Rheumatoid Arthritis Patients Research Articles

Long-Term Safety and Efficacy of Janus kinase (JAK) Inhibitors in the Treatment of Rheumatoid Arthritis

Background: Janus kinase (JAK) inhibitors are a new class of drugs for the treatment of rheumatoid arthritis (RA); however, the long-term consequences of using these drugs are still not well understood. Objective: The primary objective of this research was to examine the effectiveness and safety of JAK inhibitors for the management of rheumatoid arthritis (RA) patients. Methodology: Clinical raw data of 150 RA patients receiving JAK inhibitors was collected in different tertiary care hospitals in Lahore, Pakistan from March 2023 to June 2024. till were conducted. The anti-inflammatory effect was evaluated by the Disease Activity Score in 28 joints (DAS28) and the safety profile through adverse events, laboratory markers, and patients self-reported outcomes. The SPSS version 27 applied for raw data analysis which used the paired t-tests and multiple regression models to establish the factors that determine favorable outcomes and complications. Results: JAK inhibitors also reduced the DAS28 scores from baseline to 24 months by a mean of 3. 2 ± 1. 1 (p<0. 001). The findings stated that 12 percent of the patients at baseline and 45 percent of the patients at 24 months had achieved remission. The reported side effects were infections, 25%; gastrointestinal problems, 18%; and abnormal liver function tests, 10%. Severe adverse reactions were noted in 5% of the patients and no new safety issues were observed over the course of the treatment. Conclusion: JAK inhibitors have been shown to be useful in decreasing the activity of RA for the long-term use with reasonable side effects. The results provided evidence that JAK inhibitors were best treatment of rheumatoid arthritis (RA) but for best efficacy results closely monitoring and specific approach should be applied.

Systematic analysis of serum peptidase inhibitor 3 in psoriasis diagnosis and treatment.

Psoriasis is a chronic inflammatory skin disease. To date, there are no serum biomarkers for psoriasis that have been validated to diagnose or treat psoriasis. Peptidase inhibitor 3 (PI3) levels in serum were measured using chemiluminescence immunoassay (CLIA) in two independent cohorts including healthy controls (HC) and patients diagnosed with chronic urticaria (CU), chronic eczema (CE), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis vulgaris (PV). Receiver operating characteristic (ROC) curve analysis determined the diagnostic performance of PI3 in patients with psoriasis. The correlation between PI3 levels and the Psoriasis Area Severity Index (PASI) score was analyzed using the Spearman correlation method. Additionally, the study evaluated PI3 expression and treatment response of PV patients 12weeks before and after topical treatment with calcipotriol betamethasone and calcipotriol ointment (T#1) or topical therapy plus PSORI-CM01 granules (T#2). In cohort #1, PI3 levels effectively discriminate PV patients from HC and CU patients, with AUCs of 0.909 and 0.840, respectively. In cohort #2, AUCs for detecting PV patients among HC, CU, CE, SLE, and RA patients were 0.940, 0.926, 0.802, 0.989, and 0.951, respectively. For PsA patients, AUCs were 0.989, 0.986, 0.910, 1.000, and 0.984 compared to HC, CU, CE, SLE, and RA patients, respectively. In both cohorts, PI3 levels correlated significantly with PASI scores in PV patients (cohort #1, r = 0.433; cohort #2, r = 0.634) and PsA patients (cohort #2, r = 0.718). Moreover, univariate logistic regression analyses revealed that PV patients with higher PI3 expression had a significantly higher risk of treatment resistance, with an odds ratio of 3.45 [95% confidence interval (CI) 1.54, 7.74, p = 0.003]. Finally, PI3 levels decreased nearly 35-fold more in the responder than in the non-responder group before and after treatment. Serological PI3 is a reliable biomarker for PV diagnosis and may have the potential to predict and monitor the progression of PV before and after treatment. Key Points • This study validated PI3's diagnostic performance in two independent psoriasis cohorts using CLIA. • PI3 expression is significantly correlated with the psoriasis severity and with patients who benefited from the treatments. • Serological PI3 is a reliable biomarker for psoriasis diagnosis and may have the potential to monitor the psoriasis progression with and without treatments.

