EASI p-EASI: Predicting disease severity in atopic dermatitis patients treated with dupilumab using a combination of serum biomarkers.
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ABSTRACT:
SUBMITTER: Bakker DS
PROVIDER: S-EPMC7754122 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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EASI p-EASI: Predicting disease severity in atopic dermatitis patients treated with dupilumab using a combination of serum biomarkers.
Bakker Daphne S DS Ariens Lieneke F M LFM Giovannone Barbara B Hijnen DirkJan D Delemarre Eveline M EM Knol Edward E Nierkens Stefan S de Bruin-Weller Marjolein S MS Thijs Judith L JL Drylewicz Julia J
Allergy 20200724 12
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Project description: Not available
| S-EPMC5723207 | biostudies-literature
Project description:BackgroundAtopic dermatitis (AD) is a common chronic eczematous skin disease with severe pruritus. Several new therapeutic agents for AD such as dupilumab, an anti-IL-4Rα antibody, have been developed in recent years. We need to predict which agent is the best choice for each patient, but this remains difficult.ObjectiveOur aim was to examine clinical background factors and baseline biomarkers that could predict the achievement of improved clinical outcomes in patients with AD treated with dupilumab.MethodsA multicenter, prospective observational study was conducted on 110 patients with AD. The Eczema Area and Severity Index was used as an objective assessment, and the Patient-Oriented Eczema Measure and Numerical Rating Scale for Pruritus were used as patient-reported outcomes. In addition, some clinical background factors were evaluated.ResultsThe achievement of an absolute Eczema Area and Severity Index of 7 or less was negatively associated with current comorbidity of food allergy and baseline serum lactate dehydrogenase (LDH) levels. There were negative associations between achievement of a Patient-Oriented Eczema Measure score of 7 or less and duration of severe AD and between achievement of an itching Numerical Rating Scale for Pruritus score of 1 or less and current comorbidity of allergic conjunctivitis or baseline serum periostin level. Furthermore, signal detection analysis showed that a baseline serum LDH level less than 328 U/L could potentially be used as a cutoff value for predicting the efficacy of dupilumab.ConclusionBaseline biomarkers such as LDH and periostin and clinical background factors such as current comorbidity of food allergy and a long period of severe disease may be useful indicators when choosing dupilumab for systemic treatment for AD, as they can predict the efficacy of dupilumab.
| S-EPMC11381866 | biostudies-literature
Project description:Tape-stripping is a minimally invasive approach for skin sampling that captures the cutaneous immune/barrier abnormalities in atopic dermatitis (AD). However, tape-strips have not been used to evaluate molecular changes with therapeutic targeting. In this study, we sought to characterize the proteomic signature of tape-strips from AD patients, before and after dupilumab therapy. Twenty-six AD patients were treated with every-other-week dupilumab 300 mg for 16 weeks. Tape-strips from lesional and non-lesional skin were collected before and after treatment, and analyzed with the Olink proteomic assay. Using criteria of fold-change>1.5 and FDR < 0.05, 136 proteins significantly decreased after dupilumab treatment, corresponding to an overall mean improvement of 66.2% in the lesional vs. non-lesional AD proteome. Significant decreases after dupilumab were observed in immune markers related to general inflammation (MMP12), Th2 (CCL13/CCL17), Th17/Th22 (IL-12B, CXCL1, S100A12), and innate immunity (IL-6, IL-8, IL-17C), while the Th1 chemokines CXCL9/CXCL10 remained elevated. Proteins related to atherosclerosis/cardiovascular risk (e.g., SELE/E-selectin, IGFBP7, CHIT1/ chitotriosidase-1, AXL) also significantly decreased after treatment. Dupilumab therapy suppressed AD-related immune biomarkers and atherosclerosis/cardiovascular risk proteins. Tape-strip proteomics may be useful for monitoring therapeutic response in real-life settings, clinical trials, and longitudinal studies for AD and beyond.
