Conjunctivitis in patients with atopic dermatitis treated with dupilumab is associated with higher baseline serum levels of immunoglobulin E and thymus and activation-regulated chemokine but not clinical severity in a real-world setting

Uchida, Hideaki; Kamata, Masahiro; Nagata, Mayumi; Fukaya, Saki; Hayashi, Kotaro; Fukuyasu, Atsuko; Tanaka, Takamitsu; Ishikawa, Takeko; Ohnishi, Takamitsu; Tada, Yayoi

doi:10.1016/j.jaad.2019.12.039

Cited by 25 publications

(36 citation statements)

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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: 96%

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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Section: Discussionmentioning

confidence: 96%

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

et al. 2021

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“…Although the data from the clinical trials could not identify risk factors specific for dupilumab-associated conjunctivitis, the real-world data suggest possible risk factors. Uchida et al reported that dupilumab-associated conjunctivitis was associated with higher baseline serum levels of IgE and TARC but not with the clinical severity of AD and that a history of conjunctivitis and eosinophils showed its tendency (Uchida et al, 2020). Nahum et al (Nahum et al, 2020) and Nettis et al (Nettis et al, 2020a) reported that the main predictor for the development of dupilumab-associated conjunctivitis was a history of conjunctivitis.…”

Section: -1-3 Risk Factors For Dupilumab-associated Conjunctivitismentioning

confidence: 99%

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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“…[15][16][17] Recently, accumulating evidence has revealed that dupilumab is effective for AD and it shows tolerable safety in real-world data, although the prevalence of conjunctivitis was slightly higher in the real world than in clinical trials. [18][19][20][21] Dupilumab is effective for most AD patients; however, the extent of its effectiveness varies in individual patients. It would be helpful in practice if there are predictive parameters reflecting later effectiveness of dupilumab.…”

Section: Introductionmentioning

confidence: 99%

Higher baseline serum lactate dehydrogenase level is associated with poor effectiveness of dupilumab in the long term in patients with atopic dermatitis

Kato

Kamata

Itô

et al. 2020

The Journal of Dermatology

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Dupilumab shows high efficacy and tolerable safety for the treatment of atopic dermatitis (AD). However, the extent of its effectiveness varies in individual patients. To date, practical predictors of later effectiveness of dupilumab in AD patients have not been reported. To explore practical predictors of later effectiveness of dupilumab in AD, we retrospectively investigated the correlation of baseline demographics and baseline laboratory results with the percentage reduction in Eczema Area and Severity Index (EASI) scores at 1, 3, 6 and 12 months after initiating dupilumab. Furthermore, multiple regression analyses were conducted. Data were collected from patients’ charts. Data on 54 Japanese adult patients (43 men and 11 women) with moderate to severe AD were analyzed. Baseline serum lactate dehydrogenase (LDH) level was negatively correlated with the percentage reduction in EASI score at 3, 6 and 12 months after initiating dupilumab but not at 1 month. Multiple regression analyses also revealed that effectiveness of dupilumab at 3 and 6 months was associated with lower baseline serum LDH level. AD patients with allergic diseases tended to have lower percentage reduction in EASI at 1 month, but had higher percentage reduction in EASI in the long term than patients without allergic diseases. In conclusion, higher baseline serum LDH level was associated with poor effectiveness of dupilumab in the long term in patients with AD. Furthermore, it tended to take a longer time for AD patients with allergic diseases to respond to dupilumab, and these patients responded better to dupilumab in the long term than patients without allergic diseases.

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Conjunctivitis in patients with atopic dermatitis treated with dupilumab is associated with higher baseline serum levels of immunoglobulin E and thymus and activation-regulated chemokine but not clinical severity in a real-world setting

Cited by 25 publications

References 5 publications

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

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

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

Higher baseline serum lactate dehydrogenase level is associated with poor effectiveness of dupilumab in the long term in patients with atopic dermatitis

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