nach oben

American Journal of Clinical Dermatology

Open Access 18.01.2024 | Review Article

OX40 in the Pathogenesis of Atopic Dermatitis—A New Therapeutic Target

verfasst von: Michael Croft, Ehsanollah Esfandiari, Camilla Chong, Hailing Hsu, Kenji Kabashima, Greg Kricorian, Richard B. Warren, Andreas Wollenberg, Emma Guttman-Yassky

Erschienen in: American Journal of Clinical Dermatology

Abstract

Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient’s overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD. Despite new targeted therapies, many patients with moderate-to-severe AD fail to achieve or sustain their individual treatment goals and/or may not be suitable for or tolerate these therapies. There remains a need for a novel, efficacious, well-tolerated therapeutic option that can deliver durable benefits across a heterogeneous AD patient population. Expression of OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], a prominent T-cell co-stimulatory molecule, and its ligand [OX40L; tumor necrosis factor superfamily, member 4 (TNFSF4)] is increased in AD. As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD.

Graphical Abstract

The original online version of this article was revised due to update in graphic abstract.

A correction to this article is available online at https://doi.org/10.1007/s40257-024-00850-7.

Key Points

Atopic dermatitis (AD) is a chronic, inflammatory skin disease involving a complex interaction between skin barrier dysfunction and T-cell-mediated inflammation.

OX40, an important T-cell co-stimulatory molecule, is highly expressed in activated T cells of patients with AD; binding of OX40 to its ligand (OX40L) promotes expansion, differentiation, and survival of pathogenic effector and memory T cells.

Recent promising results from early phase clinical studies of antibodies against OX40 (rocatinlimab; telazorlimab) or OX40L (amlitelimab) in moderate-to-severe AD highlights the potential for targeting the OX40 pathway as a novel therapeutic approach for the treatment of AD.

1 Introduction

Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain [1, 2]. It is the most common inflammatory skin disease that affects nearly 20% of children, 15% of adolescents, and 10% of adults worldwide [3‐6]. In the USA, an estimated 15% of children, 9% of adolescents, and 7% of adults have AD [3, 5, 6]. Among US adults with AD, approximately 40% are affected by moderate-to-severe disease [7]. While AD typically occurs in childhood, it may continue into adulthood and ~ 25% of patients develop AD in adulthood [8, 9].

AD is driven by skin barrier disruption and dysregulation of T-cell-dependent inflammatory pathways [1, 10]. Variations in lesion phenotype and/or location seen in individuals with AD [8, 11] are attributed to multiple underlying inflammatory pathways that may evolve over time [1, 3, 8, 12‐15]. T cells play a central role in many of the inflammatory pathways involved in AD pathogenesis [15, 16], and the influx and expansion of T cells within the skin and the release of various proinflammatory cytokines contribute to multiple aspects of AD pathogenesis [1, 14‐16].

Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares. Skin pain, pruritus, irritability, sleep disturbance, interference with daily activities of school or work, and psychological stress [17, 18] lead to decreased quality of life (QoL) and significant societal and humanistic burden on patients, their families, and/or caregivers [1, 3, 12, 13]. In addition, patients often have comorbidities and secondary complications that increase the burden of disease [1, 19]. AD and its associated comorbidities and complications contribute to substantial economic burden through direct healthcare costs and indirect costs, such as loss of work productivity and absenteeism [3].

Treatment of AD remains a challenge due to its heterogeneity and highly fluctuating and unpredictable course of disease. Recent advances in understanding the pathophysiology of disease have contributed to the discovery of many new targeted therapies that have expanded treatment options for patients with AD [1, 20]. This review provides an overview of the pathogenesis of AD and the need for improved therapeutic options, and highlights new targets in OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)] and OX40 ligand [OX40L; tumor necrosis factor superfamily, member 4 (TNFSF4)] that may be advantageous given the multifaceted nature of AD. Treatment approaches aimed at these novel molecules, which can affect multiple immune pathways central to disease pathogenesis, have the potential to control AD effectively regardless of the subtype or stage of the disease.

2 Atopic Dermatitis Pathogenesis

The pathogenesis of AD is complex and multifactorial, as epidermal barrier disruption, immune dysregulation, environmental allergens, and genetic predisposition all play pathogenic roles to initiate and sustain chronic inflammation in AD [21].

Local skin inflammation and epidermal barrier dysfunction are apparent contributors of AD pathogenesis [1, 3]. Local skin inflammation, evident as acute or chronic skin lesions, shows immune infiltration of predominantly CD4+ T cells, skin-resident dendritic cells, innate lymphoid cells, and Langerhans cells [22]. Even in the absence of visible skin lesions, the presence of immune infiltrates in non-lesional skin of patients with AD, together with a pre-activation of skin dendritic cells [23, 24], suggests the underlying inflammatory processes [25, 26]. Ongoing subclinical inflammation may manifest itself by structural changes, such as hyperkeratosis, skin hyperplasia, intercellular endothelial edema with venule alteration, and basement membrane thickening [27]. Systemic inflammation plays an equally critical role in patients with AD [1, 3]. Studies have shown increased inflammatory markers from various T-cell subsets in blood from patients with moderate-to-severe AD compared with controls, and these increases correlated with greater baseline AD severity [26]. The common coexistence of AD, allergic rhinitis, and asthma further supports the involvement of systemic inflammation as high levels of circulating inflammatory cytokines in patients with AD may impact lungs, airways, and other mucosal surfaces [28‐31].

Underlying the heterogeneous clinical features, AD harbors a highly diverse endotype repertoire [32, 33]. While Th2 is the predominant inflammatory pathway in AD [16], other T-cell subsets (e.g., Th1, Th17, and Th22) and their associated cytokines also contribute to disease pathology. The degree of involvement of various subsets of T-cell-dependent inflammatory pathways is different by disease stage or by age [15] and across populations by ethnicity [1, 11, 14].

AD can evolve from an initial, acute, Th2-dominated phase characterized by diffuse lesions to a chronic phase marked by the concomitant presence of Th1, Th17, and Th22 cells that contribute to epidermal thickening and the development of poorly demarcated, scaly patches and plaques with excoriation and lichenification [15, 32, 34‐37]. Activated memory T cells are significantly increased in AD lesions and may amplify and sustain the overall immune response, influencing disease severity, recurrence, and chronicity [38‐40]. In particular, the chronic nature of AD is linked to the long-lived potential of antigen-responding T cells [40‐42]. Effector T cells also survive as memory T cells, which enable rapid recall effector responses when antigen is re-encountered and lead to the self-renewal of the long-lived memory T cell populations thought to be responsible for disease recurrence [40, 42]. Compared with adult AD, pediatric AD is associated with reduced levels of Th1-driven inflammation [43] and increased levels of Th17- and Th22-driven inflammation [14, 32], reflecting the higher incidence of impetiginized, weeping lesions [2].

AD is disproportionately more prevalent in patients of color [11]. Although Th2 immune activation is consistently observed among different ethnicities, Asian and African American patients with AD exhibit varying levels of Th1, Th17, and Th22 activation compared with white patients with AD; these differences may contribute toward phenotypic features commonly observed in Asian and African American populations [11, 14, 32, 44].

The diversity of immune responses in AD and their respective epidermal barrier correlates suggest that targeting the Th2 pathway on its own may not be adequate to achieve an optimal clinical response in patients with AD. New therapeutic approaches that target multiple T-cell subsets and a broader spectrum of immune pathways may provide clinical benefits across heterogeneous patients with AD [45, 46].

3 Need for Improved Therapeutic Options for Atopic Dermatitis

The treatment goals for AD are to optimize long-term outcomes by minimizing flares, comorbidities, secondary complications, and potential adverse effects, as well as to decrease treatment burden for patients [13, 47‐49]. Current treatment options for AD include topical regimens, phototherapy, systemic immune modulators, biologics, and small molecule Janus kinase (JAK) inhibitors [46‐51].

Despite standard use of topical agents, a significant proportion of patients with moderate-to-severe AD require systemic add-on therapy due to limited efficacy of topical agents and their potential association with skin thinning or application site pain, burning, and stinging [50, 52, 53]. The use of systemic corticosteroids is generally discouraged by clinical practice guidelines except in special circumstances [31, 47‐49, 54]. Conventional systemic immunosuppressive agents (e.g., methotrexate, cyclosporine, azathioprine) are recommended by current guidelines for the treatment of refractory AD, but mainly used off-label [31, 47, 48, 55].

