Simplified Disease Activity Index Research Articles

Factors associated with discrepancies in disease activity as assessed by SDAI and RAPID3 in patients with rheumatoid arthritis: Data from a multicenter observational study (T-FLAG).

The present study aimed to examine discrepancies between assessments based on Routine Assessment of Patient Index Data 3 (RAPID3) and Simple Disease Activity Index (SDAI) in RA patients with controlled disease activity. Data from 464 RA patients in SDAI remission or low disease activity (REM/LDA) were analyzed. Patient-reported outcome (PRO) measures, including Health Assessment Questionnaire Disability Index (HAQ-DI), 25-question Geriatric Locomotive Function Scale (GLFS-25), and Kihon checklist (KCL), were assessed. Logistic regression models were used to identify factors associated with RAPID3 moderate or high disease activity (MDA/HDA). Cutoff values of RAPID3 MDA/HDA for each PRO evaluation item were determined using receiver operating characteristic curve analysis. Among RA patients in SDAI REM/LDA, 84.9% were in RAPID3 REM/LDA. Multivariable analysis revealed that HAQ-DI, GLFS-25, and KCL were independently associated with RAPID3 MDA/HDA. Subdomain analysis of KCL revealed that activities of daily living, physical function, cognitive function, and depressive mood were significantly associated with RAPID3 MDA/HDA. Cutoff values for HAQ-DI and KCL were 0.38 and 8, respectively. In RA patients with controlled disease activity, discrepancies between RAPID3 and SDAI assessments were observed, with factors such as HAQ-DI, GLFS-25, and KCL being independently associated with RAPID3 MDA/HDA.

Factors contributing to the improvement in J-HAQ after 3 years of treatment with abatacept in biologic-naïve rheumatoid arthritis patients: Interim results of a long-term, observational, multicentre study in Japan (ORIGAMI).

We investigated the long-term effectiveness, safety, and factors affecting Japanese Health Assessment Questionnaire (J-HAQ) improvement during abatacept treatment in Japanese rheumatoid arthritis (RA) patients. The ORIGAMI study is an ongoing observational study of biologic-naïve RA patients with moderate disease activity treated with subcutaneous abatacept (125 mg, once-weekly). Patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry as an historical, weighted control group. The primary endpoint for this interim analysis was the proportion of patients with J-HAQ remission (score ≤0.5) at 3 years. Among 279 abatacept-treated and 220 csDMARD-treated patients, J-HAQ remission was achieved at 3 years in 40.5% (95% confidence interval [CI] 34.7%-46.2%) and 28.9% (95% CI 9.9%-47.8%), respectively. Age, RA duration <1 year, baseline J-HAQ score, and Simplified Disease Activity Index remission at 6 months were associated with 3-year J-HAQ remission in the abatacept group. Overall, 24/298 patients (8.1%; safety analysis set) experienced serious adverse drug reactions with an incidence of 5.3 per 100 person-years. This study confirmed the 3-year effectiveness and safety, and revealed potential factors associated with J-HAQ remission in biologic-naïve RA patients treated with abatacept in real-world clinical practice.

A study of carotid intima media thickness in patients with rheumatoid arthritis and its correlation with acute phase reactants and disease activity

Introduction: There is increased risk of cardiovascular morbidity and mortality in patients of rheumatoid arthritis (RA) due to accelerated atherosclerosis. In this study we measured Carotid artery intima media thickness (CIMT) as a surrogate marker for subclinical atherosclerosis in RA patients without pre-existing cardiovascular disease. This study also analyzed the correlation between CIMT, disease duration, Simplified Disease Activity Index (SDAI) and acute phase reactants. Methods: A cross-sectional study was conducted on 90 patients divided into two groups of 45 patients of RA and another 45 control subjects. Subjects with RA and age and sex matched healthy controls were included in the study without pre-existing CV risk factors. Complete clinical evaluation, hematological and biochemical profile done. ESR, CRP and platelet count were used as markers of acute phase reactants. All the RA patients included in the study were evaluated for their disease activity using Simplified Disease Activity Index (SDAI). All the subjects including the controls evaluated for carotid intima media thickness by using carotid ultrasonography. CIMT measured in common carotid artery bilaterally by examining throughout common carotid artery up to 2 cm proximal to bifurcation. CIMT measurement taken at the site of greatest thickness. All measurements taken in diastole, measured in phase when lumen diameter is at its smallest and IMT at its largest. Mean value of 6 readings (3 from each side) taken as final CIMT for evaluation. B mode (linear probe) USG was used to determine carotid IMT. Results: 45 cases and similar control subjects included in the study with mean age (SD) as 45.07 (14.81) years. We found female preponderance with 37 females out of 45 cases. Mean (SD) disease duration in male subjects was 5.38(2.40) years while in females was 5.09 (2.78) years. CRP was found to be significantly increased in cases group with mean (SD) of 5.75(8.85) mg/dl. ESR significantly raised to 35.22(13.55) mm/hour in cases group compared to control group where it was 16.16(5.71) mm/hr. Mean (SD) platelets (x10³/mm³) were 229.24(69.80) in cases while controls had 290.33(83.85), so platelets correlation with disease could not be established. CIMT was significantly raised in cases group. Mean (SD) CIMT in cases was 0.95(1.06) mm whereas in control group it was 0.60(0.16) mm with p value of 0.002. Moderate positive correlation was found between CIMT (mm) and SDAI and this correlation was statistically significant with p=0.001. For every 1 unit increase in CIMT, the SDAI increases by 2.92 units. A strong positive correlation between CIMT (mm) and Disease Duration (Years), and this correlation was statistically significant (rho = 0.9, p = &lt;0.001). For every 1 unit increase in CIMT (mm), the Disease Duration (Years) increases by 1.26 units. Conversely, for every 1 unit increase in Disease Duration (Years), the CIMT (mm) increases by 0.19 units. Conclusion: A strong correlation was observed between CIMT and disease duration in rheumatoid arthritis. Hence, CIMT can be a useful surrogate marker for detecting atherosclerosis in patients with RA. In view of the relation to duration of disease, established RA patients should regularly be screened to identify the evidence of atherosclerosis and manage it earlier. Prevention of cardiovascular disease in RA requires an integrated approach encompassing cardiovascular risk factors screening and management, effective and sustained control of RA disease activity, high index of suspicion and prompt investigation of suspected cardiac disease.

