DAMD If You Do: Description of Dupilumab-Associated Mucin Deficiency (DAMD)

Abstract

Purpose : Dupilumab, a monoclonal antibody directed against the interleukin-4 receptor subunit α (IL-4Rα) of IL-4 and IL-13, is increasingly being used by the clinical community to control atopic disease. Dupilumab use has been associated with a poorly understood conjunctivitis. In this study we sought to investigate the hypothesis that dupilumab use and the associated IL-13 blockade causes a relative ocular mucin deficiency.

Methods : Tear levels of mucin 5ac (Muc5AC) and total tear protein levels was evaluated from twenty-eight eyes of fourteen patients. Bilateral tear samples were acquired from seven patients on dupilumab and seven patients with no exposure to dupilumab. Study subjects were age and gender matched. In addition to tear samples, photographic documentation of ocular surface findings and a questionnaire of ocular surface symptoms was obtained. Between-group mean differences were calculated.

Results : Persons with dipilumab associated mucin defeciency (DAMD) displayed a constellation of ocular symptoms including varying degrees of conjunctivitis, blepharitis and keratitis (Fig.1A). Most persons with DAMD had bilateral, mild-to-moderate conjunctivitis with limbal hyperemia. Compared to control, ocular Muc5AC levels normalized to total tear protein was statistically significantly lower. The average Muc5AC levels for persons on dupilumab was 1.54 +/- 0.58 ng/mg and that of controls was 7.99 +/- 1.16 ng/mg (Fig.1B). Persons on dupilumab reported a statistically increased occurrence of ocular fatigue / eye strain, uncomfortable sensation, pain, red eye and itching (Table 1).

Conclusions : This study demonstrates for the first time, a relative deficiency of Muc5AC in patients on dupilumab. These results support the previously reported role of IL-13 in increasing goblet cell density and associated Muc5AC production. Further efforts are underway to better understand the relative contribution of Muc5AC deficiency in the overall presentation of conjunctivitis associated with Dupilumab use.

This is a 2020 ARVO Annual Meeting abstract.

 

Figure 1- A) Slit lamp photo of subject on dupilumab with marked ocular surface inflammation and blepharitis. B) Tear Mucin 5AC levels normalized to tear total protein in persons on dupilumab are reduced as compared to healthy subjects.

 

Table 1- Ocular symptom questionnaire revealed persons on dupilumab reported a statistically increased occurrence of ocular fatigue / eye strain, uncomfortable sensation, pain, red eye and itching.