Approved biologics, including the interleukin (IL)-4/IL-13 receptor alpha subunit (Rα) inhibitor dupilumab and the IL-13 inhibitor tralokinumab [46, 48], are additional add-on treatment options for patients with moderate-to-severe AD whose disease was not adequately controlled with topical therapies. However, in pivotal phase 3 trials, more than 60% of patients receiving dupilumab (with topical agents as needed) or tralokinumab (combined with topical corticosteroid) could not achieve clear or almost clear skin after 16 weeks of treatment [56, 57] and in a retrospective cohort study, 35% of patients lost or partially lost the response to dupilumab after 12 months of treatment [58, 59]. The use of dupilumab has also been shown to lead to adverse skin reactions such as rosacea, alopecia, and psoriasis [60‐64] and arthralgia [65‐68], which indicate possible skewing toward Th1- or Th17-mediated inflammation when only the Th2 pathway is inhibited by dupilumab. The waning efficacy and dermatologic eruptions/joint pain observed with dupilumab or tralokinumab further support that although AD is a largely Th2-driven disease, biologics specifically targeting cytokines in the Th2 immune pathway are not sufficient and may even lead to safety issues related to only targeting the Th2 arm of the T-cell response [46, 48, 60‐64].

Management strategies for patients who do not respond sufficiently or lose response to biologics are limited, including escalating biologic dose or frequency, adding a traditional systemic immunosuppressive agent, or initiating alternative systemic treatments such as JAK inhibitors [46, 48, 58]. JAK inhibitors are broad-acting therapeutics, but may be associated with significant safety concerns including the boxed warning related to cardiovascular and cancer risks [46, 48, 69] based on studies in rheumatoid arthritis [46, 70, 71]. In patients with AD, however, both risk factors and cardiovascular adverse events are less prevalent compared with rheumatoid arthritis [72]. The European Medicines Agency has published risk factors for patients using JAK inhibitors, but not changed the dermatological indications for the substance class [73].

Many patients may also fail to reach or maintain treatment goals because of issues with safety or tolerability [1, 20]. Side effects are associated with not only JAK inhibitors, but also biologics, such as ocular and skin AEs for dupilumab or tralokinumab [60‐64, 74‐76]. Fear of side effects from medications has been shown to impact adherence, and poor adherence can be a major limiting factor to achieving optimal disease outcomes in patients with AD [77]. Dosing frequency/regimen complexity with available systemic therapies may also negatively affect adherence to treatment [77].

In summary, despite available therapies, many patients with moderate-to-severe AD fail to achieve or sustain treatment goals and/or may not be suitable for, or tolerate, these therapies. Thus, there remains a need for a novel, highly efficacious, well-tolerated therapeutic option that can deliver durable benefits across AD patient populations.

4 Role of OX40 Signaling in T-cell Responses and Atopic Dermatitis Pathogenesis

T-cell-dependent inflammation, a key contributor of AD pathophysiology, is mediated by antigen stimulation through T-cell receptors, along with ligation of co-stimulatory molecules, particularly those in the TNF receptor superfamily [78]. One of these, the OX40 co-stimulatory signaling pathway, plays a critical role in effector function and long-lasting T-cell responses through promoting the development of memory T cells [79‐82], and has been implicated in AD pathogenesis [83].

OX40 belongs to a class of inducible co-stimulatory receptors and is predominantly expressed on T cells following their activation, including primary effector Th2 cells and other T-cell subsets such as Th1, Th17, and Th22 [84], and is not constitutively expressed on naïve CD4+ or CD8+ T cells. OX40 expression is further enhanced by various cytokines including IL-1, IL-2, IL-4, and TNFα [83, 84]. Following antigen stimulation, OX40 is rapidly and transiently expressed on both effector and memory T cells upon activation [84, 85], making OX40 a potential therapeutic target for T-cell-mediated diseases. The binding partner of OX40, OX40 ligand (OX40L), is a co-stimulatory molecule mainly expressed on antigen-presenting cells (APCs), such as B cells, Langerhans cells, and dendritic cells, and other cells such as type 2 innate lymphoid cells (ILC2), endothelial cells, fibroblasts, and mast cells [85, 86]. Binding of OX40L to OX40 promotes trimerization of OX40 monomers, recruitment of TNF receptor associated factor (TRAF) proteins, and activation of downstream nuclear factor kappa B (NF-κB) and phosphoinositide 3-kinase (PI3K)/Akt signaling, which enhances effector T-cell proliferation and survival, induces memory T-cell generation and persistence, and upregulates proinflammatory cytokine production [85].

OX40 pathway activation is involved in both systemic and local inflammation in patients with AD [83, 87] (Fig. 1). Systemically, while OX40L expression, primarily by monocytes, shows no differences between patients with AD and healthy controls, OX40 expression is elevated in circulating CD4+ T cells from patients with AD [87]. In the peripheral blood of patients with AD, the expression of OX40 is increased on activated skin-homing CD4+ T cells, compared with activated CD4+ T cells without skin-homing antigen expression [87]. Locally, the numbers of OX40+ cells (presumably T cells) and OX40L+ dendritic cells are greater in the lesional skin of patients with AD compared with psoriatic and non-lesional skin [88‐90]. One study showed that in patients with AD, OX40+ T cells were increased as much as tenfold in lesional skin compared with non-lesional skin [88]. In skin biopsies of AD lesions, OX40+ dermal cells and OX40L+ cells (suggested to be mast cells) were found colocalized within the dermis [87] and OX40L expression was visualized on keratinocytes [88, 90], suggesting local activity of OX40 signaling.

Although few specifics are known at present in patients with AD, OX40 might be important at several phases of AD development. During the acute stage of AD, it is likely that OX40 signaling is involved in Th2-driven inflammation, amplifying skin barrier disruption and development of symptoms such as pruritus. In early pathogenesis, Langerhans cells and inflammatory dendritic epidermal cells recognize foreign antigens that penetrate the skin through a disrupted epidermal barrier, subsequently priming Th2 cells [21, 91]. Barrier-disrupted keratinocytes can also produce cytokines, such as thymic stromal lymphopoietin (TSLP), IL-25, and IL-33. As these molecules have been shown to stimulate APCs to express OX40L, this could further potentiate T-cell expansion and differentiation by enhancing OX40 signals delivered to T cells [92‐94] (Fig. 2). Similarly, OX40L has been found to be induced on ILC2 that are also regulated by these innate cytokines, and interactions between ILC2 and T cells involving OX40L and OX40 could also contribute to initial priming of Th2 cells [86]. Activated Th2 cells upregulate production of IL-14, IL-13, and IL-31, which further disrupts epidermal barrier function by suppressing the expression of barrier-related genes such as terminal keratinocyte differentiation gene filaggrin as well as promoting epidermal hyperplasia [16, 83, 95, 96]. IL-4 and IL-13 bind to IL-4Rα expressed on T cells, B cells, macrophages, and other immune cells to promote inflammation and immunoglobulin E class switching [21, 97]. Sensory neurons express receptors for various cytokines released by skin cells and immune cells, including IL-4, IL-13, IL-31, and TSLP, to transmit pruritus and pain signals to the central nervous system, causing atopic itch, pain, and scratching [16, 91] (Fig. 2).

Transition from the acute to chronic stage of AD could also be controlled by OX40. Prolonged expression of proinflammatory cytokines, together with continued antigen presentation, may sustain expression of OX40 on activated T cells (Fig. 2). As OX40 expression is not confined to the Th2 subset, OX40 signaling may also enhance Th1 and Th17/22 pathways by driving the expansion of these T-cell subsets and by enhancing interferon gamma (IFN-γ), IL-17, or IL-22 production, resulting in sustained accumulation and activity of effector and memory Th1, Th17, and Th22, as well as Th2 cells [15, 16, 85]. A mechanistic biomarker study in humans has shown that blocking OX40 signaling not only modulates Th2 signatures [IL-31, CCL11, thymus- and activation-regulated chemokine (TARC; CCL17), and TSLP receptor], but also reduces signatures of other immune pathways upregulated in AD lesional skin, including Th1 signatures (IFN-γ and IFN-γ-induced chemokine CXCL10) and Th17/Th22 signatures (IL-23p19/IL-8/S100As) [98].

During the chronic stage of AD, OX40-mediated signals are also likely to promote the survival of various types of pathogenic T cells, which are involved in further attracting circulating immune cells to the epidermis, altering keratinocyte differentiation, and inducing epidermal thickening [95] (Fig. 2). IFN-γ produced by Th1 cells promotes cutaneous inflammation and keratinocyte apoptosis [97]. IL-17 produced by Th17 cells induces other inflammatory mediators that promote influx of T cells to lesional AD skin [97]. IL-22 produced by Th22 cells contributes to epidermal hyperplasia [97]. As signaling via OX40 has also been shown to enhance the survival of activated effector T cells when they transition into memory T cells [80, 82, 85], this induction of memory generation and persistence may additionally contribute to the chronicity of AD [40] (Fig. 2). Which cells might provide OX40L during the chronic phases of AD is unclear, but mast cells, ILC2, dendritic cells, Langerhans cells, and keratinocytes are all possibilities [85, 86, 88, 90].

In summary, increased OX40 signaling in several phases of AD disease pathogenesis would implicate a key role for the OX40 pathway in local and systemic inflammation by promoting expansion, differentiation, and survival of pathogenic T cells and subsequent T-cell memory formation, contributing to the chronic course of the disease.

