An integrated analysis of herpes virus infections from eight randomized clinical studies of baricitinib in adults with moderate‐to‐severe atopic dermatitis

Abstract

Background Atopic dermatitis (AD) is associated with an increased risk for viral infections including those caused by herpes simplex virus and varicella zoster virus. Objectives This study examined treatment‐emergent (TE) herpes simplex infection including eczema herpeticum (EH), and herpes zoster (HZ), in adult patients with AD receiving ≥1 dose of baricitinib (BARI), an oral selective inhibitor of Janus kinase 1/2. Methods We evaluated data from six double‐blinded, randomized, placebo‐controlled (PC) trials and two long‐term extension studies, within three analysis sets: PC, 2–4‐mg BARI extended and All‐BARI‐AD. Frequency, incidence rate (IR)/100 person‐years (PYs) and clinical characteristics of TE‐herpes simplex, EH and HZ were reported. Results In the All‐BARI‐AD dataset (n = 2531; 2247 PYs), herpes simplex was reported in 8.9% of patients (n = 224; IR = 10.3). Most herpes simplex events were rated as mild or moderate (93.3%), rarely led to permanent discontinuation (2.2%) and presented mostly as oral/perioral herpes simplex (51.3%). TE‐EH occurred at a low frequency (All‐BARI‐AD 1.7% n = 43; IR = 2.0) and were reported in 0.5%, 0.2% and 1.4% of patients receiving placebo, 2‐mg or 4‐mg BARI respectively. In the All‐BARI‐AD dataset, most events were investigator‐rated as mild/moderate (79.1%), affected ≤2% of the body surface area (74.2%) and occurred as single events (88.4%). Serious TE‐EH (n = 11) occurred exclusively in patients with poor disease control (vIGA‐AD™ score ≥3) at infection onset. TE‐HZ was reported in 2.1% of BARI patients (n = 53; IR = 2.3), without a dose relationship during the PC period (IR = 2.7 and IR = 0.0) or the extended dataset (IR = 3.7 and IR = 1.7) for 2‐ or 4‐mg BARI respectively. Conclusions TE‐herpes simplex was common, while occurrence of EH was uncommon. Most events of EH were localized with involvement of a small BSA and were linked to poor disease control. Events of HZ were rare in the PC dataset and without a dose dependent increase in frequency.

The Expression of Plasmacytoid Dendritic Cells and TLR7/9-MyD88-IRAKs Pathway in Chronic Eczema Lesions

“…Factors such as impaired epidermal barrier function, chronic inflammation, and disturbed skin flora all contribute to increased viral susceptibility in AD patients. [18][19][20] Chronic eczematous lesions also present similar problems. This study found that CD2AP and CD123 specifically expressed in pDC were higher in chronic eczema lesions than in normal lesions, suggesting that pDCs accumulate in chronic eczema lesions, mainly in the superficial dermis and basal layer of the epidermis.…”

Hydrolyzed Collagen Induces an Anti-Inflammatory Response That Induces Proliferation of Skin Fibroblast and Keratinocytes

“…It is well known that the transformations that occur in the skin during senescence [ 3 ] and in some diseases, such as dermatoses [ 3 ], may increase the risk of infections that originate due to a virus [ 10 ], bacteria [ 11 ], and fungi [ 12 ]. In the present study, we demonstrated for the first time that hydrolyzed types I and III collagen importantly inhibited the inflammatory response induced by LPS in human fibroblasts (CCD-1072Sk) and human keratinocytes (hKT-nh-skp-KT0026).…”

Hohe Rezidivrate des Eczema herpeticatum bei mittelschwerer bis schwerer atopischer Dermatitis – eine TREATgermany Registeranalyse

“…Odds Ratio: 0,34; 95%‐Konfidenzintervall [KI]: 0,14–0,84, Eichenfield et al 11 . relatives Risiko: 0,31, 95% KI: 0,12–0,82) und keinen Einfluss auf die Rate systemischer Infektionen hat, führte die JAK‐Hemmung zu einem erhöhten Risiko vor allem von HSV‐Infektionen (in den Baricitinib‐Studien: Inzidenzrate von 2,0) 12–15 . Zu berücksichtigen ist, dass Patienten, die aufgrund ihrer Vorgeschichte ein erhöhtes Risiko für schwere HSV‐Infektionen hatten, in den Studien für JAK‐Inhibitoren ausgeschlossen wurden, in den EMA‐Zulassungen für die Behandlung der AD jedoch nicht exkludiert sind 12 …”

“…[12][13][14][15] Zu berücksichtigen ist, dass Patienten, die aufgrund ihrer Vorgeschichte ein erhöhtes Risiko für schwere HSV-Infektionen hatten, in den Studien für JAK-Inhibitoren ausgeschlossen wurden, in den EMA-Zulassungen für die Behandlung der AD jedoch nicht exkludiert sind. 12 Um dem Ziel einer patientenindividuellen Therapie näher zu kommen, wäre es hilfreich, AD-Patienten mit einem erhöhten Risiko für ein EH zu identifizieren. In früheren Arbeiten konnten wir zeigen, dass AD-Patienten mit einem EH in der Vorgeschichte eine erhöhte Frequenz an Typ-2-polarisierten virusspezifischen T-Zellen aufweisen.…”