Composite Disease Activity Score Research Articles

South African Rheumatism and Arthritis Association 2024 updated guidelines for the management of rheumatoid arthritis.

The management of rheumatoid arthritis (RA) requires early diagnosis and prompt initiation of therapy, together with lifestyle interventions, particularly smoking cessation. These guidelines recommend a treat-to-target strategy using a composite disease activity score at each visit, with frequent follow-up and escalation or switching of disease-modifying antirheumatic drug (DMARD) therapy until the goal of low disease activity is achieved. A stepwise algorithm for DMARD therapy is provided. Screening for comorbidities and vaccination is advised.

P077 The Immunometabolic Bimodal Mechanism of NLRX1 Agonist NX-13 in a Pig Model of Ulcerative Colitis

Abstract Background In mouse models, NX-13 is an orally active, gut-restricted NLRX1 agonist that has been shown to reduce severity of disease in multiple UC models through a novel immunometabolic, bimodal mechanism. Most preclinical UC studies rely upon rodent models, the human gastrointestinal physiology, microbiome, and immune system bear a greater similarity to that of pigs. Therefore, we sought to expand and validate our preclinical NX-13 results in mice using the dextran sulfate sodium (DSS) pig model of colitis. Here, we describe the disease severity, cellular, and biomarker results, and confirm the immunometabolic MOA observed in other species. Methods Pigs were randomized by weight (n=6 per group) and were administered tablets of excipient alone (placebo), NX-13 10 mg, NX-13 50 mg, or NX-13 100mg once daily. Pigs were challenged with 1% DSS in drinking water for 6 days and monitored daily for weight gain (loss). Composite disease activity score (0-12) was taken based on the sum of three subscores (0-4) for rectal bleeding, stool consistency and overall health/activity. Necropsy was conducted on day 7. Feces were collected for fecal calprotectin (FCP) quantification. Colonic tissue was macroscopically scored and collected for analysis by flow cytometry, histopathology and gene expression. Results Oral NX-13 treatment protected against weight loss and reduced colitis development with differences as early as day 2, becoming significant between days 4 and 6 as disease worsens in placebo treated pigs (Fig1A). NX-13 yielded a dose-dependent improvement in macroscopic lesion severity and microscopic immune cell infiltration (Fig1B). Specifically, Th1 cells (Fig1C) and TNF producing myeloid cells in the colonic lamina propria were reduced by NX-13, as well as FCP levels in stool (Fig1D) and mRNA expression in the colon (Fig1E). Oral NX-13 treatment reduced inflammatory markers including TNF, monocyte and neutrophil chemo attractants, IL-6, and IL-23 (Fig3F). Additionally, NX-13 treatment affected markers specific to the bimodal immunometabolic MOA of NLRX1 activation, namely upregulation of NLRX1 and mitochondrial metabolism gene COX3 (Fig1G), and reduction of NFkB and NLRP3 (Fig1H). Conclusion NX-13 demonstrated fast and clinically meaningful improvement in disease activity, and significantly impacted on key inflammatory markers in a DSS colitis model in pigs. These results align with previous murine results and observations in the phase 1b clinical program. Therefore, they can be used to generate additional mechanistic hypotheses for translational studies in the ongoing NEXUS phase 2 trial in moderate to severe UC.

Long-term follow-up of children with chronic non-bacterial osteomyelitis—assessment of disease activity, risk factors, and outcome

IntroductionChronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone-disease of unknown origin. The National Pediatric Rheumatologic Database (NPRD) collects long-term data of children and adolescents with rheumatic diseases including CNO.ObjectiveTo assess characteristics, courses, and outcomes of CNO with onset in childhood and adolescence and to identify outcome predictors.MethodsFrom 2015 to 2021 patients with a confirmed diagnosis of CNO, who were registered in the NPRD during their first year of disease and at least one follow-up visit, were included in this analysis and observed for up to 4 years.ResultsFour hundred patients with recent diagnosis of CNO were enrolled in the NRPD during the study period. After 4 years, patient data documentation was sufficient to be analyzed in 81 patients. A significant decline of clinical and radiological lesions is reported: at inclusion in the registry, the mean number of clinical lesions was 2.0 and 3.0 MRI lesions per patient. A significant decrease of manifestations during 4 years of follow-up (mean clinical lesions 0.5, p < 0.001; mean MRI lesions 0.9 (p < 0.001)) was documented. A significant improvement of physician global disease activity (PGDA), patient-reported overall well-being, and childhood health assessment questionnaire (C-HAQ) was documented. Therapeutically, an increase of disease-modifying anti-rheumatic drugs over the years can be stated, while bisphosphonates rather seem to be considered as a therapeutic DMARD option in the first years of disease. Only 5–7% of the patients had a severe disease course as defined by a PGDA > = 4. Predictors associated with a severe disease course include the site of inflammation (pelvis, lower extremity, clavicle), increased erythrocyte sedimentation rate, and multifocal disease at first documentation. The previously published composite PedCNO disease activity score was analyzed revealing a PedCNO70 in 55% of the patients at 4YFU.ConclusionAn improvement of physician global disease activity (PGDA), patient reported overall well-being and imaging-defined disease activity measures was documented, suggesting that inactivity of CNO disease can be reached. PedCNO score and especially PGDA, MRI-defined lesions and in a number of patients also the C-HAQ seem to be reliable parameters for describing disease activity. The identification of risk factors at the beginning of the disease might influence treatment decision in the future.