5 Targeting OX40

Considering the diverse disease endotypes, targeting OX40 signaling is a promising therapeutic approach to provide sustained inhibition of pathogenic Th2 cells and other T-cell subsets associated with inflammation in AD. Three antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] are currently in clinical development for the treatment of moderate-to-severe AD (Table 1). Early phase clinical studies of these three antibodies have shown very promising results on the basis of the assessment of established instruments such as Investigator Global Assessment (IGA) 5-point scale or the Eczema Area Severity Index (EASI).

5.1 Rocatinlimab

Since OX40 expression is elevated on pathogenic T cells at sites of inflammation, targeting OX40 provides the potential for focused modulation of T cells that contribute to AD. Rocatinlimab (AMG 451/KHK4083; Table 1) is a non-fucosylated IgG1 anti-OX40 monoclonal antibody that inhibits and reduces the number of OX40+ pathogenic T cells [99‐101]. In a single-arm phase 1 trial of patients with moderate-to-severe AD (N = 22), rocatinlimab (10 mg/kg infusions on days 1, 15, and 29) led to a 74% reduction in the EASI score from baseline to week 22, and IGA 0/1 [clear (0) or almost clear (1) and a minimum two-grade improvement] was achieved in 35% of the patients at week 22 [100]. In a double-blind, placebo-controlled phase 2b study of patients with moderate-to-severe AD (N = 274), rocatinlimab demonstrated significant improvement in efficacy parameters compared with placebo, significant modulation of AD-related biomarkers, a well-tolerated safety profile, and potential for a durable response [101]. Across all rocatinlimab dose groups [subcutaneous injections of 150 mg every 4 weeks (Q4W), 600 mg Q4W, 300 mg every 2 weeks (Q2W), 600 mg Q2W], 48–61% least squares mean percent reductions in EASI score were observed from baseline to week 16, significantly greater than the 15% reduction in the placebo group. Rocatinlimab 300 mg Q2W dose group had the largest improvements at week 16: IGA 0/1 was achieved in 31% of the patients, and 75% improvement in EASI from baseline (EASI75) was achieved in 54% of the patients, compared with IGA 0/1 of 2% and EASI75 of 11% in the placebo group. At week 36, rocatinlimab 300 mg Q2W led to 88% least squares mean percent reduction in EASI score from baseline, and the IGA 0/1 and EASI75 responses were increased to 52% and 64%, respectively. Of the patients who achieved EASI75 at week 36 across rocatinlimab dose groups, the probabilities of not relapsing at week 56 ranged from 73 to 96% after treatment discontinuation at week 36 [101]. Targeting OX40 directly provides an opportunity to achieve durable efficacy by modulating pathogenic effector and memory T cells that drive disease severity and chronicity. Biomarker analysis revealed that rocatinlimab reduced mean serum concentrations of TARC/CCL17 (Th2 signature) and IL-22 (Th17/Th22 signature) throughout the active treatment period and during the off-treatment follow-up period until week 56. Steady reduction of these biomarkers over time supports the inhibitory action of rocatinlimab on Th2, Th17, and Th22 cell activities, which in turn is expected to interrupt the cycle of inflammation and improve/restore skin barrier function [101]. Rocatinlimab was well tolerated, with pyrexia (17% versus 4% in the placebo group), chills (11% versus 0%), headache (9% versus 2%), aphthous ulcer (7% versus 0%), and nausea (6% versus 2%) as the most commonly reported AEs during the 18-week double-blind period. Pyrexia and chills were mild or moderate in intensity and occurred in most patients only after the first injection, and no patients discontinued the treatment because of these events. All monoclonal antibodies have the potential for injection reaction (e.g., pyrexia) including those targeting OX40 or OX40L [102]. No signs of immunosuppression (e.g., increased rates of infection or malignancy) or immune dysregulation (e.g., autoimmunity) were observed. Consistent safety findings were reported during the whole study period to week 56. Rocatinlimab is currently being further explored in adults and adolescents with moderate-to-severe AD in the comprehensive phase 3 ROCKET program (clinicaltrials.gov, NCT05899816; NCT05651711; NCT05704738; NCT05398445; NCT05633355; NCT05724199) and its long-term extension study (clinicaltrials.gov, NCT05882877).

5.2 Telazorlimab

Telazorlimab (GBR 830/ISB 830; Table 1) is a humanized IgG1 neutralizing monoclonal antibody against OX40 that blocks the interaction with OX40L, and was evaluated in a phase 2a trial and a phase 2b trial of patients with AD. The phase 2a trial (N = 62) efficacy results showed that on day 71, telazorlimab (10 mg/kg infusions on days 1 and 29) led to a 50% improvement in EASI from baseline (EASI50) in 77% of patients versus 38% of placebo-treated patients; and IGA 0/1 was achieved by 23% of telazorlimab-treated patients compared with 13% of placebo-treated patients [98]. Telazorlimab was well tolerated. The most common treatment-emergent AE was headache, with no clinically meaningful differences between telazorlimab (13%) and placebo (25%). Treatment-emergent AEs that occurred more frequently in the telazorlimab group than in the placebo group were postprocedural infection (9% versus 0%) and myalgia (7% versus 0%). Telazorlimab showed inhibition of Th1, Th2, and Th17/Th22 signature mRNA expression in lesional skin, as well as greater reductions of hyperplasia measures (epidermal thickness and epidermal proliferation markers) compared with placebo [98]. The phase 2b trial (N = 462) efficacy results were mixed. Telazorlimab was associated with significant improvement in EASI: percent reduction from baseline in EASI score at week 16 with telazorlimab high-dose regimens was 58% with subcutaneous injections of 300 mg Q2W versus 42% with placebo and 60% with 600 mg Q2W versus 43% with placebo treatment. Numerical improvements were also seen with the two high doses of telazorlimab as compared with placebo for EASI-75 (24% versus 11% and 25% versus 19%, respectively) and IGA 0/1 (13% versus 5% and 12% versus 5%, respectively), but the differences were not statistically significant [103, 104]. The most commonly reported treatment-emergent AEs with telazorlimab were AD (300 mg versus placebo: 22% versus 21%; 600 mg versus placebo: 35% versus 16%), nasopharyngitis (21% versus 9%; 16% versus 9%), upper respiratory tract infection (16% versus 5%; 8% versus 7%), and headache (11% versus 10%; 8% versus 7%) in the phase 2b trial [103, 104]. Currently there are no ongoing or planned trials of telazorlimab for the treatment of AD. However, further development of telazorlimab for rheumatoid arthritis or other autoimmune diseases is likely [105].

5.3 Amlitelimab

Amlitelimab (KY1005; Table 1) is a human IgG4 antibody that binds to OX40L and blocks OX40L from inducing signals through OX40 [106‐109]. In a phase 2a study of patients with moderate-to-severe AD (N = 88), amlitelimab low-dose regimen (200 mg loading/100 mg maintenance infusions Q4W) resulted in a mean percentage change of EASI from baseline to week 16 of 80%, versus 49% with placebo [102]. Patients receiving high-dose regimen (500 mg loading/250 mg maintenance infusions Q4W) had 70% change of EASI from baseline compared with 49% in the placebo group. IGA 0/1 was achieved in 44% and 37% of patients receiving low- or high-dose amlitelimab compared with 8% of placebo-treated patients [102]. Treatment-emergent AEs more common with either low-dose or high-dose amlitelimab versus placebo included headache (10% versus 3%), upper respiratory tract infection (10% versus 3%), hyperhidrosis (7% versus 0%), pyrexia (7% versus 0%), aspartate aminotransferase increased (7% versus 0%), and iron-deficiency anemia (7% versus 0%) from baseline to week 16 [102]. A decrease in serum IL-22 and IL-13 levels was observed at week 16 among patients treated with amlitelimab [102]. In a phase 2b dose-ranging study, patients with moderate-to-severe AD (N = 390) received treatment with subcutaneous amlitelimab at 250 mg Q4W with 500 mg loading dose, or 250 mg, 125 mg, or 62.5 mg Q4W without loading dose. Amlitelimab resulted in significant improvements in percentage change in EASI from baseline to week 16 compared with placebo (difference from placebo in least squares mean change from baseline: 250 mg with loading, − 32.1%; 250 mg, − 27.3%; 125 mg, − 22.2%; 62.5 mg, − 30.2%), with improvements continuing through week 24 [110]. Amlitelimab was well tolerated across all dose groups (details of treatment-emergent AEs were not reported) [110]. Subcutaneous amlitelimab is being further evaluated in this 52-week phase 2b trial of adults with moderate-to-severe AD (clinicaltrials.gov, NCT05131477), and in phase 2 long-term extension studies (clinicaltrials.gov, NCT05492578, NCT05769777). A phase 3 study of amlitelimab (clinicaltrials.gov, NCT06130566) is scheduled to start at the end of 2023, with the efficacy and safety of two doses of subcutaneous amlitelimab compared with placebo in adults with moderate-to-severe AD. Collectively, these results from various clinical trials support the value of targeting the OX40-OX40L signaling pathway as a novel approach for AD treatment.

