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BACKGROUND: Understanding nutritions 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.

Background/Objectives: The therapeutic aim for rheumatoid arthritis (RA) is to control disease activity and prevent radiographic progression. Various clinical scores are used to assess disease activity in RA patients. The DAS 28 score can define states of low disease activity (LDA) and remission. Despite achieving LDA or remission, radiographic progression may, nevertheless, occur. However, the rates and frequency of this occurrence have not been analyzed in detail. (1) To characterize radiographic progression in patients with persistent DAS 28-defined LDA or remission. (2) Analyze the potential benefits of modifying therapeutic strategies in response to observed radiographic progression in patients with persistent LDA or remission. Methods: An analysis was conducted on RA patients enrolled in the SCQM (Swiss Clinical Quality Management) cohort. Persistent LDA or remission was defined as DAS 28 ≤ 3.2 or <2.6, respectively, recorded at two consecutive follow-up time points. Inclusion criteria involved patients with a minimum of two sets of radiographs taken during these LDA and/or remission periods. Radiographic progression was measured using the Ratingen score, a numerical scale ranging from 0 to 190, which quantifies joint erosions. Repair was defined as a decrease in the Ratingen score > 5 points/year, while progression was characterized by an increase of >1, >2, or >5 points change in the Ratingen score within a one-year timeframe. Results: Among 10′141 RA patients, there were 1′447 episodes of remission and 2′614 episodes of LDA, with two sets of X-rays available for assessment during these episodes. The rates of radiographic progression (>5 points change in the Ratingen score per year) were 11.2% for LDA and 8.8% for remission. Therapeutic adaptations were made in 7.0% of patients in remission and 12.9% of patients in LDA following radiographic progression. After radiographic progression despite LDA, loss of LDA was observed in 19% of patients with treatment intensification versus in 8.5% under continued treatment during follow-up within 36 months. Conclusions: We report a considerable rate of radiographic progression occurring in RA patients with LDA or clinical remission. Notwithstanding minor radiographic progression, maintaining therapeutic continuity seemed more favorable than altering the therapeutic regimen. [ABSTRACT FROM AUTHOR]

Objectives: Our objective was to assess the efficacy of golimumab (GLM) in patients with poor prognostic factors (PPFs). Methods: This is a post hoc analysis of GO-FORTH Phase 2/3 study. Cluster analysis was used to determine a patient population with high-risk patterns based on seven PPFs suggested by the European Alliance of Associations for Rheumatology recommendations and limited physical function. Radiographic progression, disease activity, and physical function and associated factors were evaluated over 52 weeks. Results: Overall, 261 rheumatoid arthritis patients were classified into three clusters characterised by high disease activity, high C-reactive protein levels, and limited physical function at baseline. GLM showed suppression of progressive modified total sharp score and decreases in Disease Activity Score 28-joint counts with erythrocyte sedimentation rate and Health Assessment Questionnaire – Disease Index, in all the clusters. In Cluster C that showed almost all the PPF characteristics, a higher rate of change in modified total sharp score ≤0 was observed in GLM 100 mg group than in GLM 50 mg group (63.9% versus 46.5%). C-reactive protein concentration and physical limitation were associated with radiographic progression of Cluster C in GLM treatment. Conclusions: GLM was effective in rheumatoid arthritis patients in a subpopulation at high risk of PPF in GO-FORTH study. A dose of 100 mg may be more beneficial in preventing radiographic progression in this population. [ABSTRACT FROM AUTHOR]

Abstract Background Complicated mild traumatic brain injury (cmTBI) is a common neurosurgical disorder that consumes a significant amount of healthcare resources without a clearly established benefit. Best practices for the management of cmTBI regarding triage, hospital admission, and the necessity for repeat imaging are controversial. Our objective is to describe the rate of radiographic progression and neurologic decline for isolated traumatic subarachnoid hemorrhage (itSAH) patients admitted to the hospital. We hypothesized that only a minority of itSAH patients suffer radiographic progression and that radiographic progression is not necessarily associated with neurologic decline. Methods Database queries and direct patient chart reviews were used to gather patient data. T-tests and Fisher’s exact tests were performed. Results A total of 340 patients with cmTBI associated with itSAH were included for analysis. The radiographic progression rate was 5.6%. There was no statistically significant association between age, gender, GCS at presentation, anticoagulation status, and risk of radiographic progression. However, subgroup analysis on anticoagulated patients did show those on warfarin had a statistically significant risk of radiographic progression (p = 0.003). No patient developed neurologic decline, irrespective of whether they developed radiographic progression. Conclusion Secondary triaging, hospital admission, ICU stay, and repeat HCT might not be necessary for awake, GCS 13–15 patients with itSAH without any other significant injuries. In the case of anticoagulant use, but not necessarily antiplatelet use, the medication should be reversed, and admission should be considered.

Objectives: The current study assesses the utility of matrix metalloprotease-3 (MMP-3) as a biomarker for joint damage in patients with rheumatoid arthritis receiving peficitinib. Methods: Rheumatoid arthritis patients with inadequate response to methotrexate were randomised to peficitinib 100 mg, peficitinib 150 mg, or placebo, combined with methotrexate, for 52 weeks; patients receiving placebo switched to peficitinib 100/150 mg at Week (W)12/28. This post hoc analysis investigated association between MMP-3 above/below upper limit of normal (ULN) at W12/28 and radiographic progression [modified total Sharp score (mTSS), joint space narrowing score, or erosion score >0.5] at W52 or swollen joint count 66 at W28, stratified by baseline glucocorticoid use and renal function. Results: MMP-3 levels decreased in both peficitinib-treated groups but more slowly in patients with baseline glucocorticoids and those with radiographic progression at W52. There was no clear correlation between MMP-3 change from baseline (CFB) at W12, CFB in mTSS, joint space narrowing score, or erosion score at W52, or CFB in swollen joint count 66 at W28. More patients with MMP-3 ≤ULN versus >ULN at W12 had radiographic non-progression at W52. MMP-3 normalisation at W12 was significantly associated with mTSS non-progression at W52. Conclusions: Normalisation of MMP-3 at W12 may be a predictor for subsequent non-progression of joint damage at W52. [ABSTRACT FROM AUTHOR]

Background: Complicated mild traumatic brain injury (cmTBI) is a common neurosurgical disorder that consumes a significant amount of healthcare resources without a clearly established benefit. Best practices for the management of cmTBI regarding triage, hospital admission, and the necessity for repeat imaging are controversial. Our objective is to describe the rate of radiographic progression and neurologic decline for isolated traumatic subarachnoid hemorrhage (itSAH) patients admitted to the hospital. We hypothesized that only a minority of itSAH patients suffer radiographic progression and that radiographic progression is not necessarily associated with neurologic decline. Methods: Database queries and direct patient chart reviews were used to gather patient data. T-tests and Fisher's exact tests were performed. Results: A total of 340 patients with cmTBI associated with itSAH were included for analysis. The radiographic progression rate was 5.6%. There was no statistically significant association between age, gender, GCS at presentation, anticoagulation status, and risk of radiographic progression. However, subgroup analysis on anticoagulated patients did show those on warfarin had a statistically significant risk of radiographic progression (p = 0.003). No patient developed neurologic decline, irrespective of whether they developed radiographic progression. Conclusion: Secondary triaging, hospital admission, ICU stay, and repeat HCT might not be necessary for awake, GCS 13–15 patients with itSAH without any other significant injuries. In the case of anticoagulant use, but not necessarily antiplatelet use, the medication should be reversed, and admission should be considered. [ABSTRACT FROM AUTHOR]

