Tender Joint Research Articles

Efficacy of N-Acetylcysteine as an Adjuvant Therapy for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Aims/Background Rheumatoid arthritis (RA) is an inflammatory autoimmune disease and N-acetylcysteine (NAC) is considered a potential therapeutic agent for RA due to strong antioxidant and anti-inflammatory properties. Therefore, this systematic review and meta-analysis aimed to evaluate the efficacy of NAC as an adjuvant therapy for RA. Methods A systematic search was conducted across five databases from inception to 1 August 2024, including CINAHL, Cochrane Library, EMBASE, PubMed, and Web of Science. The Cochrane risk-of-bias tool for randomized trials was used to assess the quality of the included studies. Sensitivity analysis was performed when significant heterogeneity was identified. Results Four studies involving 204 patients were included in our meta-analysis. The results indicated that NAC alleviated disease activity in RA patients (Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR): mean difference (MD) = 0.54). Additionally, NAC reduced inflammatory markers (erythrocyte sedimentation rate (ESR): MD = 3.00). However, the beneficial effects of NAC on oxidative stress in RA patients were not observed. Conclusion This meta-analysis demonstrated the efficacy of NAC in reducing inflammatory markers, improving joint tenderness, and swelling in patients with RA.

Patient profiles in randomised controlled trials versus a real-world study, in psoriatic arthritis: scoping review and meta-analysis.

Patients with psoriatic arthritis (PsA) in randomised controlled trials (RCTs) may not reflect patients in clinical practice. The objective was to perform a meta-analysis of PsA patients' characteristics in RCTs of biologic disease-modifying antirheumatic drugs (bDMARDs), and to compare them to patient profiles in a real-world study. Data sources: (a) Scoping literature review of phase III RCTs of bDMARDs in PsA published 2015-2020; (b) International observational study of PsA patients starting a bDMARD enrolled in 2015-2018 (PsABio: NCT02627768). Data collected at baseline included swollen and tender joint counts (SJC/TJC), enthesitis, skin involvement (body surface area -BSA-), C-reactive protein (CRP), physician global assessment (PhGA) and patient-reported outcomes (HAQ, pain). Univariate random-effects meta-analysis was conducted to calculate pooled means and proportions. Overall, 5654 patients from 10 RCTs were compared to 930 PsABio patients. Demographic data were similar. SJC/TJC were higher in RCTs than in PsABio (pooled means, 11.8/21.5 vs 5.7/11.9 respectively); enthesitis was more frequent in RCTs (64.7% vs 48.2%); as were patients with a BSA≥3% (62.2% vs 54.0%). PhGA was higher in RCTs (59.7mm vs 54.1mm). In contrast, patient-reported outcomes were similar, while CRP was significantly higher in PsABio (1.1 vs 1.4mg/dl). PsA patients starting a bDMARD in RCTs had highly active disease and a high patient-reported disease burden. In contrast, PsABio real-world patients starting a bDMARD had lower joint counts, skin disease and PhGA, but presented with similar patient-reported disease burden. The extrapolation of RCT data in clinical practice should take these elements into account.

Real-Life Data of Secukinumab in Patients with Moderate to Severe Plaque Psoriasis, Psoriatic Arthritis, and Ankylosing Spondylitis: Patient Baseline Characteristics Data from the PROMPT Study.

Secukinumab has proven to be effective and safe in psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) in the phase3 studies. However, data on real-world practice is limited. This study is an ongoing, multicenter, 2-year observational study that focuses on patients with moderate to severe plaque PsO, active PsA, or AS receiving secukinumab. The aim of this study is to present baseline data for the entire study population. A total of 127 patients were enrolled, with 101having PsO, 12 with PsA, and 14 with AS. Among the patients, approximately 54.0% were male. The mean body mass index ranged from 25.0 to 27.4kg/m2 across all groups. Patients with PsO had the longest disease duration with an average of 11.0years, followed by AS (3.0years) and PsA (1.0year). Previous biologic therapy was observed in 6.9-8.1% of patients. Baseline disease severity scores revealed moderate to severe disease. In the PsO group, the mean Psoriasis Area and Severity Index score was 16.1. For patients with PsA, the mean Tender Joint Count was 9.1, and the mean Swollen Joint Count was 6.7. In the AS group, the mean Bath Ankylosing Spondylitis Disease Activity Index score was 4.6, and the mean Ankylosing Spondylitis Disease Activity Score was 3.7. The study demonstrates disease durations, disease activity, and treatment history in Thai patients that were generally consistent with previous randomized controlled studies. Long-term data on the efficacy and safety of the treatment will be presented in future publications.