OA03 Harnessing quantitative proteomics to identify biomarkers of treatment response to etanercept in patients with rheumatoid arthritis

Abstract Background/Aims Tumour necrosis factor inhibitors (TNFi) are commonly prescribed to treat rheumatoid arthritis (RA), but response to TNFi is not universal and there are no validated pre-treatment biomarkers of treatment response at present. Proteins have many features that make them ideal potential biomarkers, as they carry out diverse biological processes, interact with drugs and can reflect post-translational modifications. This study aimed to identify protein biomarkers associated with response to TNFi in patients with RA. Methods Participants were recruited from a UK-based prospective multi-centre study of patients fulfilling either the 1987 ACR or 2010 ACR/EULAR classification for RA starting biologic treatment for the first time. Quantitative proteomics was performed using Sequential Window Acquisition of all THeoretical fragment ion spectra mass spectrometry (SWATH-MS) in sera from study participants before and after three months of treatment with the TNFi etanercept. Linear regression models were used to study the association between protein levels and the composite 28-joint count Disease Activity Score (DAS28) and its sub-components, adjusting for baseline covariates including age, biological sex disease duration and baseline DAS28. Sub-network analysis was carried out using the DIAMOnD algorithm, followed by functional enrichment analysis. Results Of the total 180 participants recruited, 134 (74.44%) were female, with a median age of 56.90 years and median pre-treatment DAS28 of 5.9. Eight individual proteins were found to be significantly associated with RA clinical outcome measures (see Table). Sub-network analysis identified the ontological theme with the strongest association as being positive regulation of response to endoplasmic reticulum (ER) stress (-log10(P) ∼ 7). Conclusion This longitudinal study of 180 patients with RA commencing etanercept has identified several putative protein biomarkers of treatment response and identified ER stress as an underlying pathway. The ER stress pathway has been previously reported to contribute to RA pathogenesis via synoviocyte proliferation and stimulation of pro-inflammatory cytokine production. Disclosure S.F. Ling: None. C. Yap: None. N. Nair: None. J. Bluett: None. A.W. Morgan: None. J.D. Isaacs: None. A.G. Wilson: None. K.L. Hyrich: None. A. Barton: None. D. Plant: None.

Evaluation of the Role of Affective Temperamental Features, Automatic Thoughts, and Symptom Interpretation on Disease Activity in Patients with Axial Spondyloarthritis.

Axial spondyloarthritis is a systemic and chronic inflammatory disease. Psychological liability to depression and anxiety influences the disease process, prognosis, and treatment outcomes of other medical conditions. Early detection and treatment of these psychiatric conditions would also help in improving the physical functioning of patients with axial spondyloarthritis by reducing the patient's anxiety and depression symptoms. We evaluated the affective temperamental features, automatic thoughts, symptom interpretation, and their relationship with disease activity in patients with axial spondyloarthritis. A total of 152 patients diagnosed with axial spondyloarthritis are recruited. Axial spondyloarthritis disease activity was calculated by Bath Ankylosing Spondylitis Disease Activity Index. Depression and anxiety levels were screened with Hospital Anxiety and Depression Scale while affective temperament was evaluated with Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-autoquestionnaire version and automatic thoughts were screened with Symptom Interpretation Questionnaire, and Automatic thoughts questionnaire. It was observed that 48% (n = 73) were female. The mean age was 43.5 (10.5) years, Bath Ankylosing Spondylitis Disease Activity Index score was 3.97 (1.14). According to the Bath Ankylosing Spondylitis Disease Activity Index scale, 53.30% (n = 81) of the patients were in high disease activity. We found that HAD-depression, HAD-anxiety, Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-autoquestionnaire version, Symptom Interpretation Questionnaire, and Automatic Thoughts Questionnaire scores were significantly higher in the high disease activity group. Patients' temperament characteristics and mood disorders may affect composite disease activity scores such as Bath Ankylosing Spondylitis Disease Activity Index. In patients with high disease activity scores despite receiving appropriate treatment, mood disorders may need to be evaluated. There is a need to develop disease activity scores unaffected by mood disorders.

