Clinical Disease Activity Score Research Articles

Intensive therapy alleviates subclinical synovitis on ultrasound and disease activity and reduces flare in rheumatoid arthritis patients who have achieved clinical target – a randomized controlled trial

ObjectiveWhether intensive therapy can alleviate subclinical synovitis and reduce flare in rheumatoid arthritis (RA) patients in clinical remission remains unclear. We designed a 1-year open-labelled, randomized controlled clinical trial to elucidate this question. MethodsRA patients in clinical remission/low disease activity (defined by DAS28-CRP≤ 3.2), however with subclinical synovitis on ultrasound [power Doppler (PD)≥1 and/or gray scale (GS)≥2] were randomized to receive maintenance or intensive treatment at a ratio of 1:1. The primary outcome was the rate of RA relapse (defined by DAS28-CRP>3.2 and an increase≥0.6). The secondary outcomes were changes of PD and GS scores, and clinical disease activity at each visit from baseline. Results108 patients with 54 in each group were enrolled. During 1-year follow-up, the relapse rate was significantly higher in maintenance group than in intensive group, regardless of all enrolled patients or those in remission [24.1% (13/54) vs. 9.1% (5/54), p=0.039; 26.2% (11/42) vs. 5.3% (2/38), p=0.026, respectively]. Although GS and PD scores were decreased at 12 months in both groups, the decline was more remarkable in intensive group than in maintenance group. The improvement of clinical disease activity score was only observed in intensive group, not maintenance group. Adverse events were comparable between two groups. Abnormal liver function tests were observed in 24 (22%) patients with 16 from intensive group. ConclusionIntensive therapy can alleviate subclinical synovitis on ultrasound and clinical disease activity, and prevent relapse in RA patients who have achieved clinical remission or low disease activity, with comparable safety profiles to maintenance therapy. Registration numberChiCTR2000029279

PADI4 (rs2240340), PDCD1 (rs10204525), and CTLA4 (231775) gene polymorphisms and polyarticular juvenile idiopathic arthritis

ABSTRACT Background Certain single nucleotide polymorphisms (SNPs) in genes such as PADI4 (coding for peptidyl arginine deiminase 4), PDCD1 (coding for programmed cell death 1), and CTLA4 (coding for cytotoxic T-lymphocyte-associated protein 4) are linked to rheumatoid arthritis (RA). However, links between SNPs rs2240340, rs10204525 and rs231775 in PADI4, PDCD1 and CTLA4 respectively, and juvenile idiopathic arthritis (JIA), the commonest type of childhood arthritis, are unclear. We aimed to determine whether any of these SNPs are associated with JIA, and to clinical indices disease activity score (JADAS 71) and functional disability score (CHAQ). Methods We genotyped the three SNPs in 150 children with polyarticular JIA and 160 healthy children, recording standard health questionnaires, clinical features and laboratory markers. Results The TT genotype of PADI4 rs2240340 (aOR/95%CI 2.64: 1.31–5.30, P = 0.006) and CT genotype of PDCD1 rs10204525 (aOR/95%CI 4.99: 2.98–8.36, P < 0.0001) were associated with JIA. The AG+GG genotype of CTLA4 rs231175 was modestly linked to disease activity (aOR/95%CI 2.44 (1.19–5.04), p = 0.015). PADI4 rs2240340 was linked to CHAQ score (genotypes p = 0.013, alleles p = 0.006), whilst PDCD1 rs10204525 was linked to anti-CCP antibodies (genotypes p = 0.004), RF (genotypes p = 0.01), and the CHAQ score (genotypes p = 0.005, alleles p = 0.013). Conclusions There are various roles for these SNPs in PADI4, CTLA4 and PDCD1 in the diagnosis and, potentially, in the management of JIA.

