

dupilumab between asthma and atopic dermatitis patients Dear Editor, Dupilumab is a monoclonal antibody that inhibits the signaling of both IL-4 and IL-13, which are involved in many allergic disorders. Dupilumab is currently approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe atopic dermatitis (AD) and moderate to severe asthma. However, an increased reporting of ocular adverse events has been published in association with dupilumab. The incidence of ocular adverse events differs based on the different indications for dupilumab. Therefore, our objectives are to determine the different rates of ocular adverse events associated with dupilumab for patients being treated for AD, asthma, or both conditions. A retrospective study of ocular adverse events associated with dupilumab from June 30, 2017, to June 30, 2020, was performed using the FDA Adverse Event Reporting System (FAERS) Database. In total, 33,097 total adverse events associated with dupilumab were reported to FAERS. Of those, 6,040 (18.2%) were ocular adverse events. These events include conjunctivitis (3.96%), eye pruritus (3.95%), ocular hyperemia (3.30%), dry eye (2.87%), increased lacrimation (2.15%), keratoconjunctivitis (1.76%), and blepharitis (0.23%). Among patients being treated for asthma only, there were 2,662 total adverse events. Three hundred and twenty-four (12.2%) of the 2,662 total adverse events were ocular adverse events (i.e., conjunctivitis [2.43%], eye pruritus [2.17%], ocular hyperemia [2.12%], dry eye [2.09%], lacrimation increase [1.96%], and keratoconjunctivitis [1.43%]). Among AD-only patients, there were 17,771 total adverse events, of which 3449 (19.4%) were ocular adverse events (i.e., conjunctivitis [4.72%], eye pruritus [4.12%], ocular hyperemia [3.89%], dry eye [3.65%], lacrimation increase [2.17%], keratoconjunctivitis [0.72%], and blepharitis [0.13%]). Among asthma and AD patients, there were 471 total adverse events, of which 117 (24.8%) were ocular adverse events (i.e., conjunctivitis [6.78%], keratoconjunctivitis [6.32%], eye pruritus [5.34%], dry eye [5.19%], ocular hyperemia [1.12%], and blepharitis [0.05%]). Limitations of this study include its retrospective design and lack of overall prescribing data for dupilumab. In addition, because data in FAERS are reported by patients and health care providers, these adverse effects have not been confirmed as being caused by dupilumab as patients with atopic dermatitis have a higher rate of ocular complications at baseline. According to the data in the FAERS database, AD patients being treated with dupilumab reported a higher percentage of ocular adverse events than asthma patients, 18.2% versus 12.2%, respectively. The reported cases of ocular events are also higher in AD patients than in asthma patients, 3,449 versus 324 cases, respectively. Patients who are being treated for both AD and asthma reported the highest percentage of ocular events (24.8%, P < 0.05). While the absolute number of reports is low for AD and asthma patients, this is likely because of the low number of patients who are being treated for both conditions simultaneously with dupilumab. The FDA data are supported by current clinical trial findings. A review of the published clinical trials for dupilumab by Akinlade et al. showed that ocular disorders were the most commonly reported adverse events in AD patients being treated with dupilumab, with the incidence ranging from 8.6 to 22.1%. Asthma patients being treated with dupilumab had relatively low incidences of ocular adverse events ranging from 0 to 1.7%. Furthermore, while the pathogenesis of ocular adverse events is currently unknown, higher severity of disease and high biomarkers such as eosinophilia have been shown to be correlated with a higher rate of ocular adverse events. Thus, the finding that patients with AD and asthma reported a higher percentage of ocular adverse events demonstrates that atopic patients with multiple atopic diseases, AD and asthma, need to be monitored carefully for ocular adverse events when being treated with dupilumab. Ophthalmology consult in this patient population before starting treatment with dupilumab may be necessary.