Keeping an eye on the ocular problems in dupilumab clinical trials

Chu, Chia-Yu

doi:10.1111/bjd.18255

Cited by 11 publications

(12 citation statements)

References 12 publications

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“…Ciclosporin is a calcineurin inhibitor that inhibits T-cell-mediated immune responses and has been shown to increase goblet cell numbers [26]. Dupilumab targets IL-13 action and secondary depletion of goblet cells and mucin production in the conjunctiva could be responsible for dupilumabassociated conjunctivitis [2][3][4][5]. Ciclosporin might be particularly useful in treatment of dupilumab-associated ocular surface disease as it could reverse some of the local immunological actions of dupilumab.…”

Section: Discussionmentioning

confidence: 99%

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Dupilumab-associated ocular surface disease: presentation, management and long-term sequelae

Popiela

Barbara

Turnbull

et al. 2021

Eye

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Objectives To determine the presenting features of ocular surface disease in patients with atopic dermatitis (AD) treated with dupilumab at a tertiary, university hospital. To establish the need for treatment of dupilumab-associated ocular surface disease and report any long-term effects on the ocular surface. Methods A retrospective analysis of consecutive patients treated with dupilumab for AD between January 2017 and August 2019 was undertaken. Data were collected on demographics, incidence and type of ocular disease features, natural history and treatment. Results A total of 50% (14/28) patients developed ocular symptoms with a mean time of onset of 6.75 (±6.1) weeks from starting dupilumab. Of these, 69% (9/13) were diagnosed with conjunctivitis associated with cicatrisation in two patients and periorbital skin changes in four. Of these nine, four had prior history of atopic keratoconjunctivitis. All were treated with topical steroids; two required additional ciclosporin drops. In all, 67% (6/9) patients went on to have on-going ocular inflammation requiring maintenance drops at a mean of 16 (±6.9) months of follow-up. All patients had improvement in their AD severity; only one patient discontinued dupilumab due to ocular side effects. Conclusion The rate of dupilumab-associated ocular surface disease was 32%. Periorbital skin changes and conjunctival cicatrisation were noted in association with conjunctivitis. Ocular surface disease improved on topical steroids and ciclosporin but 67% of patients needed on-going treatment. Close liaison with an ophthalmologist should be considered in those patients who develop conjunctivitis or have a past history of severe ocular surface disease.

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Section: Discussionmentioning

confidence: 99%

“…Dupilumab is the first biologic approved for use in treatment of moderate to severe atopic dermatitis (AD) [1][2][3][4][5]. Dupilumab targets interleukin (IL)-4 receptor blocking IL-4 and IL-13 signalling pathway.…”

Section: Introductionmentioning

confidence: 99%

Dupilumab-associated ocular surface disease: presentation, management and long-term sequelae

Popiela

Barbara

Turnbull

et al. 2021

Eye

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“…Dupilumab is currently approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe atopic dermatitis (AD) and moderate to severe asthma 1 . However, an increased reporting of ocular adverse events has been published in association with dupilumab 2 . The incidence of ocular adverse events differs based on the different indications for dupilumab.…”

mentioning

confidence: 99%

“…Asthma patients being treated with dupilumab had relatively low incidences of ocular adverse events ranging from 0 to 1.7% 5 . Furthermore, while the pathogenesis of ocular adverse events is currently unknown, higher severity of disease and high biomarkers such as eosinophilia have been shown to be correlated with a higher rate of ocular adverse events 2,4 . Thus, the finding that patients with AD and asthma reported a higher percentage of ocular adverse events demonstrates that atopic patients with multiple atopic diseases, AD and asthma, need to be monitored carefully for ocular adverse events when being treated with dupilumab.…”

mentioning

confidence: 99%

Difference in the rate of ocular adverse events with dupilumab between asthma and atopic dermatitis patients

Wang

Jorizzo

2021

Int J Dermatology

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“…First, dupilumab, by blocking the canonical Th2 cytokines, IL-4 and IL-13, could skew the immune response towards a Th1-cytokine dominated one (figure 1), with resulting elaboration of interferon gamma and reduced goblet cell density 9. Second, the decreased IL-4 and IL-13 may lead to survival of demodex mites with resultant IL17-mediated inflammation 12. Third, aberrant signalling (OX40 ligand-mediated) has been postulated to get activated, resulting in a vernal keratoconjunctivitis-like pathology 12 13.…”

Section: Introductionmentioning

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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Keeping an eye on the ocular problems in dupilumab clinical trials

Abstract: Linked Article: Akinlade et al. Br J Dermatol 2019; 181:459–473.

Cited by 11 publications

References 12 publications

Dupilumab-associated ocular surface disease: presentation, management and long-term sequelae

Dupilumab-associated ocular surface disease: presentation, management and long-term sequelae

Difference in the rate of ocular adverse events with dupilumab between asthma and atopic dermatitis patients

Dupilumab-induced ocular surface disease: a primer

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