Vitamin D Therapy in Adults With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Vitamin D deficiency has been implicated in the pathogenesis of inflammatory bowel disease. Emerging literature suggests that optimization of vitamin D levels may be associated with improvements in disease activity and quality of life. We conducted a meta-analysis exploring the effect of vitamin D on serum 25-hydroxyvitamin D (s-25[OH]D) levels, clinical improvement, and biomarkers. MEDLINE, EMBASE, the Cochrane Library, and sources for grey literature were searched from inception until September 2019. The primary outcome was s-25(OH)D mean differences. Heterogeneity was assessed using the χ 2 test and the I2 statistic. Review Manager software v. 5.3 was used. Twelve randomized controlled trials (n = 611) and 4 observational studies (n = 359) were included in the meta-analysis. On average, in the randomized controlled trials, vitamin D supplementation increased s-25(OH)D levels by 15.50 ng/mL (95% confidence interval [CI], 11.08-19.92, P ≤ 0.00001, I2 = 90%) and in observational studies they increased by 18.39 ng/mL (95% CI, 8.91-27.88, P = 0.0001, I2 = 82%). Subgroup analyses between vitamin D and placebo groups revealed that vitamin D increased s-25(OH)D by 14.85 ng/mL (95% CI, 9.96-19.73, P ≤ 0.00001, I2 = 90%) and when high doses of vitamin D were compared with low doses, high doses increased s-25(OH)D by 18.27 ng/mL (95% CI, 5.44-31.10, P = 0.005, I2 = 90%). The Harvey Bradshaw Index improved by -1.47 points (95% CI, -2.47 to -0.47, P = 0.004, I2 = 0%) and the high-sensitivity C-reactive protein decreased by -1.58 mg/L (95% CI, -2.95 to -0.21, P = 0.02, I2 = 0%). Vitamin D supplementation in patients with IBD and vitamin D deficiency is effective at correcting vitamin D levels and is associated with improvement in clinical and biochemical disease activity scores.

Therapeutic drug monitoring of adalimumab in RA: no predictive value of adalimumab serum levels and anti-adalimumab antibodies for prediction of response to the next bDMARD

BackgroundAfter adalimumab treatment failure, tumour necrosis factor inhibition (TNFi) and non-TNFi biological disease-modifying anti-rheumatic drugs (bDMARDs) are equally viable options on a group level as subsequent treatment in rheumatoid arthritis...

Functional Molecular Network Analysis Enables Prediction of Response to Vedolizumab Therapy in Anti-TNF Refractory IBD Patients.

BackgroundWe applied for the first time 2 label-free technologies, physiological intermolecular modulation spectroscopy (PIMS) and nematic protein organization technic (NPOT) in anti-tumor necrosis factor (TNF) refractory inflammatory bowel disease (IBD) patients to identify clinical responders to vedolizumab therapy and elucidate their underlying functional molecular network.MethodsPIMS analysis was performed in peripheral blood taken prior to the first vedolizumab application in 20 IBD patients (Crohn disease n = 13; ulcerative colitis n = 7) refractory to at least 1 previous anti-TNF agent therapy. Peripheral blood taken from clinical responders and nonresponders at week 14 of vedolizumab therapy were additionally subjected to NPOT analysis. Response to therapy was assessed by respective clinical disease activity scores (partial Mayo Score and Harvey–Bradshaw Index).ResultsClinical response to vedolizumab treatment was observed in 7 of 13 Crohn disease and 4 of 7 ulcerative colitis patients at week 14. Response to therapy was accurately predicted by PIMS blood analysis in 100% of ulcerative colitis and 77% of Crohn disease patients. Overall prediction of clinical response with PIMS blood analysis was achieved with a 89% positive predictive value and a 82% negative predictive value. NPOT analysis revealed the heightened expression of the proteins ITGB7, ITGAV, ITG3, PF4, and ASGH in the peripheral blood of vedolizumab responders compared to nonresponders.ConclusionsPIMS analysis of the blood of anti-TNF refractory IBD patients was able to stratify responders to vedolizumab therapy with high accuracy and specificity. NPOT technology could decipher underling molecular networks in the blood of responders, enabling subsequent personalized therapeutic approaches in IBD.

Sanhuang Shu'ai decoction alleviates DSS-induced ulcerative colitis via regulation of gut microbiota, inflammatory mediators and cytokines