Level of glial cell derived neurotrophic factor in the blood plasma of rheumatoid arthritis patients and its relationship with alexithymia

ObjectivesGlial cell derived neurotrophic factor (GDNF) has an important role in the pathogenetic mechanisms and clinical manifestations of rheumatoid arthritis (RA). Alexithymia is associated with a severe clinical course and worse prognosis, while the relationship between alexithymia and GDNF in RA patients has not been investigated before. The aims of the study were to investigate the GDNF level in blood plasma in RA patients depending on the presence of alexithymia and to evaluate the relationship of GDNF level with clinical manifestation and quality of life.Material and methodsFifteen men and 73 women with RA were examined using the Disease Activity Score with 28-joint count (DAS28) with erythrocyte sedimentation rate (ESR) index, the Simple Disease Activity Index (SDAI), the Rheumatoid Arthritis Clinical Disease Activity Index (CDAI), the Visual Analogue Scale (according to the assessment of the patient – VAS-P and the assessment of the doctor – VAS-D), the Health Assessment Questionnaire (HAQ), the Toronto Alexithymia Scale (TAS-20), the Disability Rating Index (DRI) and SF-36 indexes. Glial cell derived neurotrophic factor level in the blood plasma was determined by enzyme-linked immunosorbent assay (ELISA).ResultsForty percent of RA patients had alexithymia. Glial cell derived neurotrophic factor level in the examined patients was 3.73 ±2.59 pg/ml, in patients with alexithymia 4.08 ±2.87 pg/ml, without alexithymia 3.48 ±2.37 pg/ml (p = 0.295). Patients with alexithymia had a higher erythrocyte sedimentation rate (ESR) and index scores than patients without alexithymia – ESR: 34.29 ±14.22 vs. 22.73 ±12.03 mm/h (p = 0.017), DAS28: 6.53 ±0.66 vs. 6.09 ±0.55 (p = 0.017), VAS-D: 7.19 ±0.81 vs. 6.53 ±0.83 (p = 0.020), HAQ: 1.78 ±0.58 vs. 1.51 ±0.54 (p = 0.040). Also they had worse SF-36 indicators – physical functioning: 39.52 ±13.78 vs. 51.00 ±14.90 (p = 0.019), role functioning due to physical condition: 30.95 ±20.77 vs. 46.67 ±24.76 (p = 0.041), physical component of health: 31.47 ±11.44 vs. 41.61 ±15.88 (p = 0.028). In patients with alexithymia, a correlation was found between the GDNF level and severity of pain according to VAS-P: rS = 0.338, p = 0.044, and VAS-D: rS = 0.446, p = 0.006.ConclusionsAlexithymia was found in 40% of RA patients. Rheumatoid arthritis patients with alexithymia had a nonsignificantly higher GDNF level compared to patients without alexithymia. In RA patients with alexithymia, an association of GDNF level in the blood plasma with RA activity, loss of functional capacity and reduced quality of life was established. Alexithymia in RA patients is an important factor in the clinical manifestation of RA and modification of the pathophysiological role of GDNF.

Association of Baseline Serum Soluble Tumour Necrosis Factor Receptor Levels with the Response of Rheumatoid Arthritis to Janus Kinase Inhibitor Therapy.

