The clinical efficacy and safety of <scp>anti‐IgE</scp> therapy in recessive dystrophic epidermolysis bullosa

Chen, Fuying; Guo, Yuxin; Zhou, Kai; De-zhong, Dan; Yue, Wanbo; Yang, Wu; Zhang, Beibei; Li, Yue; Liang, Jianying; Li, Ming; Yao, Zhirong

doi:10.1111/cge.14062

Cited by 9 publications

(2 citation statements)

References 17 publications

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“…Different modalities have been used in DEB pruriginosa in individual cases or small series including thalidomide, [ 37 ] ciclosporin, [ 38 , 39 ] intravenous immunoglobulin, [ 40 ] topical ketamine and amitriptyline gel with oral mirtazapine [ 41 ] and oral janus kinase inhibitors [ 42 , 43 ]. Recent reports have demonstrated encouraging responses with omalizumab anti-immunoglobulin E monoclonal antibody, [ 44 ] and dupilumab against interleukin 4 and interleukin 13 [ 45 – 49 ]. As yet, however, there have been no formal clinical trials in DEB pruriginosa presumably due to its rarity and the inherent difficulties for sufficient statistical powering.…”

Section: Discussionmentioning

confidence: 99%

Itch in recessive dystrophic epidermolysis bullosa: findings of PEBLES, a prospective register study

Mellerio

Pillay

Ledwaba-Chapman

et al. 2023

Orphanet J Rare Dis

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Background Itch is common and distressing in epidermolysis bullosa (EB) but has not previously been studied in depth in different recessive dystrophic EB (RDEB) subtypes. Objectives As part of a prospective register study of the natural history of RDEB we explored features of itch, medications used, and correlation with disease severity and quality of life. Methods Fifty individuals with RDEB aged 8 years and above completed the Leuven Itch Scale (LIS) (total 243 reviews over a 7-year period). Data included itch frequency, severity, duration, distress, circumstances, consequences, itch surface area and medications for itch. The iscorEB disease severity score and the validated EB quality of life tool, QOLEB, were compared to LIS domains and analysed by RDEB subtype. Results Itch was frequent, present in the preceding month in 93% of reviews. Itch severity and distress were significantly greater in severe (RDEB-S) and pruriginosa (RDEB-Pru) subtypes compared to intermediate RDEB (RDEB-I). Itch medications were reported in just over half of reviews including emollients, topical corticosteroids and antihistamines; the proportion of participants not using medication despite frequent pruritus suggests limited efficacy. In inversa RDEB (RDEB-Inv) and RDEB-I, LIS domains correlated with iscorEB and QOLEB. In contrast to previous studies, correlations were lacking in RDEB-S suggesting that global disease burden relatively reduces the contribution of itch. Conclusions This comprehensive study of RDEB-associated itch highlights differences between RDEB subtypes, suggests an unmet need for effective treatments and could serve as control data for future clinical trials incorporating itch as an endpoint.

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Section: Discussionmentioning

confidence: 99%

Itch in recessive dystrophic epidermolysis bullosa: findings of PEBLES, a prospective register study

Mellerio

Pillay

Ledwaba-Chapman

et al. 2023

Orphanet J Rare Dis

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“… 121 Besides upregulation of Th2 signaling, elevated IgE levels have also been demonstrated and anti-IgE therapy with omalizumab (300mg every 4 weeks) in some individuals has led to some lessening of skin inflammation and a moderate reduction in itch. 126 Aside from biologics, oral baricitinib (2mg daily), a JAK1/2 inhibitor, has also been shown to reduce DEB itch. 127 Similarly, another JAK inhibitor, tofacitinib, also rapidly reduced itch and skin inflammation in DEB.…”

Section: Disease-modifying or Symptomatic Control Treatmentsmentioning

confidence: 99%

Innovations in the Treatment of Dystrophic Epidermolysis Bullosa (DEB): Current Landscape and Prospects