BackgroundSanhuangshu’ai decoction (SH), a traditional Chinese medicine (TCM) prescription, has been safely used to treat diarrhea, dysentery and other inflammatory diseases with little side effect and low cost for thousands of years. However, its mechanism remains elusive. This study was designed to investigate the anti-ulcerative colitis (UC) activity of SH and mechanism by detecting its anti-inflammatory, anti-oxidative, and intervention effects of intestinal flora with the dextran sodium sulfate (DSS)-induced colitis mice. MethodsThe DSS-induced colitis mice was orally administered SH for 1 week with 0.8 or 1.6 g kg−1 d-1 dosage. A clinical disease activity score was evaluated daily. The colonic tissues of the mice were collected and prepared to detect its anti-inflammatory, anti-oxidative, intervention effects of intestinal flora and hydrogen peroxide(H2O2) in vivo, cytotoxicity and ROS influencing effects in vitro. Histological colitis severity and expression of cytokines were also determined. ResultsOral administration of SH significantly prevented the development of colitis. It reduced the expression of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α in the colon. Moreover, SH administration alleviated the oxidative stress in the colon of DSS-induced colitis mice, evidenced by the decrease of myeloperoxidase (MPO) activity and malondialdehyde (MDA) level, and increase of ROS level. Furthermore, SH can prevent the decrease ofLactobacillus sp. and population abundance of intestinal flora caused by DSS. ConclusionSH significantly ameliorates the symptoms of DSS-induced colitis mice and the potential mechanism of SH may involve in multiple kinds of metabolic pathway including the regulation of gut microbiota, inflammatory mediators and cytokines.

A new Canadian inception cohort for juvenile idiopathic arthritis: The Canadian Alliance of Pediatric Rheumatology Investigators Registry

The aim was to describe the design, methods and initial findings of a new Canadian inception cohort of children with JIA, The Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) JIA Registry. The CAPRI JIA Registry was started in 2017 to collect information prospectively on children enrolled within 3 months of JIA diagnosis across Canada. The registry has a non-traditional modular design, with no artificially set times for registry visits to occur, streamlined multi-method data collection that requires 2-4 min per visit, and reports cumulative incidence of treatments, outcomes and adverse events calculated by Kaplan-Meier survival methods. A total of 166 patients, enrolled a median of 6 weeks after JIA diagnosis at 10 centres, were included. The median age at diagnosis was 9 years [interquartile range (IQR) 3, 13], 61% were female and 51% had oligoarticular JIA. The median three-variable clinical Juvenile Arthritis Disease Activity Score was 6.5 (IQR 4, 10) at enrolment, and the median time to first attainment of clinically inactive disease (CID) was 24 weeks (by 1 year, 81%). Within 1 year of diagnosis, 70% of patients had started a DMARD and 35% a biologic agent. The rates of adverse events and serious adverse events were 60 and 5.8 per 100 patient-years, respectively. This streamlined and flexible registry minimizes the burden of data collection and interference with clinic operations. Initial findings suggest that treatments for newly diagnosed patients with JIA in Canada have intensified, and now 81% of patients attain CID within 1 year of diagnosis.

P700 Effect of vitamin D in disease activity score and clinical relapse in patients with inflammatory bowel disease: A systematic review and meta-analysis

Abstract Background Vitamin D deficiency has been reported as highly prevalent among patients with inflammatory bowel disease (IBD) and current studies have demonstrated an association between low vitamin D status and an increased risk of clinically active disease, mucosal inflammation and clinical relapse. The aim of our study was to conduct a systematic review and meta-analysis exploring the effect of vitamin D supplementation in clinical and biochemical disease activity scores and relapse rate in patients with IBD. Methods We performed a search of major electronic databases (MEDLINE, EMBASE, Cochrane Library) and sources for grey literature (GreyNet international, Google Scholar, Web of Science) from inception to October 2019. Our search strategy was limited to the English and Spanish language. The results were supplemented by a manual search of the bibliographies of the shortlisted review and original study articles. Inclusion criteria: Adults (over 18 years old) with IBD (ulcerative colitis or Crohn’s disease); interventional (RCTs or non-RCTs) or observational studies; studies assessed the effect of vitamin D supplementation on disease activity scores and relapse rate. Exclusion criteria: Reviews, case reports, editorial, comment, letters; duplicates studies; insufficient data or unable to calculate outcome measures with available data. Mean difference was considered as the effect measure with 95% confidence interval (95% CI) and two sided P values. For relapse rate outcome, unadjusted OR were calculated using dichotomous data (events vs. total). Heterogeneity was assessed using χ2 test and I2 statistic. Review Manager software v.5.3 was used. Results A meta-analysis of five studies (n = 253) showed a lower relapse rate in vitamin D supplementation group compared with control group (OR: 0.33, 95% CI 0.18–0.61, p = 0.0004, I2: 0%) (Figure 1). Harvey Bradshaw Index improved by 1.52 points (95% CI: 0.14–2.90, p = 0.03, I2 51%) in vitamin D group compared with the score at baseline and C-reactive protein levels decreased compared with the levels at baseline (mean difference: 3.70 mg/l, 95% CI 0.10–7.29, p = 0.04, I2 0%) (Figures 2 and 3). Even though other studies reported different clinical remission tools such as SCCAI or CDAI, it was not possible to pool the results due to insufficient data to conduct a meta-analysis. Conclusion Our systematic review and meta-analysis provides evidence that vitamin D supplementation can improve clinical outcomes and reduce relapse rate in patients with IBD.

