Long-term follow-up and treatment outcomes of conjunctivitis during dupilumab treatment in patients with moderate-to-severe atopic dermatitis

Achten, Roselie; Bakker, Daphne; Ariëns, Lieneke F.M.; Lans, Amanda; Thijs, Judith L.; Schaft, Jorien van der; Boer, Joke de; Balak, Deepak M W; Graaf, Marlies de; Luijk, Chantal van; Bruin‐Weller, Marjolein de

doi:10.1016/j.jaip.2020.09.042

Cited by 35 publications

(97 citation statements)

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“…Results of clinical trials revealed that dupilumab is associated with increased incidence of conjunctivitis only in patients with AD but not in those with asthma, chronic rhinosinusitis with nasal polyps, or eosinophilic esophagitis ( Akinlade et al., 2019 ; Bachert et al., 2016 ; Blauvelt et al., 2017 ; Castro et al., 2018 ; de Bruin-Weller et al., 2018b ; Hirano et al., 2020 ; Rabe et al., 2018 ; Simpson et al., 2020 ; Thaçi et al., 2016 ; Wenzel et al., 2016 , 2013 ). In the real world, dupilumab-associated conjunctivitis has also been reported ( Achten et al., 2021 ; Armario-Hita et al., 2019 ; de Wijs et al., 2020a ; Faiz et al., 2019 ; Fargnoli et al., 2019 ; Jo et al., 2020a ; Liberman et al., 2020 ; Nahum et al., 2020 ; Nettis et al., 2020a ; Ribero et al., 2020 ; Ruiz-Villaverde et al., 2019 ; Touhouche et al., 2021 ; Uchida et al., 2020 ; Wang et al., 2020 ). The incidence of conjunctivitis seems to be higher in the real world (up to 62%) than in clinical trials (8.6–22.1%).…”

Section: Specific Concerns With Dupilumab Treatment In Patients With Admentioning

confidence: 98%

“…In most patients suffering from dupilumab-associated conjunctivitis, the severity is mild to moderate ( Achten et al., 2021 ; Nahum et al., 2020 ; Nettis et al., 2020a ; Touhouche et al., 2021 ), but severe cases or those with persistent conjunctivitis have been reported ( Barnes et al., 2017 ; Li et al., 2020 ; Paulose et al., 2019 ; Popiela et al, 2021 ; Vingopoulos and Lazzaro, 2020 ). Dose adjustment or discontinuation of dupilumab is needed in certain cases ( Achten et al., 2021 ). According to Bohner et al.…”

Section: Specific Concerns With Dupilumab Treatment In Patients With Admentioning

confidence: 99%

“…The most frequent signs were conjunctival injection (62%), superficial punctate keratitis (55%), and papillary reaction (28%). Achten et al. (2021) reported that the most frequently reported ophthalmological characteristics were tarsal and bulbar conjunctivitis and blepharitis (84.8%, 75.8%, and 66.7% of patients, respectively).…”

Section: Specific Concerns With Dupilumab Treatment In Patients With Admentioning

confidence: 99%

“…(2021) reported that the most frequently reported ophthalmological characteristics were tarsal and bulbar conjunctivitis and blepharitis (84.8%, 75.8%, and 66.7% of patients, respectively). Overall, 18.2% of patients presented with limbitis ( Achten et al., 2021 ). Keratitis ( Akinlade et al., 2019 ) is also reported.…”

Section: Specific Concerns With Dupilumab Treatment In Patients With Admentioning

confidence: 99%

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A Literature Review of Real-World Effectiveness and Safety of Dupilumab for Atopic Dermatitis

Kamata

Tada

2021

JID Innovations

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Specific Concerns With Dupilumab Treatment In Patients With Admentioning

confidence: 98%

Section: Specific Concerns With Dupilumab Treatment In Patients With Admentioning

confidence: 99%

Section: Specific Concerns With Dupilumab Treatment In Patients With Admentioning

confidence: 99%

Section: Specific Concerns With Dupilumab Treatment In Patients With Admentioning

confidence: 99%

See 2 more Smart Citations

A Literature Review of Real-World Effectiveness and Safety of Dupilumab for Atopic Dermatitis

Kamata

Tada

2021

JID Innovations

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“…The spectrum of findings reported is broad ranging from mild conjunctivitis to severe cicatrizing blepharoconjunctivitis. 12 However, given the small numbers of patients in these individual reports, there is still a need to understand the full spectrum of ocular conditions and clinical presentation associated with use of this medication, especially as some case series describe dupilumab-associated conjunctivitis in patients who have pre-existing meibomian gland disease, blepharitis, allergic conjunctivitis, and other syndromes associated with dry eye disease, 13 , 18 , 19 while many others describe new onset conjunctivitis after initiation on the monoclonal antibody. 16 Some publications have described eyelid pathologies, 13 while others have focused broadly on ocular surface diseases, or focused specifically on conjunctivitis.…”

Section: Introductionmentioning

confidence: 99%

Clinical Characteristics and Treatment for Dupilumab-Related Ocular Complications in Atopic Dermatitis Patients