6 Summary

AD is a challenging disease to treat due to its multifaceted and heterogeneous nature and highly fluctuating and unpredictable disease course. A need remains for a novel therapeutic approach targeting a broad spectrum of immune pathways and delivering durable benefits in a heterogeneous population. OX40, an inducible co-stimulatory molecule expressed on pathogenic Th2 cells and other effector T-cell subsets following their activation, is crucial for potentiating long-lasting T-cell responses, and as such represents an attractive target for limiting AD symptoms and providing long-term remission.

OX40 has a unique pattern of expression, increasing transiently only with antigen-driven T-cell receptor activation. Since OX40 is predominantly expressed on activated effector T cells, targeting the OX40 pathway does not affect homeostasis of naïve and resting memory T cells. As a result, neutralizing its activity will potentially preferentially inhibit those antigen-specific T cells involved in perpetuating and maintaining AD without generalized immunosuppression. Targeting the OX40 signaling pathway furthermore has the potential to reduce the number of a variety of activated pathogenic T cells and their memory counterparts, including Th1, Th2, Th17, and Th22 cells, which may allow far more profound disease control beyond inhibiting individual cytokines made by these cells. In addition, the OX40 pathway plays a unique role in the transition of activated effector T cells into memory T cells. Therefore, blocking OX40 potentially produces sustainable inhibitory effects on immune function, impacting the chronicity of AD. Neutralizing OX40 signaling also can limit the production of multiple proinflammatory cytokines made by T cells that promote skin thickening, providing another way to reduce inflammation. Several currently approved systemic therapies target the cytokine products of T cells (e.g., dupilumab that blocks IL-4 and IL-13 signaling by binding to IL-4Rα; tralokinumab that blocks IL-13) but are less likely to diminish the persistence of the pathogenic T cells themselves, as recently suggested from a study of T cells still present in the skin of patients treated with dupilumab [111]. Via effects on diverse pathogenic T-cell subsets and proinflammatory cytokines, blocking OX40 may have important therapeutic potential along the dynamics of the immune response in AD and provide broad disease control and persistent efficacy across heterogenous patient populations.

Recent promising results from early phase clinical studies of antibodies against OX40 or OX40L in moderate-to-severe AD highlight the potential of OX40 signaling as an important novel target for the treatment of AD that may open a new therapeutic paradigm to achieve a highly effective, durable response with the potential for disease modification.

Table 1

Emerging OX40 or OX40L antibodies for moderate-to-severe atopic dermatitis

Biologic agent	Target	Study type	Study duration	Dose	# of patients	Primary endpoint(s) results	References
Rocatinlimab (AMG 451 /KHK4083)	OX40	Phase 1	22 weeks	10 mg/kg infusions on days 1, 15, and 29	22	Safety profile: No deaths, serious AEs, or discontinuations due to AEs Common treatment-emergent AEs: mild or moderate pyrexia and chills No clinically meaningful changes in the laboratory, vital signs, and electrocardiogram values	[100]
Rocatinlimab (AMG 451 /KHK4083)	OX40	Phase 2b	56 weeks	Subcutaneous injections of 150 mg Q4W, 600 mg Q4W, 300 mg Q2W, 600 mg Q2W for 36 weeks	274	Least-squares mean change in EASI (95% CI) from baseline to week 16: 150 mg Q4W: − 48.3% (− 62.2, − 34.0; P = 0.0003 versus placebo) 600 mg Q4W: − 49.7% (− 64.3, − 35.2; P = 0.0002 versus placebo) 300 mg Q2W: − 61.1% (− 75.2, − 47.0; P < 0.0001 versus placebo) 600 mg Q2W: − 57.4% (− 71.3, − 43.4; P < 0.0001 versus placebo) Placebo: − 15.0% (− 28.6, − 1.4)	[101]
Telazorlimab (GBR 830/ISB 830)	OX40	Phase 2a	85 days	10 mg/kg infusions on days 1 and 29	62	Treatment-emergent AEs: Headache most common, but with no clinically meaningful differences between telazorlimab and placebo Postprocedural infection and myalgia occurred more frequently with telazorlimab than placebo Change in biomarkers: Telazorlimab showed inhibition of Th1, Th2, and Th17/Th22 signatures mRNA expression in lesional skin Telazorlimab led to greater reductions of epidermal hyperplasia measures versus placebo	[98]
Telazorlimab (GBR 830/ISB 830)	OX40	Phase 2b	66 weeks	Subcutaneous injections of 300 mg Q2W and 600 mg Q2W	462	Mean change in EASI (SD) from baseline to week 16: 300 mg Q2W: − 57.6% (36.2) versus placebo, − 42.1% (38.2) (P = 0.008) 600 mg Q2W: − 59.7% (27.1) versus placebo: − 43.3% (41.2) (P = 0.008)	[103, 104]
Amlitelimab (KY1005)	OX40L	Phase 2a	36 weeks	200 mg loading/100 mg maintenance infusions Q4W (low dose); 500 mg loading/250 mg maintenance Q4W (high dose)	89	Treatment-emergent AEs: Headache, upper respiratory tract infection, hyperhidrosis, pyrexia, increased aspartate aminotransferase and iron deficiency anemia more frequent in the amlitelimab groups versus the placebo group up to week 16 (difference of ≥ 5%) Least-squares mean change in EASI (95% CI) from baseline to week 16: Lose dose: − 80.1% (− 95.6, − 64.7; P = 0.009 versus placebo) High dose: − 70.0% (− 85.0, − 54.6; P = 0.072 versus placebo) Placebo: − 49.4% (− 66.0, − 32.7)	[102]
Amlitelimab (KY1005)	OX40L	Phase 2b	52 weeks	Subcutaneous injections of 250 mg Q4W with 500 mg loading; 250 mg, 125 mg, or 62.5 mg Q4W without loading	390	Difference from placebo in least-squares mean change in EASI (95% CI) from baseline to week 16: 250 mg with loading: − 32.1% (− 43.9, − 20.3; P < 0.0001) 250 mg: − 27.3% (− 39.1, − 15.6; P < 0.0001) 125 mg: − 22.2% (− 34.0, − 10.4; P = 0.0002) 62.5 mg: − 30.2% (− 41.9, − 18.5; P < 0.0001)	[110]

AE, adverse event; CI, confidence interval; EASI, Eczema Area Severity Index; Q2W, every 2 weeks; Q4W, every 4 weeks; SD, standard deviation

Acknowledgements

Jinling Wu, MD, PhD, of Bioscience Communications, Shannon Rao, PhD, and Julie Wang, DPM, of Amgen Inc. provided medical writing assistance, funded by Amgen Inc and Kyowa Kirin Co., Ltd.

Declarations

Funding

Sponsored by Amgen Inc. and Kyowa Kirin Co., Ltd. Writing support was funded by Amgen Inc. and provided by Jinling Wu, MD, PhD, of Bioscience Communications and Shannon Rao, PhD and Julie Wang, DPM, of Amgen Inc.

Competing interests

Michael Croft has received consulting fees or speaking honoraria from Amgen, Sanofi, UCB, MedImmune, Millenium, Perseid, Celgene, Novo Nordisk, Merck, Abbvie, Tanabe, Zai Lab, Merrimack, Pfizer, Anaptysbio, Celsius Therapeutics, HifiBio, Kiniksa, Shattuck Labs, Prometheus biosciences, Invectys, Virtici, Capella bioscience, and RAPT therapeutics, and research funds from Kyowa Kirin, Bristol Myers Squib, Janssen, and Eli Lilly. He has licensed patents on OX40 and OX40L. Ehsanollah Esfandiari is an employee of Kyowa Kirin International. Camilla Chong was an employee of Kyowa Kirin International at the time of manuscript development. Hailing Hsu and Greg Kricorian are employees and stockholders of Amgen Inc. Kenji Kabashima has received consulting fees, honoraria, grant support, and/or lecturing fees from Japan Tobacco, LEO Pharma, Maruho, Mitsubishi Tanabe, Ono Pharmaceutical, Procter & Gamble, Sanofi, Taiho, and Torii Pharmaceutical. Richard B. Warren has been a consultant and/or speaker for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly and Company, GlaxoSmithKline, Janssen, LEO Pharma, Novartis, Sanofi Genzyme, and UCB Pharma. Andreas Wollenberg has been an investigator for Beiersdorf, Eli Lilly, Galderma, LEO Pharma, MedImmune, Novartis, Pfizer, Regeneron Pharmaceuticals, and Sanofi; a consultant for AbbVie, Almirall, Anacor Pharmaceuticals, Eli Lilly, Galapagos, Galderma, LEO Pharma, MedImmune, Novartis, Pfizer, Regeneron Pharmaceuticals, Sandoz, and Sanofi, and received research grants from Beiersdorf, LEO Pharma, and Pierre Fabre. Emma Guttman-Yassky has received research funds/grants paid to her institution from Amgen, AnaptysBio, Asana Biosciences, AstraZeneca, Boehringer Ingelheim, Cara Therapeutics, Celgene, Eli Lilly, Innovaderm, Kyowa Kirin, LEO Pharma, Novartis, Pfizer, and Regeneron Pharmaceuticals, and has received consultancy fees from AbbVie, Almirall, Amgen, Arena, Asana Biosciences, Aslan Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Celgene, Connect Pharma, Eli Lilly, EMD Serono, Evidera, Galderma, Ichnos Sciences, Incyte, Janssen Biotech, Kyowa Kirin, LEO Pharma, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Sanofi, SATO Pharmaceutical, Siolta Therapeutics, Target PharmaSolutions, UCB, and Ventyx Biosciences.