Pingkui Enema Alleviates TNBS-Induced Ulcerative Colitis by Regulation of Inflammatory Factors, Gut Bifidobacterium, and Intestinal Mucosal Barrier in Rats.

Background Ulcerative colitis (UC) is a chronic recurrent inflammation of the colon, and clinical outcome of UC is still unsatisfied. Pingkui enema, a traditional Chinese medicine prescription, has been safely applied for the treatment of diarrhea and dysentery in clinic for many years. However, its mechanism is still elusive. The present study is designed to investigate the effect of Pingkui enema on trinitrobenzene sulfonic acid- (TNBS-) induced ulcerative colitis (UC) and possible mechanism in rats. Methods UC was induced by intracolonic instillation of TNBS in male Sprague-Dawley rats, which were treated with different dosages of Pingkui enema (low, medium, and high) or sulfasalazine for ten days. Survival rate was calculated. A clinical disease activity score was evaluated. Histological colitis severity was analyzed by hematoxylin-eosin (HE) staining. Content of Bifidobacterium in intestinal tissue was analyzed by RT-PCR. Concentration of IL-8, IL-13, TNF-α, D-lactic acid (D-LA), and diamine oxidase (DAO) in serum and contents of adhesin and receptor of Bifidobacterium adhesion in rat intestinal mucus were measured by ELISA. Results The results showed that Pingkui enema treatment with high dosage markedly improved the survival rate compared with untreated and sulfasalazine treated groups. All dosages of Pingkui enema reduced pathological score. High dosage of Pingkui enema and sulfasalazine treatments significantly reduced the serum concentration of IL-8, TNF-α, D-LA, and DAO and markedly increased the serum concentration of IL-13. In addition, high-dose Pingkui enema and sulfasalazine treatments increased gut content of Bifidobacterium, gut mucus expressions of adhesin, and adhesin receptor of Bifidobacterium. Conclusions Pingkui enema has therapeutic effect on TNBS-induced UC, and possible mechanism may be via regulation of gut probiotics (Bifidobacterium) and inflammatory factors and protection of intestinal mucosal barrier.

Adaptation and validation of an Arabic version of a 10-item patient-reported outcome measure of physical function in rheumatoid arthritis.

To adapt and validate an Arabic version of the short form of physical function measure (PF-10a), a generic questionnaire for physical function, in Egyptian patients with rheumatoid arthritis (RA). After standardized linguistic validation of the Arabic version of PF-10a, with forward and backward translation, the questionnaire was completed by 70 Egyptian RA patients who were diagnosed according to American College of Rheumatology/European League Against Rheumatism 2010 classification criteria, on two occasions 3-5days apart. The internal consistency and test-retest reliability were evaluated using Cronbach's alpha and intra-class correlation. The content validity of the Arabic PF-10a was tested against Health Assessment Questionnaire Disability Index (HAQ-DI), Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR). In addition, serology results, hand radiographs, and treatments received were all recorded. Most of our patients were female (88.6%) with a mean age of 49.2±10.5years. They had a mean disease duration of 7.3±7years and an active disease with a mean CDAI of 33.1±12.6. The mean value of PF-10a was 34.6±6.2. The Cronbach's alpha for Arabic PF-10a was 0.904. Intra-CLASS CORRELATION was 0.897. Arabic PF-10a correlated strongly with HAQ-DI (-0.746), moderately with CDAI, patient global assessment, and pain (-0.457, -0.417, and -0.371 respectively). The validation study showed that the Arabic PF-10a had acceptable psychometric characteristics, in terms of internal consistency and construct validity. The Arabic PF-10a is a reliable and valid instrument to be used by Arabic RA patients.