Abstract Objectives The progression of knee osteoarthritis (OA) can be defined as either radiographic progression or pain progression. This study aimed to construct models to predict radiographic progression and pain progression in patients with knee OA. Methods We retrieved data from the FNIH OA Biomarkers Consortium project, a nested case-control study. A total of 600 subjects with mild to moderate OA (Kellgren-Lawrence grade of 1, 2, or 3) in one target knee were enrolled. The patients were classified as radiographic progressors (n = 297), non-radiographic progressors (n = 303), pain progressors (n = 297), or non-pain progressors (n = 303) according to the change in the minimum joint space width of the medial compartment and the WOMAC pain score during the follow-up period of 24–48 months. Initially, 376 variables concerning demographics, clinical questionnaires, imaging measurements, and biochemical markers were included. We developed predictive models based on multivariate logistic regression analysis and visualized the models with nomograms. We also tested whether adding changes in predictors from baseline to 24 months would improve the predictive efficacy of the models. Results The predictive models of radiographic progression and pain progression consisted of 8 and 10 variables, respectively, with area under curve (AUC) values of 0.77 and 0.76, respectively. Incorporating the change in the WOMAC pain score from baseline to 24 months into the pain progression predictive model significantly improved the predictive effectiveness (AUC = 0.86). Conclusions We identified risk factors for imaging progression and pain progression in patients with knee OA over a 2- to 4-year period, and provided effective predictive models, which could help identify patients at high risk of progression.

BackgroundLaser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies.MethodsDemographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival.ResultsNinety patients met the inclusion criteria. Four patients underwent 2 ablations on the same day. Median hospitalization time was 32.5 hours. The median time to corticosteroid cessation after LITT was 13.0 days (0.0, 1229.0) and cumulative incidence of lesional progression was 19% at 1 year. Median post-procedure overall survival was 2.55 years [1.66, infinity] and 77.1% at one year as estimated by KaplanMeier. Median KPS remained at 80 through 2-year follow-up. Seizure prevalence was 12% within 1-month post-LITT and 7.9% at 3 months; down from 34.4% within 60-day prior to procedure.ConclusionsLITT for RN was not only again found to be safe with low patient morbidity but was also a highly effective treatment for RN for both local control and symptom management (including seizures). In addition to averting expected neurological death, LITT facilitates ongoing systemic therapy (in particular immunotherapy) by enabling the rapid cessation of steroids, thereby facilitating maximal possible survival for these patients.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects synovial joints and that frequently involves extra-articular organs. A multiplicity of interleukins (IL) participates in the pathogenesis of RA, including IL-6, IL-1β, transforming growth factor-beta (TGF-β), and tumor necrosis factor (TNF)-α; immune cells such as monocytes, T and B lymphocytes, and macrophages; and auto-antibodies, mainly rheumatoid factor and anti-citrullinated protein antibodies (ACPAs). Skeletal muscle is also involved in RA, with many patients developing muscle wasting and sarcopenia. Several mechanisms are involved in the myopenia observed in RA, and one of them includes the effects of some interleukins and myokines on myocytes. Myostatin is a myokine member of the TGF-β superfamily; the overproduction of myostatin acts as a negative regulator of growth and differentiates the muscle fibers, limiting their number and size. Recent studies have identified abnormalities in the serum myostatin levels of RA patients, and these have been found to be associated with muscle wasting and other manifestations of severe RA. This review analyzes recent information regarding the relationship between myostatin levels and clinical manifestations of RA and the relevance of myostatin as a therapeutic target for future research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

AbstractAbatacept (ABT) is a biological disease-modifying antirheumatic drug (bDMARDs) for rheumatoid arthritis (RA) when conventional synthetic DMARDs are ineffective. We aimed to evaluate the long-term effects of ABT on joint destruction in patients treated for over 2 years. Radiographic progression was evaluated using the van der Heijde-modified Total Sharp Score (mTSS) by two rheumatologists at ABT initiation and after 2 years. Multivariate logistic regression analysis was used to identify factors associated with structural remission, defined as the mean annual change in mTSS ≤0.5. Among the 111 patients included, 48 discontinued, and 63 continued ABT treatment until radiographic evaluation was performed. The rate of patients who achieved estimated TSS REM (yearly progression of van der Heijde modified total Sharp scores ≤0.5) was significantly lower in ABT-dropouts than in the ABT-continued group (69% vs. 48%, p = .0336 by Fisher’s exact test). Among the continued ABT cases, concomitant glucocorticoid treatment at ABT initiation was the strongest negative predictive factor of estimated TSS REM in univariate and multivariate logistic regression analyses. Radiographic progression after ABT administration should be evaluated separately for dropout and non-dropout cases. Glucocorticoids at the initiation of ABT may serve as a predictive factor for joint destruction in long-term ABT use.

Abstract Background Despite existing extensive literature, a comprehensive and clinically relevant classification system for osteoarthritis (OA) has yet to be established. In this study, we aimed to further characterize four knee OA (KOA) inflammatory phenotypes (KOIP) recently proposed by our group, by identifying the inflammatory factors associated with KOA severity and progression in a phenotype-specific manner. Methods We performed an analysis within each of the previously defined four KOIP groups, to assess the association between KOA severity and progression and a panel of 13 cytokines evaluated in the plasma and synovial fluid of our cohort’s patients. The cohort included 168 symptomatic female KOA patients with persistent joint effusion. Results Overall, our analyses showed that associations with KOA outcomes were of higher magnitude within the KOIP groups than for the overall patient series (all p-values < 1.30e−16) and that several of the cytokines showed a KOIP-specific behaviour regarding their associations with KOA outcomes. Conclusion Our study adds further evidence supporting KOA as a multifaceted syndrome composed of multiple phenotypes with differing pathophysiological pathways, providing an explanation for inconsistencies between previous studies focussed on the role of cytokines in OA and the lack of translational results to date. Our findings also highlight the potential clinical benefits of accurately phenotyping KOA patients, including improved patient stratification, tailored therapies, and the discovery of novel treatments.

