Search

Objectives CD4+CD8+ double-positive (DP) T cells are expanded in the peripheral blood of a subset of patients with RA. This study examines the clinical significance of DP T cells in RA. Methods In 70 RA patients, DP T cells were measured by flow cytometry. Clinical data were obtained, and hand and feet radiographs were scored according to the Sharp/van der Heijde (SvdH) method. The association between DP T cell frequency and erosive joint destruction was analysed by correlation and multiple logistic regression analysis. Results Nineteen RA patients (27.1%) displayed increased DP T cell frequencies, which correlated with age (r  = 0.288, P =0.016). Expansion of DP T cells was associated with the occurrence of erosions (94,7% vs 43,1%, P <0.001), with a higher SvdH joint damage score (24.5 vs 6, P =0.008) and with more frequent use of biologic or targeted-synthetic DMARDs (68.4% vs 38%, P =0.02). In patients with non-erosive disease, DP T cell frequencies correlated with the joint space narrowing score (n  = 28, r  = 0.44, P =0.02). Logistic regression revealed DP T cells to be associated with erosive disease (OR 1.90, P <0.05). Conclusion Expansion of DP T cells is associated with joint damage and frequent escalation of therapy, possibly suggesting a contribution to more severe RA. [ABSTRACT FROM AUTHOR]

• Serum CXCL10 concentrations were markedly raised in IDD patients with low back pain. • Serum CXCL10 concentrations were also significantly higher in IDD patients with muscle degeneration. • Increased CXCL10 levels positively correlated with clinical severity. Lumbar intervertebral degenerative disc disease (IDD) is a multifaceted progressive condition that commonly occurs in conjunction with lumbar disc herniation (LDH). CXCL10 mRNA appears to be increased in both IDD and LHD. This study was performed to identify the relationship between serum CXCL10 levels and disease severity in patients with IDD. 136 IDD patients with low back pain, 127 asymptomatic volunteers and 120 healthy controls were enrolled. Serum CXCL10 protein concentrations were detected using commercial human CXCL10 ELISA Kits. Serum CXCL10 mRNA were examined using qRT-PCR. Clinical severity was assessed using the visual analog scale (VAS) and Oswestry Disability Index(ODI) scores. Radiographic severity was defined using the MRI-based Pfirrmann classification of disc degeneration. Receiver operating characteristic (ROC) curve analysis was used in estimating the correlation between CXCL10 and Pfirrmann grade. The cross-sectional area (CSA) of the lumbar multifidus muscle (LMM) and psoas major (PM) were calculated, and fat infiltration was evaluated by Ropponen-Kjaer criteria. Serum CXCL10 concentrations were markedly raised in IDD patients with low back pain in contrast to asymptomatic individuals and healthy controls. Serum CXCL10 levels were positively associated with Pfirrmann grade. ROC curve analysis indicated that serum CXCL10 correlated well with Pfirrmann grade. In addition, serum CXCL10 concentrations were significantly higher in IDD patients with LMM and PM degeneration compared with IDD patients without degeneration. Increased CXCL10 levels positively correlated with VAS and ODI scores, as well as decreased CSA and fat filtration of the LMM and PM. Increased serum CXCL10 levels correspond to clinical severity and radiographic progression in IDD patients. [ABSTRACT FROM AUTHOR]

Abstract Objective Predictive biomarkers of progression in knee osteoarthritis are sought to enable clinical trials of structure-modifying drugs. A peripheral blood leukocyte (PBL) inflammatory gene signature, MRI-based bone marrow lesions (BML) and meniscus extrusion scores, meniscal lesions, and osteophytes on X-ray each have been shown separately to predict radiographic joint space narrowing (JSN) in subjects with symptomatic knee osteoarthritis (SKOA). In these studies, we determined whether the combination of the PBL inflammatory gene expression and these imaging findings at baseline enhanced the prognostic value of either alone. Methods PBL inflammatory gene expression (increased mRNA for IL-1β, TNFα, and COX-2), routine radiographs, and 3T knee MRI were assessed in two independent populations with SKOA: an NYU cohort and the Osteoarthritis Initiative (OAI). At baseline and 24 months, subjects underwent standardized fixed-flexion knee radiographs and knee MRI. Medial JSN (mJSN) was determined as the change in medial JSW. Progressors were defined by an mJSN cut-point (≥ 0.5 mm/24 months). Models were evaluated by odds ratios (OR) and area under the receiver operating characteristic curve (AUC). Results We validated our prior finding in these two independent (NYU and OAI) cohorts, individually and combined, that an inflammatory PBL inflammatory gene expression predicted radiographic progression of SKOA after adjustment for age, sex, and BMI. Similarly, the presence of baseline BML and meniscal lesions by MRI or semiquantitative osteophyte score on X-ray each predicted radiographic medial JSN at 24 months. The combination of the PBL inflammatory gene expression and medial BML increased the AUC from 0.66 (p = 0.004) to 0.75 (p

Aim. To assess the influence of anxiety and depressive disorders on joint destruction in patients with rheumatoid arthritis (RA). Materials and methods. 128 RA-patients were included, 87% were women with a mean age of 47.411.3 years and a median of RA duration 96 [48; 228] months. At the inclusion most patients had moderate (n=56, 43.7%) and severe (n=48, 37.5%) disease activity according to DAS28. Joint destruction was classified as maximal in patients with radiographic stage III, IV and/or osteonecrosis) and minimal in patients with stage I, II and no osteonecrosis. Pain intensity was measured with the BPI (Brief Pain Inventory) scale, severity of fatigue with fatigue severity scale (FSS), clinically important fatigue was diagnosed in patients with FSS4. Anxiety and depressive disorders (ADD) were diagnosed by a licensed psychiatrist in 123 (96.1%) of RA-patients in accordance with ICD-10 in semi-structured interview. Severity of depression and anxiety was evaluated with Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A). RA-patients with ADD were divided into the following treatment groups: 1 сDMARDs (n=39), 2 сDMARDs+PPT (sertraline or mianserine), n=43, 3 сDMARDs+bDMARDs (n=32), 4 сDMARDs+bDMARDs+PPT (sertraline or mianserine), n=9. Biologics treatment duration varied from 1 to 6 years, antidepressants from 6 to 96 weeks. 83 (67.5%) RA patients were assessed at five-years follow-up. Linear regression analysis was conducted to determine factors associated with maximal join destruction. Results. According to linear regression analysis, maximal joint destruction at 5 years follow-up was associated with higher baseline BPImax, longer RA and ADD duration, clinically important fatigue at baseline, baseline extraarticular RA manifestations, recurrent depressive disorder at 5-years follow-up and treatment with cDMARDs only. Conclusion. Recurrent depressive disorder without antidepressant treatment is an important predictor of progression of joint destruction in patients with rheumatoid arthritis.

