Obesity is linked to disease severity in moderate to severe atopic dermatitis-Data from the prospective observational TREATgermany registry.

BACKGROUND: There are conflicting data on a potential association between obesity and atopic dermatitis (AD). The purpose of this study was to investigate the relationship between obesity and AD disease severity. METHODS: Patients from the TREATgermany registry cohort were divided into three groups according to their body mass index (BMI). Due to low numbers, underweight patients (BMI <18.5 kg/m2) were excluded from the analysis. Physician- and patient-reported disease severity scores as well as additional phenotypic characteristics were evaluated for association with BMI. Generalized linear mixed models and multinomial logit models, respectively, were applied to investigate the association of BMI, age, sex and current systemic AD treatment with disease severity. RESULTS: This study encompassed 1416 patients, of which 234 (16.5%) were obese (BMI ≥30 kg/m2). Obesity was associated with lower educational background and smoking. Otherwise, obese and non-obese AD patients had similar baseline characteristics. Increased BMI was associated with higher oSCORAD (adjusted ß: 1.24, 95% CI: 1.05-1.46, p = 0.013) and Patient-oriented eczema measure (POEM) (adjusted ß: 1.09, 95% CI: 1.01-1.17, p = 0.038). However, the absolute difference in the overall oSCORAD was small between obese and non-obese AD patients (Δ oSCORAD = 2.5). Allergic comorbidity was comparable between all three groups, with the exception of asthma which was more pronounced in obese patients (p < 0.001). DISCUSSION: In this large and well-characterized AD patient cohort, obesity is significantly associated with physician- and patient-assessed measures of AD disease severity. However, the corresponding effect sizes were low and of questionable clinical relevance. The overall prevalence of obesity among the German AD patients was lower than in studies on other AD cohorts from different countries, which confirms previous research on the German population and suggests regional differences in the interdependence of AD and obesity prevalence.

Allergic diseases as risk factors for Long-COVID symptoms: Systematic review of prospective cohort studies.

OBJECTIVE: The role of allergy as a risk factor for Long-COVID (LC) is unclear and has not been thoroughly examined yet. We aimed to systematically review and appraise the epidemiological evidence on allergic diseases as risk factors for LC. DESIGN: This is an initial systematic review. Two reviewers independently performed the study selection and data extraction using Covidence. Risk of bias (RoB) and certainty of evidence (GRADE) were assessed. Random effects meta-analyses were used to pool unadjusted ORs within homogeneous data subsets. DATA SOURCES: We retrieved articles published between January 1st, 2020 and January 19th, 2023 from MEDLINE via PubMed, Scopus, the WHO-COVID-19 database and the LOVE platform (Epistemonikos Foundation). In addition, citations and reference lists were searched. ELIGIBILITY CRITERIA: We included prospective cohort studies recruiting individuals of all ages with confirmed SARS-CoV-2 infection that were followed up for at least 12 months for LC symptoms where information on pre-existing allergic diseases was available. We excluded all study designs that were not prospective cohort studies and all publication types that were not original articles. RESULTS: We identified 13 studies (9967 participants, range 39-1950 per study), all assessed as high RoB, due to population selection and methods used to ascertain the exposures and the outcome. Four studies did not provide sufficient data to calculate Odds Ratios. The evidence supported a possible relationship between LC and allergy, but was very uncertain. For example, pre-existing asthma measured in hospital-based populations (6 studies, 4019 participants) may be associated with increased risk of LC (Odds Ratio 1.94, 95% CI 1.08, 3.50) and findings were similar for pre-existing rhinitis (3 studies, 1141 participants; Odds Ratio 1.96, 95% CI 1.61, 2.39), both very low certainty evidence. CONCLUSIONS: Pre-existing asthma or rhinitis may increase the risk of LC.

High recurrence rate of eczema herpeticum in moderate/severe atopic dermatitis -TREATgermany registry analysis.