Aim: To study the clinical and serological predictors of radiological progression at one year in a cohort of Indian patients with early rheumatoid arthritis (RA). Methods: In this prospective open-label observational study, consecutive patients with early RA (

Abatacept (ABT) is a biological disease-modifying antirheumatic drug (bDMARDs) for rheumatoid arthritis (RA) when conventional synthetic DMARDs are ineffective. We aimed to evaluate the long-term effects of ABT on joint destruction in patients treated for over 2 years. Radiographic progression was evaluated using the van der Heijde-modified Total Sharp Score (mTSS) by two rheumatologists at ABT initiation and after 2 years. Multivariate logistic regression analysis was used to identify factors associated with structural remission, defined as the mean annual change in mTSS ≤0.5. Among the 111 patients included, 48 discontinued, and 63 continued ABT treatment until radiographic evaluation was performed. The rate of patients who achieved estimated TSS REM (yearly progression of van der Heijde modified total Sharp scores ≤0.5) was significantly lower in ABT-dropouts than in the ABT-continued group (69% vs. 48%, p =.0336 by Fisher's exact test). Among the continued ABT cases, concomitant glucocorticoid treatment at ABT initiation was the strongest negative predictive factor of estimated TSS REM in univariate and multivariate logistic regression analyses. Radiographic progression after ABT administration should be evaluated separately for dropout and non-dropout cases. Glucocorticoids at the initiation of ABT may serve as a predictive factor for joint destruction in long-term ABT use. [ABSTRACT FROM AUTHOR]

Imaging changes after stereotactic radiosurgery (SRS) can occur for years after treatment, although the available data on the incidence of tumor progression and adverse radiation effects (ARE) are generally limited to the first 2 years after treatment. A single-institution retrospective review was conducted of patients who had >18 months of imaging follow-up available. Patients who had ≥1 metastatic brain lesions treated with Gamma Knife SRS were assessed for the time to radiographic progression. Those with progression ≥18 months after the initial treatment were included in the present study. The lesions that progressed were characterized as either ARE or tumor progression based on the tissue diagnosis or imaging characteristics over time. The cumulative incidence of delayed imaging radiographic progression was 35% at 5 years after the initial SRS. The cumulative incidence curves of the time to radiographic progression for lesions determined to be ARE and lesions determined to be tumor progression were not significantly different statistically. The cumulative incidence of delayed ARE and delayed tumor progression was 17% and 16% at 5 years, respectively. Multivariate analysis indicated that the number of metastatic brain lesions present at the initial SRS was the only factor associated with late radiographic progression. The timing of late radiographic progression does not differ between ARE and tumor progression. The number of metastatic brain lesions at the initial SRS is a risk factor for late radiographic progression. [ABSTRACT FROM AUTHOR]

Objective: Assess relationship between earlier clinical improvement and radiographic progression (RP) over 2 years in guselkumab-treated patients with active psoriatic arthritis (PsA). Method: Post hoc analyses combined data from DISCOVER-2 biologic-naïve adults with active PsA randomized to either guselkumab 100 mg every 4 weeks (Q4W) or guselkumab at W0, W4, then Q8W. Correlations (Spearman's coefficient) between baseline disease parameters and total PsA-modified van der Heijde-Sharp (vdH-S) score were examined. Repeated-measures mixed models, adjusted for known RP risk factors, assessed the relationship between Disease Activity Index in PsA (DAPSA) improvement, DAPSA improvement exceeding the median or the minimal clinically important difference (MCID), or DAPSA low disease activity (LDA) at W8 and RP rate, assessed by change from baseline in vdH-S score through W100. Results: Baseline age, PsA duration, CRP level, and swollen joint count, but not psoriasis duration/severity, weakly correlated with baseline vdH-S score. Elevated baseline CRP (parameter estimate [β] = 0.17–0.18, p < 0.03) and vdH-S score (β = 0.02, p < 0.0001) significantly associated with greater RP through W100. Greater improvement in DAPSA (β = -0.03, p = 0.0096), achievement of DAPSA improvement > median (least squares mean [LSM] difference: -0.66, p = 0.0405) or > MCID (-0.67, p = 0.0610), or DAPSA LDA (-1.44, p = 0.0151) by W8 with guselkumab significantly associated with less RP through W100. The effect of W8 DAPSA LDA on future RP was strengthened over time among achievers vs. non-achievers (LSM difference enhanced from -1.05 [p = 0.0267] at W52 to -1.84 [p = 0.0154] at W100). Conclusions: In guselkumab-treated patients with active PsA, earlier improvement in joint symptoms significantly associated with lower RP rates through 2 years, indicating blockade of the IL-23 pathway may modify long-term disease course and prevent further joint damage. Key Points • Greater improvement in DAPSA at Week 8 of guselkumab treatment was significantly associated with less progression of structural joint damage at 2 years in patients with active psoriatic arthritis (PsA). • Early control of peripheral joint disease activity with blockade of the IL-23 pathway may modify long-term PsA trajectory and prevent further joint damage. [ABSTRACT FROM AUTHOR]

Abstract Background Predicting radiographic progression in axial spondyloarthritis (axSpA) remains limited because of the complex interaction between multiple associated factors and individual variability in real-world settings. Hence, we tested the feasibility of artificial neural network (ANN) models to predict radiographic progression in axSpA. Methods In total, 555 patients with axSpA were split into training and testing datasets at a 3:1 ratio. A generalized linear model (GLM) and ANN models were fitted based on the baseline clinical characteristics and treatment-dependent variables for the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) of the radiographs at follow-up time points. The mSASSS prediction was evaluated, and explainable machine learning methods were used to provide insights into the model outcome or prediction. Results The R 2 values of the fitted models were in the range of 0.90–0.95 and ANN with an input of mSASSS as the number of each score performed better (root mean squared error (RMSE) = 2.83) than GLM or input of mSASSS as a total score (RMSE = 2.99–3.57). The ANN also effectively captured complex interactions among variables and their contributions to the transition of mSASSS over time in the fitted models. Structural changes constituting the mSASSS scoring systems were the most important contributing factors, and no detectable structural abnormalities at baseline were the most significant factors suppressing mSASSS change. Conclusions Clinical and radiographic data-driven ANN allows precise mSASSS prediction in real-world settings. Correct evaluation and prediction of spinal structural changes could be beneficial for monitoring patients with axSpA and developing a treatment plan.

AbstractThe short-term effect of tocilizumab (TCZ) on the radiographic progression of rheumatoid arthritis has been reported; however, reports on its long-term effects are scarce. In this study, we aimed to evaluate its long-term effects on joint destruction in patients who had been treated with TCZ for at least two years and for whom X-rays were available. Radiographic progression was evaluated with modified Total Sharp Score (mTSS), and structural remission was defined as the mean annual change in mTSS ≤0.5. Of the 59 patients included in this study (median age, 62 years; female, 81.4%), 34 patients (57.6%) achieved structural remission. Patients who achieved structural remission were relatively younger (59 years vs. 64 years, p = .06), had relatively higher proportion of anti-citrullinated protein antibody positivity (91.2% vs. 72.0%, p = .08), relatively lower C-reactive protein level (0.6 mg/dL vs. 2.2 mg/dL, p = .05), and significantly lower erythrocyte sedimentation rate (ESR) level (28.0 mm/h vs 65.5 mm/h, p = .003) than those who did not. Multivariate logistic regression analysis demonstrated that the baseline ESR level was significantly associated with structural remission (odds ratio, 0.98; 95% confidence interval: 0.96–0.99, p = .049). The baseline ESR level is a critical determinant of the long-term effect of TCZ on joint destruction.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects synovial joints and that frequently involves extra-articular organs. A multiplicity of interleukins (IL) participates in the pathogenesis of RA, including IL-6, IL-1β, transforming growth factor-beta (TGF-β), and tumor necrosis factor (TNF)-α; immune cells such as monocytes, T and B lymphocytes, and macrophages; and auto-antibodies, mainly rheumatoid factor and anti-citrullinated protein antibodies (ACPAs). Skeletal muscle is also involved in RA, with many patients developing muscle wasting and sarcopenia. Several mechanisms are involved in the myopenia observed in RA, and one of them includes the effects of some interleukins and myokines on myocytes. Myostatin is a myokine member of the TGF-β superfamily; the overproduction of myostatin acts as a negative regulator of growth and differentiates the muscle fibers, limiting their number and size. Recent studies have identified abnormalities in the serum myostatin levels of RA patients, and these have been found to be associated with muscle wasting and other manifestations of severe RA. This review analyzes recent information regarding the relationship between myostatin levels and clinical manifestations of RA and the relevance of myostatin as a therapeutic target for future research.