The aim of this study was to investigate whether cytokines associated with tumour necrosis factor- (TNF-) α and interleukin- (IL-) 6 signalling could predict rheumatoid arthritis (RA) clinical remission (CR) with Janus kinase inhibitor (JAKinib) treatment using the Simplified Disease Activity Index (SDAI). Eighty-nine patients with RA treated with JAKinibs were enrolled, and their clinical data were collected retrospectively. CR was defined as an SDAI ≤ 3.3 after 6 months of treatment with JAKinib. The serum samples of 89 patients were analysed for IL-6, soluble IL-6 receptor (sIL-6R), soluble gp130 (spg130), and soluble TNF receptor- (sTNFR-) I and sTNFR-II titres. There were no significant differences in the baseline clinical parameters between the CR and non-CR groups. Serum levels of IL-6, sIL-6R, and sgp130 were not significantly different; whereas, the serum sTNFR-I and sTNFR-II levels were significantly lower in the CR group. Univariate and multivariate logistic regression analysis showed that the baseline log sTNFR II values (OR: 0.002; p = 0.034) were predictors of CR. Patients with RA can be stratified prior to JAKinib administration using serum sTNFR-I and sTNFR-II levels but not serum IL-6 axis cytokine levels (IL-6, sIL-6R, and sgp130).

Predictors of Remission or Combined Remission and Low Disease Activity in Rheumatoid Arthritis Patients in Taiwan: A Prospective Cohort Study.

Objectives: This study aimed to identify predictors of remission or low disease activity (LDA) in patients with rheumatoid arthritis (RA) and low-ultrasound inflammation. Methods: A total of 80 patients with RA who fulfilled the 1987 ACR criteria for RA with a disease activity score of 28 joints (DAS28) > 3.2 were recruited. Over 1 year of therapy, we conducted blood tests every 6 months to examine erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), neuraminidase 3 (Neu3), and α-2,3-sialyltrasnferse I (ST3Gal-1) levels in B cells and monocytes. Additionally, we evaluated physical function by using the Health Assessment Questionnaire-Disability Index (HAQ-DI). Data on demographic and clinical parameters were collected, and musculoskeletal ultrasonography was performed twice a year on 12 specific joints to assess synovial changes. One year later, we compared all collected data and laboratory or ultrasound results between patients achieving remission or LDA and those who did not in order to determine the predictors. Results: Age, the presence or absence of rheumatoid factor, and the number of conventional disease-modifying anti-rheumatic drugs used were not correlated with remission or LDA for DAS28 or Simplified Disease Activity Index formulas. However, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores were associated with a higher likelihood of achieving remission or LDA for DAS28-ESR. Negative anticyclic citrullinated peptide (CCP) and low HAQ-DI scores were predictors of remission or LDA for DAS28-MCP-1. Interestingly, having less than two comorbidities is a good predictor of a combined remission/low disease activity state for SDAI and DAS28-MCP-1. Furthermore, Neu3 and ST3Gal-1 levels and ST3Gal-1/Neu3 ratios in B cells and monocytes had no significant correlation with total ultrasound scores. Nevertheless, monocyte ST3Gal-1 and Neu3 correlated significantly with DAS28-ESR >5.1 and DAS-MCP-1 >4.8 (both categories belong to high disease activity), respectively (rho = 0.609 with p = 0.012, and rho = 0.727 with p = 0.011, respectively). Monocyte ST3Gal-1/Neu3 ratios connected with DAS28-ESR >5.1 and 3.3 < SDAI ≦ 11 (low disease activity), respectively (rho = 0.662 with p = 0.005, and rho = 0.342 with p = 0.048, respectively). Conclusions: In patients with RA in Taiwan, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores are predictors of remission or LDA for DAS28-ESR, which differ from the predictors for DAS28-MCP-1. Moreover, monocyte ST3Gal-1, Neu3, and their ratios correlated with different disease activity categories of DAS28-ESR, DAS28-MCP-1, and SDAI scores.

P117 Efficacy of filgotinib in patients with rheumatoid arthritis: Week 156 results from a long-term extension study

