Temporal Correlations of Skin and Blood Metabolites with Clinical Outcomes of Biologic Therapy in Psoriasis

2020 ◽  
Vol 5 (5) ◽  
pp. 877-888 ◽  
Author(s):  
Ewelina P Dutkiewicz ◽  
Kai-Ta Hsieh ◽  
Pawel L Urban ◽  
Hsien-Yi Chiu
Keyword(s):  
Disease Severity ◽  
Biologic Therapy ◽  
Sampling Technique ◽  
Mass Spectrometric ◽  
Psoriatic Skin ◽  
Dynamic Changes ◽  
Biologic Drugs ◽  
Temporal Correlations ◽  
Blood Specimens ◽  
Metabolic Biomarkers

Abstract Background Psoriasis is an inflammatory skin disease causing multisystem effects. Introduction of biologic drugs has led to promising results in treatment of this disease. Here, we carry out time-dependent profiling of psoriasis-related putative metabolic biomarkers. Methods Skin excretion specimens were collected from 17 patients with psoriasis treated with biologics for 7 months. Blood specimens were obtained from the same patients at intervals of 1–3 months. A hydrogel micropatch sampling technique was implemented to collect lesional (L) and nonlesional (NL) skin specimens. The collected skin and blood specimens were analyzed by mass spectrometric methods. Results The metabolites present on L skin—in particular, choline, and citrulline—showed greater dynamics, corresponding to the resolution of psoriasis than the metabolites present in NL skin or blood. Choline levels in L skin and blood correlated positively, while citrulline correlated negatively with the severity of individual psoriasis plaques and general disease severity, respectively. Nevertheless, the correlations between the metabolite levels in blood and general disease severity were weaker than those between the metabolite levels on L skin and severity of individual plaques. The changes of these skin metabolites were more prominent in the responders to the treatment than in the nonresponders. Conclusions The results support the feasibility of characterizing dynamic changes in psoriatic skin metabolic profiles with the hydrogel micropatch probes and mass spectrometric tests. The study represents one of few attempts to explore relationships between skin and blood metabolite concentrations. However, practical use of the methodology in close clinical monitoring is yet to be demonstrated.

scholarly journals Skin Barrier Function in Psoriasis and Atopic Dermatitis: Transepidermal Water Loss and Temperature as Useful Tools to Assess Disease Severity

2021 ◽  
Vol 10 (2) ◽  
pp. 359 ◽  
Author(s):  
Trinidad Montero-Vilchez ◽  
María-Victoria Segura-Fernández-Nogueras ◽  
Isabel Pérez-Rodríguez ◽  
Miguel Soler-Gongora ◽  
Antonio Martinez-Lopez ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Disease Severity ◽  
Water Loss ◽  
Barrier Function ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Diagnostic Tools ◽  
Psoriatic Skin ◽  
Skin Barrier Function ◽  
Healthy Controls

Multiple diagnostic tools are used to evaluate psoriasis and atopic dermatitis (AD) severity, but most of them are based on subjective components. Transepidermal water loss (TEWL) and temperature are skin barrier function parameters that can be objectively measured and could help clinicians to evaluate disease severity accurately. Thus, the aims of this study are: (1) to compare skin barrier function between healthy skin, psoriatic skin and AD skin; and (2) to assess if skin barrier function parameters could predict disease severity. A cross-sectional study was designed, and epidermal barrier function parameters were measured. The study included 314 participants: 157 healthy individuals, 92 psoriatic patients, and 65 atopic dermatitis patients. TEWL was significantly higher, while stratum corneum hydration (SCH) (8.71 vs. 38.43 vs. 44.39 Arbitrary Units (AU)) was lower at psoriatic plaques than at uninvolved psoriatic skin and healthy controls. Patients with both TEWL > 13.85 g·m−2h−1 and temperature > 30.85 °C presented a moderate/severe psoriasis (psoriasis area severity index (PASI) ≥ 7), with a specificity of 76.3%. TEWL (28.68 vs. 13.15 vs. 11.60 g·m−2 h−1) and temperature were significantly higher, while SCH (25.20 vs. 40.95 vs. 50.73 AU) was lower at AD eczematous lesions than uninvolved AD skin and healthy controls. Patients with a temperature > 31.75 °C presented a moderate/severe AD (SCORing Atopic Dermatitis (SCORAD) ≥ 37) with a sensitivity of 81.8%. In conclusion, temperature and TEWL values may help clinicians to determine disease severity and select patients who need intensive treatment.