Objective: As anaemia represents a biomarker for increased radiographic damage in rheumatoid arthritis, we aimed to investigate whether it independently predicts spinal radiographic progression in axial spondyloarthritis (axSpA). Methods: AxSpA patients with available haemoglobin levels from the prospective Swiss Clinical Quality Management Registry were included for comparison of patients with and without anaemia. Spinal radiographic progression was assessed according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in patients with ankylosing spondylitis (AS) if ≥ 2 sets of spinal radiographs were available every 2 years. The relationship between anaemia and progression (defined as an increase ≥ 2 mSASSS units in 2 years) was analysed with generalized estimating equation models after adjustment for the Ankylosing Spondylitis Disease Activity Score (ASDAS) and potential confounding, as well as after multiple imputations of missing values. Results: A total of 212/2522 axSpA patients presented with anaemia (9%). Anaemic patients had higher clinical disease activity, higher acute phase reactants and more severe impairments in physical function, mobility and quality of life. In the subgroup of patients with AS (N = 433), a comparable mSASSS progression was found in anaemic and non-anaemic patients (OR 0.69, 95% CI 0.25 to 1.96, p = 0.49). Age, male sex, baseline radiographic damage and ASDAS were associated with enhanced progression. The results were confirmed in complete case analyses and with progression defined as the formation of ≥ 1 syndesmophyte in 2 years. Conclusion: Although anaemia was associated with higher disease activity in axSpA, it did not additionally contribute to the prediction of spinal radiographic progression. Key Points • Anaemia is associated with higher disease activity and more severely impaired physical function, mobility and quality of life in axSpA. • Anaemia does not provide an additional value to ASDAS for prediction of spinal radiographic progression. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy. Methods Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. Results In total, 511 patients were included [mean (s. d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: −0.04, 0.33) for 2 vs 0 visits; and +0.08 units (−0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. Conclusions In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome. [ABSTRACT FROM AUTHOR]

In this post hoc analysis of the ARCHES trial, enzalutamide plus androgen deprivation therapy improved radiographic progression-free survival and overall survival for patients with oligometastatic (1–5 metastases) and polymetastatic (≥6 metastases) prostate cancer. Few phase 3 studies have evaluated optimal systemic treatment strategies for patients with oligometastatic hormone-sensitive prostate cancer (HSPC), who may be at risk of undertreatment. To evaluate outcomes for patients with oligometastatic and polymetastatic HSPC treated with enzalutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT. This was a post hoc analysis of data for 927 patients with nonvisceral metastatic HSPC in the ARCHES trial (NCT02677896). Patients were randomized 1:1 to enzalutamide (160 mg/d orally) plus ADT or placebo plus ADT with HSPC categorized as oligometastatic (1–5 metastases) or polymetastatic (≥6 metastases). The treatment effect on radiographic progression-free survival (rPFS), overall survival (OS), and secondary efficacy endpoints was evaluated in terms of the number of metastases. Safety was assessed. Cox proportional hazards models were used to generate hazard ratios (HRs). The Brookmeyer and Crowley method was used to generate 95% confidence intervals (CIs) for Kaplan-Meier median values. Enzalutamide plus ADT improved rPFS (HR 0.27, 95% CI 0.16–0.46; p < 0.001), OS (HR 0.59, 95% CI 0.40–0.87; p < 0.005), and secondary endpoints in patients with oligometastatic or polymetastatic disease (rPFS: HR 0.33, 95% CI 0.23–0.46; p < 0.001; OS: HR 0.55, 95% CI 0.41–0.74; p < 0.001). Safety profiles were generally similar across subgroups. Limitations include the small numbers of patients with fewer than three metastases. This post hoc analysis demonstrated the utility of enzalutamide, irrespective of metastatic burden or type of oligometastatic disease, and suggests that earlier treatment intensification with systemic potent androgen receptor inhibition is advantageous. This study considered two treatment options for metastatic hormone-sensitive prostate cancer in patients with one to five metastases or six or more metastases. Treatment with enzalutamide plus ADT improved survival and other outcomes over ADT alone, whether patients had few or many metastases. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the appropriate timing, useful findings and combination of magnetic resonance imaging (MRI) and ultrasound (US) for predicting the radiographic progression in early rheumatoid arthritis (RA). Methods: Forty-four active RA patients, who examined by both of MRI and US in the symptomatic wrist and finger joints, were recruited in Nagasaki University Hospital from 2010 to 2017 and treated by the treat-to-target therapeutic strategy for 1 year. MRI was evaluated by RA MRI scoring and US by Outcomes Measures in Rheumatology Clinical Trial, respectively. Plain radiographs were assessed by the Genant-modified Sharp score for the symptomatic side in the same manner as MRI and US. Radiographic progression was defined as an annual increase ≥0.75 at 1 year. Factors associated with radiographic progression were analysed. Also, the optimal combination of MRI and US at each timepoint was considered. Results: Logistic regression model revealed that MRI-proven bone marrow oedema at baseline and 6 months and joint counts of power-Doppler grade ≥2 articular synovitis at 3 or 6 months were significantly associated with radiographic progression at 1 year. Conclusion: This study may suggest the favourable timing and combination of MRI and US at each point to predict radiographic progression in patients with early-stage RA. [ABSTRACT FROM AUTHOR]

Abstract Objectives To analyse whether time-varying treatment with tumour necrosis factor inhibitors (TNFi) in radiographic axial spondyloarthritis (r-axSpA) has a differential impact on structural damage progression on different spinal segments (cervical versus lumbar spine). Methods Patients with r-axSpA in the Swiss Clinical Quality Management cohort were included if cervical and lumbar radiographs were available at intervals of 2 years for a maximum of 10 years. Paired radiographs were scored by two calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The relationship between TNFi use and progression in the cervical and the lumbar spine was analysed using generalised estimating equation models and adjustment for potential confounding. Radiographic progression per spinal segment was defined as an increase of ≥ 1 mSASSS unit or by the formation of ≥ 1 new syndesmophyte over 2 years. Results Mean ± SD symptom duration was 13.8 ± 9.8 years. Mean ± SD mSASSS progression per radiographic interval was 0.41 ± 1.69 units in the cervical spine and 0.45 ± 1.45 units in the lumbar spine (p = 0.66). Prior use of TNFi significantly reduced the odds of progression in the cervical spine by 68% (OR 0.32, 95% CI 0.14–0.72), but not in the lumbar spine (OR 0.99, 95% CI 0.52–1.88). A more restricted inhibition of progression in the lumbar spine was confirmed after multiple imputation of missing covariate data (OR 0.43, 95% CI 0.24–0.77 and 0.85, 95% CI 0.51–1.41, for the cervical and lumbar spine, respectively). It was also confirmed with progression defined as formation of ≥ 1 syndesmophyte (OR 0.31, 95% CI 0.12–0.80 versus OR 0.56, 95% CI 0.26–1.24 for the cervical and lumbar spine, respectively). Conclusion Disease modification by treatment with TNFi seems to more profoundly affect the cervical spine in this r-axSpA population with longstanding disease. Site-specific analysis of spinal progression might, therefore, improve detection of disease modification in clinical trials in axSpA.

