Checklist identification of candidates for systemic therapy in adult patients with atopic dermatitis in Germany: A multicentre study.

BACKGROUND: The German S2k guideline is the first to include a checklist that captures atopic dermatitis (AD) signs and symptoms as well as the lack of treatment response to identify patients eligible for systemic therapy. OBJECTIVES: Identifying candidates for a start/switch of systemic therapy in adult AD patients in Germany by applying the S2k guideline's checklist. METHODS: In this German multicentre, cross-sectional, non-interventional study (German Clinical Trials Register number: DRKS00023296), adult patients with mild to severe AD were enrolled at dermatological outpatient clinics and offices between April and October 2021. Demographics, clinical characteristics and quality of life were collected using questionnaires during one single visit. Eligibility for a start/switch of systemic AD therapy was evaluated according to the criteria of the German S2k guideline's checklist. RESULTS: Atopic dermatitis patients (575) were included in the analysis. One hundred and sixty-four patients (28.5%) received systemic (SYS) AD therapy and 411 patients (71.5%) did not (TOP). Of the TOP therapy patients, 38.7% were eligible to start systemic AD therapy, and about half of those (49.1%), were scheduled to start systemic AD therapy. The most frequent reason deciding against a systemic therapy was the patient's wish. Although 29.3% of SYS patients were eligible for a switch according to the criteria of the German S2k guideline's checklist, the majority (81.3%) did not switch AD therapy. CONCLUSIONS: This is the first study on the implementation of the German S2k guideline's checklist in everyday care of AD patients in Germany. More than one-third of the TOP patients were identified as eligible for systemic treatment. By applying the guideline's checklist criteria, another one-third of SYS patients may have benefited from a change of current systemic therapy. The use of the German S2k guideline's checklist in routine care represents an important tool to ensure effective patient care and identify inadequately treated patients.

Abrocitinib effect on patient-reported outcomes in patients with moderate-to-severe atopic dermatitis: Results from phase 3 studies, including the long-term extension JADE EXTEND study.

BACKGROUND: Abrocitinib improved signs and symptoms of moderate-to-severe atopic dermatitis (AD) at Weeks 12 and 16 in phase 3 studies, with a manageable safety profile. Patient-reported outcomes with long-term abrocitinib treatment were not reported. OBJECTIVE: To evaluate patient-reported outcomes with long-term abrocitinib treatment in patients with moderate-to-severe AD. METHODS: JADE EXTEND (NCT03422822) is an ongoing, phase 3, long-term extension study that enrolled patients from previous abrocitinib AD trials. This analysis includes patients from the phase 3 trials JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871) and JADE COMPARE (NCT03720470) who completed the full treatment period of placebo or abrocitinib (200 or 100 mg once daily) and subsequently entered JADE EXTEND and were randomised to receive once-daily abrocitinib 200 or 100 mg. Patient-reported endpoints to Week 48 included the proportion of patients who achieved Dermatology Life Quality Index (DLQI) scores of 0/1 (no effect of AD on quality of life [QoL]) and a ≥4-point improvement in Patient-Oriented Eczema Measure (POEM) score (clinically meaningful improvement). Data cut-off: April 22, 2020. RESULTS: Baseline DLQI mean scores were 15.4 and 15.3 in the abrocitinib 200- and 100-mg groups, respectively, which corresponded to a 'very large effect' on QoL; at Week 48, mean DLQI scores were lower with abrocitinib 200 mg (4.6; 'small effect' on QoL) and abrocitinib 100 mg (5.9; 'moderate effect' on QoL). Baseline POEM mean scores were 20.4 and 20.5 in the abrocitinib 200- and 100-mg groups, respectively; at Week 48, mean POEM scores were 8.2 and 11.0. Week 48 patient-reported responses with abrocitinib 200 mg and abrocitinib 100 mg were 44% and 34% for DLQI 0/1, and 90% and 77% for a ≥4-point reduction in POEM score. CONCLUSION: In patients with moderate-to-severe AD, long-term abrocitinib treatment resulted in clinically meaningful improvement in patient-reported symptoms of AD, including QoL.