Ethics approval

Not applicable.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Author contributions

Conception of the article: Greg Kricorian, Hailing Hsu, Camilla Chong, Ehsanollah Esfandiari. Literature search and data analysis: all authors. Drafting, critical revision, and final approval: all authors.

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

Unsere Produktempfehlungen

e.Med Interdisziplinär

Kombi-Abonnement

Für Ihren Erfolg in Klinik und Praxis - Die beste Hilfe in Ihrem Arbeitsalltag

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de.

Jetzt testen ¹

e.Med Dermatologie

Kombi-Abonnement

Mit e.Med Dermatologie erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes Dermatologie, den Premium-Inhalten der dermatologischen Fachzeitschriften, inklusive einer gedruckten dermatologischen Zeitschrift Ihrer Wahl.

Jetzt testen ²

Bieber T. Atopic dermatitis: an expanding therapeutic pipeline for a complex disease. Nat Rev Drug Discov. 2022;21(1):21–40.PubMedCrossRef

Wollenberg A, Christen-Zäch S, Taieb A, Paul C, Thyssen JP, De Bruin-Weller M, Vestergaard C, Seneschal J, Werfel T, Cork MJ, Kunz B, Fölster-Holst R, Trzeciak M, Darsow U, Szalai Z, Deleuran M, Von Kobyletzki L, Barbarot S, Heratizadeh A, Gieler U, Hijnen DJ, Weidinger S, De Raeve L, Svensson Å, Simon D, Stalder JF, Ring J. ETFAD/EADV Eczema task force 2020 position paper on diagnosis and treatment of atopic dermatitis in adults and children. J Eur Acad Dermatol Venereol. 2020;34(12):2717–44.PubMedCrossRef

Nutten S. Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab. 2015;66(Suppl 1):8–16.PubMedCrossRef

Kolb L, Ferrer-Bruker SJ, Atopic dermatitis. In: StatPearls. Treasure Island (FL): StatPearls Publishing, StatPearls Publishing LLC; 2022.

Hadi HA, Tarmizi AI, Khalid KA, Gajdács M, Aslam A, Jamshed S. The epidemiology and global burden of atopic dermatitis: a narrative review. Life (Basel). 2021;11(9):936.ADSPubMed

Silverberg JI, Barbarot S, Gadkari A, Simpson EL, Weidinger S, Mina-Osorio P, Rossi AB, Brignoli L, Saba G, Guillemin I, Fenton MC, Auziere S, Eckert L. Atopic dermatitis in the pediatric population: a cross-sectional, international epidemiologic study. Ann Allergy Asthma Immunol. 2021;126(4):417-428.e412.PubMedCrossRef

Chiesa Fuxench ZC, Block JK, Boguniewicz M, Boyle J, Fonacier L, Gelfand JM, Grayson MH, Margolis DJ, Mitchell L, Silverberg JI, Schwartz L, Simpson EL, Ong PY. Atopic Dermatitis in America Study: a cross-sectional study examining the prevalence and disease burden of atopic dermatitis in the US adult population. J Invest Dermatol. 2019;139(3):583–90.PubMedCrossRef

Thomsen SF. Atopic dermatitis: natural history, diagnosis, and treatment. ISRN Allergy. 2014;2014:2014354250.CrossRef

Lee HH, Patel KR, Singam V, Rastogi S, Silverberg JI. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis. J Am Acad Dermatol. 2019;80(6):1526-1532.e1527.PubMedCrossRef

10.

Gittler JK, Shemer A, Suárez-Fariñas M, Fuentes-Duculan J, Gulewicz KJ, Wang CQ, Mitsui H, Cardinale I, De Guzman SC, Krueger JG, Guttman-Yassky E. Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130(6):1344–54.PubMedPubMedCentralCrossRef

11.

Kaufman BP, Guttman-Yassky E, Alexis AF. Atopic dermatitis in diverse racial and ethnic groups-variations in epidemiology, genetics, clinical presentation and treatment. Exp Dermatol. 2018;27(4):340–57.PubMedCrossRef

12.

Silverberg JI, Gelfand JM, Margolis DJ, Boguniewicz M, Fonacier L, Grayson MH, Simpson EL, Ong PY, Chiesa Fuxench ZC. Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study. Ann Allergy Asthma Immunol. 2018;121(3):340–7.PubMedCrossRef

13.

Girolomoni G, Busà VM. Flare management in atopic dermatitis: from definition to treatment. Ther Adv Chronic Dis. 2022;13:20406223211066728.PubMedPubMedCentralCrossRef

14.

Renert-Yuval Y, Guttman-Yassky E. New treatments for atopic dermatitis targeting beyond IL-4/IL-13 cytokines. Ann Allergy Asthma Immunol. 2020;124(1):28–35.PubMedCrossRef

15.

Fania L, Moretta G, Antonelli F, Scala E, Abeni D, Albanesi C, Madonna S. Multiple roles for cytokines in atopic dermatitis: from pathogenic mediators to endotype-specific biomarkers to therapeutic targets. Int J Mol Sci. 2022;23(5):2684.PubMedPubMedCentralCrossRef

16.

Furue M, Ulzii D, Vu YH, Tsuji G, Kido-Nakahara M, Nakahara T. Pathogenesis of atopic dermatitis: current paradigm. Iran J Immunol. 2019;16(2):97–107.PubMed

17.

Na CH, Chung J, Simpson EL. Quality of life and disease impact of atopic dermatitis and psoriasis on children and their families. Children (Basel). 2019;6(12):133.PubMedPubMedCentral

18.

Reed B, Blaiss MS. The burden of atopic dermatitis. Allergy Asthma Proc. 2018;39(6):406–10.PubMedCrossRef

19.

Davis DMR, Drucker AM, Alikhan A, Bercovitch L, Cohen DE, Darr JM, Eichenfield LF, Frazer-Green L, Paller AS, Silverberg JI, Singh AM, Sidbury R. American Academy of Dermatology Guidelines: awareness of comorbidities associated with atopic dermatitis in adults. J Am Acad Dermatol. 2022;86(6):1335-1336.e1318.PubMedCrossRef

20.

Stölzl D, Weidinger S, Drerup K. A new era has begun: treatment of atopic dermatitis with biologics. Allergol Select. 2021;2021:5265–73.

21.

Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. Nat Rev Dis Primers. 2018;4(1):1.PubMedCrossRef

22.

Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet. 2020;396(10247):345–60.PubMedCrossRef

23.

Wollenberg A, Kraft S, Hanau D, Bieber T. Immunomorphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema. J Invest Dermatol. 1996;106(3):446–53.PubMedCrossRef

24.

Schuller E, Teichmann B, Haberstok J, Moderer M, Bieber T, Wollenberg A. In situ expression of the costimulatory molecules CD80 and CD86 on langerhans cells and inflammatory dendritic epidermal cells (IDEC) in atopic dermatitis. Arch Dermatol Res. 2001;293(9):448–54.PubMedCrossRef

25.

Gray CL. Proactive therapy in atopic dermatitis. Curr Allergy Clin Immunol. 2019;32(3):140–6.

26.

Brunner PM, Suárez-Fariñas M, He H, Malik K, Wen HC, Gonzalez J, Chan TC, Estrada Y, Zheng X, Khattri S, Dattola A, Krueger JG, Guttman-Yassky E. The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins. Sci Rep. 2017;7(1):8707.ADSPubMedPubMedCentralCrossRef

27.

Tang TS, Bieber T, Williams HC. Are the concepts of induction of remission and treatment of subclinical inflammation in atopic dermatitis clinically useful? J Allergy Clin Immunol. 2014;133(6):1615-1625.e1611.PubMedCrossRef

28.

Lebwohl MG, Del Rosso JQ, Abramovits W, Berman B, Cohen DE, Guttman E, Mancini AJ, Schachner LA. Pathways to managing atopic dermatitis: consensus from the experts. J Clin Aesthet Dermatol. 2013;6(7 Suppl):S2–18.PubMedPubMedCentral

29.

Drucker AM. Atopic dermatitis: Burden of illness, quality of life, and associated complications. Allergy Asthma Proc. 2017;38(1):3–8.PubMedCrossRef

30.

Ungar B, Garcet S, Gonzalez J, Dhingra N, Correa-Da-Rosa J, Shemer A, Krueger JG, Suarez-Farinas M, Guttman-Yassky E. An integrated model of atopic dermatitis biomarkers highlights the systemic nature of the disease. J Invest Dermatol. 2017;137(3):603–13.PubMedCrossRef

31.