Hou,

del Agua,

Lwin

et al. 2023

TCRM

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Dystrophic epidermolysis bullosa (DEB) is one of the major types of EB, a rare hereditary group of trauma-induced blistering skin disorders. DEB is caused by inherited pathogenic variants in the COL7A1 gene, which encodes type VII collagen, the major component of anchoring fibrils which maintain adhesion between the outer epidermis and underlying dermis. DEB can be subclassified into dominant (DDEB) and recessive (RDEB) forms. Generally, DDEB has a milder phenotype, while RDEB patients often have more extensive blistering, chronic inflammation, skin fibrosis, and a propensity for squamous cell carcinoma development, collectively impacting on daily activities and life expectancy. At present, best practice treatments are mostly supportive, and thus there is a considerable burden of disease with unmet therapeutic need. Over the last 20 years, considerable translational research efforts have focused on either trying to cure DEB by direct correction of the COL7A1 gene pathology, or by modifying secondary inflammation to lessen phenotypic severity and improve patient symptoms such as poor wound healing, itch, and pain. In this review, we provide an overview and update on various therapeutic innovations for DEB, including gene therapy, cell-based therapy, protein therapy, and disease-modifying and symptomatic control agents. We outline the progress and challenges for each treatment modality and identify likely prospects for future clinical impact.

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Neue Lokal- und Systemtherapien bei Epidermolysis bullosa

Prodinger,

Laimer

2024

hautnah

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ZusammenfassungEpidermolysis bullosa (EB) bezeichnet eine seltene, heterogene Gruppe von Genodermatosen, charakterisiert durch eine gesteigerte Fragilität von Haut und Schleimhaut. Mit zunehmender Aufklärung der molekularen Pathophysiologie haben sich in den letzten Jahren sämtliche lokale und systemische Therapieansätze in klinischen Studien etabliert. Ein bedeutender Meilenstein ist die Zulassung der FDA für die topische Gentherapie Beremagene Geperpavec (B-VEC) zur Behandlung chronischer Wunden bei dystropher EB mit Mutationen im COL7A1-Gen. Diese Therapie basiert auf modifizierten HSV-1-Vektoren, um funktionales COL7A1 in die Hautzellen zu übertagen. In einer Phase-3-Studie zeigten sich etwa drei Viertel der chronischen Wunden nach 3 Monaten komplett verschlossen, im Vergleich zu 20 % in der Placebogruppe. Klinische Studien mit RNA-basierten Therapien, wie medikamentös induzierte PTC-Readthrough und zellbasierten Therapien wie ABCB5+ mesenchymale Stammzellen zeigen Potenzial für weiteren Einsatz. Durch das 2022 speziell für EB zugelassene Filsuvez® Gel (Oleogel S‑10, Chiesi, Wien) und das topische Vitamin-D-Analogon Calcipotriol kann die Wundheilung verbessert werden, während TGF-β-Inhibitoren, z. B. Losartan, die EB-assoziierte Fibrose adressieren. Biologika wie Dupilumab, JAK- und mTOR-Inhibitoren erweitern das therapeutische Armamentarium. Immuntherapien gelten aktuell als First-line-Therapie für aggressive EB assoziierte Plattenepithelkarzinome und werden neben Multikinase-Inhibitoren (Rigosertib) in Studien untersucht. Zukünftig könnten auch MikroRNA sowohl in der Frühdiagnostik als auch topisch zur Reduktion der Tumoraggressivität eingesetzt werden. Insgesamt markieren diese Entwicklungen einen bedeutsamen Fortschritt in der therapeutischen Landschaft von EB und vermitteln Hoffnung für Betroffene und Angehörige.

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The clinical efficacy and safety of anti‐IgE therapy in recessive dystrophic epidermolysis bullosa

Cited by 9 publications

References 17 publications

Itch in recessive dystrophic epidermolysis bullosa: findings of PEBLES, a prospective register study

Itch in recessive dystrophic epidermolysis bullosa: findings of PEBLES, a prospective register study

Innovations in the Treatment of Dystrophic Epidermolysis Bullosa (DEB): Current Landscape and Prospects

Neue Lokal- und Systemtherapien bei Epidermolysis bullosa

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