المؤلفون: Deleuran, Mette, Thaci, Diamant, Beck, Lisa A., de Bruin-Weller, Marjolein, Blauvelt, Andrew, Forman, Seth, Bissonnette, Robert, Reich, Kristian, Soong, Weily, Hussain, Iftikhar, Foley, Peter, Hide, Michihiro, Bouaziz, Jean-David, Gelfand, Joel M., Sher, Lawrence, Schuttelaar, Marie L. A., Wang, Chen, Chen, Zhen, Akinlade, Bolanle, Gadkari, Abhijit, Eckert, Laurent, Davis, John D., Rajadhyaksha, Manoj, Staudinger, Heribert, Graham, Neil M. H., Pirozzi, Gianluca, Ardeleanu, Marius

المصدر: Deleuran , M , Thaci , D , Beck , L A , de Bruin-Weller , M , Blauvelt , A , Forman , S , Bissonnette , R , Reich , K , Soong , W , Hussain , I , Foley , P , Hide , M , Bouaziz , J-D , Gelfand , J M , Sher , L , Schuttelaar , M L A , Wang , C , Chen , Z , Akinlade , B , Gadkari , A , Eckert , L , Davis , J D , Rajadhyaksha , M , Staudinger ....

مصطلحات موضوعية: atopic dermatitis, biologic therapy, dupilumab, IL-4, IL-13, long-term, open label, monoclonal antibody, efficacy, quality of life, safety, DAILY PRACTICE COHORT, QUALITY-OF-LIFE, PERSISTENT ASTHMA, ADULT PATIENTS, DRUG SURVIVAL, DOUBLE-BLIND, GUIDELINES, MANAGEMENT, ECZEMA, PLACEBO

الوصف: Background: Significant unmet need exists for long-term treatment of moderate to severe atopic dermatitis (AD). Objective: To assess the long-term safety and efficacy of dupilumab in patients with AD. Methods: This ongoing, multicenter, open-label extension study (NCT01949311) evaluated long-term dupilumab treatment in adults who had previously participated in phase 1 through 3 clinical trials of dupilumab for AD. This analysis examined patients given 300 mg dupilumab weekly for up to 76 weeks at data cutoff (April 2016). Safety was the primary outcome; efficacy was also evaluated. Results: Of 1491 enrolled patients (1042.9 patient-years), 92.9% were receiving treatment at cutoff. The safety profile was consistent with previously reported trials (420.4 adverse events/100 patient-years and 8.5 serious adverse events/100 patient-years), with no new safety signals; common adverse events included nasopharyngitis, conjunctivitis, and injection-site reactions. Sustained improvement was seen up to 76 weeks in all efficacy outcomes, including measures of skin inflammation, pruritus, and quality of life. Limitations: Lack of control arm, limited number of patients with 76 weeks or longer of treatment (median follow-up, 24 weeks), and patients not receiving the approved dose regimen of 300 mg every 2 weeks. Conclusion: The safety and efficacy profile from this study supports the role of dupilumab as continuous long-term treatment for patients with moderate to severe AD.

وصف الملف: application/pdf

العلاقة: https://research.rug.nl/en/publications/637b6627-c900-4ce5-8707-e96da5ab271fTest

الإتاحة: https://doi.org/10.1016/j.jaad.2019.07.074Test
https://hdl.handle.net/11370/637b6627-c900-4ce5-8707-e96da5ab271fTest
https://research.rug.nl/en/publications/637b6627-c900-4ce5-8707-e96da5ab271fTest
https://pure.rug.nl/ws/files/116924363/Dupilumab_shows_long_term_safety_and_efficacy_in_patients_with_moderate_to_severe_atopic_dermatitis_enrolled_in_a_phase_3_open_label_extension_study.pdfTest

المؤلفون: Silverberg, Jonathan I., Pinter, Andreas, Pulka, Grażyna, Poulin, Yves, Bouaziz, Jean-David, Wollenberg, Andreas, Murrell, Dedee F., Alexis, Andrew, Lindsey, Lisa, Ahmad, Faiz, Piketty, Christophe, Clucas, Alan