scholarly journals Biologic therapy of rheumatoid arthritis

2009 ◽  
Vol 137 (3-4) ◽  
pp. 205-210 ◽  
Author(s):  
Nemanja Damjanov ◽  
Jelena Vojinovic
Keyword(s):  
Rheumatoid Arthritis ◽  
Social Impact ◽  
Biologic Therapy ◽  
Joint Damage ◽  
Chronic Arthritis ◽  
Close Monitoring ◽  
Biologic Drugs ◽  
Early Introduction ◽  
Improved Outcomes ◽  
The Individual

Rheumatoid arthritis (RA) and juvenile idiopathic/rheumatoid arthritis (JIA) are chronic, inflammatory, systemic, auto-immune diseases characterized by chronic arthritis leading to progressive joint erosions. The individual functional and social impact of rheumatoid arthritis is of great importance. Disability and joint damage occur rapidly and early in the course of the disease. The remarkably improved outcomes have been achieved initiating biologic therapy with close monitoring of disease progression. Biologic agents are drugs, usually proteins, which can influence chronic immune dysregulation resulting in chronic arthritis. According to the mechanism of action these drugs include: 1) anti-TNF drugs (etanercept, infiximab, adalimumab); 2) IL-1 blocking drugs (anakinra); 3) IL-6 blocking drugs (tocilizumab); 4) agents blocking selective co-stimulation modulation (abatacept); 5) CD 20 blocking drugs (rituximab). Biologics targeting TNF-alpha with methotrexate have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic, and functional outcomes not seen previously. The new concept of rheumatoid arthritis treatment defines early diagnosis, early aggressive therapy with optimal doses of disease modifying antirheumatic drugs (DMARDs) and, if no improvement has been achieved during six months, early introduction of biologic drugs. The three-year experience of biologic therapy in Serbia has shown a positive effect on disease outcome.

scholarly journals P232 Effectiveness of adalimumab biosimilar switching: real world data from a London rheumatology centre

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Shivanee Vigneswaran ◽  
Megan Galloway ◽  
Samuel Hanlon ◽  
Aoife Tynan ◽  
Animesh Singh
Keyword(s):  
Side Effects ◽  
Disease Activity ◽  
Real World ◽  
Biologic Therapy ◽  
Underlying Disease ◽  
Real World Data ◽  
Biologic Drugs ◽  
Control Activity ◽  
World Data ◽  
Long Term Treatment

Abstract Background Biologic drugs have revolutionised the management of many rheumatological diseases with remission or low disease activity now the realistic targets for treatment. However, given the chronic nature of most rheumatological disease and the need for long term treatment, there has been a significant increase in the cost associated with disease treatment. The advent of biosimilars offers an attractive target in reducing drug costs for payers. Biosimilar medications are thought to be equally efficacious as originator drugs. Real world data in adalimumab biosimilar switching is limited. In this audit we aim to examine the real-world outcomes from switching from originator Humira to biosimilar Amgevita in a London teaching hospital. Methods A list of all adult rheumatology patients on Amgevita was obtained through pharmacy records. All patients had been switched from Humira to Amgevita from February 2019. Using clinic letters and an in-house biologics database, data was collected on the underlying disease and the date of switch. Outcomes reviewed were disease activity scores pre and post switch, documented side effects and flare of disease activity following switch including decision to revert to originator Humira or change treatment. Results There was a total of 289 adult patients on Humira who switched to Amgevita. Of these patients, 28 in total discontinued treatment - 13 with rheumatoid arthritis, 10 with psoriatic arthritis and 5 with ankylosing spondylitis. 22 had to be switched back to Humira, with a further 4 patients approved to switchback and awaiting to restart. Two additional patients were switched to alternative biologic therapy due to inefficacy. A further 3 patients refused to switch onto Amgevita. Sixteen patients had documented flares, with one requiring admission and ten requiring local or systemic corticosteroid therapy to control activity. Seven patients had documented side effects which included chest pain, headache, rash and site reactions and one patient developed shingles post switch. Conclusion A total of 9.6% of patients switched to Amgevita had disease flare or side effects resulting in a switchback to Humira or alternative biologic therapy. For a biosimilar to be approved, efficacy and safety profiles needs to be comparable to the originator biological therapy and usually looks at two treatment naïve groups, rather than direct switch. Thereby, data on switches in therapy is limited. One systematic review looking at 11,053 patients with inflammatory arthritis treated with Etanercept and switched to Benepali, found 768 reverting to original therapy giving a lower total of 6.9%. We find that although no previous data of Amgevita, our figure of 9.6% appears high in the context of previously controlled inflammatory disease with Humira. Disclosures S. Vigneswaran None. M. Galloway None. S. Hanlon None. A. Tynan None. A. Singh None.