European guideline (EuroGuiDerm) on atopic eczema - part II: non-systemic treatments and treatment recommendations for special AE patient populations.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

European guideline (EuroGuiDerm) on atopic eczema: part I - systemic therapy.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients.

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

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.

Determinants of costs and benefits in atopic dermatitis routine care in Germany.

BACKGROUND AND OBJECTIVES: The economic burden of atopic dermatitis (AD) is of particular interest. The present study aims to analyse the association of disease-related characteristics, annual costs and treatment benefits in AD. METHODS: Between August 2017 and June 2019, a cross-sectional observational study in patients with AD was conducted in Germany. Cost-of-illness data were assessed from the societal perspective. Disease characteristics included severity, time since diagnosis and therapy, as well as atopic comorbidity and the implementation of prevention measures. Subgroup analyses of the total costs were conducted for these characteristics. A linear regression model was applied to analyse the impact of disease characteristics on the costs. Furthermore, associations of biologic treatment with outcome parameters were analysed. RESULTS: A total of 1291 patients from 111 centres were included in the analyses. The total costs amounted on average to € 3660 ± € 6428 per patient and year. Higher costs were shown in various patient groups, for example, in patients using biologics (€ 20 983 vs. € 2470). In a regression analysis, gender, education and the number of implemented prevention measures were identified as significant predictors of costs. Patients treated with biologics showed consistently better outcome parameters and were more often satisfied with their treatment. CONCLUSIONS: Gender, education and implemented prevention measures are significant cost determinants in AD. The results confirm that treatment with biologics is the main cost driver in AD. However, incremental patient-relevant benefits of high-priced therapy are reflected by the significantly better clinical outcomes in the group treated with biologics.

Atopic dermatitis: disease characteristics and comorbidities in smoking and non-smoking patients from the TREATgermany registry.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke. OBJECTIVES: In this study, AD characteristics and its atopic comorbidities are compared in smoking and non-smoking AD patients. METHODS: TREATgermany is a non-interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included in TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analysed comparing AD disease characteristics and comorbidities in smokers vs. non-smokers. RESULTS: Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n = 352; 38.8%) and non-smokers, however, lesions' intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to non-smoking patients. Smokers reported a lower number of weeks with well-controlled AD and more severe pruritus than non-smokers. Total IgE levels were more elevated in smokers and they displayed a younger age at the initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well-controlled AD and the greater pruritus remained different in smokers compared to non-smokers. In addition, smoking patients with adult-onset AD showed a 2.5 times higher chance of involvement of the feet. CONCLUSIONS: German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult-onset AD.

Patients With Atopic Dermatitis Sensitized to Pet Dander Mount IgE and T-Cell Responses to Mammalian Cystatins, Including the Human Self-Protein.

BACKGROUND: Immediate and delayed-type hypersensitivity reactions to pet-borne allergens are common in atopic diseases. In atopic dermatitis (AD), controversy surrounds the contribution to the disease of cross-reactivity to self-proteins. Human cystatin A and the cat allergen Fel d 3 belong to the cystatins, an evolutionary conserved protein family. The objective of the present study was to assess crossreactivity between mammalian cystatins and to analyze T-cell responses to cystatin in AD patients sensitized to pet dander. METHODS: cDNA coding for dog cystatin was cloned from dog skin. Sera from 245 patients with IgE-mediated sensitization to cat and dog dander were tested for IgE binding to recombinantly expressed feline, canine, and human cystatin. Of these, 141 were also diagnosed with AD. RESULTS: Cystatin-specific IgE was detected in 36 patients (14.7%), of whom 19 were considerably affected by AD. Within the AD patients, 9 had measurable IgE against all 3 cystatins. Cystatin-sensitized AD patients did not differ from non-cystatin-sensitized patients in terms of disease severity, age, or total IgE levels. T-cell cytokine measurements showed elevated IL-4 levels after stimulation with feline and human cystatin. CONCLUSIONS: The humoral response suggests that in addition to Fel d 3, the homologous protein from dog might play a role in allergy. Furthermore, human cystatin appears to be capable of driving a type 2 immune response in sensitized AD patients and may therefore be considered a so-called autoallergen, as proposed for other evolutionary conserved proteins.

