Real-life experience on effectiveness and safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis

Fargnoli, Maria Concetta; Esposito, Maria; Ferrucci, Silvia; Girolomoni, Giampiero; Offidani, Annamaria; Patrizi, Annalisa; Peris, Ketty; Costanzo, Antonio; Malara, Giovanna; Pellacani, Giovanni; Romanelli, Marco; Amerio, Paolo; Cristaudo, Antonio; Flori, Maria Laura; Motolese, Alberico; Betto, P; Patruno, Cataldo; Pigatto, Paolo D.; Sirna, Riccardo; Stinco, Giuseppe; Zalaudek, Iris; Bianchi, Luca; Boccaletti, Valeria; Cannavò, Salvatore; Cusano, Francesco; Lembo, Serena; Mozzillo, R; Gallo, Rosella; Potenza, Concetta; Rongioletti, Franco; Tiberio, Rossana; Grieco, Teresa; Micali, Giuseppe; Persechino, Severino; Pettinato, M.; Pucci, Stefano; Savi, Eleonora; Stingeni, Luca; Romano, Atelda; Argenziano, Giuseppe

doi:10.1080/09546634.2019.1682503

Cited by 77 publications

(84 citation statements)

References 21 publications

(37 reference statements)

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“…Dupilumab, a monoclonal antibody against interleukin-4 receptor alpha, has been used in numerous allergic diseases and works by blocking signaling of interleukin-4 and interleukin-13, type 2/Th2 cytokines. It has been confirmed to be effective in patients with moderate to severe AD in several double-blind, placebocontrolled studies and in clinical practice [43][44][45]. The result showed that clinical improvement is positively correlated with increased favorable microbial community and reduced abundance of S. aureus [46].…”

Section: Biological Therapy In Patients With Admentioning

confidence: 90%

A Calm, Dispassionate Look at Skin Microbiota in Atopic Dermatitis: An Integrative Literature Review

Wan

Chen

2020

Dermatol Ther (Heidelb)

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Atopic dermatitis (AD) is a chronic common inflammatory skin disorder with clinical characteristics of pruritic, dry, and recurrent flares that involve the whole body. Recent studies have demonstrated that the skin microbiota, characterized by an overgrowth of Staphylococcus aureus (S. aureus), plays a critical role in the manifestation of AD. There is striking evidence that skin microbiota can modulate the development and progression of AD. Therefore, more and more therapeutic approaches are adopted for modifying skin microbiota. Here we discuss the role of skin microbiota in the etiology and maintenance of AD; furthermore, we summarize the effects of therapeutic treatments on skin microbiota in AD based on published literature. With the help of the theoretical guidance suggested by microbial metagenome analysis, the reconstitution of microbiota should be a promising way to harness the pathogens of AD and could be used as a brandnew therapeutic strategy in clinical trials. We believe that the targeted therapy of dysbiosis in AD may possibly become a unique approach to an integrated treatment program in the near future.

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Section: Biological Therapy In Patients With Admentioning

confidence: 90%

A Calm, Dispassionate Look at Skin Microbiota in Atopic Dermatitis: An Integrative Literature Review

Wan

Chen

2020

Dermatol Ther (Heidelb)

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“…Dupilumab has been demonstrated to be an effective treatment for patients with moderateto-severe AD in clinical trials [9][10][11] and in real-life studies [2,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. To date, there have been some reports on real-world experience with dupilumab, including six multicenter studies [14,19,[22][23][24]26].…”

Section: Discussionmentioning

confidence: 99%

Use of Dupilumab in 543 Adult Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Retrospective Study