Jinno¹,

Chung²,

Tauqeer³

et al. 2022

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Purpose Ocular adverse events have been reported in association with dupilumab, a monoclonal antibody to treat allergic diseases including atopic dermatitis (AD). We describe clinical findings and treatment of dupilumab-related ocular complications. Patients and Methods Retrospective study of 19 dupilumab-treated AD patients seen for a new ocular complaint. Primary outcomes were specific ocular exam findings (conjunctival injection, corneal fluorescein staining, blepharitis, meibomian gland dysfunction (MGD)), treatments, and follow-up. Results Nineteen dupilumab-treated AD patients were included. Median age was 47 years (range 18–73). Over half were women (11/19) and majority were Caucasian (13/19). Symptom onset occurred at a mean of 99 days (range 23–520 days) from first dupilumab dose. The most common symptoms were redness (63%), tearing (47%), and pruritus (37%). Most common ocular findings were conjunctival injection (75%) and corneal staining (60%). Blepharitis was seen in about a third (30%), and 25% had MGD. Initially, 10% were observed without treatment, while 15% were treated with artificial tears alone. Other treatments included antihistamine drops (20%) and steroid drops alone (15%). In 40% of patients, a combination of steroids and various other topical eye drops were prescribed. Eighty-four percent (16/19) of patients were seen for follow-up. Steroid drops were required at follow-up in 3 out of 4 patients initially treated with antihistamines alone and in two-thirds of patients initially treated with artificial tears only. Mean follow-up period was 88 days (range 5–369). Dupilumab was discontinued in 31.5% (6/19) of patients; of those who discontinued, 3 restarted it later. Conclusion Conjunctival injection was the most frequent dupilumab-related ocular symptom and most common exam finding followed by corneal staining. Most patients initially treated with antihistamine drops or artificial tears alone subsequently required steroid drops to control symptoms. Some patients who discontinued dupilumab restarted the medication after achieving adequate control of ocular symptoms.

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Association of Serum Dupilumab Levels at 16 Weeks With Treatment Response and Adverse Effects in Patients With Atopic Dermatitis

et al. 2022

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ImportanceThe registered dose of dupilumab for adult patients with atopic dermatitis (AD) is 300 mg every other week. At present, it is unknown whether serum dupilumab levels are associated with treatment response or adverse effects.ObjectivesTo evaluate serum dupilumab levels at 16 weeks of treatment and to explore the association of serum dupilumab levels with treatment response and adverse effects in patients with AD.Design, Setting, and ParticipantsThis clinical, prospective, observational cohort study used data from the prospective BioDay Registry including adult patients with AD who started dupilumab treatment and for whom a serum sample was available at 16 weeks of treatment. All patients were treated according to the BioDay protocol in the University Medical Center Utrecht in the Netherlands. Patients received a loading dose of dupilumab 600 mg subcutaneously, followed by 300 mg every other week. Patients who had a dose adjustment or discontinued treatment before 16 weeks of treatment were excluded. Data analyses were performed from January to June 2022.Main Outcomes and MeasuresDisease severity of AD was assessed at baseline and at weeks 16 and 52 using the Eczema Area and Severity Index (EASI). Treatment response was defined as the percent reduction in EASI score vs the baseline score (eg, EASI 90 indicated a 90% reduction) and as an absolute EASI cutoff score of 7 or lower (controlled AD). Adverse effects were recorded during the first year. At 16 weeks, dupilumab serum levels and treatment responses were measured and analyzed. Multivariate logistic regression modeling was used to determine the prediction of response (EASI 90; EASI ≤7) and adverse effects at 52 weeks, with serum dupilumab levels at 16 weeks in the presence of the covariates age and sex.ResultsAmong the total of 295 patients with AD (mean [SD] age, 41.5 [15.9] years; 170 [57.6%] men), the median (IQR [range]) drug level was 86.6 μg/mL (64.6-110.0 μg/mL [10.1-382.0 μg/mL]) at 16 weeks of treatment. No significant differences were found in serum dupilumab levels between responder statuses (EASI, &lt;50, 50, 75, or 90) at week 16. Multivariate logistic regression analysis showed nonsignificant odds ratios (ORs) for serum dupilumab levels at 16 weeks regarding prediction of long-term response (EASI ≥90: OR, 0.96 [95% CI, 0.90-1.04; P = .34] and EASI ≤7: OR, 1.03 [95% CI, 0.93-1.14; P = .55]) and adverse effects (OR, 1.01 [95% CI, 0.95-1.07; P = .83]).Conclusion and RelevanceThis prospective clinical cohort study found a broad range of serum dupilumab levels at 16 weeks of treatment and no association with treatment response and adverse effects during first year of treatment. Response may be dependent on target availability of the interleukin-4 receptor subunit α, with an interpatient variability producing heterogeneity in response.

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Long-term follow-up and treatment outcomes of conjunctivitis during dupilumab treatment in patients with moderate-to-severe atopic dermatitis

Cited by 35 publications

References 9 publications

A Literature Review of Real-World Effectiveness and Safety of Dupilumab for Atopic Dermatitis

A Literature Review of Real-World Effectiveness and Safety of Dupilumab for Atopic Dermatitis

Clinical Characteristics and Treatment for Dupilumab-Related Ocular Complications in Atopic Dermatitis Patients

Association of Serum Dupilumab Levels at 16 Weeks With Treatment Response and Adverse Effects in Patients With Atopic Dermatitis

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