Heart Failure in Rheumatoid Arthritis: Clinical Implications.

This review focuses on the association between RA and heart failure, highlighting the role of inflammation and the prevalence of heart failure with preserved ejection fraction (HFpEF) in this population. The incidence of heart failure in RA patients is two to three times higher than in the general population, with inflammation playing a significant role independent of traditional cardiovascular risk factors. HFpEF accounts for about half of heart failure cases and is increasingly recognized in RA patients, although it remains underdiagnosed. Atypical presentations and non-specific symptoms further complicate diagnosis. Early control of inflammation has been shown to reduce the risk of heart failure development and progression, improving both morbidity and mortality outcomes. Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting approximately 1% of the population, with cardiovascular disease being the leading cause of premature death in these patients.

Erosion regression in patients with rheumatoid arthritis after upadacitinib-a pilot study using high resolution peripheral quantitative computed tomography.

To evaluate whether inhibition of Janus kinases (JAK) 1 could lead to erosion repair on high-resolution peripheral quantitative computer tomography (HR-pQCT) in patients with active rheumatoid arthritis (RA). This was a prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA with ≥1 bone erosion on HR-pQCT. They were given upadacitinib 15 mg once daily for 24 weeks. HR-pQCT of the metacarpophalangeal joint was performed at baseline and 24-week. The serum bone biomarkers level was evaluated before and after treatment. Twenty age-and-sex matched RA patients from another study treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) were included as active controls. Nineteen patients in the upadacitinib group completed the study procedures. After 24 weeks, despite similar improvement in disease activity, a reversed trend in the mean erosion volume change on HR-pQCT was observed comparing the upadacitinib and active control group (upadacitinib group: -0.23 ± 3.26mm3 vs control group: 1.32 ± 6.05mm3, p= 0.131). A greater proportion of erosions in the upadacitinib group demonstrated regression (27% vs 12%, p= 0.085). Using general estimating equation (GEE), the use of upadacitinib was significantly associated with erosion regression (OR: 3.61, 95% CI: 1.00-13.00, p= 0.049) after adjusting for the difference in disease duration. The serum levels of bone resorption markers reduced after upadacitinib treatment. No new safety signal was noted. Despite a similar improvement in RA disease activity after upadacitinib compared with csDMARDs, a differential regression of erosion on HR-pQCT was observed in patients received upadacitinib. The potential role of JAK1 inhibition in erosion repair should be investigated.

Clinical and Cardiometabolic Effects of Reducing Sedentary Behavior in Postmenopausal Women with Rheumatoid Arthritis.

We investigated the effects of a 4-month intervention targeting sedentary behavior on sedentary time and physical activity level, clinical parameters, cardiometabolic risk factors, inflammatory markers, and health-related quality of life in post-menopausal women with rheumatoid arthritis. This was a 4-month, parallel-group, randomized controlled trial (ClinicalTrials.gov identifier: NCT03186924). One-hundred-and-three postmenopausal rheumatoid arthritis patients were randomized (1:1) to either a newly developed intervention targeting sedentary behavior (Take a STAND for Health; TS4H) or standard of care (SOC). Sedentary behavior (primary outcome) and physical activity levels, clinical parameters, anthropometric parameters and body composition, blood samples and oral glucose tolerance test, blood pressure, muscle function, and health-related quality of life were assessed at baseline (Pre) and after 4 months (Post). Between- and within-group differences were tested using linear mixed models following the intention-to-treat principle. Total sedentary time, time in prolonged sitting bouts, standing, and stepping did not change in either group (all p ≥ 0.337). No significant between- and within-group differences were detected for any of the clinical parameters, markers of cardiometabolic health and inflammation, and health-related quality of life variables (all p ≥ 0.136). Among responders in TS4H group (those who reduced sedentary time by ≥30 min/d), Pre to Post IL-10 concentrations tended to reduce (group*time: p = 0.086; estimated mean difference [EMD]: -12.0 pg/mL [-23.5 to -0.6], p = 0.037), and general health (group*time: p = 0.047; EMD: 10.9 A.U. [-1.1 to 22.9], p = 0.086) and overall physical health tended to improve (group*time: p = 0.067; EMD: 7.9 A.U. [-0.9 to 16.6], p = 0.089). TS4H did not change sedentary behavior, physical activity levels, clinical, cardiometabolic, inflammatory or health-related quality of life outcomes. However, TS4H tended to reduce IL-10 levels and improve health-related quality of life in responders.