Minimal disease activity and associated factors in patients with psoriatic arthritis: cross-sectional study from a single center

IntroductionPsoriatic arthritis (PsA) is a heterogeneous disease with various manifestations such as dactylitis, enthesitis, spondylitis, and skin involvement. Minimal disease activity (MDA) has been successfully used in daily clinical practice and is considered a reasonable treatment target in patients with PsA. In this study, we aimed to evaluate the MDA status and associated factors in patients with PsA in our tertiary referral clinic.Material and methodsThis cross-sectional study included patients who met the CASPAR classification criteria and had at least 6 months of follow-up data between 2001 and 2021. Patients who met at least 5 of 7 criteria (tender joint count ≤ 1/68, swollen joint count ≤ 1/66, Psoriasis Area Severity Index [PASI] ≤ 1, Visual Analogue Scale [VAS] ≤ 15, patient global VAS ≤ 20, Health Assessment Questionnaire-Disability Index [HAQ-DI] ≤ 0.5, and enthesitis number ≤ 1) were considered to achieve MDA.ResultsData from 172 patients (61% female) were analyzed and included in the study. While most patients had polyarticular involvement (33.7%), mono-oligoarthritis was present in 30.2%, mixed type in 26.2%, isolated distal interphalangeal arthritis in 5.8%, isolated spondylitis in 2.9%, and arthritis mutilans in 1.2%. Overall, 95 (55.2%) of the patients were observed at MDA, which was lower in tumor necrosis factor inhibitor (TNFi) users compared to only conventional synthetic disease-modifying antirheumatic drug users. In univariate analysis, MDA was associated with higher patient age, longer psoriasis duration, late-onset PsA, and continued use of first TNFi. In multivariate analysis, higher patient age, late-onset PsA, and higher continuation rate of first TNFi were associated with MDA.ConclusionsIn the study, more than half of our patients achieved MDA status. A higher MDA rate was associated with a higher continuation rate at first-line TNFi treatment. The relatively large po­pulation who could not reach MDA status in our study indicates an unmet need for monitoring and treatment of PsA.

Association between depression and anxiety and inability to achieve remission in rheumatoid arthritis and psoriatic arthritis.

To investigate the association between depression and anxiety and the inability to achieve remission in rheumatoid arthritis(RA) and psoriatic arthritis(PsA) patients. In addition, the association between depressive and anxiety symptoms and disease activity components were explored. 400 RA and 367 PsA patients from the tREACH and DEPAR were included, respectively. Patients had a possible depression or anxiety disorder if they scored >7 on the Hospital Anxiety and Depression Scale(HADS). Remission was defined as DAS44<1.6 in RA and DAPSA≤4 in PsA. Mixed models were used to assess the association between depression/anxiety, at any timepoint during 2 years, and remission during 2 years, and to explore which disease activity components are most influenced by depression/anxiety. At baseline, 20% of RA patients had a possible depression and 30% a possible anxiety disorder. In PsA this was 18% and 23%. After adjustment for concurrent anxiety symptoms depression was associated with a lower odds of achieving remission during 2 years of follow-up (OR 0.45(95%CI 0.25-0.80) for RA and OR 0.24(95%CI 0.08-0.71) for PsA). Anxiety was not associated with remission after adjustment for concurrent depression symptoms.The presence of depression/anxiety was associated with higher tender joint count, worse general health, more pain and slightly elevated inflammation markers, but not with more swollen joints in both RA and PsA. The presence of depressive symptoms in RA and PsA patients at baseline or during follow-up was associated with a lower likelihood of achieving remission. Healthcare professionals should, therefore, be aware of symptoms of depression.