Abstract Introduction Etanercept (ETN) has been shown to slow radiographic progression of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical trials. This real-world, non-interventional study assessed radiographic progression in patients with RA or PsA treated with ETN for ≤ 36 months in outpatient care in Germany (NCT01623752). Methods Patients with RA or PsA attended ≤ 10 visits across two study phases (phase 1: seven visits, baseline to month 18; phase 2: three visits until month 36). Radiographs were taken at baseline (Rx1), months 12–18 (Rx2), and/or months 30–36 (Rx3). Historic radiographs (Rx0) taken 12–48 months pre-baseline were also evaluated (if available). The primary endpoint was the change in modified total Sharp score (mTSS). The erosion score (ES) and joint space narrowing score (JSN) were also evaluated. Results Overall, 1821 patients were enrolled (RA: n = 1378; PsA: n = 440). In patients with Rx1 and Rx2 (RA: n = 511; PsA: n = 167), the mean mTSS remained stable for both disease groups, and the annualized median change in mTSS was 0. In patients with Rx0, Rx1, and Rx2 (RA: n = 180; PsA: n = 47), annualized radiographic progression in mTSS, ES, and JSN was larger in the pre-ETN treatment phase than during ETN treatment in both disease groups. The percentage of patients with radiographic non-progression was higher during ETN treatment versus pre-ETN. Improvement in clinical disease activity and patient-reported outcomes was also observed. Conclusions This was the first real-world, non-interventional study to report systematically collected radiographic data in a large cohort of patients with RA or PsA under treatment with a biologic. In patients with available radiographic data, mean radiographic progression was lower and the proportion of patients without progression was greater during ETN treatment than in the pre-ETN period.

Objectives The multibiomarker disease activity (MBDA) score is an objective tool for monitoring disease activity in RA. Here we report a systematic review and meta-analysis of the clinical value of the MBDA score in RA. Methods We performed a systematic literature search in five medical databases—MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, Scopus and Web of Science—from inception to 13 October 2021. Original articles reporting on the performance of the MBDA score's correlation with conventional disease activity measures or the predictive and discriminative values of the MBDA score for radiographic progression, therapy response, remission and relapse were included. Results Our systematic search provided a total of 1190 records. After selection and citation searches, we identified 32 eligible studies. We recorded moderate correlations between MBDA score and conventional disease activity measures at baseline [correlation (COR) 0.45 (CI 0.28, 0.59), I 2 = 71.0% for the 28-joint DAS with CRP (DAS28-CRP) and COR 0.55 (CI 0.19, 0.78), I 2 = 0.0% for DAS28 with ESR] and at follow-up [COR 0.44 (CI 0.28, 0.57, I 2 = 70.0% for DAS28-CRP) and found that the odds of radiographic progression were significantly higher for patients with a high baseline MBDA score (>44) than for patients with a low baseline MBDA score (<30) [OR 1.03 (CI 1.02–1.05), I2 = 10.0%]. Conclusion The MBDA score might be used as an objective disease activity marker. In addition, it is also a reliable prognostic marker of radiographic progression. [ABSTRACT FROM AUTHOR]

Objectives To construct a predictive model for the Sharp/van der Heijde score (SHS) and assess its applicability in clinical research settings. Material and methods A prediction model for SHS was constructed in three steps using convolutional neural networks (CNN) and an in-house RA image database: orientation, detection and damage prediction. A predictive model for radiographic progression (ΔSHS >3/year) was developed using a graph convolutional network (GCN). A multiple regression model was used to assess the association between predicted SHS using the CNN model and clinical features. Results In the orientation and detection phases, 100% accuracy was achieved in the image orientation correction, and all predicted joint coordinates were within 10 pixels of the correct coordinates. In the damage prediction phase, the κ values between the model and expert 1 were 0.879 and 0.865 for erosion and joint space narrowing, respectively. Using a dataset scored by experts 1 and 2, a minimal overfitting was determined to the scoring by expert 1. High-titre RF was an independent risk factor of Δ SHS per year, as predicted by the CNN model in biologics users. The AUCs of the GCN model for predicting ΔSHS >3/year in patients with and without biologics at baseline were 0.753 and 0.734, respectively, superior to those of the other models. The RF titre was the most important feature in predicting ΔSHS >3/year in biologics users in the GCN model. Conclusion A high-performance scoring model for SHS that is applicable to clinical research was constructed. [ABSTRACT FROM AUTHOR]

The short-term effect of tocilizumab (TCZ) on the radiographic progression of rheumatoid arthritis has been reported; however, reports on its long-term effects are scarce. In this study, we aimed to evaluate its long-term effects on joint destruction in patients who had been treated with TCZ for at least two years and for whom X-rays were available. Radiographic progression was evaluated with modified Total Sharp Score (mTSS), and structural remission was defined as the mean annual change in mTSS ≤0.5. Of the 59 patients included in this study (median age, 62 years; female, 81.4%), 34 patients (57.6%) achieved structural remission. Patients who achieved structural remission were relatively younger (59 years vs. 64 years, p =.06), had relatively higher proportion of anti-citrullinated protein antibody positivity (91.2% vs. 72.0%, p =.08), relatively lower C-reactive protein level (0.6 mg/dL vs. 2.2 mg/dL, p =.05), and significantly lower erythrocyte sedimentation rate (ESR) level (28.0 mm/h vs 65.5 mm/h, p =.003) than those who did not. Multivariate logistic regression analysis demonstrated that the baseline ESR level was significantly associated with structural remission (odds ratio, 0.98; 95% confidence interval: 0.96–0.99, p =.049). The baseline ESR level is a critical determinant of the long-term effect of TCZ on joint destruction. [ABSTRACT FROM AUTHOR]