Can quantitative MRI be used in the clinical setting to quantify the impact of intra-articular glucocorticoid injection on synovial disease activity in juvenile idiopathic arthritis?

BackgroundJuvenile idiopathic arthritis (JIA), the most common chronic rheumatic disease of childhood, is characterised by synovitis. Clinical assessments of synovitis are imperfect, relying on composite and indirect measures of disease activity including clinician-reported measures, patient-reported measures and blood markers. Contrast-enhanced MRI is a more sensitive synovitis assessment technique but clinical utility is currently limited by availability and inter-observer variation. Improved quantitative MRI techniques may enable future development of more stringent MRI-defined remission criteria.The objective of this study was to determine the utility and feasibility of quantitative MRI measurement of synovial volume and vascularity in JIA before and twelve weeks after intra-articular glucocorticoid injection (IAGI) of the knee and to assess the acceptability of MRI to participating families.MethodsChildren and young people with JIA and a new episode of knee synovitis requiring IAGI were recruited from the Great North Children’s Hospital in Newcastle upon Tyne. Quantitative contrast-enhanced MRI was performed prior to and twelve weeks after IAGI, in addition to standard clinical assessment tools, including the three-variable clinical juvenile arthritis disease activity score (cJADAS) and active joint count.ResultsEleven young people (5 male, median age 13 years, range 7–16) with JIA knee flare were recruited and 10 completed follow-up assessment. Following IAGI, the median (interquartile range) cJADAS improved from 8.5 (2.7) to 1.6 (3.9), whilst the median synovial volume improved from 38.5cm3 (82.1cm3) to 0.0cm3 (0.2cm3). Six patients presented with frank synovitis outside normal limits on routine MRI reporting. A further three had baseline MRI reports within normal limits but the quantitative measurements identified measurable synovial uptake. Post-IAGI quantitative measurements highlighted significant improvements in 9 patients.ConclusionsIAGI led to a marked reduction in synovial volume, with quantitative MRI identifying more patients with an improved synovial volume than routine qualitative clinical reporting. Improvements in cJADAS scores were more variable with the patient/parent global assessment component contributing most to the scores. Further work is indicated, exploring the utility of quantitative MRI in the assessment of less accessible joints and comparing the impact of different treatment modalities.

High serum cholesterol: a novel risk factor for thyroid associated ophthalmopathy?

This study was aimed to investigate the association between dyslipidemia and thyroid associated ophthalmopathy (TAO). We evaluated the relationship between dyslipidemia and TAO in 218 patients with Graves' disease (GD) and found that the serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in the GD subjects with TAO (n=110) were significantly increased [(5.32±1.39) mmol/L vs. (3.18±2.12) mmol/L, (2.98±0.75) mmol/L vs. (1.25±0.98) mmol/L] than those in the GD subjects without TAO (n=108). TC and LDL-C were positively correlated with the Clinical disease activity score (CAS) [TC (r=0.7, P=0.03),LDL-C (r=0.82, P=0.03)], and the levels of TC (OR=2.56, P=0.02) and LDL-C(OR=2.01, P=0.015) were positively associated with TAO. These suggested that high serum cholesterol level is a novel risk factor for TAO, and management of blood lipids should be included in the treatment of TAO.

Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis

BackgroundThe objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA).MethodsThis was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were assessed with the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and RAMRIQ (automated quantitative RA MRI assessment system; automated RAMRIS) at months 0, 1, 3, 6 and 12. Radiographs were assessed at months 0, 6 and 12, and clinical endpoints were assessed at all timepoints. Univariate and multivariate analyses explored the predictive value of early changes in RAMRIS/RAMRIQ parameters and disease activity measures, with respect to subsequent radiographic progression.ResultsData from 109 patients with a mean RA duration of 0.7 years were included. In univariate analyses, changes in RAMRIS erosions at months 1 and 3 significantly predicted radiographic progression at month 12 (both p < 0.01); changes in RAMRIQ synovitis and osteitis at months 1 and 3 were significant predictors of RAMRIS erosions and radiographic progression at month 12 (all p < 0.01). In subsequent multivariate analyses, RAMRIS erosion change at month 1 (p < 0.05) and RAMRIQ osteitis changes at months 1 and 3 (both p < 0.01) were significant independent predictors of radiographic progression at month 12. Univariate analyses demonstrated that changes in Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) at months 1 and 3 were not predictive of month 12 radiographic progression.ConclusionsMRI changes seen as early as 1 month after RA treatment initiation have the potential to better predict long-term radiographic progression than changes in disease activity measures.Trial registrationClinicalTrials.gov, NCT01164579.

