Investigating the role of allergic contact dermatitis in residual ocular surface disease on dupilumab (ROSDD),,

Raffi, Jodie; Suresh, Raagini; Fishman, Harvey A.; Botto, Nina; Murase, Jenny E.

doi:10.1016/j.ijwd.2019.10.001

Cited by 16 publications

(14 citation statements)

References 45 publications

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“…59 Furthermore, Raffi et al emphasized the influence of underlying allergic contact dermatitis in DIOSD and the role of allergen avoidance in the remission of ocular pathology. 39 This suggests that previous allergic contact dermatitis may be exacerbated by dupilumab.…”

Section: Discussionmentioning

confidence: 99%

“…9,30,[32][33][34]37,[42][43][44] 231 out of 392 (58.9%) patients with DIOSD had previous ocular involvement. 9,10,30,31,[34][35][36][37][38][39][40]42 Most of the cases were diagnosed by an ophthalmologist, 348 were mild, 21 were moderate, and none were severe forms. Topical therapies included artificial tears, 9,10,30,33,35,37,42,44 hyaluronic acid eye drops, 35 corticosteroid eye drops, 9,30,31,33,35,37,42,44 antihistaminic, 10,31,33,42 allergen avoidance according to patch testing, 39 tacrolimus, 10,30,33 antibiotic, 35 and cyclosporine 9,35,…”

Section: Clinical Trialsmentioning

confidence: 99%

“…Lubricant (n = 6), corticosteroid (n = 7), antihistamine (n = 2), cyclosporine (n = 2) and benzalkonium chloride eye drops (n = 2), tacrolimus ointment for external eyelids (n = 1) et al39 Allergen avoidance N/A Ruiz-Villaverde et al40 Previous systemic immunosuppressive treatment No Schneeweiss et al N/A N/A Touhouche et al Lubricant (n = 15), antihistamine (n = 6), corticosteroid (n = 5) and cyclosporine eye drops (n = 2), vitamin A ointment (n = 4) et al 44 Previous and current systemic immunosuppressive treatment lubricant and corticosteroid eye drops et al 46 Topical corticosteroids (n = 23), tacrolimus (n = 6), artificial tears (n = 7) No Fukuda et al 47 M, 25 y: eye drops containing tacrolimus, corticosteroid, antihistamine, and antibiotic for 2 months; 3 surgical resections of giant papillae No M, 33 y: antihistamine and tacrolimus eyedrops No Ivert et al 48 Vaseline eye ointment, artificial tears, tacrolimus eye ointment, oral valaciclovir and antiviral prophylaxis, corticosteroid and antibiotic eye drops, glaucoma treatment et al 49 Corticosteroid (n = 11), cyclosporine (n = 3), antihistamine eye drops (n = 4), artificial tears (n = 3), hyaluronic acid (n = 2), antibiotic (n = 1), lifitegrast (n = 1), imidazoline (n = 1) et al 50 topical tacrolimus and corticosteroid ophthalmic ointment 1 Liberman et al 51 M, 56 y: artificial tears, antihistamine, tetryzoline, tetryzoline eye drops, eyelid wipes No M, 19 y: lubricant artificial tears, topical antibiotic, naphazoline/pheniramine, corticosteroid and cyclosporine eye drops No Maudinet et al 52 Warms compresses (n = 6), artificial tears (n = 5), trehalose (n = 9), corticosteroid (n = 7), antihistamine (n = 3), cyclosporine eye drops (n = 1), hyaluronic acid (n = 2y: corticosteroid, antihistamine, cyclosporine eye drops No F, 43 y: corticosteroid, antihistamine, cyclosporine eye drops No Treister et al 57 Artificial tears (n = 3), nonsteroidal anti-inflammatory (n = 2), cyclosporine (n = 1), antihistamine eye drops (n = 1), oral antibiotic (n = 3), topical antibiotic (n = 6), corticosteroid eye drops (n = 7), eyelid cleanser (n Tacrolimus eye ointment 0.03% (n = 4), corticosteroid and antibiotic eye drops (n = 1), corticosteroid eye drops (n = 6) No Yamane et al 60 F, 66 y: corticosteroid, antibiotic eye drops and ointment, artificial tears, periocular tacrolimus, oral antibiotic, oral antihistamine , 28 y: antihistamine eyedrops, Vaseline, and corticosteroid eye ointment © 2022 European Academy of Dermatology and Venereology JEADV 2022, 36, 820-835…”