Objective: To determine the efficacy of peficitinib in reducing joint damage and predictive factors affecting treatment response in Japanese patients with rheumatoid arthritis. Methods: This post hoc analysis used data from a placebo-controlled, phase 3 trial (RAJ4) of peficitinib in patients with rheumatoid arthritis and inadequate response to methotrexate. Erosion and joint space narrowing (JSN) were assessed at baseline and at Week 28/early termination of treatment using the van der Heijde-modified Sharp method. A univariate logistic regression analysis of change from baseline in a modified total Sharp score identified predictive factors with significant treatment interaction; the effects of these factors on treatment response were further evaluated using a multivariate model. Results: The analyses included 481 patients. For most joint groups, peficitinib demonstrated a reduced change from baseline at Week 28/early termination in erosion and JSN scores versus placebo; a numerically greater effect was observed with peficitinib 150 mg versus 100 mg. Baseline C-reactive protein (CRP) and prednisolone dose were identified as clinically significant negative predictive factors: the treatment effect decreased as CRP or prednisolone dose increased for both peficitinib doses. Conclusions: Peficitinib 100 mg and 150 mg reduced joint damage versus placebo, across almost all joint groups. Higher baseline CRP and/or prednisolone dose were associated with reduced peficitinib efficacy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The purposes of this systematic review were to (1) identify the commonly used definitions of radiographic KOA progression, (2) summarize the important associative risk factors for disease progression based on findings from the OAI study and (3) summarize findings from radiographic KOA progression prediction modeling studies regarding the characterization of progression and outcomes. Methods: A systematic review was performed by conducting a literature search of definitions, risk factors and predictive models for radiographic KOA progression that utilized data from the OAI database. Radiographic progression was further characterized into "accelerated KOA" and "typical progression," as defined by included studies. Results: Of 314 studies identified, 41 studies were included in the present review. Twenty-eight (28) studies analyzed risk factors associated with KOA progression, and 13 studies created or validated prediction models or risk calculators for progression. Kellgren–Lawrence (KL) grade based on radiographs was most commonly used to characterize KOA progression (50%), followed by joint space width (JSW) narrowing (32%) generally over 48 months. Risk factors with the highest odds ratios (OR) for progression included periarticular bone mineral density (OR 10.40), any knee injury within 1 year (OR 9.22) and baseline bone mineral lesions (OR 7.92). Nine prediction modeling studies utilized both clinical and structural risk factors to inform their models, and combined models outperformed purely clinical or structural models. Conclusion: The cumulative evidence suggests that combinations of structural and clinical risk factors may be able to predict radiographic KOA progression, particularly in patients with accelerated progression. Clinically relevant and feasible prediction models and risk calculators may provide valuable decision-making support when caring for patients at risk of KOA progression, although standardization in modeling and variable identification does not yet exist. [ABSTRACT FROM AUTHOR]

Background: Associations between rheumatoid arthritis (RA) and reduced skeletal muscle have been studied, and we firstly reported myopenia independently predict one-year radiographic progression in RA. Myokine myostatin can negatively regulate skeletal muscle mass and promote osteoclast differentiation. However, there is no report about their relationships in RA patients. We firstly explored the relationship of serum myostatin and disease characteristics, as well as aggravated joint destruction during one-year follow-up. Methods: Consecutive RA patients were recruited from a real-world prospective cohort and completed at least one-year follow-up. Baseline serum level of myostatin was measured by enzyme-linked immunosorbent assay. Clinical data in RA patients as well as muscle index in both RA patients and healthy controls were collected. One-year radiographic progression as primary outcome was defined by a change in the total Sharp/van der Heijde modified score ≥0.5 units. Results: Totally 344 RA patients (age 47.9 ± 12.5 years, 84.0% female) and 118 healthy control subjects (age 42.8 ± 11.3 years, 74.6% female) were recruited. Compared with healthy controls, RA patients showed a higher level of serum myostatin at baseline (3.241 ± 1.679 ng/ml vs. 1.717 ± 0.872 ng/ml, P<0.001), although lower appendicular skeletal muscle mass index (ASMI, 6.0 ± 0.9 kg/m² vs. 6.5 ± 1.0 kg/m², P<0.001). In RA patients, those with high myostatin level showed a higher rate of radiographic progression than low myostatin group (45.3% vs. 18.6%, P<0.001). Furtherly, RA patients were stratified into four subgroups according to serum myostatin and myopenia. Compared with other three subgroups, RA patients with high myostatin overlapping myopenia had the highest rate of radiographic progression (67.2% vs. 10.3%-31.4%, P<0.001), as well as the lowest proportion of remission and the highest rate of physical dysfunction during one-year follow-up. After adjustment for confounding factors, high serum myostatin (AOR=3.451, 95%CI: 2.016-5.905) and myopenia (AOR=2.387, 95%CI: 1.416-4.022) at baseline were risk factors for one-year radiographic progression, especially for those with high myostatin overlapping myopenia (AOR=10.425, 95%CI: 3.959-27.450) as the highest-risk individuals among four subgroups. Significant synergistic interaction effect was observed between high myostatin and myopenia on one-year radiographic progression (AP=66.3%, 95%CI: 43.2%-89.3%). Conclusion: Myostatin is a novel predictor of aggravated joint destruction in RA patients which has synergistic interaction with myopenia for predicting value. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether the severity of contralateral knee osteoarthritis (OA) is associated with OA progression in ipsilateral knee with early OA. Methods: Knees in early OA (Kellgren-Lawrence grade (KLG):1–2) with intact baseline demographic and clinical data were retrieved from OAI database and defined as target knees. The target knees were divided into the exposure group (contralateral knees KLG 3 to 4) and the control group (contralateral knees KLG 0 to 2). Both groups underwent propensity score matching (PSM) concerning demographic data, as well as radiographic and clinical outcomes at the baseline. The primary outcome was the upgrade of KLG in the target knee in the first 12 and 24 months. The secondary outcome was the incidence of knee arthroplasty in ipsilateral knee during the first 108 months. Results: One thousand seven hundred fifty-two knees were included, with 449 in the exposure cohort and 1276 in the control cohort. Four hundred thirty-four knees in each group were matched after PSM. Target knees in the exposure cohort showed a significantly higher rate of radiographic progression in the first 12 months (12.9% vs. 5.1%, P < 0.001) and 24 months (19.6% vs. 8.1%, P < 0.001). As for the risk of future arthroplasty, a significant difference was also found between the two groups (7.8% vs. 4.0%, P = 0.02). Kaplan–Meier analysis showed that the 108-month accumulated knee survival rate was significantly lower in the exposure group (P = 0.01). Conclusion: The ipsilateral knee with early-stage OA is prone to have worse early to mid-, and long-term prognosis in the circumstance of contralateral radiographic advanced knee OA. Key Points •Identifying early knee osteoarthritis (OA) with a high risk of radiographic progression and future arthroplasty enables early personalized intervention. •This is a novel study to investigate the relationship between the risk of future arthroplasty and contralateral knee status. •Propensity score matching holds promise to minimize selection bias in observational studies. •Knees with early OA are prone to have a high risk of radiographic progression and future arthroplasty in the circumstance of contralateral advanced knee OA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease with predominant involvement of the sacroiliac joints (SIJ) and/or the spine. Despite the fact that the prevalence of axSpA is almost the same in men and women, there is evidence of a delay in diagnosis and a more severe course of the disease in females. The available reports on the progression of structural changes in the SIJ in men and women with early axSpA are contradictory. Meanwhile, the analysis of radiographic progression in the SIJ has fundamental importance both for timely diagnosis and for assessing the effectiveness of therapy in axSpA. Such studies have not yet been carried out in the Russian Federation.Objective: to assess the radiographic progression of sacroiliitis (SI) over 3 years in men and women with early axSpA.Material and methods. The study included patients from the cohort of early axSpA CORSAR, formed at the V.A. Nasonova Research Institute of Rheumatology. Currently, it includes 175 patients with axSpA. We analyzed the data of 64 patients, followed for at least 3 years. To assess the radiographic progression of the disease at baseline and after 3 years, the sum of X-ray stages of SI in the left and right SIJ was determined (the total stage of SI). Progression was assessed by the change in the total stage of SI in the right and left SIJ (0-8) during the observation period. We also calculated the proportion of patients with deterioration (increase in the total stage of SI by at least 1 stage), with improvement (decrease in the total stage of SI by at least 1 stage) and without progression. In order to fully exclude the error in measuring the radiographic progression of SI, we counted patients with “net” progression, that is, the proportion of patients with improvement was subtracted from the proportion of patients with deterioration.Results. Among 64 patients with early axSpA, there were 37 (57.8%) men and 27 (42.2%) women. For 3 years, the median of the total stage SI in men was 0 [0; 1], in women - 0 [0; 2] (p>0.05). When assessing the progression of the total stage SI over 3 years, no significant differences were found between the number of men and women with improvement, with deterioration, “net” progression and without progression. Men with early axSpA showed a higher level of C-reactive protein (CRP) at baseline, women had higher BASDAI and ASDAS CRP values after 3 years. In 8% of patients, there was a regression of X-ray signs of SI.Conclusion. The radiographic progression of SI in patients with early axSpA does not depend on gender and disease activity. In some patients with early axSpA, reverse development of structural damage to the SIJ is possible.