Exploring pain catastrophizing and its associations with low disease activity in rheumatic inflammatory disorders.

Pain catastrophizing is a maladaptive mechanism associated with the exaggerated experience of pain, increased rumination and feelings of helplessness. The main objective of this study was to explore whether increased pain catastrophizing is independently associated with a lower proportion of low disease activity (LDA) in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA). Demographics, comorbidities, treatment, disease activity measures and patient-reported outcome data were recorded in RA, PsA and axSpA patients. Pain catastrophizing score (PCS) was assessed using a standardised questionnaire. For each diagnosis, composite disease activity scores with distinct cut-off values for LDA, i.e. DAS28-CRP (RA), DAPSA (PsA) and ASDAS-CRP (axSpA) were calculated and used as the dependent variable in logistic regression reflecting LDA achieved. A total of one thousand two hundred and twenty nine patients were included: 580 with RA, 394 with PsA and 255 with axSpA. In the multivariable analysis, pain catastrophizing was independently associated with LDA rates in axSpA (OR 0.33, 95% CI [0.12, 0.88]) amongst tested groups. In RA (OR 0.90, 95% CI [0.64, 1.28]) and PsA (OR 0.77, 95% CI [0.55, 1.07]), a statistically significant association was not observed. Higher PCS was independently associated with not achieving LDA in axSpA. Our data, however, indicate that pain catastrophizing, which also reflects a patient's personality traits and coping abilities, plays a less important role for the patient than general pain perception.

EVALUATION OF HAND AND WRIST JOINTS USING ULTRASONOGRAPHY AND DOPPLER IN PATIENTS OF RHEUMATOID ARTHRITIS: COMPARISON WITH CONVENTIONAL RADIOGRAPHY AND CLINICAL CORRELATION

Background- Ultrasound (US) together with power Doppler (PD) are progressively being employed to assess joint involvement in rheumatoid arthritis (RA). High-resolution US permits direct assessment of intra-articular and periarticular inammatory activity and structural damage in inammatory arthritis. To analyze the quality of point-of-care hand and wrist ultra Objective- sound (US) examination in patients with established rheumatoid arthritis, it's comparison with standard radiography and clinical correlation. This prospective study was performed in 32 Methodspatients. Gray scale and power doppler ultrasonography of bilateral hand and wrist joint were performed employing a high-frequency linear transducer. Various ndings were recorded together with synovial hypertrophy, Power Doppler abnormality, soft tissue thickening, tendonitis, joint effusion, periosteal reaction, and erosions. Composite ultrasound scores and Disease Activity Score 28 were calculated and compared. ResultsUltrasound detected a lot of abnormalities within hand joints than the clinical examination. Synovial hypertrophy was detected altogether in 24 (75%) patients on gray scale ultrasound, active synovitis detected by using Doppler US in 20 patients (62.5%), effusion was detected in 10 patients (37.5 %), bone erosions (mostly in DIP and PIP joints) were detected in 20 patients (62.5%) and X-ray nding was detected in 8 patients (25%). There was a positive correlation of Power Doppler with synovial hypertrophy, bone erosions, Erythrocyte Sedimentation Rate and Disease Activity Score. Ultrasound could be a helpful reliable modality for the target assess Conclusion- ment of both soft tissue and erosive joint changes occurring in early stage in rheumatoid arthritis. Power doppler scores can be applied with bigger accuracy than clinical scores of synovitis in rheumatologic practice to enable therapeutic choices and to evaluate disease outcome and response to treatment.

