scholarly journals Biomarker profiles of endothelial activation and dysfunction in rare systemic autoimmune diseases: implications for cardiovascular risk

Rheumatology ◽  
2020 ◽  
Author(s):  
Judith Wienke ◽  
Jorre S Mertens ◽  
Samuel Garcia ◽  
Johan Lim ◽  
Camiel A Wijngaarde ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Endothelial Dysfunction ◽  
Disease Activity ◽  
Connective Tissue Diseases ◽  
Endothelial Activation ◽  
Inactive Disease ◽  
Localized Scleroderma ◽  
Eosinophilic Fasciitis ◽  
Targeted Interventions

Abstract Objectives Vasculopathy is an important hallmark of systemic chronic inflammatory connective tissue diseases (CICTD) and is associated with increased cardiovascular risk. We investigated disease-specific biomarker profiles associated with endothelial dysfunction, angiogenic homeostasis and (tissue) inflammation, and their relation to disease activity in rare CICTD. Methods A total of 38 serum proteins associated with endothelial (dys)function and inflammation were measured by multiplex-immunoassay in treatment-naive patients with localized scleroderma (LoS, 30), eosinophilic fasciitis (EF, 8) or (juvenile) dermatomyositis (34), 119 (follow-up) samples during treatment, and 65 controls. Data were analysed by unsupervised clustering, Spearman correlations, non-parametric t test and ANOVA. Results The systemic CICTD, EF and dermatomyositis, had distinct biomarker profiles, with ‘signature’ markers galectin-9 (dermatomyositis) and CCL4, CCL18, CXCL9, fetuin, fibronectin, galectin-1 and TSP-1 (EF). In LoS, CCL18, CXCL9 and CXCL10 were subtly increased. Furthermore, dermatomyositis and EF shared upregulation of markers related to interferon (CCL2, CXCL10), endothelial activation (VCAM-1), inhibition of angiogenesis (angiopoietin-2, sVEGFR-1) and inflammation/leucocyte chemo-attraction (CCL19, CXCL13, IL-18, YKL-40), as well as disturbance of the Angiopoietin-Tie receptor system and VEGF-VEGFR system. These profiles were related to disease activity, and largely normalized during treatment. However, a subgroup of CICTD patients showed continued elevation of CXCL10, CXCL13, galectin-9, IL-18, TNFR2, VCAM-1, and/or YKL-40 during clinically inactive disease, possibly indicating subclinical interferon-driven inflammation and/or endothelial dysfunction. Conclusion CICTD-specific biomarker profiles revealed an anti-angiogenic, interferon-driven environment during active disease, with incomplete normalization under treatment. This warrants further investigation into monitoring of vascular biomarkers during clinical follow-up, or targeted interventions to minimize cardiovascular risk in the long term.

Challenges of achieving clinical remission in a national cohort of juvenile-onset systemic lupus erythematosus patients

Lupus ◽  
2019 ◽  
Vol 28 (5) ◽  
pp. 667-674 ◽  
Author(s):  
N Abdelrahman ◽  
M W Beresford ◽  
V Leone ◽  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Remission ◽  
Immunosuppressive Treatment ◽  
Inactive Disease ◽  
Juvenile Onset ◽  
Time To Diagnosis ◽  
National Cohort ◽  
Onset Systemic Lupus Erythematosus