Abstract Background In the GO-VIBRANT trial of intravenous golimumab in psoriatic arthritis (PsA), golimumab significantly inhibited radiographic progression. In post hoc analyses, we evaluated changes in total PsA-modified Sharp/van der Heijde scores (SHS) across levels of composite index-defined disease activity following treatment. Methods In this phase-3, double-blind, placebo-controlled trial, 480 bio-naïve patients with active PsA randomly received intravenous golimumab 2 mg/kg (N = 241; week 0, week 4, every 8 weeks [q8w]) or placebo (N = 239; week 0, week 4, week 12, week 20) followed by golimumab (week 24, week 28, q8w) through week 52. Week 24 and week 52 SHS changes in patient subgroups, defined by levels of disease activity as assessed by several composite measures (minimal disease activity [MDA], very low disease activity [VLDA], Psoriatic ArthritiS Disease Activity Score [PASDAS], Disease Activity in Psoriatic Arthritis [DAPsA], Clinical Disease Activity Index [CDAI]), were evaluated post hoc in 474 patients with evaluable radiographic data. Partially (last-observation-carried-forward methodology) and completely (nonresponder methodology) missing data were imputed. Results Across indices, golimumab-treated patients demonstrated less radiographic progression than placebo-treated patients, regardless of disease activity state achieved via golimumab, from week 0 to 24 (e.g., mean changes in PsA-modified SHS were − 0.83 vs. 0.91, respectively, in patients achieving MDA and − 0.05 vs. 1.49, respectively, in those not achieving MDA). Treatment differences observed at week 24 persisted through week 52, despite placebo-randomized patients crossing over to golimumab at week 24 (e.g., mean changes in PsA-modified SHS from week 0 to 52 for golimumab- vs. placebo→golimumab-treated patients achieving MDA were − 1.16 vs. 1.19, respectively) and regardless of whether low disease activity was achieved (0.03 vs. 1.50, respectively, in those not achieving MDA). Consistent patterns were observed for disease activity assessed using VLDA, PASDAS, DAPsA, and CDAI composite endpoints. Conclusions The extent of structural damage inhibition afforded by up to 1 year of intravenous golimumab treatment paralleled levels of PsA activity, with greater progression of structural damage observed in patients with sustained higher disease activity. Among patients not achieving low levels of disease activity across several composite indices, golimumab-randomized patients appeared to exhibit far less progression of structural damage than placebo-randomized PsA patients, illustrating a potential disconnect between responses, wherein golimumab can inhibit structural damage independent of clinical effect. Trial registration ClinicalTrials.gov. NCT02181673 . Registered 04 July 2014.

Background and objective: Matrix metalloproteinases (MMPs) are the key enzymes in the pathogenesis of cartilage and joint damage and potentially a new biomarker of the early erosive form of rheumatoid arthritis (RA). Firstly, the study aimed to compare the level of MMP-9 in plasma (PL) and synovial fluid (SF) of patients with RA and osteoarthritis (OA). Secondly, the goal was to examine the association of MMP-9 level in PL and SF with early erosive changes in RA, and finally, to determine the association of MMP-9 level with serological parameters of the disease (rheumatoid factor-RF and anti-citrulline protein antibodies-ACPA). Materials and Methods: A total of 156 subjects were involved in this study (84 patients with RA and 72 patients with OA, who were involved as a control group). MMP-9 level was measured in PL and SF of all subjects by the sandwich enzyme-linked immunosorbent assay (ELISA) method. Standard radiographs of the hands and feet were used to detect joint damage and classification into erosive or non-erosive RA. The Larsen score (LS) was used for the quantitative assessment of joint damage, and its annual change (∆ LS) was used to assess the radiographic progression of the disease. Results: MMP-9 level in PL and SF was significantly higher in RA compared to controls (PL: 19.26 ± 7.54 vs. 14.57 ± 3.11 ng/mL, p< 0.01; SF: 16.17 ± 12.25 vs. 0.75 ± 0.53 ng/mL, p < 0.001) as well as in SF of patients with erosive compared to non-erosive RA (18.43 ± 12.87 vs. 9.36 ± 7.72; p < 0.05). Faster radiographic progression was recorded in erosive compared to non-erosive early RA (11.14 ± 4.75 vs. 6.13 ± 2.72; p < 0.01). MMP-9 level in SF, but not in PL, significantly correlates with the radiographic progression in both erosive and non-erosive RA (ρ = 0.38 and ρ = 0.27). We did not find a significant association between RF and MMP-9 level in early RA, but the ACPA level significantly correlates with MMP-9 level in SF (r = 0.48). Conclusion: The level of MMP-9 in plasma and synovial fluid of patients with RA is significantly higher compared to patients with osteoarthritis. The level of MMP-9 in synovial fluid is significantly higher in erosive than non-erosive early RA. It is significantly associated with the radiographic progression of the disease and the level of anti-citrulline protein antibodies.

Introduction: The therapeutic armamentarium for spondyloarthritis has expanded considerably in recent years, and there is growing evidence to support the increasing use of IL-17 inhibitors (IL-17i) in axial spondyloarthritis (axSpA)., Areas Covered: This literature review provides an update on the role of IL-17 in the pathogenesis of axSpA, efficacy and safety from clinical trials and real-life studies on the use of IL17i in axSpA. We also review the impact of extra-musculoskeletal manifestations on the decision to treat with IL17i and the efficacy of IL17i on structural progression., Expert Opinion: There are still some unanswered questions concerning the use of IL-17i in axSpA in clinical practice such as their respective place in the management of axSpA compared to TNFα inhibitors (TNFi). Their main differences rely on their specific efficacy in extra-articular manifestations such as psoriasis, uveitis, and inflammatory bowel diseases leading to the choice of the best treatment in a given patient. Regarding their real impact on structural progression, the rate of progression under IL-17i appears to be low and presumably similar to TNFi. One final question is the advantage of blocking the two IL-17 isoforms A and F compared to the single inhibition of IL-17A.

Background: Understanding nutrition's role in multiple sclerosis (MS) can guide recommendations and intervention-based studies., Objective: Evaluate the association between nutrition and pediatric-onset MS outcomes., Methods: Prospective longitudinal multicenter study conducted as part of the US Network of Pediatric MS centers. Predictors were collected using a food screener estimating intake of various dietary food groups (e.g. dairy and fruits) and additional calculated indices (e.g. Healthy Eating Index (HEI)). Outcomes included time-from-enrollment to clinical relapse, new magnetic resonance imaging (MRI) T2 lesions, and Expanded Disability Status Scale (EDSS) increase., Results: 353 children with MS were enrolled (mean ± SD age 15.4 ± 2.9, follow-up 3.9 ± 2.6 years). Multivariable analysis demonstrated that increased dairy by 50% of recommended intake was associated with increased relapse risk by 41% (adjusted hazard ratio (HR) 1.41, 95% CI 1.07-1.86), and risk of T2 progression by 40% (1.40, 1.12-1.74). Increased intake of fruit or vegetable above recommended, and every five-point HEI increase decreased relapse risk by 25% (0.75, 0.60-0.95), 45% (0.55, 0.32-0.96), and 15% (0.84, 0.74-0.96), respectively. No associations were found with EDSS., Conclusion: This work supports the influence of dietary intake on MS course, particularly with dairy intake. Future prospective study is required to establish causation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: This study aims to investigate if addition of fibroblast-stromal cell markers to a classification of synovial pathotypes improves their predictive value on clinical outcomes in rheumatoid arthritis (RA). Methods: Active RA patients with a knee needle synovial biopsy at baseline and finished 1-year follow-up were recruited from a real-world prospective cohort. Positive staining for CD20, CD38, CD3, CD68, CD31, and CD90 were scored semiquantitatively (0-4). The primary outcome was radiographic progression defined as a minimum increase of 0.5 units of the modified total Sharp score from baseline to 1 year. Results: Among 150 recruited RA patients, 123 (82%) had qualified synovial tissue. Higher scores of CD20+ B cells, sublining CD68+ macrophages, CD31+ endothelial cells, and CD90+ fibroblasts were associated with less decrease in disease activity and greater increase in radiographic progression. A new fibroblast-based classification of synovial pathotypes giving more priority to myeloid and stromal cells classified samples as myeloid-stromal (57.7%, 71/123), lymphoid (31.7%, 39/123), and paucicellular pathotypes (10.6%, 13/123). RA patients with myeloid-stromal pathotype showed the highest rate of radiographic progression (43.7% vs. 23.1% vs. 7.7%, p = 0.011), together with the lowest rate of Boolean remission at 3, 6, and 12 months. Baseline synovial myeloid-stromal pathotype independently predicted radiographic progression at 1 year (adjusted OR: 3.199, 95% confidence interval (95% CI): 1.278, 8.010). Similar results were obtained in a subgroup analysis of treatment-naive RA. Conclusions: This novel fibroblast-based myeloid-stromal pathotype could predict radiographic progression at 1 year in active RA patients which may contribute to the shift of therapeutic decision in RA. [ABSTRACT FROM AUTHOR]