BACKGROUND: Eczema herpeticum (EH) is a disseminated skin infection caused by herpes simplex virus in atopic dermatitis (AD) patients. The frequency of EH and the clinical features of EH patients have not yet been investigated in a larger cohort. METHODS: We sought to investigate the TREATgermany cohort, a multicenter, non-interventional clinical registry of moderately to severely affected AD patients in Germany. Baseline characteristics of patients included between December 2017 and April 2021 were compared between patients without, single, and multiple EH. RESULTS: Of the 893 patients, 195 (21.8%) had at least one EH. Of the 195 patients with EH, 107 had multiple EH (54.9%), representing 12.0% of the total study population. While there were no differences in demographic characteristics, previous treatment, and disease scores at enrollment (itch, IGA, oSCORAD, EASI), patients with EH had more frequent atopic comorbidities and sensitizations to house dust mite, food, and mold. DISCUSSION: TREATgermany registry data suggest a high prevalence and recurrence rate of EH, while there appears to be no specific clinical phenotype, besides an increase in allergies, to identify EH patients in the daily routine.

Acceptance of a digital therapy recommender system for psoriasis.

BACKGROUND: About 2% of the German population are affected by psoriasis. A growing number of cost-intensive systemic treatments are available. Surveys have shown high proportions of patients with moderate to severe psoriasis are not adequately treated despite a high disease burden. Digital therapy recommendation systems (TRS) may help implement guideline-based treatment. However, little is known about the acceptance of such clinical decision support systems (CDSSs). Therefore, the aim of the study was to access the acceptance of a prototypical TRS demonstrator. METHODS: Three scenarios (potential test patients with psoriasis but different sociodemographic and clinical characteristics, previous treatments, desire to have children, and multiple comorbidities) were designed in the demonstrator. The TRS demonstrator and test patients were presented to a random sample of 76 dermatologists attending a national dermatology conference in a cross-sectional face-to-face survey with case vignettes. The dermatologist were asked to rate the demonstrator by system usability scale (SUS), whether they would use it for certain patients populations and barriers of usage. Reasons for potential usage of the TRS demonstrator were tested via a Poisson regression with robust standard errors. RESULTS: Acceptance of the TRS was highest for patients eligible for systemic therapy (82%). 50% of participants accepted the system for patients with additional comorbidities and 43% for patients with special subtypes of psoriasis. Dermatologists in the outpatient sector or with many patients per week were less willing to use the TRS for patients with special psoriasis-subtypes. Dermatologists rated the demonstrator as acceptable with an mean SUS of 76.8. Participants whose SUS was 10 points above average were 27% more likely to use TRS for special psoriasis-subtypes. The main barrier in using the TRS was time demand (47.4%). Participants who perceived time as an obstacle were 22.3% less willing to use TRS with systemic therapy patients. 27.6% of physicians stated that they did not understand exactly how the recommendation was generated by the TRS, with no effect on the preparedness to use the system. CONCLUSION: The considerably high acceptance and the preparedness to use the psoriasis CDSS suggests that a TRS appears to be implementable in routine healthcare and may improve clinical care. Main barrier is the additional time demand posed on dermatologists in a busy clinical setting. Therefore, it will be a major challenge to identify a limited set of variables that still allows a valid recommendation with precise prediction of the patient-individual benefits and harms.

Itch, sleep loss, depressive symptoms, fatigue, and productivity loss in patients with moderate-to-severe atopic dermatitis: Analyses of TREATgermany registry data.

BACKGROUND: TREATgermany is a multicenter registry including patients with moderate-to-severe atopic dermatitis (AD) from currently 74 study centers (university clinics, hospitals and practices) in Germany. As of August 31, 2021, 1,230 adult patients were enrolled. METHODS: In TREATgermany, patients and physicians fill in questionnaires pertaining to symptoms, disease severity, quality of life, depressiveness, and fatigue. In particular, limitations in work performance are assessed using the Work Limitations Questionnaire (WLQ). To assess associations between occupational performance/work limitations and symptoms, correlations and regression models were calculated. RESULTS: The examined sample of 228 employed patients reported an average of 6% at-work productivity loss within the past two weeks prior to enrolment in the registry. The WLQ productivity loss score was moderately associated with itch (r = 0.32) and sleep loss (r = 0.39) and strongly associated with depressive symptoms (r = 0.68) and fatigue (r = 0.60). CONCLUSIONS: The analyses of the registry data show that moderate-to-severe atopic dermatitis has a negative impact on the work productivity of the patients. The analyses further point out the relevant associations between work productivity, depressive symptoms, and fatigue highlighting the disease burden caused by the psychological components of AD.