Effects of ALT-801, a GLP-1 and glucagon receptor dual agonist, in a translational mouse model of non-alcoholic steatohepatitis

Body weight loss of ≥ 10% improves the metabolic derangements and liver disease in the majority of non-alcoholic steatohepatitis (NASH) patients, suggesting metabolic modulators may be effective in controlling disease. The pharmacodynamics of ALT-801, a GLP-1/glucagon receptor dual agonist optimized for NASH and weight loss, were compared to semaglutide (GLP-1 receptor agonist) and elafibranor (peroxisome proliferator-activated receptor, PPAR-α/δ, agonist) in a biopsy-confirmed, diet-induced obese (DIO) mouse model of NASH (DIO-NASH). Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks. Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet. Study endpoints included body and liver weight, liver and plasma total cholesterol and triglycerides, plasma aminotransferases, histological analysis of liver steatosis, inflammation (galectin-3) and fibrosis (collagen type 1 alpha 1), and evaluation of individual animal changes in composite Non-alcoholic Fatty Liver Disease Activity Score (NAS), and fibrosis stage. ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor. ALT-801 significantly reduced the inflammation marker galectin-3 and the fibrosis marker collagen type 1 alpha 1 vs. vehicle (p < 0.05), with ALT-801 producing greater reductions in galectin-3 vs. elafibranor (p < 0.05). Importantly, all animals treated with ALT-801 significantly improved composite NAS compared to the active controls. This study provides evidence for a potential role for ALT-801 in the therapeutic treatment of NASH.

Belgian rheumatologists' preferences regarding measures of disease activity in patients with rheumatoid arthritis: results from a mixed-methods study.

The reliability and clinical usefulness of the different composite disease activity scores and their individual components in Rheumatoid Arthritis (RA) are still debated. This study investigated which measures of disease activity were preferred by rheumatologists. A mixed-method study was performed. First, ten Belgian rheumatologists were invited for individual interviews on their current practice and preferences for measurement of RA disease activity. Results of this qualitative study and evidence from literature served as input for developing a survey. This survey asked rheumatologists to rate preferred standard disease activity score(s), their individual components, ultrasound and related patient-reported outcomes (PROs), by maximum difference scaling. The relative importance score (RIS) for each indicator was calculated using hierarchical Bayes modeling. The qualitative study included 6/10 invited rheumatologists. Composite scores and components were perceived as useful, while PROs were found subjective. Interestingly, ultrasound was used to mediate discrepancies between physician and patient. The survey based on this was sent to 244 Belgian rheumatologists, 83/244 (34%) responded, including 66/83 (80%) complete and 17/83 (20%) incomplete surveys (two missing essential information). Most rheumatologists (75/81, 93%) used a disease activity score and 68/81 (84%) preferred the DAS28-CRP. Swollen joint count obtained the highest mean ± SD RIS (22.54 ± 2.64), followed by DAS28 ESR/CRP (20.61 ± 4.06), ultrasound (16.47 ± 7.97), CRP (13.34 ± 6.11) and physician's global assessment (12.59 ± 7.83). PROs including fatigue, pain, and patient's global assessment, and Health Assessment Questionnaire, obtained the lowest mean RIS (0.34-2.54). Rheumatologists place more faith in self-assessed disease activity components or in laboratory tests. Trust in PROs to evaluate disease activity is low in clinical practice.

Outcomes Reported in Prospective Long-Term Observational Studies and Registries of Patients With Rheumatoid Arthritis Worldwide: An Outcome Measures in Rheumatology Systematic Review.

Prospective long-term observational studies (LOS) in rheumatoid arthritis (RA) lack a core set of universally collected outcome measures, particularly patient-centered outcomes, precluding accurate comparisons across studies. Our aim was to identify long-term outcome measures collected and reported in these studies. We conducted a systematic review of registries and LOS of patients with RA, searching in ClinicalTrials.gov, the Agency for Healthcare Research and Quality Registry of Patient Registries, and Google Scholar. The names and acronyms of registries and LOS were further searched in the Medline and Embase databases to retrieve published articles. Two independent reviewers undertook data collection, quality appraisal, and data extraction. We identified 88 registries/LOS that met our eligibility criteria. These were divided into 2 groups: disease-based (52 [59%]) and therapy-based (36 [41%]). Methodologic and reporting standards varied across the eligible studies. For clinical outcomes, disease activity was recorded in 88 (100%) of all LOS/registries. The most commonly reported measure (86 [98%]) was the composite outcome Disease Activity Score using 28 joints. Of the patient-centered outcomes collected, physical functioning was most frequently reported (75 [85%]) with the Health Assessment Questionnaire (75 [85%]) as the most commonly used instrument within this domain. Other domains of patient-centered outcomes were comparatively infrequently recorded: mental (29 [33%]), social (20 [23%]), and health-related quality of life (37 [42%]). Most registries/LOS collect measures of disease activity and physical function. However, there is substantial heterogeneity in the collection of relevant patient-centered outcomes that measure symptom burden and mental and social ramifications of RA.