Background: Various Joint-preserving therapy (JPT) methods have been performed and tried in recent decades, but their results and efficacy were inconsistent and controversial. The purpose of this study is to evaluate its effectiveness and whether there are statistical differences in treatment between different interventions based on published RCT studies.Methods: Following the PRISMA-NMA checklist, Medline, EMBASE, Web of Science, and Cochrane Library databases were searched and collected related RCT studies. The sources were searched from inception up to October 30, 2020. The primary outcomes including the rate of radiographic progression and conversion to THA and the secondary outcome -Harris Hip Scores (HHS) were extracted and compared in a Network meta-analysis.Results: Seventeen RCT studies involving 784 patients (918 hips) with seven interventions including CD (core decompression), CD + BG (bone graft), CD + TI (tantalum rod implantation), CD + CT (Cell therapy), CD + BG + CT, VBG (vascularized bone graft), and nonsurgical or conservative treatment for ONFH were evaluated. In the radiographic progression results, CD + CT showed a relatively better result than CD, CD + BG and non-surgical treatment, the surface under the cumulative ranking curve (SUCRA) plot displayed that CD + CT (96.4%) was the best, followed by CD (64.1%).In conversion to THA results, there were no significant differences between the JPT methods and non-surgical treatment. In HHS, there was also no significant difference, other than CD + BG showed a statistical difference than non-surgical treatment only in terms of Cis, but the SUCRA was highest in non-surgical treatment (80.5%) followed by CD + CT (72.8%).Conclusions: This Net-work meta-analysis demonstrated that there was no statistical difference in the outcome of radiographic progression and conversion to THA, also in HHS, other than CD + CT showed a relatively superior result in radiographic progression than nonsurgical treatment, namely, it's maybe an effective method for delaying disease progression or reducing disease development based on current evidence. [ABSTRACT FROM AUTHOR]

ObjectivesThis study aims to investigate if addition of fibroblast-stromal cell markers to a classification of synovial pathotypes improves their predictive value on clinical outcomes in rheumatoid arthritis (RA).MethodsActive RA patients with a knee needle synovial biopsy at baseline and finished 1-year follow-up were recruited from a real-world prospective cohort. Positive staining for CD20, CD38, CD3, CD68, CD31, and CD90 were scored semiquantitatively (0-4). The primary outcome was radiographic progression defined as a minimum increase of 0.5 units of the modified total Sharp score from baseline to 1 year.ResultsAmong 150 recruited RA patients, 123 (82%) had qualified synovial tissue. Higher scores of CD20+ B cells, sublining CD68+ macrophages, CD31+ endothelial cells, and CD90+ fibroblasts were associated with less decrease in disease activity and greater increase in radiographic progression. A new fibroblast-based classification of synovial pathotypes giving more priority to myeloid and stromal cells classified samples as myeloid-stromal (57.7%, 71/123), lymphoid (31.7%, 39/123), and paucicellular pathotypes (10.6%, 13/123). RA patients with myeloid-stromal pathotype showed the highest rate of radiographic progression (43.7% vs. 23.1% vs. 7.7%, p = 0.011), together with the lowest rate of Boolean remission at 3, 6, and 12 months. Baseline synovial myeloid-stromal pathotype independently predicted radiographic progression at 1 year (adjusted OR: 3.199, 95% confidence interval (95% CI): 1.278, 8.010). Similar results were obtained in a subgroup analysis of treatment-naive RA.ConclusionsThis novel fibroblast-based myeloid-stromal pathotype could predict radiographic progression at 1 year in active RA patients which may contribute to the shift of therapeutic decision in RA.

The prevention of joint deformity is among the most important treatment goals of psoriatic arthritis. Some biologics disease-modifying antirheumatic drugs (bDMARDs) have been demonstrated to be effective for both the skin and joints, as well as for slowing radiographic progression. However, there has been a lack of direct comparisons of bDMARDs. To evaluate the comparative effects of bDMARDs in preventing radiographic progression in psoriatic arthritis, we conducted a systematic review and network meta-analysis. On March 7 2022, a search for relevant randomized trials was conducted on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Our outcomes included radiographic non-progression, a mean change in the total radiographic score, and adverse events leading to discontinuation (DAE) at week 24. We included 11 trials on 10 bDMARDs, involving 4010 participants. Most bDMARDs were more effective than placebos in achieving radiographic non-progression, including adalimumab (odds ratio (OR) 4.7, 95% confidence interval (CI) 2.66–8.29), etanercept (OR 4.19, 95% CI 1.65–10.61), certolizumab pegol (OR 2.83, 95% CI 1.55–5.2), secukinumab 300 mg (OR 2.63, CI 1.62–4.27), infliximab (OR 2.54, CI 1.13–5.69), ixekizumab (OR 2.22, 95% CI 1.06–4.65), golimumab (OR 2.21, 95% CI 1.24–3.93), and abatacept (OR 1.54, 95% CI 1.03–2.28). A significant reduction in the total radiographic score was found in infliximab (standardized mean difference (SMD) −0.59, 95% CI −0.87, −0.3), etanercept (SMD −0.51, 95% CI −0.78, −0.23), adalimumab (SMD −0.45, 95% CI −0.64, −0.26), ixekizumab (SMD −0.37, 95% CI −0.62, −0.12), secukinumab 300 mg (SMD −0.33, 95% CI −0.50, −0.15), golimumab (SMD −0.33, 95% CI −0.58, −0.09), secukinumab 150 mg (SMD −0.25, 95% CI −0.43, −0.07), certolizumab pegol (SMD −0.23, 95% CI −0.44, −0.03), and ustekinumab (SMD −0.19, 95% CI −0.35, −0.33). No significant differences in DAE were detected between bDMARDs. In conclusion, anti-tumor necrosis factor agents (adalimumab, infliximab, and etanercept) may be preferred for treating psoriatic arthritis for their superiority in preventing radiographic progression.

ObjectiveDocumentation of quality measures (QMs) in rheumatoid arthritis (RA) is used as a surrogate for measure of quality of care, but the association of this documentation with radiographic outcomes is uncertain. We examined documentation of RA QMs, for disease activity and functional status and the association with radiographic outcomes.MethodsData were analyzed for 438 RA patients in a longitudinal cohort with complete data on van der Heijde-modified Total Sharp Score (TSS). All rheumatologist (N = 18) notes in the electronic medical record during a 24-month period were reviewed for RA QMs. Any mention of disease activity categorized as low, moderate, or high was considered documentation of the QM for disease activity. Functional status QM documentation included any mention of the impact of RA on function. Change in TSS was quantified with progression defined as ≥1 unit per year. We compared percent of visits with an RA QM documented and mean change in TSS.ResultsThe mean age in the cohort was 56.9 years, disease duration was 10.8 years, baseline DAS28 score was 3.8 (±1.6), 67.7% were seropositive, and 33.9% used a biologic DMARD. Radiographic progression was observed in 28.5%. Disease activity was documented for 29.0% of patient visits and functional status in 74.7%; neither had any significant relationship to mean TSS change (both P > 0.10).ConclusionThe documentation of RA QMs was infrequent and not associated with radiographic outcomes over 24 months.

Abstract Background The 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). Methods This 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. Results Data 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

Abstract Objective The aim of this study was to compare radiographic progression in patients with ankylosing spondylitis (AS) treated for up to 2 years with secukinumab (MEASURE 1) with a historical cohort of biologic-naïve patients treated with NSAIDs (ENRADAS). Methods Baseline and 2-year lateral cervical and lumbar spine radiographs were independently evaluated using mSASSS by two readers, who were blinded to the chronology and cohort of the radiographs. The primary endpoint was the proportion of patients with no radiographic progression (mSASSS change ≤ 0 from baseline to year 2). The Primary Analysis Set included patients with baseline (≤ day 30) and post-baseline day 31–743 radiographs. Sensitivity analyses were performed to assess the robustness of the comparison between the two cohorts, as follows: Sensitivity Analysis Set 1 included all patients with baseline (≤ day 30) and year 2 (days 640–819) radiographs; Sensitivity Analysis Set 2 included all patients with baseline and post-baseline (> day 30) radiographs. Results A total of 168 patients (84%) from the MEASURE 1 cohort and 69 (57%) from the ENRADAS cohort qualified for the Primary Analysis Set. Over 2 years, the LS (SE) mean change from baseline in mSASSS for the primary analysis was 0.55 (0.139) for MEASURE 1 vs 0.89 (0.216) for ENRADAS (p = 0.1852). Mean changes from baseline in mSASSS were lower in MEASURE 1 vs ENRADAS for the primary and sensitivity analyses. The proportion of patients with no radiographic progression was consistently higher in the MEASURE 1 vs ENRADAS cohort across all cutoffs for no radiographic progression (change in mSASSS from baseline to year 2 of ≤ 0, ≤ 0.5, ≤ 1, and ≤ 2), but the differences were not statistically significant. Conclusion Secukinumab-treated patients demonstrated a numerical, but statistically non-significant, higher proportion of non-progressors and lower change in mSASSS over 2 years versus a cohort of biologic-naïve patients treated with NSAIDs.