Infiltrations of plasma cells in synovium predict inadequate response to Adalimumab in Rheumatoid Arthritis patients

ObjectiveRheumatoid arthritis (RA) is a clinically heterogeneous and complex autoimmune disease, making the prediction of therapeutic responses a significant challenge. This study aims to assess the role of clinical and synovial biomarkers in predicting poor response to adalimumab treatment in RA patients.MethodsThis single-center prospective study included 56 RA patients who had an inadequate response to methotrexate (MTX). At baseline, comprehensive assessments including complete blood count, liver and kidney function tests, blood glucose levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), as well as counts of swollen and tender joints, Health Assessment Questionnaire (HAQ) score, pain visual analogue scale (VAS) scores, and DAS28-CRP scores were conducted. Synovial biopsies were performed, followed by an efficacy evaluation at 12 weeks of adalimumab treatment. Patients not meeting the ACR20 criteria were classified into the non-responder group, with the remainder categorized as the responder group.ResultsOut of the participants, 24 (42.9%) failed to achieve ACR20 with adalimumab treatment. Non-responders exhibited higher infiltration of plasma cells in the synovium. Multivariate logistic regression analysis identified the presence of plasma cells as an independent risk factor for inadequate response to adalimumab.ConclusionInadequate responses to adalimumab in RA patients were associated with increased plasma cell infiltrations in the synovium. These findings suggest a promising target for tailored therapies in rheumatoid arthritis.

Effects of Acupuncture on Cartilage Degradation and Joint Pain in Osteoarthritis

Osteoarthritis, resulting from joint decline, leads to various symptoms including joint pain, stiffness, tenderness, and local inflammation. These symptoms may be caused by the remodeling of the five structural phenotypes: inflammatory, subchondral bone, meniscal cartilage, atrophic, and hypertrophic phenotypes. Studies have shown that acupuncture can inhibit cartilage degradation by regulating extracellular matrix-degradation and enzyme synthesis. Notably, the efficacy of acupuncture treatment in osteoarthritis may be attributed to regulated inflammation and apoptosis of chondrocytes, as well as endogenous opioid production, and activation of the endocannabinoid systems (in the central and peripheral nervous systems), to contribute towards cartilage protection and joint pain relief. This review provides a current summary of the mechanisms of action of acupuncture in osteoarthritis, indicating that acupuncture, a therapy with fewer side effects than conventional medications, may be an effective treatment strategy for the management of osteoarthritis.

Factors for Consideration by Pediatric Rheumatologists When Scoring the Physician Global Assessment of Disease Activity in Juvenile Idiopathic Arthritis: First Step Toward an Internal Consensus.

The physician global assessment of disease activity (PhGA) is a tool used nearly ubiquitously by pediatric rheumatologists for the assessment of patient disease activity status. However, this tool lacks standardization in its scoring. This survey aimed to identify score influencing factors, along with inclusion or exclusion of extra-articular manifestations and imaging, when scoring the PhGA in juvenile idiopathic arthritis (JIA). Electronic surveys were sent to Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Care and Outcomes Improvement Network members who completed a previous survey on scoring of the PhGA. Respondents were asked to rank their top seven factors for inclusion in the PhGA for nonsystemic JIA (nsJIA) and systemic JIA (sJIA), along with ranking extra-articular manifestations and imaging for inclusion. Frequency and percentage of rank and Likert responses were analyzed, and geographic regions as well as level of experience were compared using the chi-square test and Fisher's test. A total of 276 respondents from 54 countries and six continents participated. For nsJIA, factors selected by >50% included number of swollen joints, active uveitis, duration of morning stiffness, and number of tender joints. For sJIA, factors selected by >50% were presence and duration of fever, laboratory tests, number of swollen joints, serositis, rash, hepatomegaly, lung disease, and lymphadenopathy. Agreement on the inclusion of extra-articular factors, such as uveitis, macrophage activation syndrome, and sJIA-associated lung disease, had >70% moderate or strong agreement for inclusion, whereas psoriasis had only 50.5% agreement for inclusion and imaging had 64.7% agreement for inclusion. Variations in rank between different geographic regions or level of experience were minor. This survey identifies factors that pediatric rheumatology providers find important for PhGA scoring of disease activity, documents varying agreement on inclusion of extra-articular manifestations of disease, and lays the framework for further consensus work.

Factors predicting treatment response to biological and targeted synthetic disease-modifying antirheumatic drugs in psoriatic arthritis - a systematic review and meta-analysis.