Boguniewicz M, Alexis AF, Beck LA, Block J, Eichenfield LF, Fonacier L, Guttman-Yassky E, Paller AS, Pariser D, Silverberg JI, Lebwohl M. Expert perspectives on management of moderate-to-severe atopic dermatitis: a multidisciplinary consensus addressing current and emerging therapies. J Allergy Clin Immunol Pract. 2017;5(6):1519–31.PubMedCrossRef

32.

Czarnowicki T, He H, Krueger JG, Guttman-Yassky E. Atopic dermatitis endotypes and implications for targeted therapeutics. J Allergy Clin Immunol. 2019;143(1):1–11.PubMedCrossRef

33.

Thijs JL, Strickland I, Bruijnzeel-Koomen C, Nierkens S, Giovannone B, Csomor E, Sellman BR, Mustelin T, Sleeman MA, De Bruin-Weller MS, Herath A, Drylewicz J, May RD, Hijnen D. Moving toward endotypes in atopic dermatitis: Identification of patient clusters based on serum biomarker analysis. J Allergy Clin Immunol. 2017;140(3):730–7.PubMedCrossRef

34.

Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387(10023):1109–22.PubMedCrossRef

35.

Bieber T. Atopic dermatitis. Ann Dermatol. 2010;22(2):125–37.PubMedPubMedCentralCrossRef

36.

Kim J, Kim BE, Leung DYM. Pathophysiology of atopic dermatitis: clinical implications. Allergy Asthma Proc. 2019;40(2):84–92.PubMedPubMedCentralCrossRef

37.

Peng W, Novak N. Pathogenesis of atopic dermatitis. Clin Exp Allergy. 2015;45(3):566–74.PubMedCrossRef

38.

De Bruyn Carlier T, Badloe FMS, Ring J, Gutermuth J, Kortekaas Krohn I. Autoreactive T cells and their role in atopic dermatitis. J Autoimmun. 2021;2021:120102634.

39.

Czarnowicki T, Santamaria-Babí LF, Guttman-Yassky E. Circulating CLA(+) T cells in atopic dermatitis and their possible role as peripheral biomarkers. Allergy. 2017;72(3):366–72.PubMedCrossRef

40.

Chen L, Shen Z. Tissue-resident memory T cells and their biological characteristics in the recurrence of inflammatory skin disorders. Cell Mol Immunol. 2020;17(1):64–75.PubMedCrossRef

41.

Kortekaas Krohn I, Aerts JL, Breckpot K, Goyvaerts C, Knol E, Van Wijk F, Gutermuth J. T-cell subsets in the skin and their role in inflammatory skin disorders. Allergy. 2022;77(3):827–42.PubMedCrossRef

42.

Ho AW, Kupper TS. T cells and the skin: from protective immunity to inflammatory skin disorders. Nat Rev Immunol. 2019;19(8):490–502.PubMedCrossRef

43.

Facheris P, Da Rosa JC, Pagan AD, Angelov M, Del Duca E, Rabinowitz G, Gómez-Arias PJ, Rothenberg-Lausell C, Estrada YD, Bose S, Chowdhury M, Shemer A, Pavel AB, Guttman-Yassky E. Age of onset defines two distinct profiles of atopic dermatitis in adults. Allergy. 2023;78:2202.PubMedCrossRef

44.

Sanyal RD, Pavel AB, Glickman J, Chan TC, Zheng X, Zhang N, Cueto I, Peng X, Estrada Y, Fuentes-Duculan J, Alexis AF, Krueger JG, Guttman-Yassky E. Atopic dermatitis in African American patients is T(H)2/T(H)22-skewed with T(H)1/T(H)17 attenuation. Ann Allergy Asthma Immunol. 2019;122(1):99-110.e116.PubMedCrossRef

45.

Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139(4s):S65–76.PubMedPubMedCentralCrossRef

46.

Boguniewicz M, Fonacier L, Guttman-Yassky E, Ong PY, Silverberg JI. Atopic dermatitis yardstick update. Ann Allergy Asthma Immunol. 2023;130(6):811–20.PubMedCrossRef

47.

Sidbury R, Davis DM, Cohen DE, Cordoro KM, Berger TG, Bergman JN, Chamlin SL, Cooper KD, Feldman SR, Hanifin JM, Krol A, Margolis DJ, Paller AS, Schwarzenberger K, Silverman RA, Simpson EL, Tom WL, Williams HC, Elmets CA, Block J, Harrod CG, Begolka WS, Eichenfield LF. Guidelines of care for the management of atopic dermatitis: section 3. J Am Acad Dermatol. 2014;71(2):327–49.PubMedPubMedCentralCrossRef

48.

Wollenberg A, Kinberger M, Arents B, Aszodi N, Avila Valle G, Barbarot S, Bieber T, Brough HA, Calzavara Pinton P, Christen-Zäch S, Deleuran M, Dittmann M, Dressler C, Fink-Wagner AH, Fosse N, Gáspár K, Gerbens L, Gieler U, Girolomoni G, Gregoriou S, Mortz CG, Nast A, Nygaard U, Redding M, Rehbinder EM, Ring J, Rossi M, Serra-Baldrich E, Simon D, Szalai ZZ, Szepietowski JC, Torrelo A, Werfel T, Flohr C. European guideline (EuroGuiDerm) on atopic eczema: part I—systemic therapy. J Eur Acad Dermatol Venereol. 2022;36(9):1409–31.PubMedCrossRef

49.

Wollenberg A, Kinberger M, Arents B, Aszodi N, Avila Valle G, Barbarot S, Bieber T, Brough HA, Calzavara Pinton P, Christen-Zäch S, Deleuran M, Dittmann M, Dressler C, Fink-Wagner AH, Fosse N, Gáspár K, Gerbens L, Gieler U, Girolomoni G, Gregoriou S, Mortz CG, Nast A, Nygaard U, Redding M, Rehbinder EM, Ring J, Rossi M, Serra-Baldrich E, Simon D, Szalai ZZ, Szepietowski JC, Torrelo A, Werfel T, Flohr C. European guideline (EuroGuiDerm) on atopic eczema—part II: non-systemic treatments and treatment recommendations for special AE patient populations. J Eur Acad Dermatol Venereol. 2022;36(11):1904–26.PubMedCrossRef

50.

Simpson EL, Bruin-Weller M, Flohr C, Ardern-Jones MR, Barbarot S, Deleuran M, Bieber T, Vestergaard C, Brown SJ, Cork MJ, Drucker AM, Eichenfield LF, Foelster-Holst R, Guttman-Yassky E, Nosbaum A, Reynolds NJ, Silverberg JI, Schmitt J, Seyger MMB, Spuls PI, Stalder JF, Su JC, Takaoka R, Traidl-Hoffmann C, Thyssen JP, Van Der Schaft J, Wollenberg A, Irvine AD, Paller AS. When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council. J Am Acad Dermatol. 2017;77(4):623–33.PubMedCrossRef

51.

Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, Bergman JN, Chamlin SL, Cohen DE, Cooper KD, Cordoro KM, Davis DM, Feldman SR, Hanifin JM, Margolis DJ, Silverman RA, Simpson EL, Williams HC, Elmets CA, Block J, Harrod CG, Smith Begolka W, Sidbury R. Guidelines of care for the management of atopic dermatitis: section 2. J Am Acad Dermatol. 2014;71(1):116–32.PubMedPubMedCentralCrossRef

52.

Siegfried EC, Jaworski JC, Kaiser JD, Hebert AA. Systematic review of published trials: long-term safety of topical corticosteroids and topical calcineurin inhibitors in pediatric patients with atopic dermatitis. BMC Pediatr. 2016;2016:1675.

53.

Draelos ZD, Feldman SR, Berman B, Olivadoti M, Sierka D, Tallman AM, Zielinski MA, Ports WC, Baldwin S. Tolerability of topical treatments for atopic dermatitis. Dermatol Ther (Heidelb). 2019;9(1):71–102.PubMedPubMedCentralCrossRef

54.

Drucker AM, Eyerich K, De Bruin-Weller MS, Thyssen JP, Spuls PI, Irvine AD, Girolomoni G, Dhar S, Flohr C, Murrell DF, Paller AS, Guttman-Yassky E. Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement. Br J Dermatol. 2018;178(3):768–75.PubMedPubMedCentralCrossRef

55.

Davari DR, Nieman EL, Mcshane DB, Morrell DS. Current perspectives on the systemic management of atopic dermatitis. J Asthma Allergy. 2021;2021:14595–607.

56.

Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, Silverberg JI, Deleuran M, Kataoka Y, Lacour JP, Kingo K, Worm M, Poulin Y, Wollenberg A, Soo Y, Graham NM, Pirozzi G, Akinlade B, Staudinger H, Mastey V, Eckert L, Gadkari A, Stahl N, Yancopoulos GD, Ardeleanu M. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335–48.PubMedCrossRef

57.

ADBRY^TM. Significant improvements in skin clearance and itch relief with Adbry. 2022. Updated December, 2022. https://www.adbryhcp.com/efficacy-results#legal-notification. Accessed 28 Feb 2023.

58.