Aim. To find the relationship between bone mineral density (BMD) and risk of knee OA progression in a 5-year prospective study. Materials and methods. 110 females with knee OA were examined twice with 5-year interval. Examination included filling questionnaires, VAS pain assessment, plain knee radiography and axial skeleton densitometry. I stage knee OA was established in 33 (30%) patients, II stage - in 46 (41.8%), III stage - in 26 (23.6%), and IV - in 5 (4.5%). Normal lumbar vertebrae densitometry BMD values were found in 45 patients (40.9%), osteopenia - corresponding BMD values - in 33 (30.0%), and osteoporosis - in 32 (29.1%). Normal femoral neck BMD values were identified in 60 (54.5%) patients, osteopenia - level BMD - in 48 (43.7%), osteoporosis - in 2 (1.8%). In all premenopausal patients (n=15) axial skeleton BMD values were normal. Results. In 5-year interval radiographic progression was established in 40 patients (Group 2), while in 70 (Group 1) patients no progression occurred. Both groups were comparable in terms of age and disease duration, although, more patients from Group 2 tended to have normal baseline densitometry BMD values - both in lumbar vertebrae and femoral neck: 47.5% vs 37.1%, and 62.5% vs 44.3% as compared to Group 1 patients. Patients from Group 1 more often had BMD values corresponding to osteoporosis and osteopenia: 32.9% vs 22.5%, and 55.7% vs 37.5%, respectively, as compared to Group 2 patients, although not achieving statistical significance. These differences were still identifiable after 5-year interval. Absolute BMD values at the second examination in 5 years were indicative of statistically significant increase in femoral neck and total hip BMD in Group 2 patients with knee OA progression: 0.79±0.11 vs 0.73±0.16, р

Abstract Background Biomarkers of rheumatoid arthritis (RA) disease activity typically measure inflammation or autoimmunity (e.g. CRP, RF). C1M and C3M, metabolites of type I and III collagen, are markers reflecting tissue metabolism. These markers have been documented to provide additional prognostic and predictive value compared to commonly used biomarkers. We investigated the relationship of high serum levels of C1M or C3M to radiographic progression, and benchmarked them to CRP and RF. Methods Placebo treated patients of the OSK1, 2 and 3 studies (Phase III clinical trials testing efficacy of fostamatinib) with baseline serum biomarkers C1M, C3M, CRP and RF were included (nBL = 474). Van der Heijde mTSS was calculated at baseline and 24-week (n24 = 261). Progression was defined as moderate or rapid by ΔmTSS ≥0.5 or ≥ 5 units/year. Patients were divided into subgroups; low (L), high (H) or very high (V) C1M, C3M and CRP, or RF negative, positive and high positive. Difference in clinical parameters were analyzed by Mann-Whitney or χ2tests, and modelling for prediction of progression by logistic regression including covariates (age, gender, BMI, and clinical assessment scores). Results Levels of C1M, C3M, CRP and RF were significantly (p

Objective: To compare the capacity of various disease activity indices to evaluate changes in function, IL-6 levels, and radiographic progression in early and established rheumatoid arthritis (RA).Methods: Secondary data analysis of a clinical trial assessing the efficacy of tocilizumab in patients with established RA (ACT-RAY) and a longitudinal prospective register of early arthritis (PEARL). Targeted outcomes were changes in physical function, measured with the health assessment questionnaire (HAQ), IL-6 serum levels, and radiographic progression. The “Hospital Universitario La Princesa Index” (HUPI), DAS28 using erythrocyte sedimentation rate and SDAI were the disease activity indices compared. Models adjusted for age and sex were fitted for each outcome and index and ranked based on the R2 parameter and the quasi-likelihood under the independence model criterion.Results: Data from 8,090 visits (550 patients) from ACT-RAY and 775 visits (534 patients) from PEARL were analyzed. The best performing models for HAQ were the HUPI (R2 = 0.351) and SDAI ones (R2 = 0.329). For serum IL-6 levels, the SDAI (R2 = 0.208) followed by the HUPI model (R2 = 0.205). For radiographic progression in ACT-RAY, the HUPI (R2 = 0.034) and the DAS28 models (R2 = 0.026) performed best whereas the DAS28 (R2 = 0.030) and HUPI models (R2 = 0.023) did so in PEARL.Conclusions: HUPI outperformed other indices identifying changes in HAQ and radiographic progression and performed similarly to SDAI for IL-6 serum levels.

As the COVID-19 epidemic is still ongoing, a more rapid detection of SARS-CoV-2 infection such as viral antigen-detection needs to be evaluated for early diagnosis of COVID-19 disease. Here, we report the dynamic changes of SARS-CoV-2 viral antigens in nasopharyngeal swabs of COVID-19 patients and its association with the viral nucleic acid clearance and clinical outcomes. Eighty-five COVID-19 patients were enrolled for detection of SARS-CoV-2 viral antigens, including 57 anti-SARS-CoV-2 antibody negative cases and 28 antibody positive cases. The viral antigen could be detected in 52.63% (30/57) patients with SARS-CoV-2 antibody negative at the early stage of SARS-CoV-2 infection, especially in the first 5 days after disease onset (p = 0.0018) and disappeared in about 8 days after disease onset. Viral antigens were highly detectable in patients with low Ct value (less than 30) of SARS-CoV-2 nucleic acid RT-PCT assay, suggesting the expression of viral antigen was associated with high viral load. Furthermore, positive antigen detection indicated disease progression, nine cases with positive antigen (9/30, 30.0%), in contrast to two cases (2/27, 7.40%) (p = 0.0444) with negative antigen, which progressed into severe disease. Thus, the viral antigens were persistent in early stages of infection when virus was in highly replicating status, and viral antigen detection promises to rapidly screen positive patients in the early stage of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

The concept of axial spondyloarthritis (axSpA) encompasses both non-radiographic (nr-axSpA) and traditional radiographic axSpA (r-axSpA) forms. The former was conceived following the establishment of the ASAS classification criteria for axSpA, which for the first time included the use of magnetic resonance imaging of the sacroiliac joints. This facilitated the classification of patients with axSpA who did not present substantial structural damage. This conception of nr-axSpA revolutionized the classical understanding of axSpA opening new doors for research and broadening the scope of treatment to the entire spectrum of axSpA. In this sense, epidemiologic patterns of the disease were viewed anew, and early diagnosis became a primary objective in the management of the disease. However, despite these advances, this new axSpA subtype led to some concerns within the scientific community. These issues have been addressed by several studies that set out to clarify the concept of nr-axSpA. In this review, we summarize the findings of the most relevant studies including nr-axSpA and then discuss recent advances in understanding disease clinical patterns, burden of disease, and treatment effects. Current scientific research has shown subtle differences between nr-axSpA and r-axSpA. In the near future, these advances will allow for better management of individual patients across the axSpA spectrum. [ABSTRACT FROM AUTHOR]