مصطلحات موضوعية: atopic dermatitis, humanized mAb, anti–IL-31 receptor

الوصف: Background: Nemolizumab targets the IL-31 receptor a subunit involved in atopic dermatitis (AD) pathogenesis. Objective: We sought to evaluate a new dosing strategy of nemolizumab in patients with AD. Methods: We performed a 24-week, randomized, double-blind, multicenter study of nemolizumab (10, 30, and 90 mg) subcutaneous injections every 4 weeks versus placebo, with topical corticosteroids in adults with moderate-to-severe AD, severe pruritus, and inadequate control with topical treatment (n 5 226). The Eczema Area and Severity Index (EASI), the peak pruritus (PP) numeric rating scale (NRS), and the Investigator’s Global Assessment (IGA) were assessed. Standard safety assessments were performed. Results: Nemolizumab improved EASI, IGA, and/or NRS-itch scores, with the 30-mg dose being most effective. Nemolizumab (30 mg) reduced EASI scores versus placebo at week 24 (268.8% vs 252.1%, P 5 .016); significant differences were observed by week 8 (P <_ .01). With significant improvement (P 5 .028) as early as week 4, IGA 0/1 rates were higher for 30 mg of nemolizumab versus placebo at week 16 (33.3% vs 12.3%, P 5 .008) but not week 24 because of an increased placebo/topical corticosteroid effect (36.8% vs 21.1%, P 5 .06). PP-NRS scores were improved for 30 mg of nemolizumab versus placebo at week 16 (268.6% vs 234.3%, P <.0001) and week 24 (267.3% vs 235.8%, P <.0001), with a difference by week 1 (P < .001). NRS response rates (>_4-point decrease) were greater for 30 mg of nemolizumab versus placebo at week 16 (P <_ .001) and week 24 (P <_ .01). Nemolizumab was safe and well tolerated. The most common adverse events were nasopharyngitis and upper respiratory tract infection. Conclusions: Nemolizumab resulted in rapid and sustained improvements in cutaneous signs of inflammation and pruritus in patients with AD, with maximal efficacy observed at 30 mg. Nemolizumab had an acceptable safety profile. (J Allergy Clin Immunol 2020;145:173-82.)

العلاقة: Journal of Allergy and Clinical Immunology, T. 145, nr 1, s. 173-182; https://ruj.uj.edu.pl/xmlui/handle/item/256918Test; https://www.jacionline.org/article/S0091-6749Test(19)31099-1/pdf

الإتاحة: https://doi.org/10.1016/j.jaci.2019.08.013Test
https://ruj.uj.edu.pl/xmlui/handle/item/256918Test
https://www.jacionline.org/article/S0091-6749Test(19)31099-1/pdf

المؤلفون: Grolleau, Chloé, Calugareanu, Andreea, Demouche, Sarah, Nosbaum, Audrey, Staumont-Sallé, Delphine, Aubert, Hélène, Cassius, Charles, Jachiet, Marie, Saussine, Anne, Bagot, Martine, Bachelez, Hervé, Battistella, Maxime, Hotz, Claire, Du Thanh, Aurélie, Crépy, Marie-Noëlle, Bergerat, David, Merandet, Marine, Onifarasoaniaina, Rachel, Alberdi, Antonio, How-Kit, Alexandre, Bouaziz, Jean-David, Le-Buanec, Hélène

المساهمون: Service de Dermatologie AP-HP Hôpital Saint-Louis, Hopital Saint-Louis AP-HP (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie Lyon, Hôpital Edouard Herriot CHU - HCL, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institute for Translational Research in Inflammation - U 1286 (INFINITE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), Département de Dermatologie CHU Nantes, Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), Genetic skin diseases : from disease mechanism to therapies (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de pathologie Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), Service de Dermatologie CHU Cochin, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin AP-HP, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Fondation Jean Dausset CEPH

المصدر: ISSN: 0022-202X.

مصطلحات موضوعية: AD, atopic dermatitis DEG, differentially expressed gene DI-Pso, dupilumab-induced psoriatic eruption DC, dendritic cell FDR, false discovery rate GPP, generalized pustular psoriasis GSEA, Gene Set Enrichment Analysis HC, healthy control IPA, Ingenuity Pathway Analysis KC, keratinocyte PSO, plaque psoriasis Th, T helper UR, upstream regulator, atopic dermatitis, DEG, differentially expressed gene, DI-Pso, dupilumab-induced psoriatic eruption, DC, dendritic cell, FDR, false discovery rate, GPP, generalized pustular psoriasis, GSEA, Gene Set Enrichment Analysis, HC, healthy control, IPA

الوصف: International audience ; Dupilumab is a therapeutic antibody targeting IL-4 and IL-13 receptor subunit alpha used for the treatment of patients with atopic dermatitis (AD). Cases of psoriasis-like reactions induced under dupilumab treatment (dupilumab-induced psoriatic eruption [DI-Pso]) for AD were recently reported. To understand the pathogenesis of DI-Pso, we performed gene expression profiling studies on skin biopsies of DI-Pso (n ¼ 7) compared with those of plaque psoriasis, AD, and healthy controls (n ¼ 4 each). Differential gene expression was performed using enrichment and Gene Ontology analysis. Gene expression was validated by qPCR, and protein levels were assessed by immunohistochemistry. Transcriptomic and protein analysis of DI-Pso compared with that of healthy controls, plaque psoriasis, and AD skins revealed activation of T helper 17/IL-23 pathways associated with a significant expression of IL-36, surrogate marker of pustular psoriasis. By contrast, T helper 2 representative genes' expression was strongly decreased in DI-Pso across comparison. Matching analysis with public data of pustular psoriasis skin corroborated that DI-Pso and pustular psoriasis upstream regulators overlap, greater than the overlap with plaque psoriasis. Furthermore, DI-Pso showed strongly decreased expression of many barrier skin genes compared with healthy controls, plaque psoriasis, and AD. Our data indicate that the pathogenesis of DI-Pso relied on a shift of skin immune responses from a T helper 2 to an IL-36 and T helper 17 polarization and on intensified skin barrier alterations.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36610660; inserm-04311288; https://inserm.hal.science/inserm-04311288Test; https://inserm.hal.science/inserm-04311288/documentTest; https://inserm.hal.science/inserm-04311288/file/Grolleau%20C%20Dupi.pdfTest; PUBMED: 36610660