Abstract Background/Aims In the treatment of RA, JAK inhibitors are a valuable option to meet remission or low disease activity (LDA) treatment targets following an inadequate response (IR) or intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (DMARD). FIL is a JAK1 preferential inhibitor available in two doses for the treatment of moderate to severe RA. Objectives: To evaluate long-term efficacy of two doses of FIL in clinically relevant pt populations. Methods In this interim analysis, efficacy (non-responder imputation) of FIL 200 mg (FIL200) and 100 mg (FIL100) was assessed from LTE baseline (BL) to W156 in pts with an IR to methotrexate (MTX-IR) and biologics (bDMARD-IR), enrolled from FINCH 1 (NCT02889796) and 2 (NCT02873936) parent studies (PS), respectively, receiving ≥1 FIL dose in FINCH 4 (NCT03025308). Results Study design, BL characteristics and W48 outcomes for MTX-IR1 and bDMARD-IR2 pts were reported previously. For MTX-IR and bDMARD-IR pts who received FIL200 or FIL100 in the PS, W156 remission rates using Boolean 1.0 criteria were 20.5% and 15.8%, and 18.2% and 8.9%, respectively. Adopting the Boolean 2.0 criteria slightly increased remission rates for FIL200 and FIL100 at W156: +4.2% and +4.9% for MTX-IR pts, and +1.5% and +2.4% for bDMARD-IR pts, respectively. For pts rerandomized to FIL on entering the LTE, Boolean 2.0 criteria also increased remission rates vs Boolean 1.0. Both MTX-IR and bDMARD-IR pts maintained long-term Boolean remission through W156 with FIL200 and FIL100, irrespective of prior FIL. Results for Disease Activity Score 28 with C-reactive protein (DAS28-CRP) &amp;lt;2.6, Clinical Disease Activity Index (CDAI) ≤2.8, and Simplified Disease Activity Index (SDAI) ≤3.3, and mean change from PS BL in Health Assessment Questionnaire-Disability Index (HAQ-DI) and pain are shown (Table). Similar trends in efficacy were seen for LDA and ACR response criteria. Conclusion In FINCH 4, both FIL200 and FIL100 showed sustained efficacy up to W156 in clinically relevant pt populations. Boolean 2.0 criteria classified more pts in remission, in line with the range reported in the validation study. Disclosure M.H. Buch: Consultancies; AbbVie, CESAS Medical, Galapagos, Gilead, and Pfizer (all paid to host institution). Member of speakers’ bureau; AbbVie (paid to host institution). Grants/research support; Gilead (paid to host institution). D. Aletaha: Consultancies; AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi. Member of speakers’ bureau; AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi. Grants/research support; AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi. R. Caporali: Consultancies; AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, and UCB. Member of speakers’ bureau; AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB. B. Combe: Consultancies; AbbVie, Galapagos, Gilead, Janssen, Lilly, Novartis, and Roche-Chugai. Member of speakers’ bureau; AbbVie, Celltrion, Galapagos, Janssen, Lilly, Pfizer, and Roche-Chugai. H. Schulze-Koops: Consultancies; AbbVie, Galapagos, Lilly, and Pfizer. Member of speakers’ bureau; AbbVie, Galapagos, Lilly, and Pfizer. J. Gottenberg: Consultancies; AbbVie, BMS, Galapagos, Gilead, Lilly, MSD, Novartis, and Pfizer. Grants/research support; BMS and Pfizer. Y. Tanaka: Member of speakers’ bureau; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, GSK, Mitsubishi-Tanabe, and Pfizer. Grants/research support; AbbVie, Asahi-Kasei Pharma, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Takeda. R. Blanco: Consultancies; AstraZeneca, Galapagos, Janssen, Novartis, and Pfizer. Member of speakers’ bureau; AbbVie, Amgen, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi. Grants/research support; AbbVie and Roche. T. Takeuchi: Consultancies; AbbVie GK, Astellas, Chugai, Eli Lilly Japan, Gilead Sciences, Inc., Janssen Pharm K.K., Mitsubishi-Tanabe, and Pfizer Japan Inc. Member of speakers’ bureau; AbbVie GK, AYUMI, BMS, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Gilead Sciences, Inc., Janssen Pharm K.K., Mitsubishi-Tanabe, Pfizer Japan Inc., and Sanofi K.K. Grants/research support; AbbVie GK, Asahi-Kasei Pharma, Astellas, AYUMI, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Mitsubishi-Tanabe, Nippon Kayaku, and UCB Japan. E. V. Ekoka Omoruyi: Consultancies; Galapagos and Janssen. Shareholder/stock ownership; UCB. K. Van Beneden: Shareholder/stock ownership; Galapagos. Other; Employee of Galapagos. V. Rajendran: Shareholder/stock ownership; Galapagos. Other; Employee of Galapagos. C. Watson: Shareholder/stock ownership; Galapagos. Other; Employee of Galapagos. F. De Leonardis: Other; Employee of Galapagos. P. Emery: Consultancies; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Galapagos, Gilead, Lilly, Novartis, Pfizer, Roche, and Samsung. Member of speakers’ bureau; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Galapagos, Gilead, Lilly, Novartis, Pfizer, and Samsung. Grants/research support; AbbVie, BMS, Lilly, Novartis, Pfizer, Roche, and Samsung.

Are There Sex-Related Differences in the Effectiveness of Janus Kinase Inhibitors in Rheumatoid Arthritis Patients?