Nettis¹,

Ferrucci²,

Ortoncelli³

et al. 2022

J Investig Allergol Clin

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Background: Dupilumab has been demonstrated to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, evidence of real-world experience with dupilumab in a broader population is limited to date. Methods: Adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at ten Italian academic centers, were included in the study. Physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index, DLQI) and serological markers [immunoglobulin (Ig) E and eosinophil count] after 16 weeks were analyzed. Results: We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median ± interquartile percentage change from baseline to 16 weeks of treatment in the EASI score was-87.5±22.0 (p<0.001). EASI-50, EASI-75 and EASI-90 response rates were 98.1%, 81.5%, and 50.8% after 16 weeks. At 16 weeks, 93.0% of the patients had achieved a 4point or higher improvement in DLQI from baseline. During dupilumab treatment, 12.2% of the patients developed conjunctivitis, and total IgE significantly decreased (p<0.001). Interestingly, in the multivariate logistic regression model, the risk of developing dupilumab-related conjunctivitis was associated with early AD onset [OR, 2.25; 95%CI, 1.07-4.70; p=0.03] and presence of eosinophilia [OR, 1.91; 95%CI, 1.05-3.39; p=0.03]. Conclusion: To date, this is the broadest real-life study in AD patients treated with dupilumab. We observed significant improvements induced by dupilumab in adult patients with moderate-to-severe AD, to a greater extent than those reported in clinical trials.

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“…[ 3 – 5 ] Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and in a real-world clinical context has indicated the crucial roles of T helper type 2 (Th2) cytokines, interleukin (IL)-4 and IL-13, in the pathogenesis of AD. [ 6 – 8 ] Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the elevated expression of Th2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. [ 9 , 10 ] Other lesional and blood markers including eosinophils, [ 11 – 13 ] lactate dehydrogenase (LDH), [ 14 ] total immunoglobulin E (IgE), [ 15 ] soluble IL-2 receptor, [ 16 ] CCL27, [ 14 ] IL-13, [ 17 ] IL-22, [ 9 ] IL-24, [ 18 , 19 ] IL-25, [ 20 ] IL-31, [ 21 , 22 ] IL-33, [ 23 ] thymic stromal lymphopoietin (TSLP), [ 24 ] periostin, [ 9 , 25 ] and squamous cell carcinoma antigen-2 (SCCA2) [ 26 , 27 ] are elevated in AD and show substantial correlations with its disease activity.…”

Section: Introductionmentioning

confidence: 99%

Exploration of biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab

et al. 2020

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Background: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and a real-world clinical context indicates the crucial roles of interleukin (IL)-4 and IL-13 in the pathogenesis of AD. Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the upregulated expression of T helper type 2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. However, no blood/serum biomarkers are known to predict good or poor outcome in patients with AD treated with dupilumab. Methods: Patients are at least 18 years of age and have moderate-to-severe AD with Eczema Area and Severity Index (EASI) ≥16, Investigator's Global Assessment ≥3, and body surface area ≥10%. We are going to enroll more than 130 subjects from 18 medical facilities. Clinical objective findings will be evaluated by EASI. Subjective symptoms will be assessed by Patient-Oriented Eczema Measure, Numerical Rating Scale for Pruritus (Pruritus-NRS), Skin Comfort-NRS, and Treatment Satisfaction-NRS. We will measure 18 blood/serum biomarkers including % eosinophils in blood cell count, lactate dehydrogenase, total IgE, soluble interleukin 2 receptor, CCL17, CCL18, CCL22, CCL26, CCL27, IL-13, IL-22, IL-24, IL-25, IL-31, IL-33, thymic stromal lymphopoietin, periostin, and squamous cell carcinoma antigen-2. The clinical evaluation and biomarker sampling will be performed at 0, 2, 4, 8, and 16 weeks of dupilumab treatment. We will also perform proteomic analysis (of roughly 300 proteins) of the patients’ sera obtained at 0 and 2 weeks of treatment. The primary endpoint is the association between “baseline levels of 18 biomarkers” and “% change from baseline of EASI at 16 weeks of dupilumab treatment.” Discussion: This is the first clinical trial to explore the biomarkers, including potential proteomic markers, most strongly associated with improvement in EASI in patients with moderate-to-severe AD treated with dupilumab for 16 weeks (B-PAD study). A limitation is that we will only enroll Japanese patients.

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Real-life experience on effectiveness and safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis

Abstract: Sandoz and Sanofi. A. Cristaudo has been principal investigator in clinical trials sponsored by Abbvie, Leo Pharma and Pfizer. F. Cusano received honoraria as speaker and advisory board member from Sanofi Genzyme. M. Esposito has served as a speaker for Sanofi-Genzyme.

Cited by 77 publications

References 21 publications

A Calm, Dispassionate Look at Skin Microbiota in Atopic Dermatitis: An Integrative Literature Review

A Calm, Dispassionate Look at Skin Microbiota in Atopic Dermatitis: An Integrative Literature Review

Use of Dupilumab in 543 Adult Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Retrospective Study

Exploration of biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab

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