Background and objectives The multisystem involvement and variable course of juvenile-onset systemic lupus erythematosus (JSLE) make it difficult to assess disease activity over time. International consensus definitions of inactive disease and clinical remission have been proposed. The aim of this study was to determine the proportion of patients meeting these criteria in a large national cohort of JSLE patients and the association between achieving inactive disease and clinical remission with disease activity at presentation and time to diagnosis. Methods Patients diagnosed with JSLE aged ≤17 years with a minimum of 12 months follow-up participating in the UK JSLE Cohort Study were assessed against these criteria at baseline, 1 year and final clinic visit. Results A total of 218 patients with mean follow-up duration of 4.7 years were included and analyzed at baseline visit, of which 93 and 209 were available for analysis at the 1-year and the last follow-up visits, respectively. Eighty-five percent at 1 year and 62% at final follow-up still had active disease while only 6% and 9%, respectively, achieved inactive disease according to the proposed criteria. The majority of patients continued to require immunosuppressive treatment despite their prolonged follow-up with only two patients achieving clinical remission on medication and none off medication. A large number of patients did not meet the criteria for inactive disease due to isolated laboratory abnormalities such as reduced lymphocyte count. Isolated low lymphocyte count was the reason for not fulfilling the inactive disease criteria in 20/79 (25%) patients at 1 year and 14/130 (11%) patients at final follow-up visit. No statistically significant differences in relation to time to diagnosis and disease activity at presentation were found between patients achieving inactive disease compared to those who did not, at 1 year and final follow-up. Conclusion The majority of patients failed to achieve the proposed criteria for inactive disease and continued to require immunosuppressive treatment. This reflects the high burden of disease in JSLE despite immunosuppressive therapy. A significant proportion of patients had isolated laboratory abnormalities of potentially limited clinical significance, suggesting that some modifications of the proposed criteria may be required.

scholarly journals DOP20 Can lifestyle and psychosocial factors predict flares of IBD; an exploratory study using telemedicine

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S059-S060
Author(s):  
R C A Lalisang ◽  
G Adriaans ◽  
M de Jong ◽  
A van der Meulen-de Jong ◽  
M Romberg-Camps ◽  
...  
Keyword(s):  
Disease Activity ◽  
Exploratory Study ◽  
Clinical Symptoms ◽  
Lifestyle Factors ◽  
Information Criteria ◽  
Mucosal Inflammation ◽  
Study Cohort ◽  
Telemedicine System ◽  
Targeted Interventions

Abstract Background Tight control of mucosal inflammation and prevention of disease flares are emerging treatment goals to prevent disease progression in inflammatory bowel disease (IBD). The state of the art clinical classification only marginally predict flare occurrence. Mounting evidence shows that psychosocial and lifestyle factors are associated with flares. Longitudinal monitoring of these factors has been made possible by implementing a web-based telemedicine tool, called myIBDcoach. This study is an exploration on the potential additive predictive value of data captured in a telemedicine system to predict flares. Methods Consecutive IBD patients (n = 393) were recruited from the prospective myIBDcoach telemedicine study cohort (ClinicalTrials.gov, NCT02173002). During a one-year follow-up, every 1–3 months, participants reported information on all variables displayed in Figure 1 via myIBDcoach. Variables were subdivided into two main categories; Baseline and myIBDcoach. The myIBDcoach variables were once again subdivided (Figure 1). The outcome of interest, a flare during follow-up, was defined as having clinical symptoms of disease activity (using the Monitor IBD At Home questionnaire) combined with either a faecal calprotectin > 250g/g, disease activity on endoscopy, MRI or CT. Stepwise group-Lasso logistic regression (G-LASSO) was used to estimate associations between flares and individual variables, as well as between flares and the different variable categories (Figure 1). G-LASSO performs variable selection, resulting in models that contain only the most relevant explanatory variables. Results Seven G-LASSO regressions were estimated and evaluated using the Akaike information criteria (AIC), the area under the curve (AUC) and stepwise importance using 10-fold cross-validated penalty parameter. Figure 2 shows that the overall model performance increased when consecutively adding extra variable categories, the largest increase occurred for psychosocial and lifestyle factors. All telemedicine variable categories were found to be more important compared with the baseline variable category, as shown in Figure 3. Results shown in Figure 4 indicate that the information from myIBDcoach was found to be more important than the baseline variables. Conclusion In this exploratory study, psychosocial and lifestyle factors monitored via telemedicine are of superior value to predict flares in IBD patients compared with clinical stratification. Holistic monitoring, including psychosocial and lifestyle factors, and targeted interventions are of interest for future trials and are a promising strategy to prevent flares and improve the outcome of IBD.