Patients With Atopic Dermatitis Sensitized to Pet Dander Mount IgE and T-Cell Responses to Mammalian Cystatins, Including the Human Self-Protein

Background: Immediate and delayed-type hypersensitivity reactions to pet-borne allergens are common in atopic diseases. In atopic dermatitis (AD), controversy surrounds the contribution to the disease of cross-reactivity to self-proteins. Human cystatin A and the cat allergen Fel d 3 belong to the cystatins, an evolutionary conserved protein family. The objective of the present study was to assess crossreactivity between mammalian cystatins and to analyze T-cell responses to cystatin in AD patients sensitized to pet dander. Methods: cDNA coding for dog cystatin was cloned from dog skin. Sera from 245 patients with IgE-mediated sensitization to cat and dog dander were tested for IgE binding to recombinantly expressed feline, canine, and human cystatin. Of these, 141 were also diagnosed with AD. Results: Cystatin-specific IgE was detected in 36 patients (14.7%), of whom 19 were considerably affected by AD. Within the AD patients, 9 had measurable IgE against all 3 cystatins. Cystatin-sensitized AD patients did not differ from non–cystatin-sensitized patients in terms of disease severity, age, or total IgE levels. T-cell cytokine measurements showed elevated IL-4 levels after stimulation with feline and human cystatin. Conclusion: The humoral response suggests that in addition to Fel d 3, the homologous protein from dog might play a role in allergy. Furthermore, human cystatin appears to be capable of driving a type 2 immune response in sensitized AD patients and may therefore be considered a so-called autoallergen, as proposed for other evolutionary conserved proteins. (AU)

Antecedentes: Las reacciones de hipersensibilidad de tipo inmediato y retardado a los alérgenos que están en las mascotas son comunes en las enfermedades atópicas. En este estudio, en pacientes con dermatitis atopica (DA), se analiza la reactividad cruzada con las autoproteínas y su contribución a la enfermedad. Tanto la cistatina A humana como el alérgeno felino Fel d 3 pertenecen a la familia de las cistatinas, una familia de proteínas conservadas evolutivamente. El objetivo del presente estudio fue evaluar la reactividad cruzada entre las cistatinas de mamíferos y analizar la respuestas de las células T a la cistatina en pacientes con DA sensibilizados a la caspa de las mascotas. Métodos: El ADNc que codifica la cistatina de perro se clonó a partir de piel de perro. Se analizaron sueros de 245 pacientes con sensibilización por IgE a la caspa de gato y perro para determinar la unión de IgE a cistatina felina, canina y humana expresada de forma recombinante, respectivamente. De estos 245 pacientes, 141 fueron diagnosticados de DA. Resultados: Se detectó IgE específica frente a cistatina en el 14,7% (36) de los pacientes, de los cuales 19 padecían DA. Dentro de los pacientes con DA, 9 tenían IgE medible contra las tres cistatinas. Los pacientes con DA sensibilizados frente a cistatina no difirieron de los pacientes no sensibilizados con cistatina en términos de gravedad de la enfermedad, edad o niveles totales de IgE. El análisis de citocinas de células T reveló niveles elevados de IL-4 después de la estimulación con cistatina felina y humana. Conclusión: La respuesta humoral sugiere que, además de Fel d 3, la proteína homóloga de perro también podría desempeñar un papel en la alergia. Además, la cistatina humana parece ser capaz de promover una respuesta inmune de tipo 2 en pacientes con DA sensibilizados y, por lo tanto, puede considerarse un autoalérgeno, como se ha propuesto para otras proteínas conservadas evolutivamente. (AU)

[Quality of care for patients with atopic dermatitis in Germany-no improvements in indicators after ten years]. / Qualität der dermatologischen Versorgung von Neurodermitis in Deutschland ­ keine Verbesserung der Indikatoren nach 10 Jahren.

