Dupilumab-induced ocular surface disease (DIOSD) in patients with atopic dermatitis: clinical presentation, risk factors for development and outcomes of treatment with tacrolimus ointment

Abstract

AimTo identify risk factors for the development of dupilumab-induced ocular surface disease (DIOSD) in adult patients with atopic dermatitis (AD) and describe outcomes of treatment.MethodsA retrospective institutional cohort study performed at the Rabin Medical Center, Petach Tikva, Israel. Adult patients with AD who received dupilumab from March 2018 to June 2019 were included. Demographics, AD severity scores, blood IgE levels, previous atopic keratoconjunctivitis (AKC), dermatological response to dupilumab, ophthalmological evaluation and treatment were noted. Univariate and multivariate analyses were used to identify risk factors for DIOSD.ResultsSixteen of 37 patients who were included in the study (43%) had new or exacerbated symptoms of ocular surface disease starting at 2 weeks following the first treatment. Three patients reported transient dry eye sensation which lasted 2 weeks; nine patients reported chronic dry eye sensation, and four patients (25%) had marked blepharoconjunctivitis. The presence of severe AD was the strongest predictor of DIOSD. Not a single patient with moderate AD had DIOSD. In multivariate analysis, prior AKC was a risk factor for DIOSD (R2=15.78, OR=23.28, p=0.005) while a family history of atopy was protective of DIOSD (R2=6.22, OR=0.13, p=0.05). All four patients with blepharoconjunctivitis had resolution of signs, and symptoms within days of starting periocular 0.03%–0.1% tacrolimus ointment.ConclusionsDIOSD is common in patients with AD receiving dupilumab. While most cases are mild, some patients can develop blepharoconjunctivitis which responds well to tacrolimus ointment. AD severity, and previous AKC are risk factors for DIOSD.

Incidence and risk factors for dupilumab associated ocular adverse events: a real‐life prospective study

“…Indeed, their incidence was very similar to placebo in dupilumab clinical trials for asthma, rhinosinusitis with nasal polyps and eosinophilic oesophagitis 2,5,10,11,19 . The severity of OAEs associated with dupilumab is variable, rarely leading to treatment discontinuation in clinical trials 12–17,19 and small series of cases 20–29 . OAEs appear to occur more frequently in patients with severe atopic disease at baseline including severe AD, long disease duration, presence of associated atopic conditions, high level of total serum IgE and high eosinophils blood count 18,19,27 …”

<p>Dupilumab-Associated Blepharoconjunctivits with Giant Papillae</p>

“…2,6 As AD patients are prone to herpetic keratitis, topical steroids should be used with caution and the use of periocular tacrolimus ointment may also be considered. 12 The two cases of cicatricial blepharoconjunctivitis reported in the literature either reduced 5 or stopped 4 dupilumab infusions along with topical or oral corticosteroids, respectively. 4,5 The single case of papillary blepharoconjunctivitis reported combined antibiotic/dexamethasone eyedrops along with lid hygiene measures.…”

New and Emerging Systemic Treatments for Atopic Dermatitis

“…Dupilumab had an acceptable safety profile in clinical trials, which has borne out in clinical practice [17]. Idiopathic and allergic conjunctivitis can occur with dupilumab use, although this side effect is rarely treatment limiting [13,18,19]. In the long-term open-label extension study of dupilumab, 18% of the group receiving 2 mg per kg of dupilumab and 16% of the group receiving 4 mg per kg of dupilumab reported conjunctivitis [20].…”