Hendricks AJ, Lio PA, Shi VY. Management recommendations for dupilumab partial and non-durable responders in atopic dermatitis. Am J Clin Dermatol. 2019;20(4):565–9.PubMedCrossRef

59.

Wu JJ, Lafeuille MH, Emond B, Fakih I, Duh MS, Cappelleri JC, Yin N, Feeney C, Myers DE, Dibonaventura M. Real-world effectiveness of newly initiated systemic therapy for atopic dermatitis in the United States: a claims database analysis. Adv Ther. 2022;39(9):4157–68.PubMedPubMedCentralCrossRef

60.

Quint T, Brunner PM, Sinz C, Steiner I, Ristl R, Vigl K, Kimeswenger S, Neubauer K, Pirkhammer D, Zikeli M, Hoetzenecker W, Reider N, Bangert C. Dupilumab for the treatment of atopic dermatitis in an Austrian cohort-real-life data shows rosacea-like folliculitis. J Clin Med. 2020;9:4.CrossRef

61.

Beaziz J, Bouaziz JD, Jachiet M, Fite C, Lons-Danic D. Dupilumab-induced psoriasis and alopecia areata: case report and review of the literature. Ann Dermatol Venereol. 2021;148(3):198–201.PubMedCrossRef

62.

Flanagan KE, Pupo Wiss IM, Pathoulas JT, Walker CJ, Senna MM. Dupilumab-induced psoriasis in a patient with atopic dermatitis and alopecia totalis: A case report and literature review. Dermatol Ther. 2022;35(2):e15255.PubMedCrossRef

63.

Brumfiel CM, Patel MH, Zirwas MJ. Development of psoriasis during treatment with dupilumab: a systematic review. J Am Acad Dermatol. 2022;86(3):708–9.PubMedCrossRef

64.

Napolitano M, Scalvenzi M, Fabbrocini G, Cinelli E, Patruno C. Occurrence of psoriasiform eruption during dupilumab therapy for adult atopic dermatitis: a case series. Dermatol Ther. 2019;32(6):e13142.PubMedCrossRef

65.

Schneeweiss MC, Richard W, Schneeweiss S, Anand P, Jin Y, Dicesare E, Glynn RJ, Merola JF. Joint pain in patients with atopic dermatitis receiving treatment with dupilumab: a US nation-wide cohort study. J Am Acad Dermatol. 2023;89:3.CrossRef

66.

Chrétien B, Dolladille C, Alexandre J, Fedrizzi S, Lelong-Boulouard V, Lambert JC, Ezine E. Dupilumab-associated arthralgia: an observational retrospective study in VigiBase(®). Br J Dermatol. 2021;185(2):464–5.PubMedCrossRef

67.

Tsai JH, Tsai TF. A review of dupilumab-induced adverse events to dermatologists and the potential pathogenesis in the treatment of atopic dermatitis. Dermatitis. 2023;2023:85.

68.

Bridgewood C, Wittmann M, Macleod T, Watad A, Newton D, Bhan K, Amital H, Damiani G, Giryes S, Bragazzi NL, Mcgonagle D. T helper 2 IL-4/IL-13 dual blockade with dupilumab is linked to some emergent T helper 17-type diseases, including seronegative arthritis and enthesitis/enthesopathy, but not to humoral autoimmune diseases. J Invest Dermatol. 2022;142(10):2660–7.PubMedCrossRef

69.

Shi VY, Bhutani T, Fonacier L, Deleuran M, Shumack S, Valdez H, Zhang F, Chan GL, Cameron MC, Yin NC. Phase 3 efficacy and safety of abrocitinib in adults with moderate-to-severe atopic dermatitis after switching from dupilumab (JADE EXTEND). J Am Acad Dermatol. 2022;87(2):351–8.PubMedCrossRef

70.

Rajasimhan S, Pamuk O, Katz JD. Safety of Janus kinase inhibitors in older patients: a focus on the thromboembolic risk. Drugs Aging. 2020;37(8):551–8.PubMedPubMedCentralCrossRef

71.

Ytterberg SR, Bhatt DL, Mikuls TR, Koch GG, Fleischmann R, Rivas JL, Germino R, Menon S, Sun Y, Wang C, Shapiro AB, Kanik KS, Connell CA. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386(4):316–26.PubMedCrossRef

72.

Taylor PC, Bieber T, Alten R, Witte T, Galloway J, Deberdt W, Issa M, Haladyj E, De La Torre I, Grond S, Wollenberg A. Baricitinib safety for events of special interest in populations at risk: analysis from randomised trial data across rheumatologic and dermatologic indications. Adv Ther. 2023;40(4):1867–83.PubMedPubMedCentralCrossRef

73.

Wollenberg A, Thyssen JP, Bieber T, Chan G, Kerkmann U. A detailed look at the European Medicines Agency’s recommendations for use of Janus kinase inhibitors in patients with atopic dermatitis. J Eur Acad Dermatol Venereol. 2023;37:2041.PubMedCrossRef

74.

Wu D, Daniel BS, Lai AJX, Wong N, Lim DKA, Murrell DF, Lim BXH, Mehta JS, Lim CHL. Dupilumab-associated ocular manifestations: a review of clinical presentations and management. Surv Ophthalmol. 2022;67(5):1419–42.PubMedCrossRef

75.

ADBRY (tralokinumab). Prescribing information. LEO Pharma; 2022.

76.

DUPIXENT (dupilumab). Prescribing information. Regeneron Pharmaceuticals Inc; 2022.

77.

Patel N, Feldman SR. Adherence in atopic dermatitis. Adv Exp Med Biol. 2017;1027:139–59.PubMedCrossRef

78.

Croft M. Co-stimulatory members of the TNFR family: keys to effective T-cell immunity? Nat Rev Immunol. 2003;3(8):609–20.PubMedCrossRef

79.

Gramaglia I, Weinberg AD, Lemon M, Croft M. Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses. J Immunol. 1998;161(12):6510–7.PubMedCrossRef

80.

Gramaglia I, Jember A, Pippig SD, Weinberg AD, Killeen N, Croft M. The OX40 costimulatory receptor determines the development of CD4 memory by regulating primary clonal expansion. J Immunol. 2000;165(6):3043–50.PubMedCrossRef

81.

Bansal-Pakala P, Jember AG, Croft M. Signaling through OX40 (CD134) breaks peripheral T-cell tolerance. Nat Med. 2001;7(8):907–12.PubMedCrossRef

82.

Rogers PR, Song J, Gramaglia I, Killeen N, Croft M. OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells. Immunity. 2001;15(3):445–55.PubMedCrossRef

83.

Furue M, Furue M. OX40L-OX40 Signaling in atopic dermatitis. J Clin Med. 2021;10(12):2578.PubMedPubMedCentralCrossRef

84.

Croft M, So T, Duan W, Soroosh P. The significance of OX40 and OX40L to T-cell biology and immune disease. Immunol Rev. 2009;229(1):173–91.PubMedPubMedCentralCrossRef

85.

Croft M. Control of immunity by the TNFR-related molecule OX40 (CD134). Annu Rev Immunol. 2010;2010:2857–78.

86.

Halim TYF, Rana BMJ, Walker JA, Kerscher B, Knolle MD, Jolin HE, Serrao EM, Haim-Vilmovsky L, Teichmann SA, Rodewald HR, Botto M, Vyse TJ, Fallon PG, Li Z, Withers DR, Mckenzie ANJ. Tissue-restricted adaptive type 2 immunity is orchestrated by expression of the costimulatory molecule OX40L on group 2 innate lymphoid cells. Immunity. 2018;48(6):1195-1207.e1196.PubMedPubMedCentralCrossRef

87.

Elsner JS, Carlsson M, Stougaard JK, Nygaard U, Buchner M, Fölster-Holst R, Hvid M, Vestergaard C, Deleuran M, Deleuran B. The OX40 Axis is associated with both systemic and local involvement in atopic dermatitis. Acta Derm Venereol. 2020;100(6):adv00099.PubMedCrossRef

88.

Ilves T, Harvima IT. OX40 ligand and OX40 are increased in atopic dermatitis lesions but do not correlate with clinical severity. J Eur Acad Dermatol Venereol. 2013;27(2):e197-205.PubMedCrossRef

89.

Fujita H, Shemer A, Suárez-Fariñas M, Johnson-Huang LM, Tintle S, Cardinale I, Fuentes-Duculan J, Novitskaya I, Carucci JA, Krueger JG, Guttman-Yassky E. Lesional dendritic cells in patients with chronic atopic dermatitis and psoriasis exhibit parallel ability to activate T-cell subsets. J Allergy Clin Immunol. 2011;128(3):574–82.PubMedCrossRef

90.

Suárez-Fariñas M, Dhingra N, Gittler J, Shemer A, Cardinale I, De Guzman SC, Krueger JG, Guttman-Yassky E. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J Allergy Clin Immunol. 2013;132(2):361–70.PubMedPubMedCentralCrossRef

91.

Kwatra SG, Misery L, Clibborn C, Steinhoff M. Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics. Clin Transl Immunology. 2022;11(5): e1390.PubMedPubMedCentralCrossRef

92.