Discordances between clinical and ultrasound measurements of disease activity among RA patients followed in real life.

Measurements of disease activity, such as the clinical disease activity score (DAS28) or ultrasound (US) scores, often yield discordant results. This study's objectives were to determine the proportion of disagreements between the two assessment methods in patients with rheumatoid arthritis (RA) and to describe factors associated with discrepancy in assessment. All RA patients in the Swiss registry for inflammatory arthritides (SCQM) with at least one concomitant DAS28 and US score, were included. Disease activity was categorized as remission, low-to-moderate, and high, based on previously established cut-offs, for both the DAS28 and the US score. A longitudinal analysis was performed among patients who underwent at least two assessments. Of 2369 assessments included (1091 patients), 1196 (50.4%) were discordant. The US score both over- and under-estimated disease activity compared to the DAS28 score (23.5% and 26.8% respectively). Clinical and demographic factors significantly associated with discordant results were the individual components of the DAS28 score when US was used as the reference and age, disease duration, and the swollen joint count when the DAS28 was used as the reference. The main US-related factor associated with discordance was the presence of US tenosynovitis. In the longitudinal analysis of 1081 patients, the proportion of disagreements remained essentially unchanged. Rates of disagreement between clinical and US assessments of disease activity among RA patients are high and remain high during follow-up, even when the US assessors were aware of the clinical examination findings. Both clinical- and ultrasound- related factors were associated with discordances.

Metabolic Functions of Gut Microbes Associate With Efficacy of Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases

Altered interactions between the mucosal immune system and intestinal microbiota contribute to pathogenesis of inflammatory bowel diseases (IBD). It is not clear how inhibitors of cytokines, such as antagonists of tumor necrosis factor (anti-TNF), affect the intestinal microbiome. We investigated the effects of anti-TNF agents on gut microbe community structure and function in a longitudinal 2-step study of patients with IBD. We correlated our findings with outcomes of treatment and investigated patterns of metabolites in fecal samples before and after anti-TNF therapy. We performed a prospective study of 2 cohorts of patients in Germany; the discovery cohort comprised 12 patients with IBD, 17 patients with rheumatic disease, and 19 healthy individuals (controls); fecal samples were collected at baseline and 2, 6, and 30 weeks after induction of anti-TNF therapy. The validation cohort comprised 23 patients with IBD treated with anti-TNF or vedolizumab (anti-α4β7 integrin) and 99 healthy controls; fecal samples were collected at baseline and at weeks 2, 6, and 14. Fecal microbiota were analyzed by V3-V4 16S ribosomal RNA gene amplicon sequencing. Clinical response and remission were determined by clinical disease activity scores. Metabolic network reconstruction and associated fecal metabolite level inference was performed in silico using the AGORA (Assembly of Gut Organisms through Reconstruction and Analysis) resource. Metabolomic analyses of fecal samples from a subset of patients were performed to validate metabolites associated with treatment outcomes. Anti-TNF therapy shifted the diversity of fecal microbiota in patients with IBD, but not with rheumatic disease, toward that of controls. Across timepoints, diversity indices did not vary significantly between patients with IBD who did or did not achieve clinical remission after therapy. In contrast, in silico modeling of metabolic interactions between gut microbes found metabolite exchange to be significantly reduced at baseline in fecal samples from patients with IBD and to be associated with later clinical remission. Predicted levels of butyrate and substrates involved in butyrate synthesis (ethanol or acetaldehyde) were significantly associated with clinical remission following anti-TNF therapy, verified by fecal metabolomic analyses. Metabolic network reconstruction and assessment of metabolic profiles of fecal samples might be used to identify patients with IBD likely to achieve clinical remission following anti-TNF therapy and increase our understanding of the heterogeneity of IBD.

Outcome Monitoring and Clinical Decision Support in Polyarticular Juvenile Idiopathic Arthritis.

