Conjunctivitis in atopic dermatitis patients with and without dupilumab therapy – international eczema council survey and opinion

Thyssen, Jacob P.; Bruin‐Weller, Marjolein S. de; Paller, Amy S.; Leshem, Yael Anne; Vestergaard, Christian; Deleuran, Mette; Drucker, Aaron M.; Foelster-Holst, Regina; Traidl‐Hoffmann, Claudia; Eyerich, Kilian; Taı̈eb, Alain; Su, John; Bieber, Thomas; Cork, Michael J.; Eichenfield, Lawrence F.; Guttman‐Yassky, Emma; Wollenberg, Andreas

doi:10.1111/jdv.15608

Cited by 52 publications

(77 citation statements)

References 28 publications

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“…Dupilumab, trade name Dupixent (Sanofi and Regeneron Pharmaceuticals), is a monoclonal antibody that acts as an interleukin-4 (IL-4) receptor alpha antagonist that blocks the signaling of IL-4 and IL-13. 1,2 It is increasingly being used clinically to control over expression of such Th2 cytokines found in a variety of allergic diseases. 3,4 Dupilumab was first approved by the US Food and Drug Administration for eczema in March 2017 followed by approval for moderate to severe asthma in October 2018.…”

Section: Introductionmentioning

confidence: 99%

“…5 Similar approval has been achieved outside the United States, with the European Medicine Agency authorizing dupilumab for AD September 2017 with numerous other approval under way. 1,6,7 Throughout the various trials for approval of dupilumab, conjunctivitis has been identified. In various phase 3 clinical trials, patients with AD treated with dupilumab had a 14% to 19% rate of conjunctivitis, whereas patients with AD treated with a placebo had an 8% rate of conjunctivitis.…”

Section: Introductionmentioning

confidence: 99%

“…11 How might a therapeutic that is so powerful in suppressing atopic disease of the skin cause worsening of allergic conjunctivitis? 1,5,12,13 Dermatologists prescribed topical steroid eye drops for persons with conjunctivitis. 1,5 In the setting of introduction of topical steroids, in these trials only 1 of 425 patients discontinued dupilumab because of conjunctivitis.…”

Section: Introductionmentioning

confidence: 99%

“…1,5,12,13 Dermatologists prescribed topical steroid eye drops for persons with conjunctivitis. 1,5 In the setting of introduction of topical steroids, in these trials only 1 of 425 patients discontinued dupilumab because of conjunctivitis. 5,10,14,15 As with many debilitating conditions, patients are willing to withstand significant side effects if they perceive the overall benefit of the medication results in positive outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Dupilumab-Associated Mucin Deficiency (DAMD)

Barnett

Afshari

2020

Trans. Vis. Sci. Tech.

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Purpose: Dupilumab, a monoclonal antibody directed against the interleukin-4 receptor subunit α (IL-4Rα) of IL-4 and IL-13, is increasingly being used to control atopic disease. Dupilumab use has been associated with a poorly understood conjunctivitis. In this study, we sought to investigate the hypothesis that dupilumab use and the associated IL-13 blockade causes a relative ocular mucin deficiency. Methods: Tear levels of mucin 5ac (Muc5AC) and total tear protein levels were evaluated from 28 eyes of 14 patients. Bilateral tear samples were acquired from seven patients on dupilumab and seven patients with no exposure to dupilumab. Study subjects were age and gender matched. In addition to tear samples, photographic documentation of ocular surface findings and a questionnaire of ocular surface symptoms were obtained. Between-group mean differences were calculated. Results: Compared with control, ocular Muc5AC levels normalized to total tear protein was statistically significantly lower. The average Muc5AC levels for persons on dupilumab was 1.54 ± 0.58 ng/mg and that of controls was 7.99 ± 1.16 ng/ mg. Persons on dupilumab reported a statistically increased occurrence of ocular fatigue/eye strain, uncomfortable sensation, pain, red eye, and itching. Conclusions: This study demonstrates for the first time, a relative deficiency of Muc5AC in patients on dupilumab. Translational Relevance: The results of this study support the previously reported role of IL-13 in increasing goblet cell density and associated Muc5AC production. Further efforts are underway to better understand the relative contribution of Muc5AC deficiency in the overall presentation of conjunctivitis associated with dupilumab use.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dupilumab-Associated Mucin Deficiency (DAMD)

Barnett

Afshari

2020

Trans. Vis. Sci. Tech.