Anti TNF-Alpha Treatment Improves Microvascular Endothelial Dysfunction in Rheumatoid Arthritis Patients.

Nailfold capillaroscopy is a non-invasive investigation, which allows for the study of the microvasculature (anatomical and functional). Rheumatoid arthritis (RA) is associated with a high risk of cardiovascular atherosclerotic diseases, with endothelial dysfunction (macrovascular and microvascular) representing the first step in atherosclerosis development. The aim of this study is represented by the assessment of microvascular endothelial dysfunction in RA patients by means of nailfold capillaroscopy and to assess its evolution after a period of 12 months of anti TNF-alpha treatment. The study included 70 consecutive patients with RA and 70 healthy subjects, matched for age and gender, as the control group. Rheumatoid factor, anti-cyclic citrullinated peptide antibodies, serum TNF-α, C reactive protein, and erythrocytes sedimentation rate were evaluated in all patients, but in controls, only rheumatoid factor, serum TNF-α, C reactive protein, and erythrocytes sedimentation rate were measured. The RA activity was measured by DAS28. Nailfold capillaroscopy was carried out in all patients and controls, determining the baseline nailfold capillary density (Db), nailfold capillary density during reactive hyperemia (Dh), and nailfold capillary density after venous congestion (Dc). Data were presented as mean ± standard deviation. Statistical analysis was performed using ANOVA and Pearson's correlation, with p < 0.05 being statistically significant. Db, Dh, and Dc were lower in RA patients than in controls (p < 0.0001), correlating with RA activity and TNF-α (p < 0.05). After 12 months of anti TNF-α treatment, microvascular endothelial dysfunction improved (p < 0.0001). Microvascular endothelial dysfunction can be assessed by nailfold capillaroscopy, with anti TNF-α medication contributing to its improvement.

Factors associated with interstitial lung disease in patients with rheumatoid arthritis

Aim: Interstitial lung disease (ILD) is a significant extra-articular manifestation of rheumatoid arthritis (RA). The prevalence and risk factors for ILD in RA exhibit considerable variation. This study aimed to determine the prevalence and factors associated with ILD in Thai patients with RA. Methods: This cross-sectional study enrolled 290 RA patients from the Siriraj Rheumatoid Arthritis Registry between March and December 2022. Patient characteristics, disease activity and functional status were documented. Chest radiography (CXR) was employed for ILD screening, and suspected cases were further evaluated using high-resolution computed tomography (HRCT) and pulmonary function tests. Two radiologists independently analyzed CXR and HRCT images, with any discrepancies resolved by a pulmonologist. Results: Among the 290 patients, the majority were female (89.7%) with mean age (SD) of 58.8 (11.5) years, and the median disease duration was 10 years (range 6–17 years). Patients exhibited low disease activity [mean Disease Activity Score 28-erythrocyte sedimentation rate score (SD) 2.69 (0.90)] and mild functional impairment [median Health Assessment Questionnaire score (range) 0.25 (0–0.63)]. Thirteen patients (4.5%) were diagnosed with ILD via HRCT (RA-ILD), with nonspecific interstitial pneumonia being the predominant ILD pattern (69.2%). Pulmonary function tests showed normal results in most patients, with only 15.5% presenting restrictive ventilatory defects. Age (P = 0.04), breathlessness (P &lt; 0.001), crackles (P &lt; 0.001), and functional impairment (P = 0.02) exhibited significant associations with RA-ILD. Conclusions: ILD is relatively infrequent in Thai patients with RA. However, older age, breathlessness, crackles, and functional impairment should prompt investigations for ILD in RA patients.