BACKGROUND: With AtopicHealth1, the first national care study on atopic dermatitis (AD) was conducted in 2010. At that time, about one third of the patients undergoing treatment by dermatologists showed severe limitations in quality of life, which indicated an insufficient quality of care. The aim of the present study was to characterise the current care of patients with AD undergoing dermatological treatment in comparison between different severity grades, as well as in comparison to 2010 and to psoriasis. METHODS: The Germany-wide multicentre cross-sectional study "AtopicHealth2" recorded clinical data, quality of life (DLQI), therapies, preventive behaviour and patient-defined treatment benefit (PBI). Patients with an indication for systemic therapy were considered moderately to severely affected for subgroup analyses, the others mildly affected. RESULTS: Between 2017 and 2019, 1291 patients (median age 41 years, 56.5% female) were enrolled by 111 centres. Compared with 2010, there were no improvements in quality of life (DLQI 8.5 in both studies), severity (SCORAD 45.4 vs. 42.3 in 2010) or treatment benefit (PBI 2.2 vs. 2.4 in 2010). Moderately to severely affected patients were more likely to show impaired quality of life (45.4% vs. 23.6%) and less likely to have relevant treatment benefits (PBI < 1: 21.3% vs. 13.2%) than mildly affected patients. In contrast to psoriasis, patients with AD revealed higher quality of life limitations (DLQI 8.5 vs. 6.1) and lower treatment benefit (PBI 2.2 vs. 2.8). DISCUSSION: Compared to 2010, there is no improvement in the quality of care for AD in Germany. Compared to psoriasis, patients with AD show higher burden and lower treatment benefit, which underlines the need for therapeutic innovations.

Topical therapy of atopic dermatitis with a focus on pimecrolimus.

Atopic dermatitis (AD) is a chronic and relapsing, inflammatory skin disease characterized by impaired skin barrier function and immune system dysregulation that results in dryness, skin microbiome dysbiosis and intense pruritus. It is highly heterogeneous, and its management is demanding. Patients with AD are at greater risk of comorbidities such as attention-deficit hyperactivity disorder as well as other atopic diseases. Early-onset AD cases typically improve or resolve in late childhood; however, it is proposed that the prevalence of persistent or adult-onset AD is higher than previously thought. Basic therapy consists of emollient application and trigger avoidance, and when insufficient, topical corticosteroids (TCS) are the first-line treatment. However, corticophobia/steroid aversion and TCS side-effects, particularly on sensitive skin areas, lead to low compliance and insufficient disease control. Several long- and short-term randomized controlled and daily practice studies have demonstrated that topical calcineurin inhibitors, such as pimecrolimus, have similar anti-inflammatory effects to low-to-medium strength TCS, reduce pruritus and improve the quality of life of patients. In addition, pimecrolimus does not cause skin atrophy, is steroid-sparing and has a good safety profile, with no evidence for an increased risk of malignancies or skin infections. In general, pimecrolimus cream is well-accepted and well-tolerated, encouraging patient adherence and leading to its use by many physicians as a preferred therapy for children and sensitive skin areas.

Cost-of-illness of atopic dermatitis in Germany: data from dermatology routine care.

BACKGROUND: Progress in the management of atopic dermatitis (AD) and the recent introduction of the first biologic have raised interest in the costs of treating AD. OBJECTIVES: Since there is a lack of recent data, the objective of this study was to determine the annual costs of adults with AD from the societal perspective. METHODS: A nationwide cross-sectional study was conducted in 111 dermatological offices under routine conditions. Cost parameters were collected with a standardised questionnaire on disease-related costs. This questionnaire allows the determination of costs for systemic and topical treatment, outpatient and inpatient visits, rehabilitation stays and travel costs. Direct costs were determined for the statutory health insurance (SHI) and for the patients (out-of-pocket costs). Societal costs also included the indirect costs due to incapacity to work. Costs were calculated for all severity grades and further stratified by mild and moderate-to-severe AD. RESULTS: From August 2017 to June 2019, N = 1291 adult patients from all over Germany were included. The total annual costs in the group with all severity grades (n = 706) amounted to € 3616 ± € 6452 (median € 874) per patient. For patients with mild AD (n = 367), the annual costs were € 1466 ± € 3029 (median € 551) per patient, while they were € 5229 ± € 7538 (median € 1791) for patients with moderate-to-severe AD (n = 682). The total economic burden for treating adult patients with AD in Germany is estimated at more than € 2.2 billion. CONCLUSIONS: In total, the data from this study show that compared to for example psoriasis, AD has a moderate level of costs-of-illness in Germany. The approval of new therapies is expected to lead to markedly more resource utilisation in the next years.