Background: There is evidence suggesting the existence of sex differences in the effectiveness of specific drug classes for rheumatoid arthritis (RA). Our study stands as the first to elucidate sex-related differences in the effectiveness of Janus kinase (JAK) inhibitors. Methods: The study involved 150 RA patients treated with tofacitinib, baricitinib, upadacitinib, or filgotinib between September 2017 and October 2023. Sex differences in achieving remission and low disease activity (LDA) were identified through logistic regression analyses. Sex disparities in treatment effectiveness survival were evaluated through the Kaplan-Meier estimate, employing the log-rank test for comparison. The Cox model was applied to analyze the variable sex as a potential factor that could influence the maintenance of the JAK inhibitor treatment effectiveness. Results: Concerning the achievement of remission and LDA, no differences were observed between sexes in terms of the 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). With respect to the DAS28-erythrocyte sedimentation rate (ESR), female patients, compared to males, possessed 70% lower odds of achieving remission (p = 0.018) and 66% lower odds of achieving LDA (p = 0.023). No differences were observed in treatment effectiveness survival between sexes (p = 0.703). Sex was not found to influence the survival of JAK inhibitor treatment effectiveness (p = 0.704). Conclusions: Being a female or male patient does not entail differences in the effectiveness of the JAK inhibitor treatment. Our findings encourage the consideration of a global pool of composite indices (DAS28-ESR/CRP, CDAI, SDAI) to measure RA disease activity, thus individualizing the target value as advocated by the treat-to-target strategy.

Increased epicardial adipose tissue thickness as a sign of subclinical atherosclerosis in patients with rheumatoid arthritis and ıts relationship with disease activity ındices.

Epicardial adipose tissue is a novel cardiometabolic risk factor and indicator of subclinical atherosclerosis. We aimed to evaluate the epicardial adipose tissue thickness in rheumatoid arthritis (RA) patients and its association with disease activity scores. A total of 81 rheumatoid arthritis patients and 70 age- and sex-matched healthy individuals were recruited for this cross-sectional study. Epicardial adipose tissue thickness (EATT) was measured by transthoracic two-dimensional echocardiography. Tender and swollen joint counts were recorded at the time of inclusion. The laboratory tests included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, anti-citrullinated protein antibodies, and serum lipid levels. Disease activity was calculated based on Disease Activity Scores for 28 joints (DAS-28) ESR and CRP, the Simple Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Epicardial adipose tissue thickness was significantly higher in the RA patients compared to the healthy controls (p < 0.001). We found statistically significant correlations of EATT with all disease activity indices (p < 0.001) and CRP (p = 0.002). According to a cut-off value of 6.4mm determined for epicardial adipose tissue thickness, the RA patients with thickness ≥ 6.4mm had higher disease activity scores and CRP levels. In the multivariable regression analysis, only SDAI score was found as an independent risk factor for increased EATT (OR, (95%CI), 13.70 (3.88-48.43), p < 0.001). Epicardial adipose tissue thickness measurement by echocardiography is a reliable method for assessing subclinical atherosclerosis in rheumatoid arthritis patients, and a higher disease activity score is an independent risk factor for coronary artery disease.

Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study

ObjectiveThis report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early...

Simplified vs modified (reduced) ultrasound 6 joint score in assessing disease activity in rheumatoid arthritis patients

Introduction and aim. With increasing ultrasound US assessment opportunities for tight rheumatoid arthritis (RA) management, more simplified accurate US-assessment is desired in clinical practice. Aim of the work is assessing modified vs simplified ultrasound 6-joint scores relevance in assessing rheumatoid arthritis disease activity. Material and methods. Fifty-five RA patients were subjected to detailed history, clinical, and musculoskeletal examination with disease activity assessment by clinical disease activity index, simple disease activity index and disease activity score in 28 joints. Com plete blood count, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptide antibodies were done. Patients underwent US examination (gray-scale and power Doppler) for wrist, 2nd and 3rd metacarpophalangeal and knee joints bilaterally. Synovitis composite score was added. Two US indices were constructed: simplified S6 and modified M6 joint scores. Results. Statistical significant positive correlations were high between S6/M6 score parameters (total, grey-scale (GS), power doppler (PD), Composite) and disease activity markers. Both M6 and S6 scores differentiated mild-moderate and moderate-severe disease activity patients. However, only S6 score differentiated remission from mild disease activity patients. Conclusion. Ultrasound 6-joint scores (especially simplified S6) were rapid, easy and sensitive ultrasound tools assessing rheu matoid arthritis disease activity in clinical practice.