Enhanced Association of Novel Cardiovascular Biomarkers Fetuin-A and Catestatin with Serological and Inflammatory Markers in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with increased cardiovascular disease (CVD) risk and mortality. This work aimed to evaluate the serum levels of the novel CV biomarkers fetuin-A (fet-A), Dickkopf-1 (DKK-1), galectin-3 (Gal-3), interleukin-32 (IL-32), and catestatin (CST) in RA patients and their associations with RA parameters and CVD markers. A cohort of 199 RA patients was assessed for traditional CVD risk factors, RA disease activity, and biomarker levels. Carotid ultrasound was used to measure carotid intima-media thickness (cIMT) and carotid plaque presence (cPP). Multivariate analyses examined correlations between biomarkers and RA parameters, serological markers, and CVD markers. Adjusted models showed that elevated CST expression levels were associated with rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity (OR = 2.45, p = 0.0001 and OR = 1.48, p = 0.04, respectively) in the overall cohort and for RF in men and women, respectively. In addition, fet-A concentration was inversely associated with the erythrocyte sedimentation rate (ESR) in the overall cohort (β = -0.15, p = 0.038) and in women (β = -0.25, p = 0.004). Fet-A levels were also negatively correlated with disease activity (DAS28-ESR) scores (β = -0.29, p = 0.01) and fibrinogen concentration (β = -0.22, p = 0.01) in women. No adjusted associations were observed for Gal-3, DKK-1 or IL32 concentration. The study revealed no significant associations between the biomarkers and cIMT or cPP. The measurement of CST and fet-A levels could enhance RA patient management and prognosis. However, the utility of biomarkers for evaluating CV risk via traditional surrogate markers is limited, highlighting the need for continued investigations into their roles in RA.

Anti-protein phosphatase magnesium-dependent 1A-IgM levels in patients with active ankylosing spondylitis: a potential biomarker

BackgroundAnkylosing spondylitis (AS) has been known to have auto-inflammatory nature; hence, the efficacy of autoantibodies is low. However, studies on autoantibodies are ongoing, with some studies showing associations. Previous studies showed that anti-protein phosphatase magnesium-dependent 1A (PPM1A) IgG was increased in patients with AS and associated with radiographic progression. However, the diagnostic usefulness was limited due to relatively low sensitivity and specificity. This pilot study evaluated the diagnostic utility of anti-PPM1A-IgM and anti-PPM1A-IgG in patients with active AS.MethodsSerum samples were obtained from the registry cohort of a single tertiary center in Korea. Serum levels of anti-PPM1A-IgG/IgM were measured by direct ELISA. Receiver operating characteristic (ROC) analysis was used to predict the diagnostic sensitivity and specificity of serum anti-PPM1A-IgG/IgM.ResultsSamples were collected from 28 patients with active AS, 16 healthy controls (HCs), and 28 patients with rheumatoid arthritis (RA). Although total serum IgM was lower in the RA and AS groups than in the HC group, anti-PPM1A-IgM was significantly lower in the AS group than in the other groups. In evaluating the diagnostic utility of anti-PPM1A-IgG/IgM for AS patients compared with HCs, the area under the curve (AUC) of anti-PPM1A-IgM was 0.998 (sensitivity 96.4%, specificity 100.0%). When ROC analysis of anti-PPM1A-IgM for AS patients compared with RA patients was conducted, sensitivity was 78.6% and specificity was 71.4%, with an AUC of 0.839.ConclusionDecreased anti-PPM1A-IgM levels in AS patients suggests a potential role for anti-PPM1A-IgM in the diagnosis of active AS.

Tuberculin skin test repetition after TNF-α inhibitors in patients with chronic inflammatory arthritis: a long-term retrospective cohort in endemic area

ObjectivesTo evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment.MethodsPatients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition).ResultsA total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6–12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6–10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5–13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 − 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049].ConclusionThese results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.

What is the Link between Lung Involvement and Anti-CCP Antibodies in Rheumatoid Arthritis: A Cross-sectional Study.