Perception of the coronavirus pandemic by patients with atopic dermatitis - Results from the TREATgermany registry.

BACKGROUND: TREATgermany, a registry for patients with moderate to severe atopic dermatitis (AD), established an additional questionnaire in spring 2020 to investigate the effects of the coronavirus pandemic on the daily life of patients with AD. MATERIAL AND METHODS: A questionnaire was used to analyze general information regarding a patient's experience of the coronavirus pandemic and, using the Inventory of Life-Changing Events, the resulting personal burden. To analyze possible associations between disease severity (EASI score, oSCORAD, IGA, PGA, POEM), quality of life (DLQI) and personal burden, t-tests, analyses of variance and correlations were evaluated, controlled for sex and age. RESULTS: 58 % (n = 233) of the included 400 registry patients reported high burden scores caused by the coronavirus pandemic, regardless of an actual infection. Men showed significantly higher burden scores than women, and younger than older respondents (both P = 0.03). There were no differences in burden scores related to the physician's assessment of disease severity. However, patients with higher quality of life impairments and higher disease severity perceived the burden of the coronavirus pandemic as less severe (DLQI P = 0.019, PGA P = 0.044). CONCLUSIONS: Our data show that registry patients considered the coronavirus pandemic as a life-changing event and perceived the burden differently. This should be taken into account in the treatment of patients with moderate to severe AD as well as in further studies.

Status report on the atopic dermatitis registry TREATgermany.

BACKGROUND: The TREATgermany registry collects data from children, adolescents, and adults with moderate-to-severe atopic dermatitis (AD) in Germany. For this purpose, clinical and patient-reported outcomes, the course of the disease, and applied therapies are observed. METHODS: TREATgermany recruits patients with moderate-to-severe AD according to the diagnostic criteria of the UK Working Party, an "Objective Scoring for Atopic Dermatitis" (oSCORAD) > 20 and/or currently antiinflammatory systemic treatment for AD or previous anti-inflammatory systemic treatment for AD within past 24 months before inclusion. No study related interventions will be performed. Currently, 59 dermatological practices, clinics, and university hospitals are participating in TREATgermany (as of May 2021). Based on the interim analysis of October 13, 2020, patient characteristics were described from 4,373 documented visits of adult participants (n = 1,025). RESULTS: The mean age at inclusion in TREATgermany was 42 years, 57.7% of patients were men (n = 591) and 42.3% were women (n = 434). According to oSCORAD, 85.8% of those included suffered from moderate-to-severe AD. At baseline visit, 744 patients had already received one or more systemic treatments for AD (glucocorticosteroids n = 600, ciclosporin A (CSA) n = 307, dupilumab n = 98). 597 patients received dupilumab during their participation in TREATgermany, 134 patients received CSA. CONCLUSION: With the increasing number of recruitment centers (October 2020: 38 centers; May 2021: 59 centers), TREATgermany can continue to make an important contribution to health services research for patients with moderate-to-severe AD. The registry fulfills the methodological requirements of IQWiG for the collection and processing of healthcare-related data. With the successful and expected approval of further systemic treatments, these can be compared in terms of efficacy and safety in the future. In addition, with the recruitment of children and adolescents started in 2021, this patient group can also be observed.

Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis.