Outcome assessment in the idiopathic inflammatory myopathies

2018 ◽  
Author(s):  
Lisa G. Rider ◽  
Frederick W. Miller
Keyword(s):  
Disease Activity ◽  
Endothelial Activation ◽  
Inactive Disease ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Muscle Enzyme ◽  
Activation Markers ◽  
Core Set ◽  
Trial Endpoints ◽  
Muscle Ultrasound

Due to their rarity, heterogeneity, and multispecialty nature, the myositis syndromes have limited data-driven consensus on appropriate outcome measures. Recently, two international, multispecialty consortia developed new tools and consensus on core set measures of myositis disease activity and damage, as well as response criteria that are now recommended for use as clinical trial endpoints but will also be useful in clinical practice. Magnetic resonance imaging, muscle ultrasound, selected laboratory tests, and immunological biomarkers—including cytokines, chemokines, lymphocyte flow cytometry, and endothelial activation markers—can all be helpful adjuncts to serum muscle enzyme levels in assessing disease activity and damage, but these have not yet been fully validated. Definitions of clinically inactive disease, complete clinical response, and remission have also been proposed but require further validation. These advances should enhance the development of therapies by standardizing our ability to demonstrate their efficacy in treating the idiopathic inflammatory myopathies.

scholarly journals P549 A virtual clinic enhances the quality use of anti-TNF dose intensification and rates of treatment success using a treat-to-target approach compared with standard outpatient care in Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S467-S467
Author(s):  
A Srinivasan ◽  
D R van Langenberg ◽  
R Little ◽  
M P Sparrow ◽  
P De Cruz ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Outpatient Care ◽  
Inactive Disease ◽  
Treat To Target ◽  
Model Of Care ◽  
Dose Intensification ◽  
Trough Levels

Abstract Background Virtual clinics (VC) represent a novel model-of-care which promote quality use of biologics and facilitate a treat-to-target (T2T) approach. We aimed to evaluate the clinical and process-driven outcomes of intensified anti-TNF therapy for secondary loss of response (SLoR) in a VC compared with standard outpatient care (SoC). Methods A retrospective multicenter, parallel observational cohort study of patients with Crohn’s disease (CD) who underwent anti-TNF dose intensification to address SLoR with up to 2-years of follow-up was undertaken. Objective assessments of disease activity and anti-TNF trough levels at SLoR then during subsequent 6-month semesters were compared longitudinally between VC and SoC groups. ‘Anti-TNF escalation success’ was the primary endpoint, defined as achieved when two consecutive 6-month semesters of objective assessment demonstrated inactive disease. Dose intensification was defined as ‘appropriate’ if there was both objective evidence of disease activity, plus anti-TNF trough levels at or below the lower limit of the therapeutic range prior to intensification. ‘Treatment escalation failure’ was defined by the occurrence of one or more of biologic switching, discontinuation or further intensification; recommencement of corticosteroids, or IBD-related surgery. Results 149 patients (69 VC vs. 80 SoC) underwent infliximab (n = 94) or adalimumab (n = 55) dose intensification with similar baseline patient, disease and treatment characteristics between cohorts. The median duration of follow-up post dose-intensification was 1.9 and 1.5 years for the SoC and VC cohorts respectively (p = 0.37). There were higher rates of appropriate dose intensification (82.6 vs. 40.0%, p < 0.01) across the VC cohort. Higher proportions of anti-TNF escalation success (60.9 v 35.0%, p < 0.01), biomarker remission (i.e., C-Reactive Protein (<5mg/l) and faecal calprotectin (<150 μg/ml) normalisation, log-rank tests, p = 0.06 and p < 0.01 respectively), tight disease monitoring (84.1 vs. 28.8%, p < 0.01) and de-escalation of intensified therapy (21.3 vs. 10.0%, p = 0.03) were also achieved by the VC cohort following dose-intensification. Conclusion This study favoured a VC-led model of care over standard outpatient-based IBD care in facilitating an effective T2T approach to CD management. A VC model of care improved quality use of intensified anti-TNF therapy through processes that promoted appropriate dose intensification and encouraged more frequent anti-TNF dose de-escalation. Moreover, tight semester-based monitoring using a T2T-based strategy facilitated by the VC was associated with improved treatment outcomes.