Microstructural abnormality of white matter tracts in rheumatoid arthritis

BackgroundStructural and functional brain imaging studies have reported abnormalities of gray matter morphology and functional activities in patients with rheumatoid arthritis (RA). However, it is largely unknown whether patients with RA show alterations of white matter microstructural organization. ObjectivesTo automatically identify alteration of white matter microstructure in patients with RA and further examine how this alteration associates with clinical characteristics. MethodsThis single-institutional prospective study included 66 participants (33 patients with RA [52 ± 9 years, 29 women] and 33 sex/age-matched healthy controls [53 ± 12 years, 27 women]), who underwent diffusion MRI scan from January 2021 to December 2021. The white matter microstructure was assessed using fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Voxelwise analyses were conducted on white matter skeleton using an automated, observer-independent tract-based spatial statistics analysis. The relationship between white matter microstructural alterations and clinical and neuropsychological variables was evaluated using correlation analysis. ResultsCompared with healthy controls, patients with RA exhibited lower fractional anisotropy in several major white matter tracts (threshold-free cluster enhancement at P < 0.05 for multiple comparison correction, permutation test), involving the forceps minor, bilateral inferior fronto-occipital fasciculus, bilateral anterior thalamic radiation, and bilateral uncinate fasciculus. Lower fractional anisotropy values in the patients with RA were significantly associated with pain-related assessments, including tender joint count (r = -0.43, P = 0.015), Clinical Disease Activity Index score (r = -0.36, P = 0.049), pain severity rated through visual analogue scale (r = -0.45, P = 0.012), and Simplified Disease Activity Index score (r = -0.36, P = 0.045). No significant group difference was found in mean diffusivity, axial diffusivity, and radial diffusivity. ConclusionsWe report the first anatomical evidence for aberrant microstructure organization of several major white matter tracts and its associations with pain processing in patients with rheumatoid arthritis.

Remission definitions guiding immunosuppressive therapy in rheumatoid arthritis: which is best fitted for the purpose?

ObjectiveTo assess which definition of remission best predicts good radiographic outcome (GRO) and good functional outcome (GFO) in rheumatoid arthritis, focusing the updated American College of Rheumatology/European Alliance of Associations...

Real-world effects of Yishen Tongbi decoction for rheumatoid arthritis: protocol for a prospective, observational, multicenter cohort study with validation against double-blind, randomized, controlled trial.

Introduction: Rheumatoid arthritis (RA) is a globally challenging and refractory autoimmune disease, constituting a serious menace to human health. RA is characterized by recurrent pain and is difficult to resolve, necessitating prolonged medication for control. Yishen Tongbi decoction is a traditional Chinese herbal compound prescribed for treating RA. We have completed a 3-year RCT study that confirmed the clinical efficacy of Yishen Tongbi decoction for RA. Notably, we observed a faster clinical remission rate compared to MTX by week 4 of treatment. In our forthcoming study, we intend to conduct a comprehensive assessment of the efficacy and safety of Yishen Tongbi decoction in the real-world treatment of RA through a prospective study. Methods and analysis: This prospective, multicenter, real-world observational study will be conducted at two designated centers in China from October 2023 to August 2025. The study will include 324 patients with active rheumatoid arthritis. One group will receive Yishen Tongbi decoction combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The other group will receive standard treatment. Standard treatment can be further divided into subgroups: csDMARDs, targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and biologic disease-modifying antirheumatic drugs (bDMARDs). In each group, the number of tender joints, number of swollen joints, pain score, patient global assessment, physician global assessment, disease activity index (DAS28-ESR or DAS28-CRP), clinical disease activity index (cDAI), simplified disease activity index (sDAI) and relevant laboratory data will be compared. Clinical indicators and disease activity of the patients will be assessed at baseline, week 4 and week 12 after the initiation of treatment. The primary outcome will be the American College of Rheumatology 20% improvement criteria (ACR20) attainment rate among patients at week 12 after treatment. Every adverse event will be reported. Ethics and dissemination: This study has been approved by the Ethics Committee of the first affiliated Hospital of Guangzhou University of traditional Chinese Medicine (NO.K-2023-009). The results of the study will be published in national and international peer-reviewed journals and at scientific conferences. The researchers will inform participants and other RA patients of the results through health education. Clinical Trial Registration: https://www.chictr.org.cn/index.html, identifier ChiCTR2300076073.