BACKGROUND: As an evidence resource for the currently planned European Academy of Allergy and Clinical Immunology (EAACI) clinical practice guideline "systemic treatment of atopic dermatitis (AD)," we critically appraised evidence on systemic treatments for moderate-to-severe AD. METHODS: We systematically identified randomized controlled trials (RCTs) investigating the safety and efficacy of systemic treatments for AD up to February 2020. Primary efficacy outcomes were clinical signs, AD symptoms and health-related quality of life. Primary safety outcomes included cumulative incidence rates for (serious) adverse events. Trial quality was assessed applying the Cochrane Risk of Bias Tool 2.0. Meta-analyses were conducted where appropriate. RESULTS: 50 RCTs totalling 6681 patients were included. Trial evidence was identified for apremilast, azathioprine (AZA), baricitinib, ciclosporin A (CSA), corticosteroids, dupilumab, interferon-gamma, intravenous immunoglobulins (IVIG), mepolizumab, methotrexate (MTX), omalizumab, upadacitinib and ustekinumab. Meta-analyses were indicated for the efficacy of baricitinib [EASI75 RD 0.16, 95% CI (0.10;0.23)] and dupilumab [EASI75, RD 0.37, 95% CI (0.32;0.42)] indicating short-term (ie 16-week treatment) superiority over placebo. Furthermore, efficacy analyses of AZA and CSA indicated short-term superiority over placebo; however, nonvalidated scores were used and can therefore not be compared to EASI. CONCLUSION: The most robust, replicated high-quality trial evidence is present for the efficacy and safety of dupilumab for up to 1 year in adults. Robust trial evidence was further revealed for AZA, baricitinib and CSA. Methodological restrictions led to limited evidence-based conclusions for all other systemic treatments. Head-to-head trials with novel systemic treatments are required to clarify the future role of conventional therapies.

Systemic Immunomodulatory Treatments for Patients With Atopic Dermatitis: A Systematic Review and Network Meta-analysis.

Importance: Most clinical trials assessing systemic immunomodulatory treatments for patients with atopic dermatitis are placebo-controlled. Objective: To compare the effectiveness and safety of systemic immunomodulatory treatments for patients with atopic dermatitis in a systematic review and network meta-analysis. Data Sources: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, Global Resource of Eczema Trials database, and clinical trial registries were searched from inception to October 28, 2019. Study Selection: English-language randomized clinical trials of 8 weeks or more of treatment with systemic immunomodulatory medications for moderate to severe atopic dermatitis were included. Titles, abstracts, and articles were screened in duplicate. Of 10 324 citations, 39 trials were included. Data Extraction and Synthesis: Data were extracted in duplicate, and the review adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses for Network Meta-Analyses guidelines. Random-effects bayesian network meta-analyses were performed and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Main Outcomes and Measures: Prespecified outcomes were change in signs of disease, symptoms, quality of life, itch, withdrawals, and serious adverse events. Results: A total of 39 trials with 6360 patients examining 20 medications and placebo were included. Most trials were conducted for adults receiving up to 16 weeks of therapy. Dupilumab, 300 mg every 2 weeks, was associated with improvement in the Eczema Area and Severity Index score vs placebo (mean difference, 11.3-point reduction; 95% credible interval [CrI], 9.7-13.1 [high certainty]). Cyclosporine (standardized mean difference, -1.1; 95% CrI, -1.7 to -0.5 [low certainty]) and dupilumab (standardized mean difference, -0.9; 95% CrI, -1.0 to -0.8 [high certainty]) were similarly effective vs placebo in clearing clinical signs of atopic dermatitis and may be superior to methotrexate (standardized mean difference, -0.6; 95% CrI, -1.1 to 0.0 [low certainty]) and azathioprine (standardized mean difference, -0.4; 95% CrI, -0.8 to -0.1 [low certainty]). Several investigational medications for atopic dermatitis are promising, but data to date are limited to small early-phase trials. Safety analyses were limited by low event rates. Conclusions and Relevance: Dupilumab and cyclosporine may be more effective for up to 16 weeks of treatment than methotrexate and azathioprine for treating adult patients with atopic dermatitis. More studies directly comparing established and novel treatments beyond 16 weeks are needed and will be incorporated into future updates of this review.