scholarly journals Weight loss is associated with sustained improvement of disease activity and cardiovascular risk factors in patients with psoriatic arthritis and obesity: a prospective intervention study with two years of follow-up

2020 ◽  
Author(s):  
Eva Klingberg ◽  
Sofia Björkman ◽  
Björn Eliasson ◽  
Ingrid Larsson ◽  
Annelie Bilberg
Keyword(s):  
Risk Factors ◽  
Weight Loss ◽  
Cardiovascular Risk ◽  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Cardiovascular Risk Factors ◽  
Weight Loss Treatment ◽  
The Metabolic Syndrome ◽  
Median Weight Loss

Abstract Background Obesity is overrepresented in patients with psoriatic arthritis (PsA) and associated with increased disease activity. We have previously shown in 41 patients with PsA (Caspar criteria) and obesity (body mass index; BMI ≥33 kg/m2) that weight loss treatment with Very Low Energy Liquid Diet (VLED), 640 kcal/day during 12-16 weeks, followed by a structured reintroduction of an energy restricted diet resulted in a median weight loss of 18.6% and concomitantly a significant improvement of the disease activity in joints, entheses and skin. The objectives of this follow-up were to study the effects of the weight loss treatment on disease activity in longer term (12 and 24 months) and to study the effects on cardiovascular risk factors. Methods The patients were assessed with 66/68 joints count, Leeds enthesitis index (LEI), body surface area, blood pressure, BMI, questionnaires and fasting blood samples at the 12- and 24-month visits.Results In total, 39 and 35 PsA patients attended the 12- and the 24-month visits, respectively. Median weight loss since baseline was 16.0 % (IQR 10.5–22.4) and 7.4% (IQR 5.1–14.0) at the 12- and 24-months follow-up. The 66/68 swollen/tender joints score, LEI, CRP and HAQ score were still significantly reduced at the 12- and 24-month visits compared to baseline. The number of patients with Minimal Disease Activity increased from 28.2% (11/39) at baseline, to 38.5% (15/39; p=0.008) and 45.7 % (16/35; p=0.016) at the 12- and 24-month visits.The weight loss was also associated with improved levels of serum lipids, glucose and urate and the antihypertensive treatment was reduced or stopped in five patients during the follow-up.Conclusions Weight loss treatment, with VLED included in the program, was associated with long-term improvement of measures of disease activity, self-reported function and markers of the metabolic syndrome after 24-months follow-up.Trial registration ClinicalTrials.gov identifier: NCT02917434, Registered September 28, 2016- Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT02917434

scholarly journals New Features for Measuring Disease Activity in Pediatric Localized Scleroderma

2018 ◽  
Vol 45 (12) ◽  
pp. 1680-1688 ◽  
Author(s):  
Suzanne C. Li ◽  
Xiaohu Li ◽  
Elena Pope ◽  
Katie Stewart ◽  
Gloria C. Higgins ◽  
...  
Keyword(s):  
Disease Activity ◽  
Age Of Onset ◽  
Skin Lesions ◽  
Inactive Disease ◽  
Localized Scleroderma ◽  
Relative Importance ◽  
Skin Texture ◽  
Disease Patterns ◽  
Disease Extension ◽  
Multicenter Prospective Study

