Dupilumab in the treatment of genodermatosis: A systematic review

Abstract

Summary Dupilumab interferes with the signaling pathways of IL‐4 and IL‐13 and is effective in treating atopic dermatitis. Specific genodermatoses, including Netherton syndrome, epidermolysis bullosa pruriginosa, and hyper‐IgE syndrome, are Th2 skewed diseases with activation of type 2 inflammation. We performed this systematic review to investigate the therapeutic role of dupilumab in the treatment of genodermatosis. A systematic search was conducted of the PubMed, Embase, Web of Science, and Cochrane databases from inception to December 13, 2021. The review included studies with relevant terms including “dupilumab,” “genodermatosis”, “Netherton syndrome”, “ichthyosis”, “epidermolysis bullosa” and “hyper‐IgE syndrome”. The initial search yielded 2,888 results, of which 28 studies and 37 patients with genodermatosis were enrolled. The assessed genodermatoses included Netherton syndrome, epidermolysis bullosa pruriginosa, hyper‐IgE syndrome, Hailey‐Hailey disease, and severe eczema associated with genetic disorders. Most of the reported cases showed significant clinical improvement after the initiation of dupilumab treatment without major adverse events. Decreased immunoglobulin E levels and cytokine normalization have also been documented. In conclusion, Dupilumab may have a potential therapeutic role in certain genodermatoses skewed towards T helper 2 (Th2) immunity, including Netherton syndrome, epidermolysis bullosa pruriginosa, hyper‐IgE syndrome, Hailey‐Hailey disease, and severe eczema associated with some genetic disorders.

Multiple tiny blisters symmetrically distributed on the back, chest, and behind the ears

“…These are advantageous in alleviating pain or itching in patients and for narrowing wounds. [6][7][8][9] Certain therapies aimed at restoring C7 function in DEB wounds have appeared in clinical trials with profound biologic effects (defined as ≥ 50% wound closure): including modified HSV-1 mediated COL7A1 gene delivery (ClinicalTrials.gov number, NCT04491604), transplantation of COL7A1-engineered autologous keratinocytes (NCT04227106) or fibroblasts (NCT04213261), topical delivery of an antisense oligonucleotide targeting pre-mRNA ofCOL7A1 (NCT03605069), and intravenous recombinant C7 (NCT03752905). 1,10 Though the long-term persistence and consequences of immunogenicity will require further investigation in a larger cohort of patients, gene therapy has generated new hope for improved patient care.…”

“…Apart from steroids and cyclosporine, other clinical treatments that have emerged include dupilumab, baricitinib, cannabinoid, and kallikreins (a family of epidermal secreted proteases). These are advantageous in alleviating pain or itching in patients and for narrowing wounds 6–9 . Certain therapies aimed at restoring C7 function in DEB wounds have appeared in clinical trials with profound biologic effects (defined as ≥ 50% wound closure): including modified HSV‐1 mediated COL7A1 gene delivery (ClinicalTrials.gov number, NCT04491604), transplantation of COL7A1 ‐engineered autologous keratinocytes (NCT04227106) or fibroblasts (NCT04213261), topical delivery of an antisense oligonucleotide targeting pre‐mRNA of COL7A1 (NCT03605069), and intravenous recombinant C7 (NCT03752905) 1,10 .…”

Multiple winzige, symmetrisch verteilte Bläschen auf dem Rücken, der Brust und hinter den Ohren

“…Neben Steroiden und Cyclosporin gibt es weitere klinische Behandlungen wie Dupilumab, Baricitinib, Cannabinoid und Kallikreine (eine Familie epidermaler sezernierter Proteasen). Diese können Schmerzen oder Juckreiz bei Patienten lindern und Wunden verkleinern 6‐ 9 . Bestimmte Therapien, die auf die Wiederherstellung der C7‐Funktion in DEB‐Wunden abzielen, wurden in klinischen Studien mit starken biologischen Wirkungen (definiert als ≥ 50% Wundverschluss) getestet: darunter die modifizierte HSV‐1‐vermittelte COL7A1‐Gentherapie (ClinicalTrials.…”

Biologika bei Genodermatosen ‐ Neue Indikationsgebiete für etablierte pharmakologische Wirkstoffe?

“…11 Wu et al geben in der aktuellen Ausgabe des JDDG im Rahmen einer systematischen Übersichtsarbeit einen Überblick zu möglichen neuen off label-Indikationen für Dupilumab auf dem Gebiet der Genodermatosen. 12 Dupilumab ist ein monoklonaler Antikörper, dessen entzündungshemmende und selektiv immunsupprimierende Eigenschaften über die Bindung an die α-Untereinheit des Interleukin (IL)-4-Rezeptors vermittelt werden. Hierdurch kommt es zur Blockade der proinflammatorischen Zytokine Interleukin (IL)-4 und IL-13 mit konsekutiver Hemmung der Signalwege zweier treibender Faktoren der Typ-2-Inflammation.…”

“…Wu et al. geben in der aktuellen Ausgabe des JDDG im Rahmen einer systematischen Übersichtsarbeit einen Überblick zu möglichen neuen off label‐Indikationen für Dupilumab auf dem Gebiet der Genodermatosen 12 . Dupilumab ist ein monoklonaler Antikörper, dessen entzündungshemmende und selektiv immunsupprimierende Eigenschaften über die Bindung an die α‐Untereinheit des Interleukin (IL)‐4‐Rezeptors vermittelt werden.…”