How Does Ultrasound Global OMERACT-EULAR Synovitis Score (GLOESS) for Rheumatoid Arthritis (RA) Activity Assessment Perform in Real-Life?

OBJECTIVE: This study aimed to assess the effectiveness of the Global OMERACT-EULAR Synovitis Score (GLOESS) of bilateral second to fifth metacarpophalangeal joints (MCP 2-5) in evaluating rheumatoid arthritis (RA) activity in a real-life setting. METHODS: This cross-sectional study included consecutive RA patients without hyperalgesia. Clinical data were extracted from electronic medical records. Evaluations were conducted on bilateral MCP 2-5 by two independent experts in musculoskeletal ultrasound (MSUS). Correlation between clinical and ultrasonographic parameters was analyzed, aiming to define a cutoff value for detecting disease activity. RESULTS: Sixty-nine patients were included. The mean DAS28-ESR was 4.3 (±1.4), and the median GLOESS was 7 (13). The correlation between GLOESS and DAS28 was moderate (r = .62; P < .05). A total GLOESS score of ≤3 and all joints with both GS and PD ≤1 showed good sensitivity and specificity for detecting disease activity (remission/low vs moderate/high, P = 0). CONCLUSION: In a real-life scenario, GLOESS for MCP 2-5 emerges as a valuable measure of RA activity. The optimal cutoff distinguishing remission/low from moderate/high disease activity was determined to be GLOESS ≤3, with all MCP joints exhibiting both GS and PD scores of ≤1.

Diagnostic Value of Dual-Energy CT Virtual Noncalcium for the Assessment of Bone Marrow Edema of Wrist in Patients with Rheumatoid Arthritis.

RATIONALE AND OBJECTIVES: To evaluate the value of dual-energy CT (DECT) virtual noncalcium (VNCa) images in the diagnosis of wrist bone marrow edema (BME) in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: 43 patients with wrist involvement in active RA prospectively underwent DECT and MRI. Functional DECT images reconstruction yielded VNCa images. MRI served as the reference standard for diagnosing BME. BME diagnosis differences between VNCa images and MRI were compared. Differences in CT values between BME and normal bone marrow were assessed. The optimal CT value for detecting BME in VNCa images was determined through ROC curve analysis. The correlation between VNCa images scores and RA disease activity was evaluated. RESULTS: There was a high agreement between VNCa images and MRI in diagnosing BME (Kappa=0.831). VNCa images showed a significant difference in CT values between BME and normal bone marrow (P < 0.001). A cut-off value of - 54.8 HU yielded a sensitivity, specificity, and accuracy of 90.72%, 94.30%, and 93.33%, respectively, for detecting BME on VNCa images. The area under the ROC curve was 0.937 for distinguishing BME from normal bone marrow. Conventional CT images showed no statistically significant difference (P = 0.174) in CT values between BME and normal bone marrow. The VNCa images BME scores were positively correlated with RA disease activity (r = 0.399). CONCLUSION: The DECT VNCa technique demonstrates its potential for diagnosing wrist BME in patients with RA and provides a valuable tool for assessing disease activity in RA. IMPORTANT FINDINGS: The DECT VNCa technique has the ability to distinguish between BME and normal bone marrow. The VNCa images BME scores were positively correlated with the disease activity in RA.

Prodromal symptoms of rheumatoid arthritis in a primary care database: variation by ethnicity and socioeconomic status.

OBJECTIVES: To assess whether prodromal symptoms of rheumatoid arthritis (RA), as recorded in the Clinical Practice Research Datalink Aurum (CPRD) database of English primary care records, differ by ethnicity and socioeconomic status. METHODS: A cross-sectional study to determine the coding of common symptoms (≥0.1% in the sample) in the 24 months preceding RA diagnosis in CPRD Aurum, recorded between January 1st 2004 to May 1st 2022. Eligible cases were adults with a code for RA diagnosis. For each symptom, a logistic regression was performed with the symptom as dependent variable, and ethnicity and socioeconomic status as independent variables. Results were adjusted for sex, age, BMI, and smoking status. White ethnicity and the highest socioeconomic quintile were comparators. RESULTS: In total, 70115 cases were eligible for inclusion, of which 66.4% female. Twenty-one symptoms were coded in > 0.1% of cases so were included in the analysis. Patients of South Asian ethnicity had higher frequency of codes for several symptoms, with the largest difference by odds ratio being muscle cramps (OR 1.71, 1.44-2.57) and shoulder pain (1.44, 1.25-1.66). Patients of Black ethnicity had higher prevalence of several codes including unintended weight loss (2.02, 1.25-3.28) and ankle pain (1.51, 1.02-2.23). Low socioeconomic status was associated with morning stiffness (1.74, 1.08-2.80) and falls (1.37, 2.03-1.82). CONCLUSION: There are significant differences in coded symptoms between demographic groups, which must be considered in clinical practice in diverse populations and to avoid algorithmic bias in prediction tools derived from routinely collected healthcare data.