Abstract 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.

BackgroundMechanical stress are one of the pathogenesis of axial spondyloarthritis (axSpA). During pregnancy, the mechanical overload on the spine and pelvis increases due to gravid uterus. We aimed to investigate whether pregnancy affects radiographic progression in patients with radiographic axSpA (r-axSpA) based on computed tomography (CT) evaluations.Materials and methodsThis retrospective study included women with r-axSpA aged 19–49 years who underwent at least two CT evaluations of the whole spine and/or sacroiliac joints (SIJs) at intervals of 2–4 years. To compare radiographic progression after delivery, we classified the patients into two groups: delivery group and controls. The delivery group was restricted to women who had the first CT ∼2 years before delivery and the second CT ∼2 years after delivery. The CT Syndesmophyte Score (CTSS) (0–522) and SIJ scores (0–40) were used to evaluate spinal syndesmophytes and erosion, joint space narrowing, and sclerosis of the SIJs.ResultsA total of 21 women in the delivery group and 38 women in the control group were included. The median (Q1–Q3) CTSS at baseline in the delivery group and controls was 19 (16–23) and 20 (13.25–27.75), and the median progression was 1 (0–3) and 0 (0–1) during the median 2.9-year follow-up, respectively. The median (Q1–Q3) SIJ score at baseline in the delivery group and controls was 13 (8–22) and 11 (6–22), and the median progression was 1.5 (0–3) and 1 (0–2), respectively. Using cut-off 0.5, 52.9, and 61.9% of r-axSpA patients and 39.3 and 44.4% of controls showed progression of whole spine and SIJs, respectively. However, no difference in proportion of spinal and SIJ progression and absolute score changes per time point was observed between two groups. Moreover, the SIJ score changes were comparable according to the delivery method.ConclusionPregnancy and delivery do not affect the radiographic progression of the spine and SIJs in women with r-axSpA assessed by CT.

ObjectiveThis study aimed to identify trajectories of radiographic progression of the spine over time and use them, along with associated clinical factors, to develop a prediction model for patients with ankylosing spondylitis (AS).MethodsData from the medical records of patients diagnosed with AS in a single center were extracted between 2001 and 2018. Modified Stoke Ankylosing Spondylitis Spinal Scores (mSASSS) were estimated from cervical and lumbar radiographs. Group-based trajectory modeling classified patients into trajectory subgroups using longitudinal mSASSS data. In multivariate analysis, significant clinical factors associated with trajectories were selected and used to develop a decision tree for prediction of radiographic progression. The most appropriate group for each patient was then predicted using decision tree analysis.ResultsWe identified three trajectory classes: class 1 had a uniformly increasing slope of mSASSS, class 2 showed sustained low mSASSS, and class 3 showed little change in the slope of mSASSS but highest mSASSS from time of diagnosis to after progression. In multivariate analysis for predictive factors, female sex, younger age at diagnosis, lack of eye involvement, presence of peripheral joint involvement, and low baseline erythrocyte sedimentation rate (log) were significantly associated with class 2. Class 3 was significantly associated with male sex, older age at diagnosis, presence of ocular involvement, and lack of peripheral joint involvement when compared with class 1. Six clinical factors from multivariate analysis were used for the decision tree for classifying patients into three trajectories of radiographic progression.ConclusionWe identified three patterns of radiographic progression over time and developed a decision tree based on clinical factors to classify patients according to their trajectories of radiographic progression. Clinically, this model holds promise for predicting prognosis in patients with AS.

BackgroundAnkylosing spondylitis (AS) is characterized by back pain which can lead to spinal ankylosis. Anti-tumor necrosis factor (TNF) dramatically alleviates symptoms, but spinal damage can still be progressive even during anti-TNF treatment. Smoking is a one of well-known risk factors for structural damage in AS. However, it has not been confirmed that smoking can affect radiographic progression even during anti-TNF treatment.ObjectiveTo investigate factors associated with radiographic progression during anti-TNF treatment with a focus on smoking status which is known as one of poor prognostic factors for AS.Materials and methodsWe conducted a retrospective cohort study of AS patients who began the first-line anti-TNF treatment between 2001 and 2018 according to availability of smoking data. All enrolled patients were observed until the last visit, the first-line anti-TNF discontinuation, or December 2019. Radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The mSASSS progression rate (units/year) was calculated using the baseline mSASSS, the final mSASSS during observation period, and the duration between them. Univariable and multivariable logistic regression analyses were performed to identify associated factors of mSASSS progression rate > 1 unit/year.ResultsAmong 459 AS patients, 185 (40.3%) patients were never smokers, 62 (13.5%) were ex-smokers and 212 (46.2%) were current smokers at baseline. Ex- and current smokers had higher mSASSS progression rates than never smokers [never smoker 0.1 (0.0–0.7), ex-smoker 0.6 (0.0–1.5), and current smoker 0.6 (0.0–1.5) units/year, P < 0.001]. In the multivariable logistic analysis, current smoking [adjusted odds ratio (OR) 1.69, 95% CI 1.01–2.82, P = 0.047] and higher baseline mSASSS [adjusted OR 1.03, 95% CI 1.01–1.04, P < 0.001] were associated with a mSASSS progression rate > 1 unit/year.ConclusionCurrent smoking is a modifiable risk factor for radiographic progression in patients with AS on anti-TNF treatment. Quitting smoking should be strongly recommended.

