The side effects profile of dupilumab in patients with atopic dermatitis (AD) were outlined in study data published in the Journal of the American Academy of Dermatology. Results of a cohort study demonstrated that dupilumab was rarely associated with serious infections. However, rates of conjunctivitis were significantly increased in patients taking dupilumab vs methotrexate (MTX) or other common AD therapies.
Investigators analyzed longitudinal claims data from Optum Clinformatics, a US-based commercial insurance database. Claims entered into the database from March 1, 2017 through December 31, 2019 were included. The database contained information on insurance plan enrollment, healthcare utilization, patient demographics, and inpatient and outpatient visits. Patients with a clinical diagnosis of AD were eligible for inclusion. The investigators assembled 3 active comparator cohorts: patients treated with dupilumab vs patients treated with MTX; dupilumab vs cyclosporine; and dupilumab vs mycophenolate. The primary outcome was a diagnosis of conjunctivitis within 6 months of drug initiation. Propensity score matching was used to ensure comparability of treatment groups. Briefly, propensity score matching incorporated the following participant characteristics: age at cohort entry, year of cohort entry, sex, history of past serious and opportunistic infections, previous medication use, comorbid conditions, and AD severity. The relative risk (RR) for conjunctivitis was computed for each dupilumab treatment group vs comparator drugs.
The analytic cohort comprised 1775 patients initiating dupilumab, 1034 initiating MTX, 186 initiating cyclosporine, and 257 initiating mycophenolate. The 6-month risk for any conjunctivitis was 6.48% in the dupilumab group, 3.29% in the MTX group, 4.87% in the cyclosporine group, and 1.17% in the mycophenolate group. After stratification by conjunctivitis subtype, the 6-month risk for bacterial conjunctivitis, allergic conjunctivitis, and keratoconjunctivitis was 1.47% (vs 0.97%), 2.14% (vs 077%), and 1.07%, (vs 0.97%) respectively, in the dupilumab (vs MTX) group. Viral conjunctivitis was observed in just 2 dupilumab users.
After propensity score matching, cohort 1 had 774 pairs of patients initiating dupilumab vs MTX; cohort 2 had 186 pairs of patients initiating dupilumab vs cyclosporine; and cohort 3 had 238 pairs of patients initiating dupilumab vs mycophenolate. The relative risk for any conjunctivitis was significantly increased in dupilumab users compared with MTX (RR, 2.45; 95% confidence interval [CI], 1.47-4.08) and mycophenolate (RR, 7.00; 95% CI, 2.12-23.2). Although the RR for conjunctivitis was increased with dupilumab vs cyclosporine, the difference was not statistically significant (RR, 1.56; 95% CI, 0.69-3.50). The 6-month risk for serious infection in dupilumab users was not significantly different in dupilumab and other drugs.
In this study of patients with AD, dupilumab users had approximately 2-fold increased risk for developing conjunctivitis compared with MTX users within 6 months of drug initiation. These trends persisted across conjunctivitis subtypes. Results were similar when cyclosporine and mycophenolate were used as comparator drugs. Serious infections were not more common in dupilumab users compared with patients using other medications. However, investigators noted that very few serious infections occurred, reducing the statistical robustness of these estimates. In addition, although the source population was large, few patients qualified for inclusion in the study.
That the analyses were based on few events was cited by the investigators as a limitation of the study. They also noted that differential surveillance was a concern.
Further research in a larger cohort is necessary to confirm the risk for conjunctivitis in dupilumab users. “While dupilumab shows a low risk of serious infections…[it is] associated with a clinically meaningful increase in conjunctivitis that needs to be managed in practice,” investigators wrote.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry.
Please see the original reference for a full list of authors’ disclosures.
Schneeweiss MC, Kim SC, Wyss R, Schneeweiss S, Merola JF. Dupilumab and the risk of conjunctivitis and serious infection in patients with atopic dermatitis: a propensity score-matched cohort study [published online October 7, 2020]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2020.09.084