Objectives: The Simple Erosion Narrowing Score (SENS) is a simplification of the Sharp/van der Heijde score (SHS). Previous studies found SENS and SHS to have very similar measurement properties, but suggest that SENS has a lower discriminative ability that may result in reduced power. Therefore, we aimed to quantify the effect of using SENS rather than SHS on the power to show between-group differences in radiographic progression., Methods: Using data from two clinical trials in rheumatoid arthritis (DRESS and BeSt), SENS was derived from the SHS. Criterion validity of the SENS in relation to the SHS was assessed by calculating the Spearman correlation. The power of both scores to show a difference between groups was compared using bootstrapping to generate 10.000 replications of each study. Then, the number of replications with a significant difference in progression (using ANCOVA adjusted for baseline scores) were compared., Results: Correlations between SENS and SHS were all >0.9, indicating high criterion validity of SENS compared with SHS as a reference standard. There was one exception, the DRESS study showed a somewhat lower correlation for the change score at 18 months (0.787). The loss in power of SENS over SHS was limited to at most 19% (BeSt year 5). In addition, the difference in power between SENS and SHS is smaller at higher levels of power., Conclusion: SENS appears to be a reasonable alternative to SHS, with only a limited loss of power to show between-group differences in radiographic progression., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Objective: In prostate cancer treated with androgen deprivation therapy (ADT), the initial sign of treatment resistance is often prostate-specific antigen (PSA) progression, followed by radiographic progression. However, the association between these two forms of progression remains unclear, especially in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with androgen receptor pathway inhibitors. We sought to evaluate the association between radiographic progression, PSA progression, and outcomes of apalutamide therapy in mCSPC., Methods: We analyzed individual participant-level data for patients randomized within the TITAN trial who experienced radiographic progression during follow-up (N = 326). This study investigated radiographic progression without simultaneous or preceding PSA progression, as defined by the Prostate Cancer Working Group 2 (discordant progression), and explored the association of such progression with radiographic progression-free survival., Key Findings and Limitations: Among the patients who developed radiographic progression, 115 (35.3%) had been treated with apalutamide plus ADT (the apalutamide group) and 211 (64.7%) with placebo plus ADT (the placebo group). Discordant progression occurred in 52.2% of patients (60 of 115) in the apalutamide group and 27.5% (58 of 211) in the placebo group (p < 0.001). A multivariable logistic regression analysis showed that discordant progression was associated with apalutamide treatment. We found evidence of an association between discordant progression and shorter radiographic progression-free survival., Conclusions and Clinical Implications: This study found that nearly half of the patients with mCSPC treated with apalutamide who experienced radiographic progression developed it without corresponding PSA progression, suggesting that heavy reliance on PSA monitoring may be inadequate for assessing disease activity in this context., Patient Summary: In patients who have metastatic castration-sensitive prostate cancer (mCSPC) and are being treated with apalutamide, radiographic images may show cancer progression even if prostate-specific antigen tests indicate no change. This highlights the importance of regular imaging when using apalutamide to manage mCSPC., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: Obesity conveys a risk for RA development, while paradoxically, associating with less radiographic progression after RA diagnosis. Using MRI we can study this surprising association in detail from MRI-detected synovitis and osteitis to MRI-detected erosive progression, which precedes radiographic progression. Previous research suggested obesity associates with less osteitis and synovitis. We therefore aimed to (i) validate the previously suggested association between BMI and MRI-detected osteitis/synovitis; (ii) study whether this is specific for ACPA-positive or ACPA-negative RA or also present in other arthritides; (iii) study whether MRI-detected osteitis associates with MRI-detected erosive progression; and (iv) study whether obesity associates with MRI-detected erosive progression., Methods: We studied 1029 early arthritis patients (454 RA, 575 other arthritides), consecutively included in Leiden Early Arthritis Clinic. At baseline patients underwent hand-and-foot MRI that were RAMRIS-scored, and 149 RA patients underwent follow-up MRIs. We studied associations between baseline BMI and MRI-detected osteitis/synovitis (using linear regression), and erosive progression (using Poisson mixed models)., Results: In RA, higher BMI associated with less osteitis at disease onset (β = 0.94; 95% CI: 0.93, 0.96) but not with synovitis. Higher BMI associated with less osteitis in ACPA-positive RA (β = 0.95; 95% CI: 0.93, 0.97), ACPA-negative RA (β = 0.97; 95% CI: 0.95, 0.99) and other arthritides (β = 0.98; 95% CI: 0.96, 0.99). Over 2 years, overweight and obesity associated with less MRI-detected erosive progression (P = 0.02 and 0.03, respectively). Osteitis also associated with erosive progression over 2 years (P < 0.001)., Conclusions: High BMI relates to less osteitis at disease onset, which is not confined to RA. Within RA, high BMI and less osteitis associated with less MRI-detected erosive progression. This suggests that the protective effect of obesity on radiographic progression is exerted via a path of less osteitis and subsequently fewer MRI-detected erosions., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: to compare the impact of continuous or on-demand use of nonsteroidal anti-inflammatory drugs (NSAIDs) on the activity and radiographic progression of early axial spondyloarthritis (axSpA).Subjects and methods. The investigation enrolled patients from the early spondyloarthritis cohort who met the 2009 Assessment of Spondyloarthritis International Society (ASAS) criteria for axSpA. This analysis included 68 patients who had been followed up for at least 24 months. The mean age at the time of inclusion in the investigation was 28.5±5.8 years; the mean disease duration was 24.1±15.4 months; 63 (92.6%) patients were HLA-B27-positive. The patients were divided into two groups: 1) 35 patients used NSAIDs at maximum therapeutic doses continuously during the follow-up period; 2) 33 patients received these drugs on-demand, depending on the presence and severity of back pain.Results and discussion. After 2-year follow-up, the median stage of radiographic sacroiliitis (SI) in Group 1 was unchanged and remained equal to 4; that in Group 2 in this period significantly increased from 3 to 4 scores (p < 0.05). At baseline, the patient groups did not differ in C-reactive protein (CRP) levels, the Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP), and the Bath Ankylosing Spondylitis Functional Index (BASFI); however, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was higher in Group 1 (p < 0.05). The number of patients with active SI, as evidenced by magnetic resonance imaging (MRI), and the degree of its severity did not differ significantly between groups. After 2 years, all the patients retained low disease activity according to ASDAS-CRP, BASDAI, and CRP levels; and these measures did not differ significantly between groups either; the BASFI became higher in Group 1. MRI findings indicated that the number of patients with active SI decreased, but no differences were found between the groups.Conclusion. In patients with early axSpA, the continuous intake of NSAIDs can slow radiographic progression to a greater extent than their on-demand use.

Abstract Background Previous studies have revealed that hepatitis B virus (HBV) infection may be related to rheumatoid arthritis (RA), but there are no studies on the presence of HBV antigens or nucleic acid in synovium from patients with RA with HBV infection. In the present study, we investigated the presence of HBV in the synovium and its clinical significance in RA. Methods Fifty-seven consecutive patients with active RA (Disease Activity Score 28-joint assessment based on C-reactive protein ≥ 2.6) and available synovial tissue who had completed 1 year of follow-up were recruited from a prospective cohort. The patients were divided into chronic HBV infection (CHB, n = 11) and non-CHB groups according to baseline HBV infection status. Clinical data were collected at baseline and at 1-, 3-, 6-, and 12-month follow-up. Radiographic changes of hand/wrist at baseline and month 12 were assessed with the Sharp/van der Heijde-modified Sharp score (mTSS). HBV in synovium was determined by immunohistochemical staining for hepatitis B virus surface antigen and hepatitis B virus core antigen (HBcAg) and by nested PCR for the HBV S gene. Results HBcAg was found in the synovium of patients with RA with CHB (7 of 11, 64%), which was confirmed by PCR for the HBV S gene. Compared with the non-CHB group, more CD68-positive macrophages, CD20-positive B cells, and CD15-positive neutrophils infiltrated the synovium in the CHB group (all p

Abstract Background Identification of risk factors for rapid joint destruction in early rheumatoid arthritis (RA) can be helpful for optimizing treatment, and improving our understanding of destructive arthritis and its mechanisms. The objective of this study was to investigate the relationship between early RA patient characteristics and subsequent rapid radiographic progression (RRP). Methods An inception cohort of patients with early RA (symptom duration