The therapeutic response of patients with psoriatic arthritis (PsA) varies greatly and is often unsatisfactory. Accordingly, it is essential to individualise treatment selection to minimise long-term complications. This study aimed to identify factors that might predict treatment response to biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) in patients with PsA and to outline their potential application using artificial intelligence (AI). Five electronic databases were screened to identify relevant studies. A random-effects meta-analysis was performed for factors that were investigated in at least four studies. Finally, 37 studies with a total of 17,042 patients were included. The most frequently investigated predictors in these studies were sex, age, C-reactive protein (CRP), the Health Assessment Questionnaire (HAQ), BMI, and disease duration. The meta-analysis revealed that male sex (odds ratio (OR) = 2.188, 95% confidence interval (CI) = 1.912-2.503) and higher baseline CRP (1.537, 1.111-2.125) were associated with greater treatment response. Older age (0.982, 0.975-0.99), higher baseline HAQ score (0.483, 0.336-0.696), higher baseline DAPSA score (0.789, 0.663-0.938), and higher baseline tender joint count (TJC) (0.97, 0.945-0.996) were negatively correlated with the response to therapy. The other factors were not statistically significant but might be of clinical importance in the context of a complex AI test battery. Further studies are needed to validate these findings and identify novel factors that could guide personalised treatment decisions for PsA patients, in particular in developing AI applications. In accordance with the latest medical developments, decision-support tools based on supervised learning algorithms have been proposed as a clinical application of these predictors. Key messages • Given the often unsatisfactory and unpredictable therapeutic response in patients with Psoriatic Arthritis (PsA), treatment selection must be highly individualized. • A systematic literature review was conducted to identify the most reliable predictors of treatment response to biologic and targeted synthetic disease-modifying antirheumatic drugs in PsA patients. • The potential integration of these predictors into AI tools for routine clinical practice is discussed.

Effectiveness of N-3 fatty acids supplementation on spondyloarthritis: A systematic review and meta-analysis

Background & AimsThe study aims to systematically review and meta-analyze randomized controlled trials (RCTs) assessing the effects of n-3 fatty acids (FA) supplementation on spondyloarthritis (SpA) disease activity, inflammatory markers, and imaging. MethodsThe study protocol was developed and registered online in advance. The PubMed, SCOPUS, and Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases were systematically searched for RCTs up to April 2024. Two independent reviewers screened, assessed for eligibility, and extracted data from the eligible RCTs. The revised Cochrane Risk of Bias tool was used to assess the quality of trials. The random-effects model was used to calculate the pooled estimates. ResultsWe included four RCTs, involving 245 patients with SpA. Supplementation with n-3 FA did not improve physician-reported outcomes [number of tender joints (four trials, standardized mean difference (SMD): -0.22; 95% confidence interval (CI): -0.74 to 0.29; I2=61%), number of swollen joints (two trials, SMD: -0.13; 95% CI: -0.42 to 0.15; I2=0%)], and patient-reported outcomes [pain (three trials, SMD: -0.16; 95% CI: -1.03 to 0.70; I2=74%), Health Assessment Questionnaire (three trials, SMD: -0.04; 95% CI: -0.78 to 0.70; I2=71%). The other nine pre-specified outcomes were not analyzed due to lack of information from the original RCTs which were evaluated as «some concerns» or «high risk» of bias. ConclusionsIn the present systematic review and meta-analysis including placebo-controlled RCTs, n-3 FA supplementation did not show improvement in the reported outcomes. Future RCTs should be conducted with homogenous intervention, placebo, and outcomes to re-examine possible beneficial effects.

Exploring the Relationship between Vitamin D Deficiency and Disease Activity in Rheumatoid Arthritis Patients

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by inflammation, pain, and joint damage. Vitamin D deficiency worsens inflammation and increases RA disease activity. Aim of the study: This study aimed to explore the relationship between Vitamin D deficiency and disease activity in rheumatoid arthritis patients. Methods: This cross-sectional study was conducted in the Department of Medicine, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2003 to December 2003. The study included 100 rheumatoid arthritis patients, divided into two groups- Group A: 50 patients with normal Vitamin D level and Group B: 50 patients with Vitamin D deficiency. Result: No significant difference was found between the groups in demographic characteristics. Group B exhibited significantly greater disease severity compared to Group A. The Disease Activity Score (DAS28) was higher in Group B (4.2 ± 1.3) than in Group A (2.8 ± 1.1), with a p-value &lt; 0.001. CRP levels were also elevated in Group B (12.4 ± 3.5 mg/L vs. 5.3 ± 2.1 mg/L; p &lt; 0.001). Group B had more swollen joints (6.2 vs. 3.5) and tender joints (7.3 vs. 4.1), with p &lt; 0.001. ESR levels were higher in Group B (38.7 vs. 22.4 mm/h; p &lt; 0.001). Negative correlations were found between Vitamin D levels and DAS28 (r = -0.48), CRP (r = -0.51), and ESR (r = -0.52). Conclusion: This study concludes that Vitamin D deficiency is significantly associated with increased disease activity, inflammation, and joint involvement in rheumatoid arthritis patients.

Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis.

The high prevalence of osteoporosis in rheumatoid arthritis (RA) is due to inflammation that stimulates differentiation of osteoclasts, a process involving circulating monocytes and T cell-derived factors. The aim of this study was to evaluate relations between circulating monocytes, T cell subsets, and changes in bone characteristics before and after treatment with biological disease-modifying antirheumatic drugs (bDMARDs) in RA. Thirty patients with untreated early RA who met the American College of Rheumatology/EULAR 2010 criteria were included. Data were collected before and 48 weeks after treatment with methotrexate (MTX) together with one of three bDMARDs (abatacept, tocilizumab, or certolizumab pegol). Disease activity was measured using the Clinical Disease Activity Index, swollen or tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates. Proportions of monocyte and CD4+ T cell subsets in blood samples were analyzed by flow cytometry. Bone densitometry was performed using high-resolution peripheral quantitative computed tomography (HR-pQCT). HR-pQCT revealed an overall decrease in cortical (P = 0.009) and trabecular (P = 0.034) bone mineral density, although a subset of patients showed no bone loss after 48 weeks of treatment. The overall bone loss was not associated with age, body mass index, sex, intraarticular glucocorticoid injections, or baseline disease activity. Loss of trabecular bone volume fraction correlated with high proportions of circulating CXCR3+Th2 cells (r = -0.38, P = 0.04) and CXCR3+Th17 cells (r = -0.36, P = 0.05) at baseline. Similarly, no loss of trabecular bone volume fraction correlated with high proportions of regulatory T cells (r = 0.4, P = 0.03) at baseline. However, the associations were not significant when corrected for confounders and multiple testing. MTX together with bDMARDs efficiently reduce disease activity but only prevent bone loss in a subset of patients with RA after 48 weeks of treatment. The correlations of circulating baseline T helper cell and regulatory T cell populations with trabecular bone changes suggest a potential novel role for these cells in systemic bone homeostasis during early RA.

Arthralgia with risk of progression to psoriatic arthritis: role of clinical assessments and ultrasound as prognostic factors.

Referral of patients from dermatology to rheumatology practices due to psoriasis is unnecessary delayed. Many times musculoskeletal symptoms are the first reason for consultation. We aimed to estimate the proportion of ARP-PsA (arthralgia with risk to progression) defined by patients with arthralgia and the presence of psoriasis and/or a family history. Also, identify clinical, laboratory, and imaging prognostic factors of PsA progression within the ARP-PsA group over a one-year follow-up period. Patients were included in a comprehensive arthralgia evaluation program, with the ARP-PsA criteria defined as arthralgia with Pso and/or a family history of Pso, not referred from dermatology. Baseline characteristics were analyzed, and the progression to PsA at one year was assessed. Multivariate analysis identified predictor features for progression. Of the 1419 patients, 8.4% met ARP-PsA criteria, and 29% of this subgroup developed PsA at one year. Baseline differences between those who developed PsA and those who did not included family history, Pso duration, pain severity, joint count, and imaging findings (X-ray and ultrasound). Multivariate analysis revealed the predictive significance of a combination of Pso plus family history of psoriasis disease, synovitis by Power Doppler ultrasound, ultrasound enthesopathy findings, and low tender joint count. The frequency of patients ARP-PsA was 8.4%, of whom 29% developed PsA at 1-year. The main predictor variables for this progression were identified.

Association of enthesitis with severity of psoriasis in psoriatic arthritis: an observational study.

The relationship between dermatological and articular manifestations of psoriatic disease remains incompletely elucidated. There is no strong correlation between the severity of cutaneous psoriasis and the clinical phenotypes of psoriatic arthritis (PsA). This study aims to examine the correlation between the severity of psoriasis and various clinical features, including measures of severity and activity of PsA, in a real-world clinical setting. Seventy-six consecutive adult patients of both genders with confirmed diagnoses of psoriatic arthritis (PsA) and psoriasis were included in the study. The Psoriasis Area and Severity Index (PASI) was assessed alongside various PsA variables: tender joint count (TJC), swollen joint count (SJC), duration of morning stiffness, presence of dactylitis and number of affected digits, presence of enthesitis and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), patient's global assessment (PGA), and examiner's global assessment (EGA). Associations were analyzed using the Spearman correlation test and the Kruskal-Wallis test. Statistical significance was established at p = 0.05. Forty-two men and thirty-four women, median age of 56 (range 33-85) years, participated in the study. The median duration of psoriasis was 216 (range 0-600) months and median duration of PsA was 120 (range 7-456) months. There was no significant correlation between PASI and any PsA variables, except for the correlation between PASI and the presence of enthesitis (ρ = 0.285; p = 0.013). Moreover, older patients and patients with a long history of psoriasis manifested more often with enthesis as a sign of PsA. Our findings emphasize the correlation between the severity of psoriasis and presence of enthesitis in patients with PsA.