Emerging Role of Interleukin-38 (IL-38) in the Development of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an incurable autoimmune disease. The role of interleukin-38 (IL-38), an anti-inflammatory cytokine, in RA is not fully understood, and its clinical relevance in RA remains unclear. This study aims to investigate the correlation of IL-38 with disease activity and the clinical manifestation of RA. In this cross-sectional study, patients with treatment-naïve RA (n = 63) and healthy controls (HC) (n = 60) were consecutively enrolled over a 15-month period. Patients with RA were categorized into three subgroups-low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)-using the Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP). Circulating levels of IL-38, tumour necrosis factor (TNF), IL-6, IL-17, IL-1β, and 25(OH)D were assessed using enzyme-linked immunosorbent assay (ELISA). Clinical data, including duration, tender joints count (TJC), swollen joints count (SJC), patient global assessment (PGA), evaluator global assessment (EGA), bone mineral density (BMD), clinical disease activity index (CDAI), simplified disease activity index (SDAI), DAS28-CRP, joint musculoskeletal ultrasound (MSUS), and serological indicators were recorded. We determined the correlation between IL-38 and disease activity, as well as clinical manifestation in RA. At the macroscopic level, musculoskeletal ultrasonography of joints in different stages of disease activity in RA suggests that, as the disease progresses, arthritis in the hand becomes more severe, accompanied by synovial thickening and pronounced blood flow signals in the joint area. The expression of IL-38, TNF, IL-6, IL-17 and IL-1β significantly increased in patients with RA compared to HC. Noteworthy differences were observed in the blood flow signal score, synovial signal score, IL-38, TNF, IL-6, IL-17 and IL-1β among the three subgroups (LDA, MDA and HDA). As disease activity increased in patients with RA, the blood flow signal score, synovial signal score and expression of TNF, IL-6, IL-17 and IL-1β exhibited a gradual increase, while the expression of IL-38 showed the opposite pattern. Inverse correlations were identified between IL-38 and pro-inflammatory cytokines (IL-6, IL-17), as well as key clinical parameters, including disease duration, SJC, TJC and DAS28-CRP score. IL-38, intricately linked to the pathogenesis of RA, emerges as a promising therapeutic target for the management of this debilitating disease.

Efficacy Of Baricitinib in Patients With Moderate-To-Severe Rheumatoid Arthritis Up to 6.5 Years Of Treatment: Results Of A Long-Term Study.

To evaluate the long-term efficacy of once-daily baricitinib 4 mg or 2 mg in patients with active rheumatoid arthritis who had inadequate response (IR) to MTX, csDMARDs, or bDMARDs. Data from three completed phase III studies, RA-BEAM (MTX-IR), RA-BUILD (csDMARD-IR), and RA-BEACON (bDMARD-IR), and one completed long-term extension study (RA-BEYOND) were analyzed up to 6.5 years (340 weeks [RA-BEAM] and 336 weeks [RA-BUILD and RA-BEACON]). Low disease activity (LDA) (Simplified Disease Activity Index [SDAI] ≤11), clinical remission (SDAI ≤3.3), and physical function (Health Assessment Questionnaire Disability Index [HAQ-DI] ≤0.5) were the main outcomes assessed. Completer and non-responder imputation (NRI) analyses were conducted on each population. At week 340 or 336, LDA was achieved in 37%/83% of MTX-IR, 35%/83% of csDMARD-IR, and 23%/73% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. Remission was achieved in 20%/40% of MTX-IR, 13%/32% of csDMARD-IR, and 9%/30% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. HAQ-DI ≤0.5 was reached in 31%/51% of MTX-IR, 25%/46% of csDMARD-IR, and 24%/38% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. Treatment with baricitinib 4 mg or 2 mg demonstrated efficacy up to 6.5 years with maintained LDA/remission results across SDAI, CDAI and DAS28-hsCRP consistent with previously reported data, and was well tolerated.

Efficacy and Safety of Upadacitinib in Rheumatoid Arthritis: Real-Life Experience from a Prospective Longitudinal Multicentric Study.

We provide the first prospective longitudinal multicenter experience on Upadacitinib efficacy and safety profile in Rheumatoid Arthritis (RA) in a real-life context, focusing on clinimetric and ultrasonographic (US) data. RA patients referred to three Italian tertiary Centers who started Upadacitinib were enrolled as per ACR/EULAR classification criteria and prospectively reviewed. The primary aim of this study was to assess changes in clinimetric and ultrasonographic scores through time (at baseline, after 1 month, 3 months, and 6 months from the beginning of the therapy). Secondary aims were to: (i) estimate the impact of biologic lines of treatment and concomitant therapies on response to therapy; (ii) explore changes in laboratory parameters; and (iii) find potential predictive factors associated with response to therapy. Seventy-one patients (49 Females and 22 Males) were included. Clinimetric scores, including the Disease Activity Score (DAS28-CRP) and Simplified Clinical Disease Activity Index (SDAI), and US findings (synovial hypertrophy and power Doppler) significantly improved (p = 0.029, p = 0.001, p = 0.001, p = 0.001, respectively). Regression analysis revealed a significant association between the concomitant csDMARDs therapy at baseline and the lack of improvement in synovial hypertrophy [OR -4.824, p = 0.010] as well as with DAS28-CRP [OR -0.690, p = 0.045], whereas the presence of increased ESR or CRP at baseline was able to predict a significant improvement in SDAI [OR 8.481, p = 0.003]. No adverse events, such as deep venous thrombosis, pulmonary embolism, or herpes zoster virus infection, were reported during this study observation. Our real-life experience confirms the efficacy of Upadacitinib in terms of clinical and ultrasonographic improvement, as well as displaying a good safety profile.