Personalized cardiovascular risk assessment in Rheumatoid Arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs.

BACKGROUND & OBJECTIVES: This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs': TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction. PATIENTS & METHODS: A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC). RESULTS: In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation. Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs. CONCLUSIONS: Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes.

Development of a novel clinimetric tool: PAtient Reported Disease Activity Index in Rheumatoid Arthritis (PARDAI-RA) by PANLAR, for the assessment of patients living with rheumatoid arthritis.

BACKGROUND: Clinical experience has shown that a single measure is not sufficient to assess disease activity in rheumatoid arthritis (RA). Various clinimetric tools are necessary to address the many clinical situations that can arise. METHODS: In order to develop a comprehensive measurement tool, the Pan American League of Associations for Rheumatology searched for the most frequent measures of disease activity applied in RA by means of a semi-systematic review of the available literature. RESULTS: We found that the most frequently reported measures of disease activity were the 28-joint Disease Activity Score, C-reactive protein, and the erythrocyte sedimentation rate, followed by patient-reported measures of pain and stiffness and many other composite indices and patient-reported outcome measures. The most frequent physician-reported sign of disease was the swollen joint count, and the most frequently self-reported feature was the increase in disease activity or flares. CONCLUSION: In this article, we present a new clinimetric tool developed based on expert consensus and on data retrieved from our search. Disease activity can be better assessed by combining various data sources, such as clinical, laboratory, and self-reported outcomes. These variables were included in our novel clinimetric tool. Key Points • The goal of treatment of RA is to achieve the best possible control of inflammation, or even remission; therefore, disease management should include systematic and regular evaluation of inflammation and health status. • Clinimetric tools evaluate a series of variables (e.g., symptoms, functional capacity, disease severity, quality of life, disease progression) and can reveal substantial prognostic and therapeutic differences between patients. • Our clinimetric tool, which is based on a combination of data (e.g., clinical variables, laboratory results, PROMs), can play a relevant role in patient assessment and care.

Opuntia monacantha: Validation of the anti-inflammatory and anti-arthritic activity of its polyphenolic rich extract in silico and in vivo via assessment of pro- and anti-inflammatory cytokines.

ETHNOPHARMACOLOGICAL RELEVANCE: Opuntia monacantha belongs to the cactus family Cactaceae and is also known by cochineal prickly pear, Barbary fig or drooping prickly pear. It was traditionally used to treat pain and inflammation. O. monacantha cladodes showed pharmacological effects such as antioxidant potential owing to the presence of certain polysaccharides, flavonoids, and phenols. AIM OF THE STUDY: This research aimed to evaluate the anti-inflammatory as well as the anti-arthritic potential of ethanol extract of Opuntia monacantha (E-OM). MATERIALS AND METHODS: In vivo edema in rat paw was triggered by carrageenan and used to evaluate anti-inflammatory activity, while induction of arthritis by Complete Freund's Adjuvant (CFA) rat model was done to measure anti-arthritic potential. In silico studies of the previously High performance liquid chromatography (HPLC) characterized metabolites of ethanol extract was performed by using Discovery Studio 4.5 (Accelrys Inc., San Diego, CA, USA) within active pocket of glutaminase 1 (GLS1) (PDB code: 3VP1; 2.30 Å). RESULTS: EOM, particularly at 750 mg/kg, caused a reduction in the paw edema significantly and decreased arthritic score by 80.58% compared to the diseased group. It revealed significant results when histopathology of ankle joint was examined at 28th day as it reduced inflammation by 18.06%, bone erosion by 15.50%, and pannus formation by 24.65% with respect to the diseased group. It restored the altered blood parameters by 7.56%, 18.47%, and 3.37% for hemoglobin (Hb), white blood count (WBC), and platelets, respectively. It also reduced rheumatoid factor RF by 13.70% with concomitant amelioration in catalase (CAT) and superoxide dismutase (SOD) levels by 19%, and 34.16%, respectively, in comparison to the diseased group. It notably decreased mRNA expression levels of COX-2, IL-6, TNF-α, IL-1, NF-κß and augmented the levels of IL-4 and IL-10 in real time PCR with respect to the diseased group and piroxicam. HPLC analysis previously performed showed that phenolic acids and flavonoids are present in E-OM. Molecular docking studies displayed pronounced inhibitory potential of these compounds towards glutaminase 1 (GLS1), approaching and even exceeding piroxicam. CONCLUSIONS: Thus, Opuntia monacantha could be a promising agent to manage inflammation and arthritis and could be incorporated into pharmaceuticals.