Effect of apremilast on hand and whole-body MRI assessments of inflammation in patients with psoriatic arthritis (MOSAIC): a phase 4, multicentre, single-arm, open-label study.

The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE. MOSAIC was a phase 4, multicentre, single-arm, open-label study conducted at 29 sites across ten countries (Belgium, Canada, Denmark, Germany, Italy, Russia, Spain, Switzerland, the UK, and the USA). Adults aged 18 years or older with a documented diagnosis of psoriatic arthritis for a duration of 3 months to 5 years self-enrolled and were included if they met the classification criteria for active psoriatic arthritis at screening. Patients were required to have at least three swollen and three tender joints with hand involvement and at least one active enthesitis site according to the Spondyloarthritis Research Consortium of Canada enthesitis index or the Leeds enthesitis index. Patients were excluded if they had previous treatment with a biological disease-modifying antirheumatic drug or previous treatment with more than two conventional synthetic disease-modifying antirheumatic drugs. After a 5-day titration period, patients received apremilast 30 mg orally twice per day. Concomitant stable methotrexate up to 25 mg per week was permitted. The primary endpoint was change from baseline to week 24 in a composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis in the hand as assessed by PsAMRIS. The full analysis set and safety population included all enrolled patients who received at least one dose of apremilast. This completed study is registered with ClinicalTrials.gov (NCT03783026). Between Feb 6, 2019, and May 11, 2022, 123 patients were enrolled in the MOSAIC study. Of these 123 patients, 122 (99%) were treated with apremilast and included in the full analysis set and safety population. 67 (55%) of 122 patients were female, 55 (45%) were male, and 116 (95%) were White. 80 (66%) of 122 patients completed 48 weeks of treatment. The least squares mean change from baseline to week 24 in the composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis as assessed by PsAMRIS was -2·32 (95% CI -4·73 to 0·09). 95 (78%) of 122 patients had at least one treatment-emergent adverse event. Six (5%) patients had a severe treatment-emergent adverse event and six (5%) patients had a serious treatment-emergent adverse event. No serious treatment-emergent adverse events were considered to be related to apremilast. Apremilast improved inflammation in joints and entheses on assessment of MRI measures in the hand and the whole body. Our findings encourage the use of MRI, including whole-body MRI, as an objective outcome measure in trials in patients with psoriatic arthritis. Amgen.

N6‑methyladenosine methyltransferase METTL14 is associated with macrophage polarization in rheumatoid arthritis.

Rheumatoid arthritis (RA) is largely caused by the inflammatory response triggered by macrophage polarization. Through epigenetic reprogramming, the inflammatory state of macrophages can be modified. Macrophage polarization is associated with the RNA epigenetic alteration N6-methyladenosine (m6A) RNA methylation. However, the specific function and underlying mechanisms of m6A methylation in the role of macrophage polarization in RA remain to be elucidated. The mRNA expression levels of m6A methylase genes and signaling pathway components associated with RA macrophages were determined in the present study using reverse-transcription quantitative PCR. Methyltransferase 14 (METTL14) protein expression levels were determined using western blot analysis, and the levels of specific cellular secretion factors were determined using ELISA and flow cytometry. The results of the present study demonstrated that elevated METTL14 expression was associated with joint tenderness, and METTL14 expression was positively correlated with both C-reactive protein and rheumatoid factor expression levels. Moreover, METTL14 exhibited potential in the prediction of visual analogue scale. Pro-inflammatory cytokines (TNF-α) and M1 macrophage markers (CD68+CD86+) were also positively associated with METTL14 expression. The results of the Kyoto Encyclopedia of Genes and Genomes analysis revealed that METTL14 was strongly associated with the MAPK signaling pathway. Notably, JNK and ERK2 exhibited a positive correlation with the M1 macrophage marker, CD68+CD86+, which was positively associated with the pro-inflammatory factor, TNF-α. JNK and ERK2 expression levels were markedly increased in the METTL14 high-expression group, compared with in the low-expression group; however, p38 and ERK1 expression levels were not significantly different between these groups. Collectively, the results of the present study demonstrated that METTL14 expression was significantly increased in the peripheral blood and synovial tissue of patients with RA, highlighting the potential association with both immunoinflammatory markers and clinical symptoms. In addition, it was suggested that METTL14 may exacerbate the downstream inflammatory response, through mediating macrophage polarization via the MAPK pathway.