Abstract Background Previous studies have revealed that hepatitis B virus (HBV) infection may be associated with rheumatoid arthritis (RA), while there are no further clinical studies regarding the role of HBV infection in RA progression during disease-modifying anti-rheumatic drug (DMARD) therapy. Here, we aimed to explore the influence of HBV infection on radiographic and clinical outcomes among patients with RA in a clinical practice setting. Methods Thirty-two consecutive patients with RA (Disease Activity Score 28-joint assessment based on C-reactive protein (DAS28-CRP) ≥2.6) with chronic HBV infection (CHB) were retrospectively recruited as the CHB group and 128 age-matched, sex-matched, and disease activity-matched contemporary patients with RA without CHB were included in the non-CHB group. Clinical data were collected at baseline and visits at month 1, 3, 6, and 12. The therapeutic target was defined as DAS28-CRP 24 months). The primary outcome was the percentage of patients with one-year radiographic progression (a change in modified total Sharp score ≥0.5). Results Compared with the non-CHB group, a significantly higher percentage of patients with one-year radiographic progression was observed in the CHB group (53% vs. 17%, p

Rheumatoid arthritis (RA) is an autoimmune rheumatic disease characterized by chronic erosive arthritis and systemic inflammatory changes, which lead to early disability and worse quality of life in patients. Current imaging techniques have become a new stage of not only in diagnosing, but also in assessing their course and in predicting outcomes. Joint ultrasonography in RA is now considered to be one of the available and widely used techniques. This review of literature provides a detailed analysis of publications on joint ultrasonography in RA. Their results are controversial and frequently cast any doubt on the informative value of this technique. The large number of original publications suggests that rheumatologists are taking a great interest in this method. The review gives the current points of view on the pathogenetic rationale, diagnostic value, and prognostic potential of using ultrasound in patients with RA. It discusses the issues of a methodology for diagnostic procedures, the need of using power Doppler imaging, and current semiquantitative inflammation rating scales. The review presents the existing guidelines for the use of ultrasound in RA, confirming the importance of this imaging technique.

Abstract Background Early and intensive targeted treatment with disease modifying anti-rheumatic drugs (DMARDs) has been shown to lead to substantial reductions in disease activity and radiograph damage in patients with early rheumatoid arthritis (RA). The aim of this quasi-experimental study was to compare the first-year radiographic progression rates between a treat-to-target (T2 T) strategy with initial combination therapy (strategy II, started in 2012) versus an initial step-up monotherapy (strategy I, started in 2006). Methods A total of 128 patients from strategy II was individually matched with 128 patients from strategy I on sex, age (± 5 yrs.) and baseline disease activity (± 0.5 on the DAS28). Differences in radiographic progression (Sharp/van der Heijde) scores (SHS) and the number of patients experiencing a minimal clinically important difference (MCID; ≥ 5 SHS points) between both strategies were tested with Mann Whitney U and chi-square tests. Next, linear and logistic regression analyses were performed to examine which baseline variables were associated with radiographic progression scores and the probability of experiencing an MCID within 1 year. Results Patients with initial combination therapy had slightly higher baseline disease activity scores and pain scores, but better mental health scores. Patients with initial monotherapy had significantly more, and more frequently clinically relevant, radiographic progression after 1 year. Experiencing a MCID was independently associated with fewer tender joints (p = 0.050) and higher erythrocyte sedimentation rate (p = 0.015) at baseline. Conclusion Treating early RA patients with initial combination therapy results in better radiographic outcomes than initial monotherapy in daily clinical practice. Trial registration Netherlands Trial Register NTR578, 12 January 2006.

Abstract Background Pain is the principal clinical symptom of osteoarthritis (OA), and development of safe and effective analgesics for OA pain is needed. Drug development of new analgesics for OA pain is impaired by substantial change in pain in patients receiving placebo, and more data describing clinical characteristics and pain categories particularly associated with this phenomenon is needed. The purpose of this post-hoc analysis was to investigate clinical characteristics and pain categories and their association with radiographic progression and placebo pain reduction (PPR) in OA patients as measured the Western Ontario and McMasters Arthritis (WOMAC). Methods Pooled data from the placebo groups of two phase III randomized clinical trials in patients with knee OA followed for 2 years were analyzed. Differences between individual sub-scores and pain categories of weight-bearing and non-weight bearing pain over time were assessed. Selected patient baseline characteristics were assessed for association with PPR. Association between pain categories and radiographic progression was analyzed. Results The reduction of pain in placebo-treated patients was significantly higher in the composite of questions related to weight-bearing pain compared to non-weight-bearing pain of the target knee. Baseline BMI, age and JSW were not associated with pain change. Pain reduction was higher in the Target knee, compared to the Non-Target knee at all corresponding time-points. A very weak correlation was found between weight-bearing pain and progression in the non-target knee. Conclusions These results indicate that the reduction in pain in patients treated with placebo is significantly different between pain categories, as weight-bearing pain was significantly more reduced compared to non-weight-bearing pain. Further research in pain categories in OA is warranted. Trial Registration NCT00486434 (trial 1) and NCT00704847 (trial 2)

Achievement of minimal disease activity (MDA) is the main goal of the Treat-to-target (T2T) strategy in early psoriatic arthritis (ePsA). Radiographic progression in patients with ePsA treated according to the T2T strategy has been studied insufficiently. Objective: To study the frequency of achievement of MDA and X-ray progression in patients with early PsA treated according to the T2T strategy 1 year after initiation of treatment. Subjects and methods. Forty patients (22 women) with active ePsA, who met the CASPAR criteria (mean age was 38,4±11,1 years, the median duration of PsA – 7,0 [4,0; 18,0] months, the duration of psoriasis – 38,0 [9,5; 114,0] months, DAS – 3,8 [3,2; 4,7]), were included in the REMARKA study. At the start of the study all patients received subcutaneous methotrexate (MTX) in a dose of 20–25 mg/week. If high or moderate disease activity persisted after 3–6 months, patients (n=21) were transferred to combined therapy with MTX and a biological agent (BA). The remaining 19 patients continued MTX monotherapy. Initially and one year later, the MDA criteria were evaluated (tender joint count ≤1, swollen joint count ≤1, PASI ≤1 or BSA ≤3, pain on visual analog scale (VAS) ≤15 mm, patient global assessment of activity on VAS ≤20 mm, HAQ ≤0,5, tender enthesis count ≤1) and digital radiography of hands and feet was performed. Radiographic progression was assessed by an independent radiologist using the modified method of Sharp/van der Heijde: total score (TS) = erosion score (ES) + joint space narrowing score (JSNS). Results and discussion. At the time of enrollment, 23 patients (57%) with ePsA had erosions. One year later the number of patients with erosions increased to 26 (65%). The TS has significantly increased, although its median has not changed (before treatment – 91.5 [72; 108,5], after one year – 91.5 [73,5; 111,5], p0,05). In 29 out of 40 patients (72,5%), no radiographic progression was detected neither in the ES nor in the JSN; 13 out of 29 (45%) received MTX and 16 (55%) – MTX + BA. In 11 out of 40 (27,5%) patients, negative radiographic changes according to ES (n=10) and JSNS (n=4) were detected, with three patients having progression in both scores. In this group, 6 patients (54,5%) received MTX monotherapy and 5 (45,5%) – MTX + BA. After 1 year, 25 (62,5%) patients achieved MDA. Among patients who did not achieve MDA (n=15) after 1 year, the ES was significantly higher at the beginning of the study compared to those who achieved MDA: median 3 [2; 9] and 0 [0; 3], respectively (p< 0,05). In the group of patients who did not achieve MDA in a year, radiographic progression was more significant. Conclusion. In russian cohort more than half of patients with ePsA had erosions. After one year of follow up 72,5% of patients with ePsA treated according to the T2T strategy showed no radiographic progression, and a quarter of patients (27,5%) had negative radiographic changes, regardless of the type of the therapy. Patients with ePsA, who achieved MDA, had less prominent radiographic progression in a year.