Inconsistent assessment and treatment may impair juvenile idiopathic arthritis (JIA) outcomes. We aimed to improve polyarticular JIA (rheumatoid factor-positive and -negative) outcomes by standardizing point-of-care disease activity monitoring and implementing clinical decision support (CDS) to reduce treatment variation. We performed a quality improvement initiative in an outpatient pediatric rheumatology practice. The interventions, implemented from April to November 2016, included standardized disease activity measurement, disease activity target review, and phased introduction of polyarticular JIA CDS to guide medication selection, dosing, treatment duration, and tapering. Process measures included visit-level target attestation (goal: 50%) and CDS use (goal: 15%). Our goal was to reduce the polyarticular JIA clinical Juvenile Arthritis Disease Activity Score (cJADAS-10) by at least 10%. Included patients had at least 2 visits from April 2016 through July 2017, and were classified as having early (≤ 6 mos) or established disease (> 6 mos). Patients with polyarticular JIA (n = 97; 81% established disease) were observed for 10.3 months (interquartile range: 6.4-12.3). Target attestation and CDS use occurred in a mean of 77% and 45% of polyarticular JIA visits, respectively. The median cJADAS-10 decreased significantly in both early (16.5 to 2.7, p < 0.001) and established polyarticular JIA (2.1 to 1.0, p = 0.01). A high proportion of patients with early disease received biologic therapy (73.7%). In established disease, although prescription of nonbiologic and biologic disease-modifying antirheumatic drugs remained similar overall, adalimumab prescribing increased (12.8% to 23.1%, p = 0.008). Implementation of structured disease activity monitoring and CDS in polyarticular JIA was associated with significant reductions in disease activity scores in both early and established disease.

Exposure-response modeling of tocilizumab in rheumatoid arthritis using continuous composite measures and their individual components.

Tocilizumab has a direct effect on inflammatory markers. Therefore, composite measures for disease activity assessment in rheumatoid arthritis (RA) using these inflammatory markers may not be suitable for tocilizumab treatment. We used a modelling approach to describe the tocilizumab exposure-response relationship and to investigate the different dynamics of the individual components of the routinely used continuous composite measures. Pharmacokinetic (PK), clinical and laboratory data were obtained from a prospective, observational, single-centre study involving 35 subjects with RA treated with intravenous tocilizumab. A population PK/pharmacodynamic analysis was performed using nonlinear mixed effects models. The population for model development comprised 1086, 1083 and 1082 observations calculated with the disease activity score based on 28 joint (DAS28) and the simplified and clinical disease activity scores (SDAI, CDAI). The tocilizumab exposure-response relationship was described with an indirect-response model. Two main groups of individual components were identified based on their different dynamics under tocilizumab treatment: (i) tender and swollen joint counts and patient and evaluator global assessment showed a slower decrease of their baseline value (half-life: 4.6weeks, RSE: 24%) and the need for higher serum drug concentration (EC50 : 4.60μg/mL, RSE: 103%, IIV: 359%) than (ii) C-reactive protein and erythrocyte sedimentation rate (half-life: 2.3weeks, RSE 19%; EC50 : 0.878μg/mL, RSE: 41%, IIV: 238%). Our study confirms a different dynamics of the individual components of the most frequently used continuous composite measures under tocilizumab treatment which should be taken into account to avoid misassessment of disease activity.

Malar rash is a predictor of subclinical airway inflammation in patients with systemic lupus erythematosus: a pilot study.

Systemic lupus erythematosus (SLE) is a chronic, auto-immune, multi-organ disease that can affect both the skin and the lungs. Malar rash is a common skin manifestation of SLE and is linked to SLE disease activity, whereas lung involvement is a generally negative prognostic factor for these patients. However, a sensitive and non-invasive screening tool for potential lung involvement in SLE patients is still not available. This study aimed to investigate the relationship between malar rash and airway inflammation in adult SLE patients who were not known to have any lung involvement (clinical or radiologic). The study comprised of the measurement of the concentration of NO in exhaled breath or fraction of exhaled nitric oxide (FeNO) and levels were compared between those with and without malar rash. This tool is considered as a sensitive and non-invasive method that is routinely used in patients with asthma or other respiratory diseases to identify airway inflammation. A total of 125 patients (100 females, 25 males) were enrolled during the study period from January 2011 to December 2014. Patients with malar rash (N = 35) had a significant decrease in serum levels of C4 (p < 0.05) compared to patients without malar rash (N = 90). The mean levels of FeNO in overall patients were 36.44 ± 8.87ppb. A statistically significant difference in FeNO50 values between patients with malar rash (43.46 ± 6.72ppb) and without (29.43 ± 3.64ppb) was found (p < 0.001). FeNO50 values were inversely correlated only with serum C4 (p < 0.01). However, no correlation between FeNO50 values and SLE clinical disease activity scores was found. The presence of a malar rash may predict sub-clinical airway inflammation in SLE patients. Further prospective studies are needed to confirm the usefulness of FeNO measurements in monitoring SLE-associated airway inflammation.