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confidence: 99%

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Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review

Neagu

Dianzani

Avallone

et al. 2022

Acad Dermatol Venereol

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Atopic dermatitis (AD) is a chronic, inflammatory skin disorder that most frequently occurs in children, but it can also affect adults. Even though most AD cases can be managed with topical treatments, moderate‐to‐severe forms require systemic therapies. Dupilumab is the first human monoclonal antibody approved for the treatment of AD. Its action is through IL‐4 receptor alpha subunit inhibition, thus blocking IL‐4 and IL‐13 signaling pathways. It has been shown to be an effective, well‐tolerated therapy for AD, as well as for asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and eosinophilic esophagitis (EoE). However, an increasing incidence of dupilumab‐induced ocular surface disease (DIOSD) has been reported in patients treated with dupilumab, as compared to placebo. The aim of this study was to summarize scientific data regarding DIOSD in AD patients treated with dupilumab. A search of PubMed and clinicaltrials.gov databases was performed. There was no limit to study design. All AD cases were moderate‐to‐severe. DIOSD was either dermatologist‐, allergist‐, or ophthalmologist‐assessed. Evidence shows that DIOSD occurs most frequently in patients with atopic dermatitis and not in other skin conditions, neither in patients with asthma, CRSwNP, nor EoE who are on dupilumab treatment. Further studies are warranted in order to establish a causal relationship between dupilumab and ocular surface disease. Nevertheless, ophthalmological evaluations prior to dupilumab initiation can benefit AD patients with previous ocular pathology or current ocular symptomatology. Also, patch testing for ocular allergic contact dermatitis might be advantageous in patients with a history of allergic conjunctivitis. Furthermore, TARC, IgE, and circulating eosinophils levels might be important biomarkers for a baseline assessment of future candidates to dupilumab treatment. However, TARC measurements should be resumed for research purposes only.

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Section: Discussionmentioning

confidence: 99%

Section: Clinical Trialsmentioning

confidence: 99%

mentioning

confidence: 99%

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Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review

Neagu

Dianzani

Avallone

et al. 2022

Acad Dermatol Venereol

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“…In the analysis of adults in dupilumab clinical trials, prior history of conjunctivitis, baseline AD severity, and elevation of circulating levels of certain biomarkers (thymus and activation-regulated chemokine [TARC, CCL17], IgE, and blood eosinophils) were associated with risk of conjunctivitis in patients in the AD trials [ 26 ]. Retrospective studies of dupilumab-treated patients with AD in clinical practice also showed significant positive associations of certain biomarkers (TARC, IgE) and prior history of ocular disorders, with an increased risk of conjunctivitis [ 41 , 42 ]. However, the number of conjunctivitis events among adolescent patients in the present analysis was too small to evaluate the relationships between baseline characteristics and the incidence of conjunctivitis.…”

Section: Discussionmentioning

confidence: 99%

Conjunctivitis in Dupilumab Clinical Trials for Adolescents with Atopic Dermatitis or Asthma