Spondyloarthritis (SpA) is currently evaluated as predominantly peripheral or axial according to the current classification. The definition of axial SpA (axSpA) has been included imaging findings (X-rays or magnetic resonance imaging) or associated clinical findings in addition to chronic back pain. New bone formation is the most important predictors of disease progression. Therefore it is the main target of disease management. Prevention of new bone formation might control an important cause of morbidity. X-rays are currently the standard method in evaluating the new bone formation. Sacroiliac joint graphs are recognized as key imaging in the diagnosis and classification, but its importance is limited in progression. Spinal X-rays are used in the follow-up of disease progression. Various radiographic scores, which are consisted of defined lesions, are used for progression. In this review, the imaging methods and scoring systems which are used to evaluate the disease course or progression of axSpA will be evaluated. In addition to the contribution of these methods used to follow up, the limitations also will be discussed. [ABSTRACT FROM AUTHOR]

Objectives: The clinical benefit of conventional disease-modifying antirheumatic drugs (cDMARDs) for treating ankylosing spondylitis (AS) is generally limited to improvements in peripheral arthritis. However, cDMARDs could be conditionally considered as alternatives to established drugs for improving axial manifestations in exceptional circumstances. However, there are few studies of the impact of cDMARDs on radiographic progression outcomes. Therefore, we investigated the effectiveness of cDMARDs on radiographic progression in AS. Methods: Among 1280 AS patients at a single hospital from 2000 to 2018, 301 who had been treated with sulfasalazine (SSZ) or methotrexate (MTX) were enrolled. For each patient, the entire follow-up period was split into 1-year intervals. Each interval was classified as either an "on-cDMARD" interval, which was a period of treatment with SSZ alone, MTX alone, or a combination of SSZ and MTX, or an "off-cDMARD" interval, which was a period without cDMARD treatment. Radiographic progression was scored using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The relationship between cDMARD use and radiographic progression within the intervals, defined as the rate of mSASSS progression, was investigated using linear models with adjustment for potential confounding covariates and for clustering among observations from the same patient. Results: The 732 on-cDMARD intervals and 1027 off-cDMARD intervals were obtained from enrolled patients. In multivariable regression analysis, there was no significant association between cDMARDs and the rate of mSASSS progression (β = −0.081, p = 0.418). The mean adjusted mSASSS change per year was 0.610 from on-cDMARD intervals and 0.691 from off-cDMARD intervals. Conclusion: Treatment with cDMARDs may not reduce radiographic progression in AS patients. [ABSTRACT FROM AUTHOR]

Objectives The aim of this prospective study was to examine whether ultrasound or clinical abnormalities at enthesal sites predict radiographic progression at entheses in psoriatic arthritis (PsA). Methods Consecutive PsA patients were included and subjected to clinical and ultrasound assessments at 14 entheses at baseline, 6 and 12 months. Radiographs were performed at 0 and 12 months. By US, we investigated structural (erosions, osteophytes) and inflammatory changes [grey scale (0–32) and power Doppler (0–14, range global ultrasound score 0–140)], and radiographs were evaluated for enthesophytes and erosions (score range 0–56). Multivariate regression models were conducted to identify the possible association of clinical and ultrasound findings with radiographic progression. Results We examined 83 patients at baseline, of whom 43 (51.8%) had complete clinical, ultrasound and X-ray data. Twenty-four of 43 patients (55.8%) developed radiographic progression of entheses. These patients were younger (49.6 vs 59.3, P  =0.005), had shorter disease duration (9.7 vs 17.9 years, P =0.015) and lower clinical disease activity at 6-months [disease activity in psoriatic arthritis (DAPSA) 6.7 vs 17.0, P =0.018] as compared with patients without progression. Non-progressors had higher ultrasound enthesophyte scores at baseline than progressors (20 vs 15, P <0.05). The multivariate regression analysis revealed that 48.6% of the variance of the X-ray score at 12-months follow-up (RegcoeffB = 0.827, P =0.000) could be explained by the baseline US enthesophyte score. Conclusion Our data indicate that radiographic progression at entheses is linked with age, disease duration and ultrasound verified enthesophytes at baseline. No other ultrasound parameter predicted radiographic progression at entheses. [ABSTRACT FROM AUTHOR]

To evaluate the short term effect of maximally tolerated dose of non-steroidal anti-inflammatory drugs (NSAIDs) on disease activity and radiographic progression of axial spondyloarthritis (axSpA) patients. A six-week prospective study on thirty patients with active axSpA. All patients were assessed at baseline visit, a follow-up visit after 2 weeks, and 6 weeks of treatment with a maximally tolerated dose of NSAID. Disease activity was assessed by determining Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS), and functional assessment by using Bath Ankylosing Spondylitis Functional Index (BASFI). Spinal mobility was assessed by the mean improvement in Bath Ankylosing Spondylitis Metrology Index (BASMI). Magnetic Resonance Imaging (MRI) of sacroiliac joints (SIJs) was taken at baseline and at the end of the study and was evaluated according to Berlin scoring method. Improvement in laboratory activity markers and all disease activity scores has been observed at week 6 of maximally tolerated dose of NSAIDs which were significant (p < 0.001). Additionally, ASDAS clinically important improvement was achieved in 63.3% of patients, and BASDAI50 was achieved in 30% and 56.7% of patients at week 2 and week 6, respectively. Furthermore, Berlin score showed an improvement by 14.2% with a reduction in bone marrow edema signal intensity of SIJs in 40% of patients. In Egyptian cohort of patients with axSpA, intake of maximally tolerated dose of NSAID could improve the health-related quality of life, disease activity scores, and sacroiliac joint inflammation on MRI. [ABSTRACT FROM AUTHOR]

Background: Numerous cross-sectional studies have reported the associations between rheumatoid arthritis (RA) and reduced skeletal muscle. We firstly explored the dynamic change of skeletal muscle and its effect on RA clinical outcomes in a real-world prospective cohort. Methods: Consecutive RA patients were treated according to the treat-to-target strategy and completed at least 1-year follow up. Clinical data and muscle index (assessed by bioelectric impedance analysis) were collected at baseline and visits at 3, 6, 9 and 12 months. Myopenia was defined by appendicular skeletal muscle mass index ⩽7.0 kg/m2 in men and ⩽5.7 kg/m2 in women. A 1-year radiographic progression as primary outcome was defined by a change in the total Sharp/van der Heijde modified score ⩾0.5 units. Results: Among 348 recruited patients, 315 RA patients (mean age 47.9 years, 84.4% female) completed 1-year follow up. There were 143 (45.4%) RA patients showing myopenia at baseline. Compared with those without baseline myopenia, RA patients with baseline myopenia had higher rate of 1-year radiographic progression (43.4% versus 21.5%, all p < 0.05). Baseline myopenia was an independent risk factor for 1-year radiographic progression with adjusted odds ratio (AOR) of 2.5-fold, especially among RA patients in remission at baseline both defined by Disease Activity Score in 28 joints (DAS28) including C-reactive protein (DAS28-CRP) or erythrocyte sedimentation rate (DAS28-ESR) with AOR of 18.5~42.9-fold. Further analysis of six subtypes of dynamic skeletal muscle change showed that newly acquired myopenia at endpoint was associated with radiographic progression (AOR of 5.4-fold). Conclusions: Reduced skeletal muscle is an independent predicting factor for 1-year aggravated joint destruction, especially in remission RA. The importance of dynamic monitoring of skeletal muscle and muscle improvement therapy are worth exploration. [ABSTRACT FROM AUTHOR]