Objective.To identify clinical features that define disease activity in pediatric localized scleroderma (LS), and determine their specificity and importance.Methods.We conducted a multicenter prospective study of patients with active and inactive LS skin lesions. A standardized evaluation of a single designated study lesion per subject was performed at 3 visits. We evaluated the pattern and correlation between assessed features and physician’s global assessments of activity (PGA-A).Results.Ninety of 103 subjects had evaluable data; 66 had active and 24 inactive disease. Subjects had similar age of onset, sex, and disease patterns. Linear scleroderma was the most common subtype. Features specific for active disease included erythema, violaceous color, tactile warmth, abnormal skin texture, and disease extension. Scores for these variables changed over time and correlated with PGA-A of the lesion. Active and inactive lesions could not be distinguished by the presence or level of skin thickening, either of lesion edge or center. However, in active lesions, skin thickening scores did correlate with PGA–A scores. Regression analysis identified the combination of erythema, disease extension, violaceous color, skin thickening, and abnormal texture as predictive of PGA-A at study entry. Damage features were common irrespective of activity status.Conclusion.We identified variables strongly associated with disease activity, expanding upon those used in current measures, and determined their relative importance in physician activity scoring. Skin thickening was found to lack specificity for disease activity. These results will help guide development of a sensitive, responsive activity tool to improve care of patients with LS.

scholarly journals Serum Calprotectin (S100A8/A9): A Promising Biomarker in Diagnosis and Follow-up in Different Subgroups of Juvenile Idiopathic Arthritis

2021 ◽  
Author(s):  
Céline La ◽  
Phu Quoc Lê ◽  
Alina Ferster ◽  
Laurence Goffin ◽  
Delphine Spruyt ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Added Value ◽  
Response To Treatment ◽  
Inactive Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Minimal Disease ◽  
Active Disease

Abstract IntroductionIn the management of juvenile idiopathic arthritis (JIA), there is a lack of diagnostic and prognostic biomarkers. This study assesses the use of serum calprotectin (sCal) as a marker to monitor disease activity, and as a classification and prognosis tool of response to treatment or risk of flares in patients with JIA. MethodsEighty-one patients with JIA from the CAP48 multicentric cohort were included in this study, as well as 11 non-pediatric healthy controls. An enzyme-linked immunosorbent assay (ELISA) method was used to quantify sCal with a commercial kit.ResultsPatients with an active disease compared to healthy controls and to patients with inactive disease showed an 8-fold and a 2-fold increased level of sCal respectively. sCal was found to be correlated with the CRP and even more strongly with the ESR. Evolution of DAS28 scores correlated well with evolution of sCal, as opposed to evolution of CRP. With regard to CRP, sCal could differentiate forms with active oligoarthritis from polyarthritis and systemic forms. However, sCal brought an added value compared to the CRP as a prognosis marker. Indeed, patients with active disease and reaching minimal disease activity (according to JADAS) at 6 months following the test had higher sCal levels, while patients with inactive disease had higher sCal levels if a flare was observed up to 3 to 9 months following the test.ConclusionsThis study confirms the potential uses of serum calprotectin as a biomarker in the diagnosis and follow-up of JIA.

scholarly journals Weight loss is associated with sustained improvement of disease activity and cardiovascular risk factors in patients with psoriatic arthritis and obesity: a prospective intervention study with two years of follow-up

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Eva Klingberg ◽  
Sofia Björkman ◽  
Björn Eliasson ◽  
Ingrid Larsson ◽  
Annelie Bilberg
Keyword(s):  
Risk Factors ◽  
Weight Loss ◽  
Cardiovascular Risk ◽  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Cardiovascular Risk Factors ◽  
Weight Loss Treatment ◽  
The Metabolic Syndrome ◽  
Median Weight Loss