In Rheumatoid Arthritis (RA), pulmonary involvement is one of the most frequent extra-articular manifestations. Several studies have demonstrated an association between RA-related lung disease and the positivity of anti-cyclic citrullinated peptide (anti-CCP) antibodies. Our aim is to describe the frequency of pulmonary involvement in the RA population and investigate the association between anti-CCP antibodies and diverse lung compartment involvement in RA patients. An observational retrospective cross-sectional study was conducted, during which data were collected from the medical records of the patients with RA who had been tested for anti-CCP antibodies and had thoracic high resolution computerized tomography (HRCT) evaluation from January 2011 to March 2022. The univariate and multivariate analyses using logistic regression models was performed to calculate odds ratios (ORs) with 95% CIs. A total of 390 patients with RA were included, the mean age of patients was 58.99 ± 12.44 years, with a predominance of females (85.9%). Two hundred and fifty-two (64.6%) patients were positive for anti-CCP antibodies. The frequency of RA-related lung diseases was 14.4% (n=56). The different manifestations observed in the thoracic HRCT included Nodules (67.9%), Interstitial lung disease (ILD) (28.6%), bronchiectasis (25%), fibrosis (21.4%), obliterative bronchiolitis (7.1%), and pleuritis (1.8%). In univariate and multivariate analysis, pulmonary involvement was associated with positive anti-CCP antibodies with an odds ratio (OR) of 5.25 (95% CI: 2.17-12.70, p < 0.0001). The study demonstrated a positive association between anti-CCP antibodies and pulmonary involvement in RA and highlighted the importance of tight monitoring in RA patients with positive anti-CCP for pulmonary complications.

Association between IL-6, miRNA-146a, MALAT1 genetic polymorphisms and risk of rheumatoid arthritis.

Aim: This study aimed to investigate the associations between single nucleotide polymorphisms (SNPs) of IL-6 (-174G/C), microRNA146a (rs2910164C/G) and MALAT1 (rs619586A/G) and susceptibility to rheumatoid arthritis (RA) in Egyptians.Methods: SNPs were genotyped in 101 RA patients and 104 controls. Expression levels were evaluated either by Enzyme-linked immunosorbent assay (ELISA) for IL-6 or quantitative real-time PCR (qRT-PCR) for miR-146a and MALAT1.Results: IL-6-174 GC (OR=3.422) genotype, IL-6-174 C allele (OR=2.565), miR-146a (rs2910164) CG (OR=2.190) and MALAT1 (rs619586) AA (OR=4.125) genotypes and A allele (OR=6.122) could be considered as risk factors for RA. An increase in the expression of IL-6, miR-146a and MALAT1 was detected in RA patients, which was independent of any SNP.Conclusion: SNPs of IL-6, miR-146a and MALAT1were linked to RA predisposition in Egyptians.

Dose-effect relationship of moxibustion for rheumatoid arthritis of liver and kidney deficiency and its effect on fatigue: a randomized controlled trial