et al. 2021

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Background Conjunctivitis is a known comorbidity of atopic dermatitis. Dupilumab clinical trials for moderate-to-severe atopic dermatitis in adults showed a higher conjunctivitis incidence for dupilumab-treated patients than placebo-treated patients, whereas trials for uncontrolled asthma reported lower rates for both dupilumab and placebo. Objective The objective of this study was to evaluate the incidence and severity of conjunctivitis in dupilumab clinical trials in adolescents with moderate-to-severe atopic dermatitis or uncontrolled asthma. Methods We evaluated the incidence of conjunctivitis in adolescents (aged 12 to < 18 years) in three phase III trials. Ocular events were diagnosed and treated based on patient-reported symptoms and an external eye examination by study investigators, in most cases without an ophthalmologic referral. In LIBERTY AD ADOL (16-week, randomized, placebo-controlled, double-blinded trial), adolescents with moderate-to-severe atopic dermatitis were randomized to subcutaneous placebo, dupilumab 300 mg every 4 weeks, or dupilumab every 2 weeks (200 mg, patients < 60 kg at baseline; 300 mg, ≥ 60 kg at baseline). In LIBERTY AD PED-OLE (open-label extension), pediatric patients from previous dupilumab atopic dermatitis trials received dupilumab 2 mg/kg or 4 mg/kg weekly (up to 300 mg) or 300 mg every 4 weeks. In LIBERTY ASTHMA QUEST (randomized, double-blinded, placebo-controlled trial), patients with uncontrolled moderate-to-severe asthma were randomized to 52 weeks of add-on therapy with dupilumab 200 or 300 mg every 2 weeks or matched-volume placebo. Results In ADOL, more dupilumab-treated (17/165; 10.3%) than placebo-treated patients (4/85; 4.7%) reported one or more conjunctivitis event. All events were mild to moderate in severity; 12 (7.3%) dupilumab-treated and 4 (4.7%) placebo-treated patients received treatment. Most patients with conjunctivitis (dupilumab, 12/17; placebo, 4/4) recovered/resolved during the treatment period. The risk of conjunctivitis showed no relationship with dupilumab serum concentration. In PED-OLE, 12/275 adolescents (4.4%) reported one or more conjunctivitis event. Most conjunctivitis events were mild to moderate. Ten patients received treatment for conjunctivitis. Ten patients recovered/resolved during the study. In QUEST, similar low proportions of dupilumab-treated (2/68, 2.9%) and placebo-treated (1/39, 2.6%) adolescents reported one or more conjunctivitis event. All events were mild to moderate. One dupilumab-treated patient received treatment for conjunctivitis. All cases recovered/resolved during the study. No patients in these trials discontinued study treatment temporarily or permanently because of conjunctivitis. In ADOL, one case of unspecified viral keratitis (specific viral etiology not known) in the dupilumab 300-mg every 4 weeks group and one case of allergic blepharitis in the placebo group were reported; both events resolved during ...

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“…A small cohort study reported improvement in ocular surface disease after patch testing and avoidance of triggers such as emulsifier/surfactants and fragrances 22…”

Section: Discussionmentioning

confidence: 99%

Dupilumab-induced ocular surface disease: a primer

Reji

Haque

Goyal³

et al. 2022

BMJ Case Rep

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The management of atopic diseases has been revolutionised by precision therapies and biological drugs that target specific immune proteins. This report elucidates a unique complication from the use of the monoclonal antibody, dupilumab, that primary care providers and subspecialists need to be aware of. A patient in her 40s consulted us for severe atopic asthma, food allergy and eczema involving the face and body. She had previously failed treatments and was started on dupilumab (which binds to the interleukin-4 [IL4] receptor and inhibits both IL-4 and IL-13). She quickly achieved remission of asthma, rhinitis and eczema. Therapy was, however, complicated by severe blepharoconjunctivitis, dry eyes and periorbital dermatitis, consistent with dupilumab-induced ocular surface disease and dupilumab-associated mucin deficiency. Following aggressive treatment of ocular disease, the patient was able to continue dupilumab injections for asthma and eczema. It is presumed that dupilumab-induced cytokine imbalance results in ocular goblet cell dysfunction, mucin deficiency and ocular disease.

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Investigating the role of allergic contact dermatitis in residual ocular surface disease on dupilumab (ROSDD),,

Cited by 16 publications

References 45 publications

Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review

Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review

Conjunctivitis in Dupilumab Clinical Trials for Adolescents with Atopic Dermatitis or Asthma

Dupilumab-induced ocular surface disease: a primer

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