scholarly journals C-Reactive Protein and Lymphocyte are important indicators of severe coronavirus disease and poor prognosis in elderly patients

2020 ◽  
Author(s):  
Qinglin He ◽  
Xiafen Hu ◽  
Xiaochen Xiang ◽  
Siyang Chen ◽  
Wanxin Liu ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Disease Severity ◽  
Area Under The Curve ◽  
Reference Interval ◽  
The Elderly ◽  
C Reactive Protein ◽  
Roc Curve Analysis ◽  
Dynamic Changes ◽  
Reactive Protein ◽  
Risk Of Death

Abstract Objective：To explore the value of C-reactive protein (CRP) and lymphocyte (L) in the assessment of disease severity and prognosis of elderly COVID-19 patients.Methods: A total of 194 positive COVID-19 patients were collected from Tianyou Hospital and Puren Hospital, affiliated hospital of Wuhan University of Science and Technology. Their demographic characteristics were analyzed. The dynamic changes of CRP and L in peripheral blood were retrospectively studied.Results: (1) There were significant statistical differences in CRP, L in clinical typing and clinical outcome in patients over 60 years old compared with those under 60 years old. Survival analysis showed that the risk of death was greater in patients over 60 than in those under 60.（2）In 125 patients over 60 years old, the hospitalized patients with severe or critical types of disease had significantly higher CRP than those with moderate type (p<0.01). In the outcome of the elderly patients, the CRP of the patients with the outcomes of discharge, improvement, aggravation and death increased successively (p<0.01). According to the analysis of Logistic regression model, the increase of CRP constitutes a risk factor for death in elderly patients. (3) In the ROC curve analysis to distinguish the death outcome and non-death outcome of COVID-19 patients, the area under the curve (AUC) of CRP and L was 0.751 and 0.720 respectively. CRP and L had good diagnostic accuracy for the death outcome of patients. (4) Changes in CRP were correlated with changes in CT imaging and were consistent with changes in the course of the disease.Conclusions: (1) The data collected in this research showed that the cumulative survival rate of patients over 60 years old was lower than that of patients under 60 years old. With the increase of age, the CRP of patients showed an increasing trend, and the L of patients showed a characteristic lower than the normal reference interval. (2) CRP and L are important monitoring indicators of COVID-19 in elderly patients. Combined with CT examination and observation of their dynamic changes, CRP and L are of important clinical guiding value for the judgment of disease severity and the evaluation of prognosis.

scholarly journals Potential Factors for Prediction of Disease Severity of COVID-19 Patients

2020 ◽  
Author(s):  
Huizheng Zhang ◽  
Xiaoying Wang ◽  
Zongqiang Fu ◽  
Ming Luo ◽  
Zhen Zhang ◽  
...  
Keyword(s):  
Disease Severity ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Medical Center ◽  
Demographic Data ◽  
Contributing Factors ◽  
Global Epidemic ◽  
Potential Factors ◽  
Critical Patients ◽  
Blood Specimens