To observe the effects of moxibustion with different frequency on the disease activity and fatigue of rheumatoid arthritis (RA) with liver and kidney deficiency on the basis of western medication treatment. A total of 135 RA patients with liver and kidney deficiency were randomly divided into a high-frequency moxibustion group (45 cases, 3 cases dropped out), a low-frequency moxibustion group (45 cases, 2 cases dropped out) and a western medication group (45 cases, 2 cases dropped out, 1 case discontinued). Leflunomide tablet was taken orally in the western medication group, once a day, 20 mg a time. On the basis of the treatment in the western medication group, moxibustion was applied at ashi points and bilateral Shenshu (BL 23) and Sanyinjiao (SP 6) in the two moxibustion groups, 15 min a time. The treatment was given once a day, 5 times a week in the high-frequency moxibustion group and once every other day, 3 times a week in the low-frequency moxibustion group. A total of 12-week treatment was required in the 3 groups. Before and after treatment, the 28 joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), TCM syndrome score, average grip strength (GS) of both hands, 30-second sit-to-stand (STS), timed up and go (TUG), 20-meter walk test (20MWT), self rating anxiety scale (SAS) score and self rating depression scale (SDS) score were observed; before treatment, after treatment and in follow-up of 1, 3 months after treatment completion, the scores of fatigue visual analogue scale (VAS), Bristol rheumatoid arthritis fatigue numerical rating scale (BRAF-NRS) and Bristol rheumatoid arthritis fatigue multi-dimensional questionnaire (BRAF-MDQ) were observed, and the relieving of disease was evaluated by American College of Rheumatology (ACR)20/50/70 standards in the 3 groups. After treatment, the DAS28 scores, ESR, CRP, RF, TCM syndrome scores, TUG, 20MWT, SAS scores and SDS scores were decreased compared with those before treatment (P<0.01, P<0.05), while the average GS of both hands and STS were increased compared with those before treatment (P<0.01, P<0.05) in the 3 groups. After treatment, in the high-frequency moxibustion group, the DAS28 score, ESR, CRP, TCM syndrome score, SAS score and SDS score were lower (P<0.01, P<0.05), while the average GS of both hands and STS were higher (P<0.01, P<0.05) than those in the low-frequency moxibustion group and the western medication group; the TUG and 20MWT were decreased compared with those in the western medication group (P<0.01, P<0.05). After treatment, in the low-frequency moxibustion group, the DAS28 score, ESR, CRP, TCM syndrome score, TUG, SAS score and SDS score were lower (P<0.05, P<0.01), while the average GS of both hands was higher (P<0.01) than those in the western medication group. In each time point after treatment, the scores of fatigue VAS and BRAF-NRS were decreased compared with those before treatment in the 3 groups (P<0.01), while the BRAF-MDQ scores were decreased compared with those before treatment in the high-frequency moxibustion group and the low-frequency moxibustion group (P<0.01). After treatment, the BRAF-MDQ score was decreased compared with that before treatment in the western medication group (P<0.01). In the high-frequency moxibustion group, the scores of fatigue VAS, BRAF-NRS and BRAF-MDQ of each time point after treatment were lower than those in the western medication group (P<0.01), the scores of fatigue VAS and BRAF-NRS in follow-up of 1 month after treatment completion as well as the BRAF-MDQ score after treatment were lower than those in the low-frequency moxibustion group (P<0.01, P<0.05). In the low-frequency moxibustion group, the scores of fatigue VAS, BRAF-NRS and BRAF-MDQ of each time point after treatment were lower than those in the western medication group (P<0.01, P<0.05). After treatment, the proportions of ACR20 and ACR50 in the high-frequency moxibustion group and the low-frequency moxibustion group were higher than those in the western medication group (P<0.01), the proportion of ACR70 in the high-frequency moxibustion group was higher than those in the low-frequency moxibustion group and the western medication group (P<0.05, P<0.01), and the proportion of ACR70 in the low-frequency moxibustion group was higher than that in the western medication group (P<0.05). On the basis of the western medication treatment, moxibustion can effectively reduce the disease activity and improve fatigue status in RA patients with liver and kidney deficiency, and its efficacy is positively correlated with treatment frequency.

Predictive factors of methotrexate monotherapy success in patients with rheumatoid arthritis in a national referral center: a cohort study

BackgroundMethotrexate (MTX) remains the recommended first-line treatment for rheumatoid arthritis (RA); however, its response varies and is influenced by various factors. This study aimed to identify predictors of MTX monotherapy treatment success in an Indonesian cohort.MethodsThis retrospective cohort study included newly diagnosed RA patients receiving MTX monotherapy. Treatment success was defined as achieving remission or low disease activity according to Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR) after 12 months of MTX therapy. The association between demographic, clinical, and laboratory factors and achieving therapy targets was evaluated using multivariate logistic regression analysis.ResultsAmong 254 subjects, 59.4% achieved treatment success with MTX monotherapy, with remission attained in 33% and low disease activity in 26.4%. Most subjects were female (95.7%) with a mean age of 48 ± 11 years. Multivariate analysis revealed that lower disease activity (OR 1.97; 95% CI [1.04–3.72]), normal ESR (OR 2.58; 95% CI [1.05–6.34]), normoweight (OR 2.55, 95% CI [1.45–4.49]), and tender joint count ≤ 5 (OR 2.45, 95% CI [1.31–4.58]) were significant predictors of treatment success.ConclusionThe rate of MTX monotherapy success in our study was 59.4%. Lower disease activity, normal ESR, normoweight, and fewer tender joints at baseline were significant predictors of treatment success.

Obesity might not alter tofacitinib drug survival in rheumatoid arthritis patients.