Drug-drug interaction assessment based on a large-scale spontaneous reporting system for hepato- and renal-toxicity, and thrombocytopenia with concomitant low-dose methotrexate and analgesics use.

BACKGROUND: Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment and is highly effective with low-dose intermittent administration. MTX is occasionally used in combination with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP)/paracetamol for pain or inflammation control. With MTX treatment, the side effects, such as hepatotoxicity, renal failure, and myelosuppression should be considered. These are also seen with analgesics treatment. METHODS: We used a large spontaneously reported adverse event database (FAERS [JAPIC AERS]) to analyze whether the reporting of adverse events increased upon MTX and analgesic therapy in patients with RA. RESULTS: After identifying RA cases, the crude reporting odds ratios (cRORs) for hepatotoxicity, renal failure, and thrombocytopenia associated with the use of MTX, APAP, or NSAIDs were calculated by disproportionality analysis, which revealed significantly higher cRORs for these events. No analgesics showed consistent positive signals for drug-drug interaction (DDI) with concomitant low-dose MTX analyzed using four algorithms for DDI interaction (the Ω shrinkage measure, additive or multiplicative, and combination risk ratio models). However, in renal failure and thrombocytopenia, loxoprofen (Ω025 = 0.08) and piroxicam (Ω025 = 0.46), and ibuprofen (Ω025 = 0.74) and ketorolac (Ω025 = 3.52), respectively, showed positive signals in the Ω shrinkage measure model, and no consistency was found among adverse events or NSAIDs. CONCLUSIONS: Studies using spontaneous reporting systems have limitations such as reporting bias or lack of patient background; however, the results of our comprehensive analysis support the results of previous clinical or epidemiological studies. This study also demonstrated the usefulness of FAERS for DDI assessment.

Impact of socioeconomic status on biologics utilization in rheumatoid arthritis: revealing inequalities and healthcare efficiency.

Background/Aims: This cross-sectional study aimed to investigate biologics treatment disparities in rheumatoid arthritis (RA) patients based on socioeconomic status (SES). Methods: Data from the KOrean Observational Study Network for Arthritis (KORONA) database were analyzed to assess various factors associated with SES, health behaviors, and biologics use. Logistic regression and structured equation modeling (SEM) were utilized for data analysis. Results: Among 5,077 RA patients included, 393 (7.7%) patients were identified as biologics users. Within the entire cohort, 31.8% of the participants were in the low-income and low-education groups, and 39.3% of the participants were in the high-income and high-education groups. Despite the patients with low income or low education experienced higher disease activity at diagnosis, had more comorbidities, exhibited higher medication compliance, underwent more check-ups, and had more hospital admissions than their counterparts, the odds of patients with low-income receiving biologics were 34% lower (adjusted odds ratio = 0.76, 95% confidence interval: 0.60-0.96, p = 0.021) after adjustment for demographics and comorbidities. SEM and pathway analyses confirmed the negative impact of low SES on biologics use. Conclusions: The findings suggest that SES plays a significant role in biologics use among RA patients, indicating potential healthcare inefficiencies for low SES patients. Moreover, adverse healthcare habits negatively affect biologics use in RA patients. The study highlights the importance of considering socioeconomic factors while discussing biologics use and promoting equitable access to biologics for optimal RA management.

Assessment of COVID-19 Morbidity and Mortality Among Patients With Autoimmune Diseases at King Abdulaziz University Hospital.