P128 A subgroup analysis of the efficacy of filgotinib for patients with moderately active RA following an inadequate response to methotrexate

P128 A subgroup analysis of the efficacy of filgotinib for patients with moderately active RA following an inadequate response to methotrexate

O13 Which composite measure best reflects disease activity and predicts treatment change in psoriatic arthritis?

Abstract Background/Aims Multiple composite measures of disease activity are available and used in psoriatic arthritis (PsA) research; however, poor agreement remains amongst clinicians on the optimal measure of disease activity. Research to date has focused on polyarticular PsA, despite oligoarticular disease accounting for around half of cases in clinical practice. We aim to compare the ability of Composite Psoriatic Disease Activity Index (CPDAI), Psoriatic ArthritiS Disease Activity Score (PASDAS), Disease Activity score for PSoriatic Arthritis (DAPSA), GRAppa Composite scorE (GRACE) and Disease Activity Score 28 CRP (DAS28-CRP) to assess disease activity and predict treatment change, amongst usual care patients with oligoarticular and polyarticular psoriatic disease. Methods The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise (GRACE) dataset was utilised. Oligoarthritis was defined as &amp;lt; 5 active joints. Reference measures were clinician and patient opinions on disease control and whether treatment was escalated. Patients with baseline data for all composite measures were included. The ability of each composite measure to predict treatment change and capture disease activity was compared using the Mann-Whitney U test. Results Data were available for 271 patients (152 oligoarthritis, 119 polyarthritis). The mean age, duration of PsA and psoriasis were similar for both groups. A higher proportion of oligoarticular patients were male. Patients with polyarticular disease had higher disease activity in skin, enthesitis and dactylitis. Using both patient and physician definitions of disease control, all composite measures were able to differentiate between patients with active and quiescent disease, regardless of disease subtype (p &amp;lt; 0.05). PASDAS demonstrated the largest differentiation in score. Differences between active and inactive disease scores were more pronounced in oligoarticular disease. PASDAS demonstrated the greatest ability to predict treatment change in both oligoarticular and polyarticular disease. Interestingly, DAPSA could not predict treatment change in polyarticular patients, p = 0.074 (Table 1). Conclusion This is the first study to compare composite measures, in oligoarticular and polyarticular PsA in a multinational cohort. All composite measures of disease activity were able to differentiate between active and inactive disease in both subtypes. PASDAS demonstrated the largest discrimination in both polyarticular and oligoarticular disease, suggesting greatest clinical and research utility. Disclosure L. Tucker: None. P. Helliwell: None. L. Coates: None.

The Increased Levels of Fecal Calprotectin in Children With Active Enthesitis Related Arthritis and MRI Signs of Sacroiliitis: The Results of a Single Center Cross-Sectional Exploratory Study in Juvenile Idiopathic Arthritis Patients.

Enthesitis related arthritis (ERA) is a specific subtype of juvenile idiopathic arthritis (JIA), often regarded as an undifferentiated form of juvenile spondyloarthritis (jSpA). While gut is increasingly recognized as origin and/or target of inflammation in adult onset spondyloarthritis (SpA), the incidence of gut involvement in ERA patients is largely unknown. The aim of this study was to measure the concentration of fecal calprotectin (fCAL), a surrogate marker of gut inflammation, in patients with different subtypes of JIA, as well as to correlate the results with various demographic, clinical, laboratory, imaging, and treatment characteristics. The cross-sectional exploratory study involving 71 patients with ERA, other forms of JIA and children complaining musculoskeletal symptoms was therefore conducted. Along with fCAL assessment, a detailed clinical and laboratory examination was performed, including the calculation of a composite disease activity scores. Moreover, MRI of the sacroiliac joints was performed in all ERA and other patients complaining of low back pain. The median concentration of fCAL was highest in ERA patients (33.2 mg/kg, p = 0.02), with a significant difference between those with inactive and active disease (20.0 vs. 57.4, p = 0.01), as well as those with and without MRI signs of sacroiliitis (22.6 vs. 54.3, p = 0.04). The fCAL did not differ depending on the NSAID use (23 vs. 20, p = 0.18), although weak correlation was observed with the treatment duration (r = 0.25, p = 0.03). In conclusion, our findings indicate that a parallel inflammation in musculoskeletal system and gut can occur not just in adults with SpA, but in children with ERA as well.