Obese rheumatoid arthritis (RA) patients often show reduced responses to traditional treatments, including TNF inhibitors (TNFi). Considering the different mechanisms of action it is important to evaluate the efficacy of tofacitinib in obese patients. This study aims to explore the impact of obesity on the drug survival of tofacitinib in RA patients. This retrospective cohort study included RA patients treated with tofacitinib. Patients were categorized into obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) groups. The primary outcome was drug survival, assessed using Kaplan-Meier and logistic regression analyses. The study comprised 80RA patients, with 31 (39%) classified as obese. At the 12-month mark, the drug survival rate for tofacitinib was higher in the obese group (81%) compared to the non-obese group (59%). Contrary to univariable analysis, multivariate analysis did not identify obesity as asignificant predictor of drug survival. Other variables including sex, hypertension, diabetes mellitus, and anti-cyclic citrullinated peptide (anti-CCP) positivity also showed no significant association with tofacitinib drug survival. The findings indicate that obesity does not alter the drug survival rate for tofacitinib among RA patients. Univariate analysis reported apotentially higher drug survival rate in obese patients; however, the lack of statistical significance in multivariate analysis and the study's retrospective nature necessitate further research to validate these observations and guide personalized therapeutic strategies for this population.

Moving forward in Rheumatoid Arthritis-Associated Interstitial Lung Disease Screening.

Patients with rheumatoid arthritis (RA) are at increased risk of developing interstitial lung disease compared to the general population, a complication that is associated with significant morbidity and high mortality. Given its frequency and severity, ILD should always be considered during both the initial assessment and follow-up of RA patients. However, there is currently no consensus on which RA patients should be screened for ILD. In recent years, several scientific societies have developed specific screening proposals. According to the recommendations of the Spanish, American, and Austrian rheumatology societies, it is not necessary to screen all individuals with RA, and it should be tailored to each patient based on clinical risk factors. In contrast, the Portuguese Societies of Rheumatology and Pulmonology advocate for systematic screening of all RA patients. Risk factors for the development of ILD in RA patients are well identified, and several screening tools for RA-ILD based on these risk factors have been developed. However, all of these tools still require further validation. To address this issue, the ANCHOR-RA study, a multinational cross-sectional initiative, has been launched to develop a multivariable model for predicting RA-ILD, which could provide valuable guidance for screening practices in clinical settings. In addition to certain biochemical and genetic predictive markers, lung ultrasound appears to be a useful screening tool. When combined with clinical evaluation and risk factor assessment, it can help identify which patients require a thoracic HRCT evaluation, which remains the gold standard for confirming an ILD diagnosis.

Bivalent chromatin accommodates survivin and BRG1/SWI complex to activate DNA damage response in CD4+ cells

BackgroundBivalent regions of chromatin (BvCR) are characterized by trimethylated lysine 4 (H3K4me3) and lysine 27 on histone H3 (H3K27me3) deposition which aid gene expression control during cell differentiation. The role of BvCR in post-transcriptional DNA damage response remains unidentified. Oncoprotein survivin binds chromatin and mediates IFNγ effects in CD4+ cells. In this study, we explored the role of BvCR in DNA damage response of autoimmune CD4+ cells in rheumatoid arthritis (RA).MethodsWe performed deep sequencing of the chromatin bound to survivin, H3K4me3, H3K27me3, and H3K27ac, in human CD4+ cells and identified BvCR, which possessed all three histone H3 modifications. Protein partners of survivin on chromatin were predicted by integration of motif enrichment analysis, computational machine-learning, and structural modeling, and validated experimentally by mass spectrometry and peptide binding array. Survivin-dependent change in BvCR and transcription of genes controlled by the BvCR was studied in CD4+ cells treated with survivin inhibitor, which revealed survivin-dependent biological processes. Finally, the survivin-dependent processes were mapped to the transcriptome of CD4+ cells in blood and in synovial tissue of RA patients and the effect of modern immunomodulating drugs on these processes was explored.ResultsWe identified that BvCR dominated by H3K4me3 (H3K4me3-BvCR) accommodated survivin within cis-regulatory elements of the genes controlling DNA damage. Inhibition of survivin or JAK-STAT signaling enhanced H3K4me3-BvCR dominance, which improved DNA damage recognition and arrested cell cycle progression in cultured CD4+ cells. Specifically, BvCR accommodating survivin aided sequence-specific anchoring of the BRG1/SWI chromatin-remodeling complex coordinating DNA damage response. Mapping survivin interactome to BRG1/SWI complex demonstrated interaction of survivin with the subunits anchoring the complex to chromatin. Co-expression of BRG1, survivin and IFNγ in CD4+ cells rendered complete deregulation of DNA damage response in RA. Such cells possessed strong ability of homing to RA joints. Immunomodulating drugs inhibited the anchoring subunits of BRG1/SWI complex, which affected arthritogenic profile of CD4+ cells.ConclusionsBvCR execute DNA damage control to maintain genome fidelity in IFN-activated CD4+ cells. Survivin anchors the BRG1/SWI complex to BvCR to repress DNA damage response. These results offer a platform for therapeutic interventions targeting survivin and BRG1/SWI complex in autoimmunity.