Background The coronavirus disease 2019 (COVID-19) pandemic has raised significant concerns about the effects of the virus on patients with autoimmune diseases. Therefore, understanding the COVID-19 outcomes in this population is crucial for effective prevention and management. Objective This study aimed to investigate the association between autoimmune diseases and the severity of COVID-19 in terms of mortality and morbidity. Despite substantial advancements in pandemic-related research concerning COVID-19 and autoimmune diseases, there remain noteworthy gaps in our comprehension of this association, particularly due to limited investigations conducted in Saudi Arabia. Methods This was a retrospective record review of a tertiary center from January 2020 to January 2022. We included 120 patients, among whom 40 were diagnosed with autoimmune diseases, and 80 were age- and sex-matched controls. Afterward, we assessed their demographics, year of admission, intensive care unit (ICU) admission, health status, length of hospitalization, comorbidities, diagnosis of autoimmune diseases, and type of immunosuppressant therapy. Results Most of the included patients (mean age: 45.4 years) were females (65.8%). The ratio of non-autoimmune diseases to autoimmune diseases was 2:1, the mean length of hospitalization was 8.83 ± 8.16 days, and the median was seven days (interquartile range (IQR) = 3 to 11 days). Among them, 17.5% were admitted to the ICU and 10% died. The prevalence of autoimmune diseases was higher in women than in men (77.5%). The most common diseases were systemic lupus erythematosus (40%), rheumatoid arthritis (20%), and ankylosing spondylitis (10%). Regarding COVID-19 outcomes, ICU admissions were higher among patients with autoimmune diseases than those with non-autoimmune diseases (35% vs. 8.8%) (p<0.05). This trend was also observed in mortality, with a higher percentage of deaths among patients with autoimmune diseases (27.5% vs. 1.7%) (p<0.05). In addition, there were no significant differences between genders in terms of ICU admission, health status outcomes, or length of hospitalization among patients with autoimmune diseases (p>0.05). Notably, 25 patients were administered immunosuppressants. Of these, 18 (72%) used steroids only, while seven (28%) used both biological and steroid therapy. However, no significant associations were observed between the type of treatment used and outcomes such as ICU admission, health status at discharge, and length of hospitalization (p>0.05).  Conclusion This study suggests that individuals with autoimmune diseases have more severe COVID-19 outcomes, as shown by ICU admission and mortality rates, than patients with non-autoimmune diseases. Furthermore, we observed that the use of immunosuppressant medications among patients with autoimmune diseases showed no noticeable effect on these outcomes.

Content validity testing of the INTERMED Self-Assessment in a sample of adults with rheumatoid arthritis and rheumatology healthcare providers.

BACKGROUND: Care complexity can occur when patients experience health challenges simultaneously with social barriers including food and/or housing insecurity, lack of transportation or other factors that impact care and patient outcomes. People with rheumatoid arthritis (RA) may experience care complexity due to the chronicity of their condition and other biopsychosocial factors. There are few standardised instruments that measure care complexity and none that measure care complexity specifically in people with RA. OBJECTIVES: We assessed the content validity of the INTERMEDS Self-Assessment (IMSA) instrument that measures care complexity with a sample of adults with RA and rheumatology healthcare providers (HCPs). Cognitive debriefing interviews utilising a reparative framework were conducted. METHODS: Patient participants were recruited through two existing studies where participants agreed to be contacted about future studies. Study information was also shared through email blasts, posters and brochures at rheumatology clinic sites and trusted arthritis websites. Various rheumatology HCPs were recruited through email blasts, and divisional emails and announcements. Interviews were conducted with nine patients living with RA and five rheumatology HCPs. RESULTS: Three main reparative themes were identified: (1) Lack of item clarity and standardisation including problems with item phrasing, inconsistency of the items and/or answer sets and noninclusive language; (2) item barrelling, where items asked about more than one issue, but only allowed a single answer choice; and (3) timeframes presented in the item or answer choices were either too long or too short, and did not fit the lived experiences of patients. Items predicting future healthcare needs were difficult to answer due to the episodic and fluctuating nature of RA. CONCLUSIONS: Despite international use of the IMSA to measure care complexity, patients with RA and rheumatology HCPs in our setting perceived that it did not have content validity for use in RA and that revision for use in this population under a reparative framework was unfeasible. Future instrument development requires an iterative cognitive debriefing and repair process with the population of interest in the early stages to ensure content validity and comprehension. PATIENT OR PUBLIC CONTRIBUTION: Patient and public contributions included both patient partners on the study team and people with RA who participated in the study. Patient partners were involved in study design, analysis and interpretation of the findings and manuscript preparation. Data analysis was structured according to emergent themes of the data that were grounded in patient perspectives and experiences.