Major reduction of ultrasound-detected synovitis during subcutaneous tocilizumab treatment: results from a multicentre 24 week study of patients with rheumatoid arthritis

Objective: Few studies have investigated the efficacy of subcutaneous tocilizumab (TCZ-SC) on ultrasound-detected inflammation. This study aimed to explore the clinical efficacy of TCZ-SC treatment in rheumatoid arthritis (RA) patients and to evaluate the response by ultrasound compared to Composite Disease Activity Scores (CDAS). Method: This open-label, single-arm study enrolled RA patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs initiating TCZ-SC 162 mg once weekly for 24 weeks, with clinical assessments at baseline, 2, 4, 8, 12, 16, 20, and 24 weeks. Ultrasound examinations [semi-quantitative score (0–3) of 36 joints and four tendons] were performed at baseline, 4, 12, and 24 weeks. CDAS and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) response, and sum scores of ultrasound grey scale/Doppler were calculated. Changes during follow-up were explored by the Mann–Whitney test and correlations by Spearman’s rho. Results: In total, 133 patients (mean ± sd age 55.9 ± 12.0 years) were assessed clinically and 110 patients were also examined with ultrasound. All clinical and ultrasound scores decreased significantly after 4 weeks (p < 0.001). At 24 weeks there was EULAR good response in 87.7% and ACR 70% response in 47.4%. Ultrasound scores had no or low correlations with patient-reported outcomes. At 24 weeks, CDAS remission was achieved in 27.4–83.5% and a sum score Doppler of 0 was found in 53.3%. Conclusions: Clinical and ultrasound scores decreased rapidly. Ultrasound scores were not associated with patient-reported variables. Half of the patients reached ultrasound remission, while there were large discrepancies in the percentage of patients reaching remission based on different CDAS. Trial registration: Study ML28691, registered 28 January 2014, ClinicalTrials.gov identifier: NCT02046616

Salivary Oral Microbiome of Children With Juvenile Idiopathic Arthritis: A Norwegian Cross-Sectional Study.

BackgroundThe oral microbiota has been connected to the pathogenesis of rheumatoid arthritis through activation of mucosal immunity. The objective of this study was to characterize the salivary oral microbiome associated with juvenile idiopathic arthritis (JIA), and correlate it with the disease activity including gingival inflammation.MethodsFifty-nine patients with JIA (mean age, 12.6 ± 2.7 years) and 34 healthy controls (HC; mean age 12.3 ± 3.0 years) were consecutively recruited in this Norwegian cross-sectional study. Information about demographics, disease activity, medication history, frequency of tooth brushing and a modified version of the gingival bleeding index (GBI) and the simplified oral hygiene index (OHI-S) was obtained. Microbiome profiling of saliva samples was performed by sequencing of the V1-V3 region of the 16S rRNA gene, coupled with a species-level taxonomy assignment algorithm; QIIME, LEfSe and R-package for Spearman correlation matrix were used for downstream analysis.ResultsThere were no significant differences between JIA and HC in alpha- and beta-diversity. However, differential abundance analysis revealed several taxa to be associated with JIA: TM7-G1, Solobacterium and Mogibacterium at the genus level; and Leptotrichia oral taxon 417, TM7-G1 oral taxon 352 and Capnocytophaga oral taxon 864 among others, at the species level. Haemophilus species, Leptotrichia oral taxon 223, and Bacillus subtilis, were associated with healthy controls. Gemella morbillorum, Leptotrichia sp. oral taxon 498 and Alloprevotella oral taxon 914 correlated positively with the composite juvenile arthritis 10-joint disease activity score (JADAS10), while Campylobacter oral taxon 44 among others, correlated with the number of active joints. Of all microbial markers identified, only Bacillus subtilis and Campylobacter oral taxon 44 maintained false discovery rate (FDR) < 0.1.ConclusionsIn this exploratory study of salivary oral microbiome we found similar alpha- and beta-diversity among children with JIA and healthy. Several taxa associated with chronic inflammation were found to be associated with JIA and disease activity, which warrants further investigation.

Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis

BackgroundUpadacitinib is an oral selective Janus kinase inhibitor to treat rheumatoid arthritis. The efficacy and safety of upadacitinib as compared with abatacept, a T-cell costimulation modulator, in patients with rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs (DMARDs) are unclear.MethodsIn this 24-week, phase 3, double-blind, controlled trial, we randomly assigned patients in a 1:1 ratio to receive oral upadacitinib (15 mg once daily) or intravenous abatacept, each in combination with stable synthetic DMARDs. The primary end point was the change from baseline in the composite Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP; range, 0 to 9.4, with higher scores indicating more disease activity) at week 12, assessed for noninferiority. Key secondary end points at week 12 were the superiority of upadacitinib over abatacept in the change from baseline in the DAS28-CRP and the percentage of patients having clinical remission according to a DAS28-CRP of less than 2.6.ResultsA total of 303 patients received upadacitinib, and 309 patients received abatacept. From baseline DAS28-CRP values of 5.70 in the upadacitinib group and 5.88 in the abatacept group, the mean change at week 12 was −2.52 and −2.00, respectively (difference, −0.52 points; 95% confidence interval [CI], −0.69 to −0.35; P<0.001 for noninferiority; P<0.001 for superiority). The percentage of patients having remission was 30.0% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P<0.001 for superiority). During the treatment period, one death, one nonfatal stroke, and two venous thromboembolic events occurred in the upadacitinib group, and more patients in the upadacitinib group than in the abatacept group had elevated hepatic aminotransferase levels.ConclusionsIn patients with rheumatoid arthritis refractory to biologic DMARDs, upadacitinib was superior to abatacept in the change from baseline in the DAS28-CRP and the achievement of remission at week 12 but was associated with more serious adverse events. Longer and larger trials are required in order to determine the effect and safety of upadacitinib in patients with rheumatoid arthritis. (Funded by AbbVie; SELECT-CHOICE Clinicaltrials.gov number, NCT03086343.)

Semi-quantitative analysis of 18F fluorodeoxyglucose uptake in the assessment of disease activity and therapeutic response in rheumatoid arthritis: An institutional experience.

18F fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) can be used to image synovial inflammation in patients with rheumatoid arthritis (RA). Recently, clinical application of novel therapies for RA, such as tumor necrosis factor-α (TNF-α) inhibitor and anti-interleukin-6 receptor antibody, has been introduced. The radiological assessment of disease activity changes of patients who underwent these therapies will help the clinicians to obtain more information about the patients and to decide drug withdrawal or change of medication. It is considered that 18F-FDG PET scan is generally very expensive; however, the information from 18F-FDG PET about patients during biological treatments helps discontinuation of these treatments with incomplete response despite its high costs and with possible side effects such as malignant lymphoma. In this study, we evaluated if the 18F-FDG uptake of the affected joints represented by standardized uptake value (SUV) correlated with the clinical assessment of patients with RA. In addition, we would like to evaluate if there was a correlation between the difference of SUV and improvement of clinical findings in RA patients undergoing anti TNF therapies. RA patients who underwent anti-TNFα therapies in a tertiary care hospital were assessed using whole-body 18F-FDG PET/computed tomography (CT). PET assessments were performed on hip joints, knees, shoulders, wrists, ankles, MCP, and PIP for a total of 28 joints in each patient. The 18F–FDG uptake was then quantified using the maximum SUV (SUVmax) prior to, and 6 months after the initiation of treatment with anti-TNF-α drugs. Disease activity score (DAS28 and DAS28-C-reactive protein [CRP]) were recorded and white blood cell, matrix metalloproteinases (MMP-3) and rheumatoid factor (RF) were examined in all patients. The average of SUVmax among measured joints, or the sum of these joints (total SUVmax), correlated with DAS28 (r = 0.671, P < 0.001), DAS28-CRP (r = 0.623, P < 0.001), ESR (r = 0.542, P < 0.001), CRP (r = 0.411, P = 0.002), MMP-3 (r = 0.399, P = 0.006), and RF (r = 0.447, P = 0.002). There were correlations between ΔSUV and ΔDAS28 (r = 0.651, P < 0.001), ΔSUV and ΔDAS28-CRP (r = 0.682, P < 0.001), ΔSUV and ΔESR (r = 0.449, P = 0.023), and ΔSUV and ΔMMP-3 (r = 0.457, P = 0.027), respectively. The number of PET-positive joints and the cumulative SUV significantly correlated with the DAS28, which is a composite disease activity score (DAS) that combines the swollen and tender joint counts, the erythrocyte sedimentation rate (DAS28-ESR) or CRP serum levels (DAS28 − CRP) or RF (DAS28 − RF) or metalloproteinases-3 (DAS28-MMP-3). At baseline and at 6 months' post-treatment with anti-TNFα drugs, there was a significant correlation between the PET results, either visual, the cumulative SUVs or the composite SUV index, and the comprehensive clinical assessment (DAS28), the CRP levels and the number of joints positive for RA, and cumulative synovial thickness. By reflecting inflammatory activity, 18F-FDG PET may enhance the diagnostic performance and expectation of disease prognosis in RA, especially with early synovial inflammation. The intensity of uptake varied from mild to intense (SUVmax values from 3.10 to 6.0). Overall, these values correlated well with the clinical evaluation of involved joints. 18F–FDG PET imaging data provided a distribution of joint involvement with varying degrees of severity and phase of disease activity (moderate, low, and remission) in the same patient. PET/CT imaging with 18F-FDG shows better image quality, provides more confirmative diagnostic information, and will be promising imaging modality in diagnosis and management of RA.