Forefoot inflammation in recent-onset ACPA-positive and ACPA-negative RA: clinically similar, but different in underlying inflamed tissues

ObjectivesAlthough joint swelling is traditionally interpreted as synovitis, recent imaging studies showed that there is also inflammation of tenosynovium and intermetatarsal bursae in the forefoot. We aimed to increase our...

Predictors for severe persisting pain in rheumatoid arthritis are associated with pain origin and appraisal of pain

ObjectivesTo determine the proportion of patients with rheumatoid arthritis (RA) with severe persisting pain and to identify predictive factors despite treatment-controlled disease activity.MethodsThis prospective multicentre study included outpatients with RA...

Safety and efficacy of intra-articular triamcinolone acetonide injection versus standard of care in patients with rheumatoid arthritis flare

Triamcinolone acetonide is a commonly used corticosteroid for rheumatoid arthritis (RA) flares, providing extended relief. However, there is limited data from controlled trials comparing the efficacy of intra-articular corticosteroid (IACS) injections to standard care, particularly with non-steroidal anti-inflammatory drugs (NSAIDs). This non-randomized, single-center, open-label study evaluated the safety and efficacy of IACS injections in RA patients experiencing knee joint flare-ups. A total of 64 patients were screened and 44 received IACS (triamcinolone acetonide) and 15 were included in the control group. Significant improvements were observed in the IACS group in pain, swelling, and morning stiffness at week 2, which were sustained through weeks 6 and 12. The swollen joint count significantly reduced by week 12, while the tender joint count showed improvement by week 2. Pain reduction was substantial, as indicated by significant decrease in visual analog scale scores for pain, swelling, and mobility. The disease activity score-28 improved significantly across all time points. In addition, the C-reactive protein level decreased significantly at week 2 and its decreasing trend continued until weeks 6 and 12. By week 2, all patients had ceased NSAID use. The study demonstrated the effectiveness of IACS in reducing RA flare severity, particularly in terms of pain, swelling, and functional impairment, with no major safety concerns reported.

Thermal Characteristics of the Small Joints of the Hands Between Patients with Rheumatoid Arthritis and Healthy Controls.

Objectives: This study aimed to investigate the thermal characteristics of the small joints of the hands between patients with Rheumatoid arthritis and healthy controls. Patients and Methods: Fifty-two patients with Rheumatoid arthritis and twenty-six healthy controls were included in the study. Joint tenderness was evaluated using Ritchie Articular index. Joint tenderness was scored from 0 to 3. Thermal data was collected from the hand regions of individuals. A FLIR T450sc microbolometer infrared thermal camera with 320x240 resolution was used for the thermography of individuals. Bilaterally proximal interphalangeal joints (1-5) and metacarpophalangeal joints (1-5) were evaluated. The mean temperature was compared between patients and healthy controls Results: The mean temperature values of the joints in the patients with a Rheumatoid arthritis RAI score of 0, 1, 2,3 were 32.43 ± 1.59°C; 32.71 ± 1.36°C; 33.12 ± 1.23°C; 33.60 ± 0.99 respectively. The mean temperature was 31.14 ± 1.51°C in healthy controls. The mean temperature values of the joints in the Rheumatoid arthritis patients with RAI score of 0 was higher compared to healthy controls (p&lt;0.05). Patients with a Ritchie sensitivity score of 1 had a higher mean temperature compared to patients with score of 0 (p&lt;0.05). In Rheumatoid arthritis patients, the joints with a RAI score of 1 had higher mean temperature values than the joints with RAI score of 0 (p&lt;0.05). The mean temperature values of the joints with RAI score of 2 were also higher than the joints with RAI score of 1 (p&lt;0.05). Conclusion: Thermal imaging may be an objective tool for diagnosis and assessing disease activity in Rheumatoid arthritis.