Cost-effectiveness analysis of upadacitinib as a treatment option for patients with rheumatoid arthritis in the Kingdom of Saudi Arabia.

AIM: To evaluate cost-effectiveness of upadacitinib (targeted synthetic-disease modifying anti-rheumatic drug [ts-DMARD]) as first-line (1 L) treatment versus current treatment among patients with rheumatoid arthritis (RA) in the Kingdom of Saudi Arabia (KSA), who had an inadequate response to prior conventional-synthetic (csDMARDs) and/or biologic-DMARDs (bDMARDs). METHODS: This Excel-based model included patients with moderate (Disease Activity Score [DAS28]: >3.2 to ≤5.1) or severe RA (DAS28 > 5.1). Cost-effectiveness of current treatment (1 L: adalimumab-originator/biosimilar; second-line (2 L): other bDMARDs/tofacitinib) was compared against a new treatment involving two scenarios (1 L: upadacitinib, 2 L: adalimumab-biosimilar [scenario-1]/adalimumab-originator [scenario-2]) for a 10-year time-horizon from societal perspective. Model outcomes included direct and indirect costs, quality-adjusted life-years (QALYs), hospitalization days, number of orthopedic surgeries, and incremental cost-utility ratio (ICUR) per QALY. RESULTS: With the current pathway, estimated total societal costs for 100 RA patients over 10-year period were Saudi Riyal (SAR) 50,450,354 (United States dollars [USD] 13,453,428) (moderate RA) and SAR50,013,945 (USD13,337,052) (severe RA). New pathway (scenario-1) showed that in patients with moderate-to-severe RA, upadacitinib led to higher QALY gain (+8.99 and +15.63) at lower societal cost (cost difference: -SAR2,023,522 [-USD539,606] and -SAR3,373,029 [-USD899,474], respectively). Thus, as 1 L, upadacitinib projects "dominant" ICUR per QALY over current pathway. Moreover, in alternate pathway (scenario-2), upadacitinib also projects "dominant" ICUR per QALY for patient with severe RA (QALY gain: +15.63; cost difference: -SAR 164,536 [-USD43,876]). However, moderate RA was associated with additional cost of SAR1,255,696 (USD334,852) for improved QALY (+8.99) over current pathway (ICUR per QALY: SAR139,742 [USD37,264]). Both scenarios resulted in reduced hospitalization days (scenario-1: -14.83 days; scenario-2: -11.41 days) and number of orthopedic surgeries (scenario-1: -8.36; scenario-2: -6.54) for moderate-to-severe RA over the current treatment pathway. CONCLUSION: Upadacitinib as 1 L treatment in moderate-to-severe RA can considerably reduce healthcare resource burden in KSA, majorly due to reduced drug administration/monitoring/hospitalization/surgical and indirect costs.

Translation, transcultural adaptation into Brazilian Portuguese and concurrent validity of the rheumatoid arthritis assessment scale (RAKAS-13/Brazil).

BACKGROUND: Knowledge of patients about Rheumatoid Arthritis (RA) is a necessary aspect to better approach self-management support in a patient-centered manner. The research instrument known as the Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS), consisting of 13 items, is simple, reliable and reproducible, and can be applied in both clinical practice and research protocols. OBJECTIVE: This study aimed to translate and culturally adapt the RAKAS vocabulary into Brazilian Portuguese and to evaluate its concurrent validity. METHODS: The RAKAS was translated into Brazilian Portuguese and administered to 52 elderly women with RA recruited between May 2021 and May 2022. Concurrent validity was assessed using the Spearman's correlation coefficient between RAKAS and Patient Knowledge Questionnaire (PKQ). RESULTS: The participants considered RAKAS-13/BRAZIL easy to understand and did not report any doubts in answering the final version. Concurrent validity of the RAKAS-13/BRAZIL was low compared to the PKQ (ρ = 0.283, p = 0.038). CONCLUSION: The Brazilian Portuguese version of the RAKAS (RAKAS-13/BRASIL) proved to be a questionnaire that was easy and quick to administer to assess patient knowledge about Rheumatoid Arthritis, despite its low correlation with the PKQ in the present study.

Assessment of Disease Activity, Structural Damage, and Function in Rheumatoid Arthritis.