AbstractObjectiveCoronavirus disease 2019 (COVID-19) is an escalating global epidemic caused by SARS-CoV-2, with a high mortality in critical patients. Effective indicators for predicting disease severity in SARS-CoV-2 infected patients are urgently needed.MethodsIn this study, 43 COVID-19 patients admitted in Chongqing Public Health Medical Center were involved. Demographic data, clinical features, and laboratory examinations were obtained through electronic medical records. Peripheral blood specimens were collected from COVID-19 patients and examined for lymphocyte subsets and cytokine profiles by flow cytometry. Potential contributing factors for prediction of disease severity were further analyzed.ResultsA total of 43 COVID-19 patients were included in this study, including 29 mild patients and 14 sever patients. Severe patients were significantly older (61.9±9.4 vs 44.4±15.9) and had higher incidence in co-infection with bacteria compared to mild group (85.7%vs27.6%). Significantly more severe patients had the clinical symptoms of anhelation (78.6%) and asthma (71.4%). For laboratory examination, 57.1% severe cases showed significant reduction in lymphocyte count. The levels of Interluekin-6 (IL6), IL10, erythrocyte sedimentation rate (ESR) and D-Dimer (D-D) were significantly higher in severe patients than mild patients, while the level of albumin (ALB) was remarkably lower in severe patients. Further analysis demonstrated that ESR, D-D, age, ALB and IL6 were the major contributing factors for distinguishing severe patients from mild patients. Moreover, ESR was identified as the most powerful factor to predict disease progression of COVID-19 patients.ConclusionAge and the levels of ESR, D-D, ALB and IL6 are closely related to the disease severity of COVID-19 patients. ESR can be used as a valuable indicator for distinguishing severe COVID-19 patients in early stage, so as to increase the survival of severe patients.

scholarly journals Dynamic Changes in Circulating Plasma B-type Natriuretic peptide levels and its Influencing Factors in Patients with Hemorrhagic Fever with Renal Syndrome

2020 ◽  
Author(s):  
Ning Ma ◽  
Yongguo Li ◽  
Yanxin Huang ◽  
Mingyan Xu ◽  
Yue Zhao ◽  
...  
Keyword(s):  
Disease Severity ◽  
Natriuretic Peptide ◽  
Blood Volume ◽  
Cardiac Injury ◽  
Hemorrhagic Fever ◽  
Disease Stage ◽  
Pathological State ◽  
Dynamic Changes ◽  
Factors Affecting ◽  
Multiple Organs

Abstract Background: Typically, Hemorrhagic fever with renal syndrome (HFRS) occurs in five sequential stages: Febrile, hypotensive, oliguric, polyuria, and convalescent stage. The pathophysiological process involves the release of inflammatory mediators, the fluctuation of blood volume and the injury of the Multiple organs, and all the factors mentioned above may cause the elevation of the level of plasma B-type natriuretic peptide (BNP). In addition, the physiological effects of BNP in regulating blood volume and promoting angiogenesis may in theory alleviate the pathological state of HFRS. So, this study is to explore the clinical application of BNP in HFRS by dynamically monitoring the BNP levels and analyzing the factors associated with BNP expression.Methods: Eighty-six in-patients with HFRS were divided into the mild, moderate and severe groups according to disease severity. Mixed-effects linear model was used to analyze the differences in BNP expression according to disease severity and disease stage. The factors affecting BNP expression were analyzed using a linear regression model for each disease stage.Results: BNP showed dynamic changes that corresponded with disease progression. The more severe the disease, the overall BNP level was higher. Disease severity, neutrophil count and pulse pressure were independent factors for BNP, while cardiac injury related indicators were not.Conclusions: In HFRS the main factors promoting BNP expression were inflammation and blood volume, rather than heart disease. BNP can be regarded as an index for judging the severity of the disease and guiding body fluid treatment.

scholarly journals Proteomic blood profiling in mild, severe and critical COVID-19 patients

2020 ◽  
Author(s):  
Hamel Patel ◽  
Nicholas J Ashton ◽  
Richard J.B Dobson ◽  
Lars-Magnus Andersson ◽  
Aylin Yilmaz ◽  
...  
Keyword(s):  
Disease Severity ◽  
Distress Syndrome ◽  
Differential Expression Analysis ◽  
Severe Pneumonia ◽  
Protein Profiling ◽  
Data Exploration ◽  
Blood Protein ◽  
Blood Proteins ◽  
Dynamic Changes ◽  
Web Based

AbstractThe recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in the majority of individuals leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. The purpose of this study is to explore the proteomic differences between mild, severe and critical COVID-19 positive patients. Blood protein profiling was performed on 59 COVID-19 mild (n=26), severe (n=9) or critical (n=24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/. Our results demonstrate that dynamic changes in blood proteins that associate with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.

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