Conjunctivitis Among Individuals with Moderate-to-Severe Atopic Dermatitis Treated with Dupilumab in the United States

Background: In clinical trials of patients with moderate-to-severe atopic dermatitis (msAD), conjunctivitis occurred at higher rates in patients randomized to dupilumab versus placebo. However, the real-world incidence of conjunctivitis among patients with msAD is unknown.

Objectives: To investigate the incidence of conjunctivitis among individuals with msAD treated with dupilumab in a real-world setting.

Methods: An observational cohort study was conducted using medical and pharmacy claims data from the Optum Research Database in the US. Using a validated algorithm, a msAD population of patients at least 12 years of age from 28 March 2017 - 30 November 2019 was identified.
Within this population, initiators of dupilumab were identified and 1:1 propensity score (PS)-matched to dupilumab-naïve patients who met the msAD algorithm, which required treatment with other msAD therapies (approved as of 2019). Patients were required to have continuous enrollment in their health plan with complete medical and pharmacy benefits during baseline (12 months prior to cohort entry, defined as the date of dupilumab initiation or dispensing/administration of other msAD therapy). Cohorts were evaluated to confirm balance, defined as an absolute standardized difference less than 0.1, in baseline comorbidities and proxy measures of AD severity. Conjunctivitiswas identified using a validated algorithm beginning the day after cohort entry. Incidence rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for conjunctivitis were estimated via Poisson regression models.

Results: In the msAD cohorts, 2,446 dupilumab initiators and 12,117 dupilumab-naïve patients meeting inclusion criteria were identified. After PS matching and removal of patients with conjunctivitis or keratitis codes in the 30 days prior to cohort entry, 2,175 dupilumab initiators and 2,189 dupilumab-naïve patients remained. Most baseline characteristics were well-balanced between the dupilumab and comparator cohorts; 3 remained imbalanced and were included in the adjusted outcome models. The adjusted IRR for conjunctivitis comparing dupilumab and dupilumab-naïve cohorts was 1.86 (95% CI 1.51, 2.30), indicating an increased incidence among dupilumab initiators.

Conclusions: Results from this study indicate an increased risk of conjunctivitis in patients initiating dupilumab versus dupilumab-naïve patients with msAD. Results mirror those from existing literature and clinical trials and do not alter the known benefit-risk profile for dupilumab. Strengths of the study include the use of validated algorithms to identify both the study population and outcome events, use of PS matching and additional adjustment to balance the cohorts on AD severity, and a large sample size.