Ito T, Wang YH, Duramad O, Hori T, Delespesse GJ, Watanabe N, Qin FX, Yao Z, Cao W, Liu YJ. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med. 2005;202(9):1213–23.PubMedPubMedCentralCrossRef

93.

Besnard AG, Togbe D, Guillou N, Erard F, Quesniaux V, Ryffel B. IL-33-activated dendritic cells are critical for allergic airway inflammation. Eur J Immunol. 2011;41(6):1675–86.PubMedCrossRef

94.

Chu DK, Llop-Guevara A, Walker TD, Flader K, Goncharova S, Boudreau JE, Moore CL, Seunghyun In T, Waserman S, Coyle AJ, Kolbeck R, Humbles AA, Jordana M. IL-33, but not thymic stromal lymphopoietin or IL-25, is central to mite and peanut allergic sensitization. J Allergy Clin Immunol. 2013;131(1):187–200.PubMedCrossRef

95.

Guttman-Yassky E, Krueger JG, Lebwohl MG. Systemic immune mechanisms in atopic dermatitis and psoriasis with implications for treatment. Exp Dermatol. 2018;27(4):409–17.PubMedCrossRef

96.

Leung DY, Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches. J Allergy Clin Immunol. 2014;134(4):769–79.PubMedPubMedCentralCrossRef

97.

Guttman-Yassky E, Waldman A, Ahluwalia J, Ong PY, Eichenfield LF. Atopic dermatitis: pathogenesis. Semin Cutan Med Surg. 2017;36(3):100–3.PubMedCrossRef

98.

Guttman-Yassky E, Pavel AB, Zhou L, Estrada YD, Zhang N, Xu H, Peng X, Wen HC, Govas P, Gudi G, Ca V, Fang H, Salhi Y, Back J, Reddy V, Bissonnette R, Maari C, Grossman F, Wolff G. GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;144(2):482-493.e487.PubMedCrossRef

99.

Papp KA, Gooderham MJ, Girard G, Raman M, Strout V. Phase I randomized study of KHK4083, an anti-OX40 monoclonal antibody, in patients with mild to moderate plaque psoriasis. J Eur Acad Dermatol Venereol. 2017;31(8):1324–32.PubMedPubMedCentralCrossRef

100.

Nakagawa H, Iizuka H, Nemoto O, Shimabe M, Furukawa Y, Kikuta N, Ootaki K. Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to severe atopic dermatitis. J Dermatol Sci. 2020;99(2):82–9.PubMedCrossRef

101.

Guttman-Yassky E, Simpson EL, Reich K, Kabashima K, Igawa K, Suzuki T, Mano H, Matsui T, Esfandiari E, Furue M. An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: a multicentre, double-blind, placebo-controlled phase 2b study. Lancet. 2023;401(10372):204–14.PubMedCrossRef

102.

Weidinger S, Bieber T, Cork MJ, Reich A, Wilson R, Quaratino S, Stebegg M, Brennan N, Gilbert S, Omalley JT, Porter-Brown B. Safety and efficacy of amlitelimab, a fully human non-depleting, non-cytotoxic anti-OX40 ligand monoclonal antibody, in atopic dermatitis: results of a phase IIa randomized placebo-controlled trial. Br J Dermatol. 2023;189(5):531–9.PubMedCrossRef

103.

Phase 2b study to evaluate the efficacy and safety of isb 830 in adults with moderate to severe atopic dermatitis. 2022. https://clinicaltrials.gov/ct2/show/results/NCT03568162?view=results.

104.

Sher L, Rewerska B, Acocella A, Gudi G, Salhi Y, Mbow M, Changela K, Mozaffarian N. 472 Telazorlimab in atopic dermatitis: phase 2b study shows improvement at 16 weeks. J Invest Dermatol. 2021;141(5):S82.CrossRef

105.

Ichnos Sciences pipeline. 2023. https://www.ichnossciences.com/pipeline/. Accessed 15 Nov 2023.

106.

Webb GJ, Hirschfield GM, Lane PJ. OX40, OX40L and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol. 2016;50(3):312–32.PubMedCrossRef

107.

Saghari M, Gal P, Gilbert S, Yateman M, Porter-Brown B, Brennan N, Quaratino S, Wilson R, Grievink HW, Klaassen ES, Bergmann KR, Burggraaf J, Van Doorn MBA, Powell J, Moerland M, Rissmann R. OX40L inhibition suppresses KLH-driven immune responses in healthy volunteers: a randomized controlled trial demonstrating proof-of-pharmacology for KY1005. Clin Pharmacol Ther. 2022;111(5):1121–32.PubMedPubMedCentralCrossRef

108.

Tkachev V, Furlan SN, Watkins B, Hunt DJ, Zheng HB, Panoskaltsis-Mortari A, Betz K, Brown M, Schell JB, Zeleski K, Yu A, Kirby I, Cooley S, Miller JS, Blazar BR, Casson D, Bland-Ward P, Kean LS. Combined OX40L and mTOR blockade controls effector T cell activation while preserving T(reg) reconstitution after transplant. Sci Transl Med. 2017;9:408.CrossRef

109.

Sanofi Immunology Investor Event Presentation. 2022. https://www.sanofi.com/assets/dotcom/content-app/events/investor-presentation/2022/2022-immunology-investor-event/2022_29_03_Sanofi_Immunology_Investor_Event_Presentation.pdf. Accessed 14 Nov 2023.

110.

Weidinger SBA, Papp K, Reich A, Lee CH, Worm M, Lynde C, Kataoka Y, Foley P, Weber C, Wong W, Rynkiewicz N, Yen K, O'Malley JT, Bernigaud C. 227 Efficacy and safety of amlitelimab (an anti-OX40 ligand antibody) in patients with moderate-to-severe atopic dermatitis: 24-week results from a Phase 2b trial (STREAM-AD). J Invest Dermatol. 2023;143(11):S370.CrossRef

111.

Bangert C, Rindler K, Krausgruber T, Alkon N, Thaler FM, Kurz H, Ayub T, Demirtas D, Fortelny N, Vorstandlechner V, Bauer WM, Quint T, Mildner M, Jonak C, Elbe-Bürger A, Griss J, Bock C, Brunner PM. Persistence of mature dendritic cells, T(H)2A, and Tc2 cells characterize clinically resolved atopic dermatitis under IL-4Rα blockade. Sci Immunol. 2021;6:55.CrossRef

Titel: OX40 in the Pathogenesis of Atopic Dermatitis—A New Therapeutic Target
verfasst von: Michael Croft
Ehsanollah Esfandiari
Camilla Chong
Hailing Hsu
Kenji Kabashima
Greg Kricorian
Richard B. Warren
Andreas Wollenberg
Emma Guttman-Yassky
Publikationsdatum: 18.01.2024
Verlag: Springer International Publishing
Erschienen in: American Journal of Clinical Dermatology
Print ISSN: 1175-0561
Elektronische ISSN: 1179-1888
DOI: https://doi.org/10.1007/s40257-023-00838-9

Leitlinien kompakt für die Dermatologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Dermatologie

Hirsutismus bei PCOS: Laser- und Lichttherapien helfen

26.04.2024 Hirsutismus Nachrichten

Laser- und Lichtbehandlungen können bei Frauen mit polyzystischem Ovarialsyndrom (PCOS) den übermäßigen Haarwuchs verringern und das Wohlbefinden verbessern – bei alleiniger Anwendung oder in Kombination mit Medikamenten.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

22.04.2024 DGIM 2024 Nachrichten

Um Menschen nach der Flucht aus einem Krisengebiet bestmöglich medizinisch betreuen zu können, ist es gut zu wissen, welche Erkrankungen im jeweiligen Herkunftsland häufig sind. Dabei hilft eine Internetseite der CDC (Centers for Disease Control and Prevention).

Kein Abstrich bei chronischen Wunden ohne Entzündungszeichen!

16.04.2024 DGIM 2024 Nachrichten

Den Reflex, eine oberflächliche chronische Hautwunde ohne Entzündungszeichen in jedem Fall abzustreichen, sollte man nach einer neuen „Klug-entscheiden“-Empfehlung unterdrücken.

Update Dermatologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Graphical Abstract

1 Introduction

2 Atopic Dermatitis Pathogenesis

3 Need for Improved Therapeutic Options for Atopic Dermatitis

4 Role of OX40 Signaling in T-cell Responses and Atopic Dermatitis Pathogenesis

5 Targeting OX40

5.1 Rocatinlimab

5.2 Telazorlimab

5.3 Amlitelimab

6 Summary

Acknowledgements

Declarations

Funding

Competing interests

Ethics approval

Patient consent to participate/publish

Availability of data and material

Code availability

Author contributions

Unsere Produktempfehlungen

e.Med Interdisziplinär

e.Med Dermatologie

Leitlinien kompakt für die Dermatologie

Neu im Fachgebiet Dermatologie

Hirsutismus bei PCOS: Laser- und Lichttherapien helfen

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Kein Abstrich bei chronischen Wunden ohne Entzündungszeichen!

Update Dermatologie