Development and initial validation of a composite disease activity score for systemic juvenile idiopathic arthritis.

To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively.

A clinical and radiographic comparison of patients with psoriatic arthritis from different ethnic backgrounds

There are few papers concerning ethnic differences in disease expression in PsA, which may be influenced by a number of genetic, lifestyle and cultural factors. This article aims to compare clinical and radiographic phenotypes in people of South Asian (SA) and North European (NE) origin with a diagnosis of PsA. This was a cross-sectional observational study recruiting patients of SA and NE origin from two hospitals in a well-defined area in the North of England. A total of 58 SA and 48 NE patients were recruited. SA patients had a more severe clinical phenotype with more tender (median 5 vs 2) and swollen (median 1 vs 0) joints, more severe enthesitis (median 3 vs 1.5), more patients with dactylitis (24% vs 8%), more severe skin disease (median PASI 2.2 vs 1) and worse disease activity as measured by the composite Psoriatic Arthritis Disease Activity Score (mean 4.5 vs 3.6). With regards to patient-completed measures, SA patients had worse impact with poorer quality of life and function (mean HAQ 0.9 vs 0.6; mean PsAQoL 10.8 vs 6.2; mean 36-item short form physical component score 33.5 vs 38.9). No significant differences in current MTX and biologics use were found. SA patients had a worse clinical phenotype and worse impact of disease than NE patients. Further studies are needed to confirm and explore the reasons behind these differences.

Vitamin B12 Deficiency Alters the Gut Microbiota in a Murine Model of Colitis.

Purpose: Inflammatory bowel disease (IBD) refers to a spectrum of autoimmune diseases, which result in chronic intestinal inflammation. Previous findings suggest a role for diet, nutrition and dysbiosis of the gut microbiota in both the development and progression of the condition. Vitamin B12 is a key cofactor of methionine synthase and is produced solely by microbes. Previous work links increased levels of homocysteine, a substrate of methionine synthase, MetH, to IBD indicating a potential role for vitamin B12 deficiency in intestinal injury and inflammation. This study assessed the role of vitamin B12 in shaping the gut microbiota and determining responses to intestinal injury using a reproducible murine model of colitis.Methods: The effects of vitamin B12 supplementation and deficiency were assessed in vivo; 3-week-old post-weanling C57Bl/6 mice were divided into three dietary treatment groups: (1) sufficient vitamin B12 (50 mg/Kg), (2) deficient vitamin B12 (0 mg/Kg) and (3) supplemented vitamin B12 (200 mg/Kg) for a period of 4 weeks. Intestinal injury was induced with 2% dextran sodium sulphate (DSS) via drinking water for 5 days. The impact of varying levels of dietary vitamin B12 on gut microbiota composition was assessed using 16S rRNA gene sequencing from fecal samples collected at day 0 and day 28 of the dietary intervention, and 7 days following induction of colitis on day 38, when blood and colonic tissues were also collected.Results: No significant alterations were found in the gut microbiota composition of disease-free animals in response to dietary interventions. By contrast, after DSS-induced colitis, >30 genera were significantly altered in vitamin B12 deficient mice. Altered B12 levels produced no significant effect on composite disease-activity scores; however, administration of a B12 deficient diet resulted in reduced DSS-induced epithelial tissue damage.Conclusions: Vitamin B12 supplementation does not alter the gut microbiota composition under healthy conditions, but does contribute to differential microbial responses and intestinal dysbiosis following the induction of experimental colitis.