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Expert Consensus on Managing Dupilumab-Related Ocular Surface Disorders in People With Atopic Dermatitis
TAKE-HOME MESSAGE
- This article highlights consensus guidelines by the British Association of Dermatologists and the Royal College of Ophthalmologists on managing dupilumab-related ocular surface disorders (DROSD) in patients with atopic dermatitis. Dupilumab treatment for atopic dermatitis should generally not be delayed, except for acute problems (infections) or severe eye conditions. The prophylactic use of lubricant drops is not recommended. Dermatologists should assess the severity of DROSD and refer children younger than 7 years for ophthalmology advice owing to neuro-ocular development concerns. For patients aged 7 years and older, dermatologists can initiate treatment and consult ophthalmology only in severe or unresponsive cases.
- Dermatologists should assess the urgency and seek ophthalmology advice in young children with DROSD and in severe or unresponsive cases.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Atopic dermatitis (AD) is the most common inflammatory skin condition which affects all ages. New therapies, including the monoclonal antibody therapy dupilumab, offer excellent efficacy. However, in clinical trials, and emphasised in real-world observations, the unexpected increased frequency of ocular adverse effects became apparent. The effectiveness of dupilumab and the unpredictability of ocular adverse effects mean that clinicians need guidance on counselling patients prior to treatment and on managing them if they arise.
OBJECTIVES
The British Association of Dermatologists (BAD) and Royal College of Ophthalmologists collaborated on this consensus guidance on managing dupilumab-related ocular surface disorders (DROSD).
METHODS
A multidisciplinary group was formed of adult and paediatric dermatologists and ophthalmologists with DROSD expertise, patient representation, and BAD Clinical Standards Unit. A literature search was conducted, and the results reviewed. All recommendations were reviewed, discussed and voted on.
RESULTS
The recommendations pertain to dermatology and ophthalmology management, and apply to all ages, unless otherwise stated. Importantly, initiation of dupilumab for AD should not be delayed for most eye disorders except acute new problems, e.g. infections, or potentially severe conditions, e.g. a history of corneal transplant (ophthalmology advice should be sought first). There is insufficient evidence to recommend lubricant drops prophylactically. Dermatologists should assess eye complaints to diagnose DROSD; a severity grading system is provided. DROSD management differs slightly in those aged <7 years as ocular complications may affect neuro-ocular development; therefore, irrespective of DROSD severity, this population should be referred for ophthalmology advice. In those aged ≥7 years, dermatologists should feel confident to trial treatment and reserve ophthalmology advice for severe or non-responding cases. Discussion about dupilumab withdrawal should be prompted by a significant impact on quality of life, threat to sight, or other complications.
CONCLUSIONS
Although dupilumab is a highly effective agent for treating AD, the risk of ocular adverse effects should not inhibit clinicians or patients from using it, but clinicians should be aware of them. If a patient develops DROSD, there are clear pathways to assess severity and offer initial management; where ineffective, dermatologists should assess the urgency and seek advice from or initiate referral to ophthalmology. While the evidence reviewed for these guidelines reflects the extensive literature on dupilumab, we believe our advice has relevance for ocular surface disorders in atopic dermatitis (AD) patients treated with tralokinumab and lebrikizumab.
Additional Info
Disclosure statements are available on the authors' profiles:
An expert consensus on managing dupilumab-related ocular surface disorders in people with atopic dermatitis 2024
Br J Dermatol 2024 Sep 05;[EPub Ahead of Print], MR Ardern-Jones, SJ Brown, C Flohr, P Hossain, AD Irvine, GA Johnston, M Lane, SM Langan, P Laws, D O'Driscoll, D O'Kane, A Payne, G Petrof, AE Pink, S Rauz, S Robbie, SK Gore, M Shah, RT Woolf, C Wang, S Tumbeva, MF Mohd MustapaFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Atopic dermatitis is the most common inflammatory skin condition among both children and adults. Dupilumab, a monoclonal antibody that inhibits both IL-4 and IL-13, is very effective in approximately 60% of patients. However, approximately 26% of patients treated with dupilumab have ocular adverse effects, chiefly conjunctivitis, dry eye, blepharitis, and keratitis — a group of conditions known as ocular surface disorders (OSD). The biggest risk factor for dupilumab-related OSD (DROSD) is pre-existing OSD; however, DROSD can also occur de novo, usually within 4 months of initiating therapy. There is little consensus on the ideal management of DROSD.
This study from the UK involved the development of DROSD management guidelines by a group of experts (from both the British Association of Dermatologists and the Royal College of Ophthalmologists) based on an extensive literature review, professional experience, and discussion followed by voting.
Treatment with dupilumab need not be delayed if pre-existing OSD is present — unless other acute eye conditions, such as infectious conjunctivitis, are present or if the patient has had a corneal transplant or keratoconus, in which case, consultation with ophthalmology should occur first. Most patients can be managed by the dermatologist by asking about symptoms of ocular adverse effects at each visit, including any reported redness, change in vision, ocular discomfort, frank pain, discharge, or photophobia. If any of these are reported, the eye can be examined for redness, corneal clarity, discharge, and gross visual acuity.
Patients do not require an ophthalmology referral if the signs and symptoms of DROSD are mild. However, amblyopia is a concern in patients younger than 8 years; therefore, early referral is advised for this group. For mild DROSD, initial treatment with ocular lubricants is indicated. If ineffective, a topical antihistamine can be added, and a non-urgent referral to ophthalmology can be made within 4 weeks. Topical tacrolimus application on the eyelid margins can be considered if antihistamine drops are ineffective. The ophthalmologist may consider treatment with topical cyclosporine, corticosteroids, or serum eye drops.
Severe cases are identified using the acronym "RAPID" — denoting redness plus one of the following: acuity loss, pain, intolerance to light, or damage to the cornea — and the patient should be sent to an ophthalmologist within 24 hours.
Discontinuation of dupilumab for DROSD is usually not required unless one of the following rare events occurs: progressive visual loss, conjunctival scarring, prolonged dependence on topical steroids (>8 weeks), or significant loss of quality of life.
This study is limited by the fact that many of the recommendations are opinions based on limited data. It is not known whether the conclusions can also be applied to other IL-13 inhibitors used for atopic dermatitis, such as tralokinumab and lebrikizumab. Our knowledge regarding the safety and effectiveness of dupilumab and other biologic agents is progressing so rapidly that these recommendations are likely to require frequent revision.