Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis

Mennini, Maurizio; Dahdah, Lamia; Fiocchi, Alessandro

doi:10.1056/nejmc1700366

Cited by 167 publications

(34 citation statements)

References 34 publications

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“…Ten of the combined 15 (66.7%) patients achieved the greater than 50% improvement threshold for regional or total SCORAD (P = 0.016). Furthermore, the rate of patients achieving 75% clinical improvement (40%) significantly differed from reports of similar improvements attributable to placebo (13.3%; P = 0.04) (23,24). The combined mean improvement for the cohort was 63.9%; responders averaged 84.1% improvement and partial to nonresponders averaged 21.7% improvement.…”

Section: R Mucosa Was Associated With Clinical Improvement and Safetcontrasting

confidence: 40%

First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis

et al. 2018

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Section: R Mucosa Was Associated With Clinical Improvement and Safetcontrasting

confidence: 40%

First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis

et al. 2018

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“…Dupilumab was well tolerated in most patients, with only 11.9% of patients suffering from blepharoconjunctivitis, a finding which is in contrast to studies reporting eye symptoms in up to 62% of cases [18]. Although the underlying mechanism of blepharoconjunctivitis in AD patients is still not completely elucidated, some authors have suggested that the blockade of IL-4 and IL-13 may increase the activity of specific ligands, such as OX40 ligand, involved in atopic keratoconjunctivitis [31]. It can be assumed that the relatively low incidence of this side effect might be due to the systematic use of lipid emulsion eye drops combined with hyaluronic acid eye drops in all patients from the first day of dupilumab.…”

Section: Discussionmentioning

confidence: 89%

Clinical Response and Quality of Life in Patients with Severe Atopic Dermatitis Treated with Dupilumab: A Single-Center Real-Life Experience

Ferrucci

Casazza

Angileri

et al. 2020

JCM

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Dupilumab is an anti-interleukin-4 receptor monoclonal antibody that was recently approved for the treatment of atopic dermatitis (AD). In this single-center retrospective study, clinical baseline data of 117 severe AD patients treated with dupilumab were collected. At baseline and at weeks 4 and 16, disease severity was assessed through the Eczema Area and Severity Index (EASI) and quality of life through the Dermatology Life Quality Index (DLQI) questionnaire, Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), Peak Pruritus Numerical Rating Scale (NRS-itch), and VAS-sleep. Response to dupilumab was defined as animprovement of ≥75% in EASI from baseline (EASI75). At multivariate analysis, AD onset before 18 years [OR, 2.9; 95% CI, 1.2-7.2; p = 0.0207] and absence of hypereosinophilia [OR, 2.24; 95% CI, 1.03-4.86; p = 0.0412] were identified as significant predictive parameters for response to dupilumab in terms of EASI75 at week 4 but not at week 16. Significant reductions in EASI, DLQI, POEM, HADS, NRS-itch, and VAS-sleep were found between week 4 versus baseline (p < 0.0001 for all) and week 16 versus baseline (p < 0.0001 for all). Early AD onset and absence of hypereosinophilia may be suggested as predictive markers of early response to dupilumab. We confirmed the efficacy and safety of this agent along with the improvement of life quality in severe AD patients.

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“…Other clinical trials using anti-inflammatory medications for other primary indications such as psoriasis and rheumatoid arthritis also measured changes in depressive symptoms as a second outcome (Kappelmann et al, 2018). The IL-6 decoy receptor Tocilizumab (Traki et al, 2014) and the IL-4 Rα agonist Dupilumab (Simpson et al, 2017), both showed statistically significant improvements in depressive symptoms. Collectively, the modest success of clinical trials targeting inflammatory pathway in depression provide rationale to pursue novel targets within neuroinflammatory pathways of depression.…”

Section: Inhibition Of the Nlrp3 Inflammasome And Neuroinflammationmentioning

confidence: 99%

Principles of inflammasome priming and inhibition: Implications for psychiatric disorders

Herman

Pasinetti

2018

Brain, Behavior, and Immunity

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The production of inflammatory proteins by the innate immune system is a tightly orchestrated procedure that allows the body to efficiently respond to exogenous and endogenous threats. Recently, accumulating evidence has indicated that disturbances in the inflammatory response system not only provoke autoimmune disorders, but also can have deleterious effects on neuronal function and mental health. As inflammation in the brain is primarily mediated by microglia, there has been an expanding focus on the mechanisms through which these cells initiate and propagate neuroinflammation. Microglia can enter persistently active states upon their initial recognition of an environmental stressor and are thereafter prone to elicit amplified and persistent inflammatory responses following subsequent exposures to stressors. A recent focus on why primed microglia cells are susceptible to environmental insults has been the NLRP3 inflammasome. Its function within the innate immune system is regulated in such a manner that supports a role for the complex in gating neuroinflammatory responses. The activation of NLRP3 inflammasome in microglia results in the cleavage of zymogen inflammatory interleukins into functional forms that elicit a number of consequential effects in the local neuronal environment. There is evidence to support the principle that within primed neuroimmune systems a lowered threshold for NLRP3 activation can cause persistent neuroinflammation or the amplified production of inflammatory cytokines, such as IL-1β and IL-18. Over the course of an individual's lifetime, persistent neuroinflammation can subsequently lead to the pathophysiological signatures that define psychological disorders. Therefore, targeting the NLRP3 inflammasome complex may represent an innovative and consequential approach to limit neuroinflammatory states in psychiatric disorders, such as major depressive disorder.

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Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis

Cited by 167 publications

References 34 publications

First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis

First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis

Clinical Response and Quality of Life in Patients with Severe Atopic Dermatitis Treated with Dupilumab: A Single-Center Real-Life Experience

Principles of inflammasome priming and inhibition: Implications for psychiatric disorders

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