Clinical outcomes in elderly-onset rheumatoid arthritis (EORA), starting after the age of 60, are conflicting. Thus, we aimed to investigate in a unique biopsy-driven, treatment-naïve early arthritis cohort, the relationship between synovial pathobiology of elderly- (EORA) and younger-onset rheumatoid arthritis (YORA) patients through clinical, imaging and treatment response outcome-measures. Patients (n = 140) with early RA (<12months) starting before (YORA, n = 99) or after (EORA, n = 41) age 60 had an ultrasound-guided synovial biopsy prior to conventional immunosuppressive therapy and after 6 months. Clinical, ultrasound and radiographic data were collected prospectively and compared between groups and against immunohistological features. Using multivariate logistic regression, we determined predictors of clinical response (disease activity score-28-erythrocyte sedimentation rate [DAS28-ESR]<3.2) at 6 months and radiographic progression (≥1-unit-increase in Sharp van der Heijde [SvdH] score) at 12 months. EORA patients were more frequently male and presented most commonly with an abrupt, polymyalgia rheumatica-like onset and extra-articular features. Both before and after treatment, DAS28-ESR was similar but ultrasound synovial-thickening (p <0.05) and power-Doppler (p <0.01) synovitis and SvdH (p <0.001) scores were higher in EORA patients. EORA was independently associated with poor treatment response at 6 months (OR=0.28, p = 0.047) and radiographic progression at 12 months (OR=4.08, p = 0.029). Synovial pathotype, synovitis scores and cellular infiltration were similar before treatment, but a pauci-immune-fibroid pathotype tended to be more common in YORA at 6 months (p = 0.093). Moreover, YORA patients had a marked improvement of all synovitis parameters (p <0.001), whereas EORA presented only mild decreases in synovitis (p <0.05), sublining macrophage (p <0.05) and T cell scores (p <0.05), with no significant changes in lining macrophages, B cells or plasma cells. Early EORA presents differently and has a worse overall prognosis than YORA, with poorer clinical, histological, ultrasonographic and radiographic outcomes. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis (axSpA) is a group of debilitating, chronic, rheumatic conditions characterized by inflammation and new bone formation, mainly involving the spine and the sacroiliac joints. The lack of biomarkers in axSpA is well known. Despite significant treatment advances in recent years thanks to the introduction of drugs with a new mode of action, such as new biologic and targeted synthetic disease-modifying antirheumatic drugs, no relevant improvement in the identification of disease biomarkers has been achieved. Common parameters, such as erythrocyte sedimentation rate and C-reactive protein, which are routinely used to measure systemic inflammation, are the sole markers available to date and are not adequate to assess disease activity in all patients. The aim of this study is to review the most promising serum biomarkers that may help treatment decision in axSpA via a proper assessment of disease activity and identification of negative prognostic factors. [ABSTRACT FROM AUTHOR]

Objective: The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings. Methods: Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required to adhere to a treat-to-target strategy. Biosamples (serum, urine) were acquired every 3 months, radiography of hands and feet every 6 months, and ultrasound of hands and feet every 3 months in a subset. Primary endpoint was radiographic progression by the Sharp/van der Heijde score. Results: A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. At baseline, the majority was female (76%), mean age 55.7 years, and mean disease duration 6.5 years. Patients had a mean of 8.4 swollen and 13.6 tender joints, 44-joint count Disease Activity Score (DAS44) 3.8, 77.7% rheumatoid factor-positive or anticitrullinated protein antibody-positive. Percentage of patients in DAS and American College of Rheumatology remission at 2 years was 52.2% and 27.1%, respectively. Percentage of patients with radiographic progression (> 0.5) at 1 and 2 years was 38.2% and 59.9%, respectively. Conclusion: The RA BIODAM prospective study succeeded in generating an extensive list of clinical, imaging (2343 radiographs), and biosample (4638 sera) resources that will be made available to expedite the identification and validation of biomarkers for radiographic damage endpoints. [ABSTRACT FROM AUTHOR]

Introduction: Machine learning is applied to characterize the risk and predict outcomes in multi-dimensional data. The prediction of radiographic progression in axial spondyloarthritis (axSpA) remains limited. Hence, we tested the feasibility of supervised machine learning algorithms to predict radiographic progression in axSpA. Methods: This is a retrospective and hospital-based study. Clinical and laboratory data obtained from two independent axSpA groups were used as training and testing datasets. Radiographic progression over 2 years was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and mSASSS worsening by ≥ two units was defined as progression. Seven machine learning models with different algorithms were fitted, and their performance for the testing dataset was assessed using receiver-operating characteristic (ROC) and precision-recall (PR) curve. Results: The training and testing groups had equivalent characteristics, and radiographic progression was identified in 25.3% and 23.7%, respectively. The generalized linear model (GLM) and support vector machine (SVM) were the top two best-performing models with an average area-under-curve (AUC) of ROC of over 0.78. SVM had the higher AUC of PR compared with GLM (0.56 versus 0.51). Balanced accuracy was over 65% in all models. mSASSS was the most informative variable, followed by the presence of syndesmophyte(s) at the baseline and sacroiliac joint grades. Conclusions: Clinical and radiographic data-driven predictive models showed reasonable performance in the prediction of radiographic progression in axSpA. Further modelling with larger and more detailed data could provide an excellent opportunity for the clinical translation of the predictive models to the management of high-risk patients. Key Points • Clinical and radiographic data-driven predictive models showed reasonable performance in the prediction of radiographic progression in axSpA. • Further modelling with larger and more detailed data could provide an excellent opportunity for the clinical translation of the predictive models to the management of high-risk patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to determine whether there is a relationship between radiographic slip progression and symptomatic worsening after decompression without fusion for low-grade degenerative lumbar spondylolisthesis (DLS).Methods: A retrospective review of 1-2-level minimally invasive surgical decompression for grade I-II DLS was performed. Included subjects had a minimum of 1-year follow-up with prospectively collected baseline and follow-up Oswestry Disability Index (ODI) scores.Results: Fifty-six patients (33 females, 58.9%), having a mean age 65.6 years (SD 10.0), met inclusion criteria. Spondylolisthesis slip percentage increased in 55.4% (31/56) of patients. Slip percentage increased significantly (p = 0.002) from baseline (mean 17.2; SD 8.0) to follow-up (mean 20.1; SD 9.6). A logistic regression model identified that females were more likely to have progressive slips compared to males (odd ratio 6.09, 95% CI 1.77-21.01; p = 0.004). ODI scores and spondylolisthesis slip percentage did not correlate at baseline (r = 0.0170; p = 0.90) nor follow-up (r = 0.094; p = 0.49). There was no correlation between the change in ODI scores and change in slip percentage from baseline to final follow-up (r = 0.0474; p = 0.73). Of the 31 patients with slip progression, there was no difference in mean ODI score changes (p = 0.91) for those with 1-5% progression (13/31 [41.9%]; - 18.0 [SD 19.7]) compared to those with > 5% slip progression (18/31 [58.1%]; - 18.7 [SD 16.4]).Conclusions: Despite a small degree of slip progression in the majority of patients, there was no correlation with symptom worsening, as measured by the ODI. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate radiographic progression according to the presence or absence of uveitis in patients with ankylosing spondylitis (AS). Patients and methods: A total of 598 patients (529 males, 69 females, mean age 38.1±9.2 years; range, 18 to 73 years) from the Observation Study of Korean Spondyloarthropathy Registry who met the modified New York criteria for AS were included in this study. At baseline, all data were stratified into two groups according to the presence or absence of uveitis. Baseline and radiographic progression were assessed for five years in this registry. Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was read by two radiologists. Reliability was assessed using inter- and intra-class correlation coefficient for each radiograph. Comparison of mSASSS changes was analyzed by analysis of covariance model after adjusting for confounding factors. Results: The evaluation of mSASSS showed good agreement between the two readers. A total of 193 patients (32.27%) had a history of uveitis that presented at a mean age of 39.6 years, including 30 females (15.54%). There were statistically significant differences in age (p=0.01), sex (p=0.04), hip joint involvement (p<0.01), and human leukocyte antigen B27 carrier state (p=0.02) between the two groups according to uveitis. A simple comparison revealed no significant difference in mSASSS change for five years between the two groups (mean: 3.05±0.62 vs. 3.78±0.78, p=0.47). After adjusting for confounding factors in multiple comparisons by Bonferroni correction, patients with uveitis had no significant association with mSASSS change for five years (mean: 6.29±1.32 vs. 5.49±1.39, p=0.68). Conclusion: Our study confirms that there is no significant association between uveitis and radiographic progression in patients with AS after adjusting for confounding factors. [ABSTRACT FROM AUTHOR]