The primary goal in the treatment of rheumatoid arthritis (RA) is to control disease activity, prevent structural damage in joints, and normalize function. Therefore, reliable tools are needed to disease activity, physical function, and radiographic progression in RA. We herein describe methods recently used to assess RA.

Assessment of Musculoskeletal Ultrasound of Rheumatoid Arthritis.

Musculoskeletal ultrasound (MSUS) is a valuable tool that is used in outpatient clinics or at the bedside to assess multiple joint sites, including small joints. It provides detailed images of structures commonly observed in rheumatoid arthritis (RA), such as synovitis, tenosynovitis, bone erosions, cartilage damage, and synovial fluid accumulation. MSUS is frequently used in the management of RA and provides more objective information for an early diagnosis and disease activity assessment through imaging findings.

Assessment of oral methotrexate intolerance in Japanese adult patients with rheumatoid arthritis.

AIM: The objective of this study was to assess the gastrointestinal side (GI) effects of oral methotrexate (MTX) in Japanese adult patients with rheumatoid arthritis (RA). METHODS: In this single-center retrospective study, 112 Japanese adult patients (over 18 years old) with RA were examined by Methotrexate Intolerance and Severity assessment in Adults (MISA) questionnaire. RESULTS: Forty-five (40.2%) of patients were MTX intolerant (MISA score ≥1). Twelve patients (11.2%) were moderate-to-severe MTX intolerant (MISA cross-product score ≥4). The most common GI side effects of MTX were gastric discomfort (26.8%), followed by loss of appetite or dysgeusia (14.3%), fatigue and lethargy (12.5%), and nausea (10.7%). CONCLUSIONS: Japanese adult patients with RA showed a high prevalence of MTX intolerance even in low-dose oral MTX. The MISA questionnaire was practical for finding patients with MTX intolerance.

Disparities in burden of disease in patients with rheumatoid arthritis across racial and ethnic groups.

To examine racial/ethnic differences in rheumatoid arthritis (RA) disease burden and change in clinical outcomes over time. We included CorEvitas Rheumatoid Arthritis Registry patients from two time periods (2013-2015 and 2018-2020). Clinical Disease Activity Index (CDAI) (as a continuous measure and as a dichotomous measure) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) were assessed at each visit. Marginal means and their corresponding 95% confidence interval (CI) by race/ethnicity were estimated for each outcome using adjusted mixed effects linear and logistic regression models. Overall and pairwise tests were conducted to detect differences between race/ethnicity groups. Of 9,363 eligible patients (8,142 White, 527 Black, 545 Hispanic, 149 Asian), most (76%-85%) were female. At Visit 1, the mean disease duration ranged from 9.8-11.8 years. Estimated CDAI was significantly higher for Hispanics compared to Whites at Visit 1 (11.1 vs. 9.9; pairwise P = 0.033) and Visit 2 (9.2 vs. 8.0, pairwise P = 0.005). Disease activity improved over the 5-year study period among all race/ethnicity groups, though Hispanics improved less than Whites. Disease activity improved over the 5-year period across all racial/ethnicity groups, and disparities between racial/ethnicity groups in disease activity and functional status did persist over time, suggesting that further effort is needed to understand the drivers of these discrepancies to close this race/ethnicity gap. Key Points • Disease activity improved over the 5-year period across all racial and ethnic groups. • Disparities between racial and ethnic groups in disease activity and functional status did persist over time, suggesting that further effort is needed to understand the drivers of these discrepancies and close this racial gap.

The Extent and Nature of Functional Limitations According to the Health Assessment Questionnaire Disability Index in Patients with Rheumatoid Arthritis and Severe Functional Disability.

BACKGROUND: For a subgroup of people with rheumatoid arthritis (RA) and severe disability, insight into their limitations is crucial for adequate treatment. AIM: To describe the extent and nature of functional limitations in people with RA and severe disability and to explore the associations of the extent of the functional limitations with patient characteristics, disease characteristics, and outcome measures. METHODS: Baseline data of 215 participants in an RCT on the (cost-)effectiveness of longstanding physiotherapy were used. Functional limitations were assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI). The total HAQ-DI including eight domain scores were calculated. Associations between high HAQ-DI scores (≥2, yes/no) and other variables were examined using the Student's t-test or Chi-squared test where appropriate. RESULTS: The participants (90% women, age 58.8 ± 12.8 years) had a mean HAQ-DI score of 1.7 ± 0.5. The majority (56%) showed a moderate-to-severe disability in all domains. Higher HAQ-DI scores seemed to be associated with advanced age, longer disease duration, unemployment, joint replacements, and outcomes for daily functioning and physical quality of life, but not with measures of disease activity. CONCLUSIONS: Our findings indicate that a comprehensive assessment of all areas of daily activities in this subgroup is necessary in order to provide appropriate (non-)pharmacological care.