| S-EPMC7423990 | biostudies-literature
Project description:BackgroundDupilumab, targeting the interleukin-4α receptor and inhibiting the action of interleukin-4 and interleukin-13, was recently approved for treatment of moderate to severe atopic dermatitis. There is limited data on long-term effects and safety among patients with severe atopic dermatitis treated with dupilumab. Weight gain was observed among patients treated with dupilumab in our clinic. The aim was to describe weight change in a cohort study of patients with severe atopic dermatitis treated with dupilumab from baseline to follow-up after 12 months, and to analyze if weight change was associated with effect of treatment, reported appetite, and/or disturbed night sleep due to itching.MethodsAll patients with atopic dermatitis receiving systemic treatment at the Unit of Dermatology, Karolinska University Hospital, have been registered and monitored consecutively since January 2017. This cohort constituted all patients who started treatment on dupilumab or methotrexate between 10 January 2017 and 30 June 2019 with at least 6 months of follow-up within the study period. The following variables were monitored at start of and during treatment: Eczema Severity Score Index, Patient-Oriented Eczema Measure, visual analogue scale for pruritus 10 cm, Montgomery-Åsberg Depression Rating Scale, Dermatology Life Quality Index, and weight. Data analyses were performed using two-sample Wilcoxon-Mann-Whitney rank-sum test, or the Wilcoxon matched-pairs sign-rank test with a p-value < 0.05 considered as statistically significant.ResultsPatients treated with dupilumab (n = 12) gained weight (mean 6.1 kg, range [0.1-18.0], p = 0.002) after 1 year on treatment. The majority of patients showed a good response to treatment with dupilumab (n = 11); at follow-up at 6, 9, or 12 months, they reached EASI-90 (n = 6), EASI-75 (n = 4), or EASI-50 (n = 1). There was no significant association between weight gain and treatment response, reported appetite, or disturbed night-sleep due to itch. Patients treated with methotrexate showed no significant weight change (n = 8).ConclusionsTo our knowledge, this is the first report on a possible association between weight gain and dupilumab treatment; the extent of the association is yet to be seen, as is the mechanism behind this finding.
| S-EPMC7510313 | biostudies-literature
Project description:Atopic dermatitis is associated with work productivity loss. Little is known about how patients perceive their work ability and quality of working life, and how this is affected by treatment. Our primary objective was to investigate work ability and quality of working life at baseline and during treatment in the long term. A registry-embedded prospective observational cohort study was conducted consisting of patients with atopic dermatitis starting dupilumab in routine clinical care. The instruments used were the Work Ability Index (WAI; questions 1, 2, and 3) and the Quality of Working Life Questionnaire (QWLQ). Ninety-three patients were included of whom 72 were (self-)employed (77%). From baseline to 48 weeks, the mean WAI-1 score (general work ability, range 0-10) improved from 6.8 (±2.0) to 7.9 (±1.3), WAI-2 (physical work ability, range 1-5) from 3.7 (±0.9) to 4.3 (±0.7), and WAI-3 (mental/emotional work ability, range 1-5) from 3.4 (±0.9) to 3.9 (±0.8) (p = 0.001, p = 0.005, p < 0.001, respectively). The mean QWLQ total score improved from 74.0 (±9.1) to 77.5 (±9.6) and subscale "Problems due to health situation" improved from 37.4 (±22.3) to 61.5 (±23.1) (range 0-100; p = 0.032, p < 0.001, respectively). In conclusion, patients with moderate-to-severe atopic dermatitis starting dupilumab report decreased work ability and quality of working life, mainly due to health-related problems. Significant improvement of work ability and quality of working life is observed with dupilumab treatment.
| S-EPMC8453967 | biostudies-literature
Project description:Dupilumab is the only biologic therapy currently approved in Europe and the United States for severe atopic dermatitis in patients 6 years of age or older. Off-label use is rationalized in younger children with severe atopic dermatitis. Decisions about vaccination for children on dupilumab are complex and depend on both the child's current treatment and the type of vaccination required. To achieve consensus on recommendations for vaccination of pediatric patients with atopic dermatitis treated with or planning to start dupilumab, a review of the literature and a modified-Delphi process was conducted by a working group of 5 panelists with expertise in dermatology, immunology, infectious diseases and vaccination. Here, we provide seven recommendations for vaccination of pediatric patients with atopic dermatitis treated with or planning to start dupilumab. These recommendations serve to guide physicians' decisions about vaccination in children with atopic dermatitis treated with dupilumab. Furthermore, we highlight an unmet need for research to determine how significantly dupilumab affects cellular and humoral immune responses to vaccination with live attenuated and inactivated vaccines.
| S-EPMC8169786 | biostudies-literature
Project description:Atopic dermatitis (AD) is an inflammatory skin condition that relies largely on subjective evaluation of clinical signs and symptoms for diagnosis and severity assessment. Using multivariate data, we attempted to construct prediction models that can diagnose the disease and assess its severity. We combined data from 28 mild-moderate AD patients and 20 healthy controls (HC) to create random forest models for classification (AD vs. HC) and regression analysis to predict symptom severities. The classification model outperformed the random permutation model significantly (area under the curve: 0.85 ± 0.10 vs. 0.50 ± 0.15; balanced accuracy: 0.81 ± 0.15 vs. 0.50 ± 0.15). Correlation analysis revealed a significant positive correlation between measured and predicted total SCORing Atopic Dermatitis score (SCORAD; r = 0.43), objective SCORAD (r = 0.53), eczema area and severity index scores (r = 0.58, each p < 0.001), but not between measured and predicted itch ratings (r = 0.21, p = 0.18). We developed and tested multivariate prediction models and identified important features using a variety of serum biomarkers, implying that discovering the deep-branching relationships between clinical measurements and serum measurements in mild-moderate AD patients may be possible using a multivariate machine learning method. We also suggest future methods for utilizing machine learning algorithms to enhance drug target selection, diagnosis, prognosis, and customized treatment in AD.