Background: Radiographs are widely used to evaluate radiographic progression with modified stoke ankylosing spondylitis spinal score (mSASSS). Objective: This pilot study aimed to develop a deep learning model for grading the corners of the cervical and lumbar vertebral bodies for computer-aided detection of mSASSS in patients with ankylosing spondylitis (AS). Methods: Digital radiographic examination of the spine was performed using Discovery XR656 (GE Healthcare) and Digital Diagnost (Philips). The disk points were detected between the bodies using a key-point detection deep learning model from the image obtained in DICOM (digital imaging and communications in medicine) format from the cervical and lumbar spinal radiographs. After cropping the vertebral regions around the disk point, the lower and upper corners of the vertebral bodies were classified as grade 3 (total bony bridges) or grades 0, 1, or 2 (non-bridges). We trained a convolutional neural network model to predict the grades in the lower and upper corners of the vertebral bodies. The performance of the model was evaluated in a validation set, which was separate from the training set. Results: Among 1280 patients with AS for whom mSASSS data were available, 5,083 cervical and 5245 lumbar lateral radiographs were reviewed. The total number of corners where mSASSS was measured in the cervical and lumbar vertebrae, including the upper and lower corners, was 119,414. Among them, the number of corners in the training and validation sets was 110,088 and 9326, respectively. The mean accuracy, sensitivity, and specificity for mSASSS scoring in one corner of the vertebral body were 0.91604, 0.80288, and 0.94244, respectively. Conclusion: A high-performance deep learning model for grading the corners of the vertebral bodies was developed for the first time. This model must be improved and further validated to develop a computer-aided tool for assessing mSASSS in the future. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate spinal radiographic progression in specific age ranges of ankylosing spondylitis (AS) patients. Methods: Longitudinal data for 1125 AS patients at a single hospital from 2000 to 2018 were retrospectively reviewed. Radiographic intervals were obtained from patients with consecutive spinal radiographs. The radiographic progression rate was defined as the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change per year within each interval. Using generalized estimating equations (GEEs), estimated marginal means were calculated for the mSASSS progression rate across age groups after adjusting for potential confounders. Results: We obtained 4016 radiographic intervals and stratified them into five groups based on patient age at the interval start: <20 (n = 122); 20–29 (n = 1124); 30–39 (n = 1690); 40–49 (n = 794); and ⩾50 years (n = 286). The mean (SD) mSASSS progression rate for all the intervals was 0.8 (1.9). The GEE-estimated mean mSASSS progression rate increased with age, peaking in the 30–39 age group with a value of 1.15 [95% confidence interval (CI) 1.03, 1.27], and decreased slightly thereafter. In the presence of risk factors, rapid progression occurred at earlier ages: the GEE-estimated mean mSASSS progression rate in those with elevated C-reactive protein levels and preexisting syndesmophytes was 2.82 (95% CI 1.93, 3.71) in the 20–29 age group. Conclusion: Spinal structural damage in AS seems to progress most rapidly when patients are age 30–39 years. An awareness of the trends in radiographic progression with advancing age could improve understanding of the natural course of AS. [ABSTRACT FROM AUTHOR]

Abstract Baricitinib is an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 that has proved effective and well tolerated in the treatment of rheumatoid arthritis (RA) in an extensive programme of clinical studies of patients with moderate-to-severe disease. In a phase 2b dose-ranging study of baricitinib in combination with traditional disease-modifying antirheumatic drugs (DMARDs) in RA patients, magnetic resonance imaging showed that baricitinib 2 mg or 4 mg once daily provided dose-dependent suppression of synovitis, osteitis, erosion and cartilage loss at weeks 12 and 24 versus placebo. These findings correlated with clinical outcomes and were confirmed in three phase 3 studies (RA-BEGIN, RA-BEAM and RA-BUILD) using X-rays to assess structural joint damage. In patients naïve to DMARDs (RA-BEGIN study), baricitinib 4 mg once daily as monotherapy or combined with methotrexate produced smaller mean changes in structural joint damage than methotrexate monotherapy at week 24. Differences versus methotrexate were statistically significant for combined therapy. In patients responding inadequately to methotrexate (RA-BEAM study), baricitinib 4 mg plus background methotrexate significantly inhibited structural joint damage at week 24 versus placebo, and the results were comparable to those observed with adalimumab plus background methotrexate. In patients responding inadequately to conventional synthetic DMARDs (csDMARDs; RA-BUILD study), baricitinib 4 mg again significantly inhibited radiographic progression compared with placebo at week 24. Benefits were also observed with baricitinib 2 mg once daily, but the effects of baricitinib 4 mg were more robust. The positive effects of baricitinib 4 mg on radiographic progression continued over 1 and 2 years in the long-term extension study RA-BEYOND, with similar effects to adalimumab and significantly greater effects than placebo. Findings from the phase 3 studies of patients with RA were supported by preclinical studies, which showed that baricitinib has an osteoprotective effect, increasing mineralisation in bone-forming cells. In conclusion, baricitinib 4 mg once daily inhibits radiographic joint damage progression in patients with moderate-to-severe RA who are naïve to DMARDs or respond inadequately to csDMARDs, including methotrexate, and the beneficial effects are similar to those observed with adalimumab.

Abstract Background The multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors. Methods Four cohorts were analyzed: the BRASS and Leiden registries and the OPERA and SWEFOT studies (total N = 953). Treatments included conventional DMARDs and anti-TNFs. Associations of radiographic progression (ΔTSS) per year with the adjusted MBDA score, seropositivity, and clinical measures were evaluated using linear and logistic regression. The adjusted MBDA score was (1) validated in Leiden and SWEFOT, (2) compared with other measures in all four cohorts, and (3) used to generate curves for predicting risk of radiographic progression. Results Univariable and bivariable analyses validated the adjusted MBDA score and found it to be the strongest, independent predicator of radiographic progression (ΔTSS > 5) compared with seropositivity (rheumatoid factor and/or anti-CCP), baseline TSS, DAS28-CRP, CRP SJC, or CDAI. Neither DAS28-CRP, CDAI, SJC, nor CRP added significant information to the adjusted MBDA score as a predictor, and the frequency of radiographic progression agreed with the adjusted MBDA score when it was discordant with these measures. The rate of progression (ΔTSS > 5) increased from

Abstract Background Radiographic damage in rheumatoid arthritis (RA) includes erosions and joint space narrowing (JSN). Different mechanisms may underlie their development. The objective of this study was to evaluate predictors of these entities separately. Methods Consecutive early RA patients (symptom duration ≤12 months) from a defined area (Malmö, Sweden) recruited during 1995–2005 were investigated. Radiographs of hands and feet were scored by a trained reader according to the modified Sharp-van der Heijde score. Fat mass and lean mass distribution were measured at baseline using dual energy x-ray absorptiometry. Potential predictors of erosion and JSN progression from inclusion to the 5-year follow-up were evaluated. Results Two hundred and thirty-three patients were included. Radiographs at baseline and 5 years were available for 162 patients. The median (interquartile) progression of erosion and JSN scores were 4 (0–8) and 8 (1–16), respectively. Rheumatoid factor (RF) was a robust significant predictor of both erosion and JSN score progression. In adjusted analyses, anti-CCP antibodies predicted erosions while the erythrocyte sedimentation rate was predictive of both outcomes. Smoking and high baseline disease activity (DAS28 > 5.1) predicted progression of erosions. Baseline erosion score was associated with progression of both erosion and JSN progression, while baseline JSN score was predictive only of the progression of JSN. Overweight/obesity (BMI ≥ 25 kg/m2) was a significant negative predictor of JSN score progression (β = − 0.14, p = 0.018, adjusted for RF, age, baseline JSN score) also when additionally adjusting for ever smoking (p = 0.041). Among female patients, this effect was observed in those of estimated post-menopausal age (> 51 years), but not in younger women. The truncal to peripheral fat ratio was associated with less JSN score progression in women, but not in men. Conclusions Overweight RA patients had less JSN progression, independent of smoking status. This effect was seen in particular among older women (mainly post-menopausal), but not younger. Truncal fat was associated with less JSN progression in female patients. Smoking predicted erosion progression, and erosions may precede JSN. BMI and fat distribution may influence cartilage damage in early RA and might be related to hormonal factors.