ERAMRS: a new MR scoring system for early rheumatoid arthritis of the wrist.

To (i) devise a new semi-quantitative scoring system known as Early Rheumatoid Arthritis Magnetic Resonance Score (ERAMRS) to assess inflammation of the wrist on magnetic resonance imaging in early rheumatoid arthritis and to (ii) test ERAMRS and other MR scoring systems against everyday used clinical scorings. One hundred six treatment-naïve patients (81 females, 25 males, mean age 53 ± 12years) with early rheumatoid arthritis (ERA) underwent clinical/serological testing as well as 3-T MRI examination of the most symptomatic wrist. Clinical assessment included Disease Activity Score-28 and Health Assessment Questionnaire; erythrocyte sedimentation rate and C-reactive protein were measured. MR imaging data was scored in all patients using three devised MR semi-quantitative scoring systems, namely, the (a) ERAMRS system, (b) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) system, and the (c) McQueen Score system. Synovitis was present in 106 (100%), tenosynovitis in 98 (92%), and bone marrow edema in 84 (79%) of 106 ERA wrists. ERAMRS had the highest correlation with clinical disease activity scores (r = 0.476, p < 0.001) and serological parameters (r = 0.562, p < 0.001). RAMRIS system had the lowest correlation (r = 0.369, p < 0.001 for clinical disease activity; r = 0.436, p < 0.001 for serological parameters). RAMRIS synovitis subscore had a lower correlation than ERAMRS for clinical disease activity (r = 0.410, p < 0.001) and for serological parameters (r = 0.456, p < 0.001). The ERAMRS system, designed to grade inflammation on wrist MRI in ERA, provided the best correlation with all clinical scoring systems and serological parameters, indicating its improved clinical relevance over other MR scoring systems. • We devised a clinically relevant, easy-to-use semi-quantitative scoring system for scoring inflammation on MRI of the wrist in patients with early rheumatoid arthritis. • ERAMRS system showed better correlation with all clinical and serological assessment of inflammation in patients with early rheumatoid arthritis indicating its improved clinical relevance over other MR scoring systems.

Association of serum retinol and circulating inflammatory cells with disease activity in ulcerative colitis patients

Purpose The purpose of this study is to explore the association of serum retinol and number of circulating inflammatory cells and disease activity in patients with ulcerative colitis. Design/methodology/approach A total of 60 patients with ulcerative colitis were enrolled in a cross-sectional pilot study. Patients were recruited from specialized clinic of Tabriz University of Medical Sciences, Iran between April and August 2015. Mayo clinic index was used to assess clinical disease activity score. Blood samples were collected. Serum retinol was assessed using HPLC to determine vitamin A status. Complete blood count and lymphocyte phenotyping were performed by automated hematology analyzer and flow-cytometric analysis, respectively. Findings According to Mayo scoring, 68.33 per cent of patients had mild and 31.66 per cent had moderate or severe disease activity. About 43.33 per cent of patients were vitamin A deficient, with 23.33 per cent having moderate to severe deficiency (serum retinol &lt; 20 µg/dl). Lower levels of serum retinol and higher count and percentages of CD3+, CD8+ T cells and neutrophil to lymphocyte ratio were statistically associated with disease activity according to univariate analysis (p = 0.002, 0.037, &lt;0.001, 0.031, 0.002 and 0.039); however, in binary logistic regression, only lower levels of serum retinol were independently associated with disease activity with a OR of 0.564 (p = 0.021; 95 per cent CI 0.35-0.92). Originality/value Vitamin A deficiency was detected in this study population. Patients with moderate to severe disease activity demonstrated lower serum retinol, higher CD8+ T cells and neutrophil to lymphocyte ratio compared to patients with mild disease activity.