| S-EPMC10621918 | biostudies-literature
Project description:BackgroundModerate-to-severe atopic dermatitis (AD) in the adolescence is a high burden disease, and its treatment can be very challenging due to paucity of approved systemic drugs for this age and their side-effects. Dupilumab was recently approved for treatment of adolescent AD.ObjectivesA multicentre, prospective, real-world study on the effectiveness and safety of dupilumab in adolescents (aged from ≥12 to <18 years) with moderate-to-severe AD was conducted. The main AD clinical phenotypes were also examined.MethodsData of adolescents with moderate-to-severe AD treated with dupilumab at label dosage for 16 weeks were collected. Treatment outcome was assessed by EASI, NRS itch, NRS sleep loss and CDLQI scores at baseline and after 16 weeks of treatment. The clinical scores were also evaluated according to clinical phenotypes.ResultsOne hundred and thirty-nine adolescents were enrolled in the study. Flexural eczema and head and neck eczema were the most frequent clinical phenotypes, followed by hand eczema and portrait-like dermatitis. Coexistence of more than 1 phenotype was documented in 126/139 (88.5%) adolescents. Three patients (2.1%) contracted asymptomatic SARS-CoV-2 infection and 1 of the discontinued dupilumab treatment before the target treatment period. A significant improvement in EASI, NRS itch, NRS sleep loss and CDLQI was observed after 16 weeks of treatment with dupilumab. This outcome was better than that observed in clinical trials. Dupilumab resulted effective in all AD phenotypes, especially in diffuse eczema. Twenty-eight (20.1%) patients reported adverse events, conjunctivitis and flushing being the most frequent. None of patients discontinued dupilumab due to adverse event.ConclusionsDupilumab in adolescent AD showed excellent effectiveness at week 16 with consistent improvement of all clinical scores. Moreover, dupilumab showed a good safety profile also in this COVID-19 pandemic era.
| S-EPMC9542087 | biostudies-literature
Project description:IntroductionDupilumab is approved to treat moderate-to-severe atopic dermatitis (AD) in several countries in patients as young as 6 years of age. Since its approval, practical issues related to the use of dupilumab for AD have arisen, with particular interest in transitioning from current therapies and managing medication overlap, considerations for special populations of patients with AD, and management of potential adverse events.MethodsThis article aims to review the literature addressing several practical management issues related to dupilumab use for AD and to provide a framework for clinical decision-making in these circumstances and sub-populations. Each statement was reviewed, revised and voted on by authors to provide their level of agreement and degree of uncertainty for each statement.ResultsAn agreement level > 80% was achieved for all of the statements.ConclusionThe expert panel provides statements considering the practical management of patients with AD taking dupilumab to inform clinical decision-making in specific but frequently encountered clinical situations.
| S-EPMC8435113 | biostudies-literature
Project description:ImportanceSince the increased use of dupilumab for atopic dermatitis (AD) in daily practice, several cases have been reported on the development of cutaneous T-cell lymphomas (CTCL) and lymphoid infiltrates.ObjectiveTo provide insight in the clinical and histopathologic features of patients with AD clinically suspected for CTCL during dupilumab treatment.Design, setting, and participantsThis retrospective observational case series included adult (≥18 years) patients with AD treated with dupilumab between October 2017 and July 2022 at the University Medical Center Utrecht in the Netherlands.Main outcomes and measuresRelevant patient, disease, and treatment characteristics were evaluated. Skin biopsies before, during, and after treatment were collected and reassessed.ResultsFourteen patients (54.5% male) with a median (IQR) age of 56 (36-66) years suspected for CTCL with deterioration of symptoms during dupilumab treatment were included. Of 14 patients, 3 were retrospectively diagnosed with preexistent mycosis fungoides (MF). Eleven patients with AD were eventually diagnosed with a lymphoid reaction (LR). These patients showed MF-like symptoms; however, histopathologic findings were different, and included sprinkled distribution of small hyperchromatic lymphocytes in the upper epidermal section, a dysregulated CD4:CD8 ratio, and CD30 overexpression, without loss of CD2/CD3/CD5. The median time to clinical worsening was 4.0 months (IQR, 1.4-10.0). Posttreatment biopsies showed complete clearance of the LR in all patients.Conclusions and relevanceThis study found that dupilumab treatment can cause a reversible and benign LR, which mimics a CTCL, though has distinctive histopathologic features.
| S-EPMC10585590 | biostudies-literature