Pengaruh Emosi Positif Terhadap Hasil Pengobatan Penyakit Rheumatoid Arthritis

This study evaluates the impact of positive emotions on rheumatoid arthritis (RA) treatment outcomes through a meta-analysis of 47 studies (2015-2024) involving 12,384 patients. The primary findings reveal a significant positive correlation between positive emotions and improved RA treatment outcomes (r = 0.42, p &lt; 0.001), with the strongest effects observed in enhanced quality of life (r = 0.51) and physical function (r = 0.45). Patients exhibiting high positive emotions demonstrated greater reductions in pain (d = 0.38), decreased inflammation (d = 0.29), and improved physical function (d = 0.45) compared to control groups. Moreover, moderator analyses uncovered stronger effects among elderly patients (? = 0.012, p = 0.025) and those with longer RA duration (? = 0.018, p = 0.009). Finally, mediational analyses indicated that positive emotions contributed to improved treatment adherence (indirect effect = 0.09, 95% CI [0.05, 0.13]) and increased physical activity (indirect effect = 0.07, 95% CI [0.03, 0.11]) in RA patients. These findings extend Fredrickson's (2001) Broaden-and-Build theory and support Keefe et al.'s (2002) biopsychosocial model. Compared to meta-analyses by Brosseau et al. (2018) and Zhou et al. (2020), this study provides more comprehensive evidence on the role of positive emotions in various RA treatment outcomes. The novelty of this research lies in the analysis of previously unexplored mediating and moderating mechanisms, as well as a comparison of effectiveness with pharmacological interventions (SMD = 0.18, 95% CI [-0.05, 0.41], p = 0.124). These results support the integration of positive emotion-based interventions in RA management and expand upon Strand et al.'s (2019) findings on patient expectations in RA treatment.

Clo-miR-14: a medicinally valued spice-derived miRNA with therapeutic implications in rheumatoid arthritis.

Plant microRNAs (miRNA) are regularly consumed orally along with diet, gaining attention for their RNA-based drug potential because of their ability to regulate mammalian gene expression specifically at the post-transcriptional level. Medicinally valued plants are well known for their anti-inflammatory property; however, the contribution of their miRNA in managing inflammation has been less studied. We investigated miRNA from four medicinally valued regularly consumed spices, and validated one of the most potential miRNA 'Clo-miR-14' for its thermal stability, and absorption in the plasma samples of RA patient's by RT-PCR. In vitro and in vivo studies were performed to investigate the effect of Clo-miR-14 in ameliorating rheumatoid arthritis (RA) like symptoms. Our results suggest that 'Clo-miR-14,' an exogenous miRNA present in Curcuma longa, absorbed through regular diet, has robust thermal stability at 100°C in humans. It significantly reduced pro-inflammatory cytokines (TNF, IL-1β, IL-6) and RA-like symptoms, suggesting that plant-based miRNA could be a promising candidate as an RNA-based drug for RA pathogenesis.

Effects of tofacitinib on bone turnover markers and bone modulators in patients with rheumatoid arthritis

Key-pointsBone turnover makers (P1nP, B-ALP, CTX), bone modulators (Dkk1, sclerostin) and BMD were measured prospectively in rheumatoid arthritis patients treated with tofacitinib.Sclerostin increased significantly after treatment with tofacitinib, P1nP and B-ALP (markers of bone formation) decreased significantly.