[68 Ga]Ga-FAPI-04 PET/CT may be a predictor for early treatment response in rheumatoid arthritis

BackgroundThe identification of biomarkers predicting the treatment response of rheumatoid arthritis (RA) is important. [68 Ga]Ga-FAPI-04 showed markedly increased uptake in the joints of patients with RA. The purpose of this study is to investigate whether [68 Ga]Ga-FAPI-04 PET/CT can be a predictor of treatment response in RA. ResultsNineteen patients diagnosed with RA in the prospective cohort study were finally enrolled. Both total synovitis uptake (TSU) and metabolic synovitis volume (MSV) in [68 Ga]Ga-FAPI-04 and [18F]FDG PET/CT of the responders were significantly higher than those in non-responders according to Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) response criteria at 3-months’ follow-up (P < 0.05). The PET joint count (PJC) detected in [68 Ga]Ga-FAPI-04 and [18F]FDG PET/CT were also significantly higher in CDAI responders than non-responders (P = 0.016 and 0.045, respectively). The clinical characteristics of disease activity at baseline did not show significant difference between the responders and non-responders, except CRP (P = 0.035 and 0.033 in CDAI and SDAI response criteria, respectively). The baseline PJCFAPI, TSUFAPI and MSVFAPI > cutoff values in [68 Ga]Ga-FAPI-04 PET/CT successfully discriminated CDAI and SDAI responders and non-responders at 3-months’ follow-up. Conclusion[68 Ga]Ga-FAPI-04 uptake at baseline were significantly higher in early responders than those in non-responders.Trial registration ClinicalTrials. NCT04514614. Registered 13 August 2020, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000A4PN&selectaction=Edit&uid=U0001JRW&ts=2&cx=-x9t7cp

[Rheumatoid arthritis: remission without biotherapy? The experience of Burkina Faso (West Africa)].

the objective of this study was to evaluate the therapeutic response of patients treated with disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis (RA). descriptive and analytical single-center cross-sectional study conducted in Burkina Faso from January 2019 to December 2021 in patients with RA meeting American Rheumatism Association/European League against rheumatism criteria. Therapeutic response was assessed according to the criteria of the European League Against Rheumatism, the clinical disease activity index and the simplified disease activity Index after at least six months of treatment. one hundred and three patients, including 85 women were included. The average age of the patients was 50.14 years ± 15.04 years. Eighty-seven patients (84.47%) were ACPA positive and 50 patients (48.54%) had radiological damage at inclusion. The mean DAS28-CRP, CDAI and SDAI were 5.17, respectively; 32.16 and 35.48 at inclusion compared to 2.53; 7.83 and 8.76 after at least six months of treatment (p<0.0001). Ninety-six patients (93.20%) were treated with methotrexate. According to the criteria of the European League Against Rheumatism, 89 patients (86.41%) were good responders, 62 patients (60.19%) were in remission. Major improvement was observed in 53 patients (51.46%) as assessed by the Clinical Disease Activity Index and the Simplified Disease Activity Index. despite the unavailability of biotherapies in sub-Saharan Africa, remission of RA can be obtained by optimizing treatment with DMARDs and "tight control".

Real-World Clinical Equivalence of Generic and Branded Tofacitinib: A Prospective Longitudinal Cohort Study in Patients With Rheumatoid Arthritis

ObjectivesTo explore the clinical efficacy and safety of generic tofacitinib vs brand name tofacitinib in patients with rheumatoid arthritis (RA) in a single-center comparative study based on a prospective real-world cohort. MethodsPatients with RA receiving tofacitinib, either generic (Kelejia) or branded (Xeljanz), from March 2017, to December 31, 2022, were enrolled. The primary outcome was the simplified disease activity index (SDAI)–defined remission rate at month 6. Secondary outcomes included the rates of remission and low disease activity defined by other composite scores; European Alliance of Associations for Rheumatology response rate, and ultrasonic synovitis scores at months 1, 3, 6, and 12. Cost-effectiveness was investigated. Propensity score–based inverse probability of treatment weighting was adopted to reduce selection bias. ResultsA total of 204 patients were enrolled: 59 in the generic group and 145 in the branded group. An SDAI-defined remission was achieved in 41.1% and 39.2% of patients in the generic and branded groups, respectively, at month 6 (P=.85). Rates of remission and low disease activity achievement, changes in clinical disease activity scores, and power Doppler and gray scale synovitis scores at months 1, 3, 6, and 12 were comparable between the 2 groups. Similar proportions of patients in the groups achieved moderate/good response at months 1, 3, 6, and 12. Rates of drug retention and adverse effects were also similar in the 2 groups. Both Kelejia and Xeljanz were cost-effective, but Kelejia had a lower average cost-effectiveness ratio. ConclusionGeneric tofacitinib (Keljia) had equivalent clinical efficacy and safety and better cost-effectiveness compared with its originator (Xeljanz).