Abstract Background Obesity is overrepresented in patients with psoriatic arthritis (PsA) and associated with increased disease activity. We have previously shown in 41 patients with PsA (Caspar criteria) and obesity (body mass index; BMI ≥33 kg/m2) that weight loss treatment with Very Low Energy Liquid Diet (VLED), 640 kcal/day during 12–16 weeks, followed by a structured reintroduction of an energy restricted diet resulted in a median weight loss of 18.6% and concomitantly a significant improvement of the disease activity in joints, entheses and skin. The objectives of this follow-up were to study the effects of the weight loss treatment on disease activity in longer term (12 and 24 months) and to study the effects on cardiovascular risk factors. Methods The patients were assessed with 66/68 joints count, Leeds enthesitis index (LEI), body surface area, blood pressure, BMI, questionnaires and fasting blood samples at the 12- and 24-month visits. Results In total, 39 and 35 PsA patients attended the 12- and the 24-month visits, respectively. Median weight loss since baseline was 16.0% (IQR 10.5–22.4) and 7.4% (IQR 5.1–14.0) at the 12- and 24-months follow-up. The 66/68 swollen/tender joints score, LEI, CRP and HAQ score were still significantly reduced at the 12- and 24-month visits compared to baseline. The number of patients with Minimal Disease Activity increased from 28.2% (11/39) at baseline, to 38.5% (15/39; p = 0.008) and 45.7% (16/35; p = 0.016) at the 12- and 24-month visits. The weight loss was also associated with improved levels of serum lipids, glucose and urate and the antihypertensive treatment was reduced or stopped in five patients during the follow-up. Conclusions Weight loss treatment, with VLED included in the program, was associated with long-term improvement of measures of disease activity, self-reported function and markers of the metabolic syndrome after 24-months follow-up. Trial registration ClinicalTrials.gov identifier: NCT02917434, Registered September 28, 2016- Retrospectively registered.

Disease activity trajectories in early axial spondyloarthritis: results from the DESIR cohort

2016 ◽  
Vol 76 (6) ◽  
pp. 1036-1041 ◽  
Author(s):  
Anna Molto ◽  
Sophie Tezenas du Montcel ◽  
Daniel Wendling ◽  
Maxime Dougados ◽  
Antoine Vanier ◽  
...  
Keyword(s):  
Disease Activity ◽  
Axial Spondyloarthritis ◽  
High Disease Activity ◽  
Inactive Disease ◽  
Joint Involvement ◽  
Asas Criteria ◽  
Very High ◽  
Trajectory Modelling ◽  
Over Time

BackgroundDisease activity may change over time in axial spondyloarthritis (axSpA). The objectives were to identify patterns of disease activity evolution in patients with early axSpA.MethodsPatients from the prospective early axSpA cohort (DEvenir des Spondyloarthrites Indifférenciées Récentes (DESIR)) who fulfilled the Assessment in SpondyloArthritis Society (ASAS) criteria for axSpA at baseline and with at least three Ankylosing Spondylitis Disease Activity Score (ASDAS) values available over the 3 years of follow-up were analysed. Statistical analyses: trajectories were estimated by group-based trajectory modelling; predisposing baseline factors for such trajectories were identified by univariate and multivariable multinomial (logit) regression; work disability over time was compared between the trajectories by Cox hazard model.ResultsIn all, 370 patients were analysed: mean disease duration was 1.6 (±0.9) years. The five distinct trajectories of disease activity over the 3 years were (t1) ‘persistent moderate disease activity’ (n=134 (36.2%)); (t2) ‘persistent inactive disease’ (n=66 (17.8%); (t3) ‘changing from very high disease activity to inactive disease’ ((n=29 (7.8%)); (t4) ‘persistent high disease activity’ (n=126 (34.1%)) and (t5) ‘persistent very high disease activity’ (n=15 (4.1%)). After adjustment for other characteristics, t2 was associated with a white-collar job (OR=2.6 (95% CI 1.0 to 6.7)) and t3 with male gender (OR=7.1 (1.6 to 32.2)), higher education level (OR=9.4 (1.4 to 63.4)) and peripheral joint involvement (OR=6.2 (1.23 to 31.32)). Patients from (t4) and (t5) were more often declared work disabled over follow-up (HR=5.2 (1.5 to 18.0) and HR=8.0 (1.3 to 47.9), respectively).ConclusionsTrajectory modelling of disease activity was feasible in early axSpA: more than 30% patients (141/370) were in a trajectory with a persistent high disease activity. Persistent high disease activity trajectories were significantly associated with consequences on work.Trial registration numberNCT01648907.

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