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“…An expert consensus gives recommendations how to deal with this problem in clinical practice (Thyssen et al in this issue). 1 Independent from any kind of treatment, often people with 'sensitive skin' also complain about ocular problems. The nature of 'sensitive eyes' is not well defined.…”

mentioning

confidence: 99%

Skin, eye and other problems

Ring

2019

Acad Dermatol Venereol

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Efficacy and Safety of Lebrikizumab, a High-Affinity Interleukin 13 Inhibitor, in Adults With Moderate to Severe Atopic Dermatitis

et al. 2020

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IMPORTANCE Interleukin 13 (IL-13) is a central pathogenic mediator driving multiple features of atopic dermatitis (AD) pathophysiology.OBJECTIVE To evaluate the efficacy and safety of lebrikizumab, a novel, high-affinity, monoclonal antibody targeting IL-13 that selectively prevents formation of the IL-13Rα1/IL-4Rα heterodimer receptor signaling complex, in adults with moderate to severe AD. DESIGN, SETTING, AND PARTICIPANTSA phase 2b, double-blind, placebo-controlled, dose-ranging randomized clinical trial of lebrikizumab injections every 4 weeks or every 2 weeks was conducted from January 23, 2018, to May 23, 2019, at 57 US centers. Participants were adults 18 years or older with moderate to severe AD.INTERVENTIONS Patients were randomized 2:3:3:3 to placebo every 2 weeks or to subcutaneous injections of lebrikizumab at the following doses: 125 mg every 4 weeks (250-mg loading dose [LD]), 250 mg every 4 weeks (500-mg LD), or 250 mg every 2 weeks (500-mg LD at baseline and week 2). MAIN OUTCOMES AND MEASURESThe primary end point was percentage change in the Eczema Area and Severity Index (EASI) (baseline to week 16). Secondary end points for week 16 included proportion of patients achieving Investigator's Global Assessment score of 0 or 1 (IGA 0/1); EASI improvement of at least 50%, 75%, or 90% from baseline; percentage change in the pruritus numeric rating scale (NRS) score; and pruritus NRS score improvement of at least 4 points. Safety assessments included treatment-emergent adverse events.RESULTS A total of 280 patients (mean [SD] age, 39.3 [17.5] years; 166 [59.3%] female) were randomized to placebo (n = 52) or to lebrikizumab at doses of 125 mg every 4 weeks (n = 73), 250 mg every 4 weeks (n = 80), or 250 mg every 2 weeks (n = 75). Compared with placebo (EASI least squares mean [SD] percentage change, −41.1% [56.5%]), lebrikizumab groups showed dose-dependent, statistically significant improvement in the primary end point vs placebo at week 16: 125 mg every 4 weeks (−62.3% [37.3%], P = .02), 250 mg every 4 weeks (−69.2% [38.3%], P = .002), and 250 mg every 2 weeks (−72.1% [37.2%], P < .001). Differences vs placebo-treated patients (2 of 44 [4.5%]) in pruritus NRS improvement of at least 4 points were seen as early as day 2 in the high-dose lebrikizumab group (9 of 59 [15.3%]). Treatment-emergent adverse events were reported in 24 of 52 placebo patients (46.2%) and in lebrikizumab patients as follows: 42 of 73 (57.5%) for 125 mg every 4 weeks, 39 of 80 (48.8%) for 250 mg every 4 weeks, and 46 of 75 (61.3%) for 250 mg every 2 weeks; most were mild to moderate and did not lead to discontinuation. Low rates of injection-site reactions (1 of 52 [1.9%] in the placebo group vs 13 of 228 [5.7%] in all lebrikizumab groups), herpesvirus infections (2 [3.8%] vs 8 [3.5%]), and conjunctivitis (0% vs 6 [2.6%]) were reported.CONCLUSIONS AND RELEVANCE During 16 weeks of treatment, lebrikizumab provided rapid, dose-dependent efficacy across a broad range of clinical manifestations in adult patients with moderate to severe ...

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Conjunctivitis in atopic dermatitis patients with and without dupilumab therapy – international eczema council survey and opinion

Cited by 52 publications

References 28 publications

Dupilumab-Associated Mucin Deficiency (DAMD)

Dupilumab-Associated Mucin Deficiency (DAMD)

Skin, eye and other problems

Efficacy and Safety of Lebrikizumab, a High-Affinity Interleukin 13 Inhibitor, in Adults With Moderate to Severe Atopic Dermatitis

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