الإتاحة: https://doi.org/10.1016/j.jid.2022.10.015Test
https://inserm.hal.science/inserm-04311288Test
https://inserm.hal.science/inserm-04311288/documentTest
https://inserm.hal.science/inserm-04311288/file/Grolleau%20C%20Dupi.pdfTest

المؤلفون: Cassius, Charles, Branchtein, Mylene, Battistella, Maxime, Amode, Reyhan, Lepelletier, Clémence, Jachiet, Marie, Masson, Adèle de, Frumholtz, Laure, Chasset, François, Amoura, Zahir, Mathian, Alexis, Samri, Assia, Monfort, Jean-Benoit, Bachmeyer, Claude, Bengoufa, Djaouida, Cordoliani, Florence, Bagot, Martine, Bensussan, Armand, Bouaziz, Jean-David, Buanec, Hélène Le

المصدر: Rheumatology; Sep2020, Vol. 59 Issue 9, p2282-2286, 5p

مصطلحات موضوعية: ATOPIC dermatitis, COMPARATIVE studies, DERMATOMYOSITIS, FLOW cytometry, IMMUNITY, PSORIASIS, T cells, PHENOTYPES, CYTOTOXINS

مستخلص: Objectives Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are important for antibacterial immunity and may have regulatory roles. MAIT cells are decreased during SLE. However, their frequencies and phenotype have not been investigated in DM. We studied MAIT cell frequencies and phenotype in DM patients with active and inactive disease (after treatment). Methods Peripheral blood flow cytometry analysis of MAIT cells was compared between DM (n  = 22), SLE (n  = 10), psoriasis (n  = 7) and atopic dermatitis (n  = 5) patients, and healthy controls (n  = 19). Results A dramatic decrease of circulating MAIT cell frequency was observed in active DM and SLE patients compared with healthy controls and other inflammatory skin diseases [active DM: median = 0.25% (interquartile range 0.19–0.6%), P  < 0.0001; active SLE: median = 0.61 (0.55–0.77), P  < 0.0001 vs healthy controls: 2.32% (1.18–4.45%)]. MAIT cells from active DM patients had an abnormal phenotype including increased expression of CD25 and cytotoxic T-lymphocyte-associated protein 4 that correlated with their low frequency in the blood. Conclusion In DM, peripheral blood MAIT cells are dramatically reduced and have an activated/exhausted phenotype that may be linked to increased activation-induced cell death. [ABSTRACT FROM AUTHOR]

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المؤلفون: Faiz, Sarah, Giovannelli, Jonathan, Podevin, Céline, Jachiet, Marie, Bouaziz, Jean-David, Reguiai, Ziad, Nosbaum, Audrey, Lasek, Audrey, Ferrier le Bouedec, Marie-Christine, Du Thanh, Aurélie, Raison-Peyron, Nadia, Tetart, Florence, Duval-Modeste, Anne-Bénédicte, Misery, Laurent, Aubin, François, Dompmartin, Anne, Morice, Cécile, Droitcourt, Catherine, Soria, Angèle, Arnault, Jean-Philippe

المصدر: Journal of the American Academy of Dermatology; Jul2019, Vol. 81 Issue 1, p143-151, 9p

مستخلص: Background: Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials.Objective: We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort.Methods: We included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up.Results: We included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10-9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10-9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10-6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs.Limitations: No control group, missing data.Conclusion: This real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia. [ABSTRACT FROM AUTHOR]

: Copyright of Journal of the American Academy of Dermatology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Jendoubi, Fatma, Shourik, Jason, Seneschal, Julien, Giordano‐Labadie, Francoise, Raison‐Peyron, Nadia, Du‐Thanh, Aurélie, Tetart, Florence, Valois, Aude, Droitcourt, Catherine, Clément, Aude, Nosbaum, Audrey, Crepy, Marie Noelle, Jachiet, Marie, Bouaziz, Jean David, Bernier, Claire, Soria, Angéle, Paul, Carle, Barbarot, Sebastien, Tauber, Marie

المصدر: British Journal of Dermatology; Oct2022, Vol. 187 Issue 4, p602-603, 2p

مصطلحات موضوعية: ATOPIC dermatitis, DUPILUMAB, COHORT analysis

مستخلص: This strategy seems to be more effective in older patients, patients with lower topical corticosteroid usage and those in whom this strategy was implemented when the patient was in clinical good response to reduce the treatment burden, rather than for an AE. [Extracted from the article]

: Copyright of British Journal of Dermatology is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)