Assessment of antiarthritic potential of Asparagus dumosus using formaldehyde and CFA-induced arthritic models in rats via modulation of oxidative stress biomarkers and mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2.

Medicinal plants play a pivotal role in the prevention of chronic non-communicable diseases including arthritis. Despite the traditional use of Asparagus dumosus in arthritis, it has not been studied yet for its effectiveness in arthritis. This study was aimed to explore the antiarthritic potential of A. dumosus in formaldehyde and complete Freund's adjuvant (CFA)-induced arthritic rats. Body weight, arthritic index, hepatic oxidative stress, hematological, biochemical and inflammatory markers were assessed using ELISA, whilst qRT-PCR studies were carried out for the mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2 genes. GCMS and HPLC analysis were performed to identify the secondary metabolites of A. dumosus. From day 8 to 28 post-administration of formaldehyde and CFA, oral administration of A. dumosus (600, 300 and 150 mg/kg) showed a noteworthy improvement (p < 0.001) in the body weights, immune organ weights, serum levels of rheumatoid (RA) factor, C-reactive protein, TNF-α and IL-6 levels in arthritic rats similar to the effect of piroxicam and methotrexate. Subsequently, the administration of A. dumosus to formaldehyde and CFA-challenged rats, caused a marked decrease (p < 0.001) in the mRNA expression of IL-1b, IL-6, OPG, RANKL, TNF-α and COX-2 genes in treated rats. Likewise, when assessed for antioxidant potential, A. dumosus produced a pronounced (p < 0.001) reduction in malondialdehyde (MDA) levels and hydrogen peroxide (H2O2) production, whilst a dose-dependent (p < 0.001) increase in catalase (CAT) and superoxide dismutase (SOD) activities was recorded. GCMS profiling of A. dumosus presented benzaldehyde, 3-hydroxy-4-methoxy-, 1-decanol and undecane as plant compositions, whereas HPLC fingerprinting displayed quercetin, benzaldehyde, 3-hydroxy-4-methoxy-, gallic acid and cinnamic acid as plants constituents. These results depict that A. dumosus possesses anti-arthritic effect mediated possibly through attenuation of arthritic indices, chronic inflammatory and oxidative stress biomarkers along with down-regulation in the mRNA expression of arthritic candid genes.

Development and preclinical assessment of nanoemulgel loaded with phytoconstituents for the management of rheumatoid arthritis.

In recent years, natural ingredients have gained importance for therapeutic treatment due to their minimal toxicity. However, the delivery of these phytoconstituents poses a challenge to provide better efficacy. Current research reports the development of nanoemulgel (NEG) loaded with ginger oleoresin (GOR) and lipid guggul extract (LGE) for the management of rheumatoid arthritis (RA). The nanoemulsion (NE) was developed using the spontaneous emulsification technique by the pseudo-ternary method. The optimized nanoemulsion exhibited globule size of 16.08 ± 2.55 nm, PDI of 0.187 ± 0.06, and zeta potential of - 22.4 ± 0.31 mV. The cumulative release from in vitro diffusion studies at pH 7.4 was about 99.72 ± 3.47%, 57.98 ± 2.11%, and 86.42 ± 5.13% of 6-gingerol, E-guggulsterone, and Z-guggulsterone respectively at the end of 24 h. The ex vivo studies on porcine ear skin showed sustained release with 92.8 ± 3.21% for 6-gingerol, 55.61 ± 0.91% for E-guggulsterone, and 84.2 ± 4.22% for Z-guggulsterone released at the end of 24 h. The cell culture studies on RAW 264.7 cells indicated a robust inhibition of LPS-induced IL-6 and TNF-α production indicating its efficacy in the management of RA. The preclinical studies on male Wistar rats suggest that the developed NEG exhibited a comparable decrease in paw edema inflammation as compared to the marketed diclofenac sodium gel. These encouraging results demonstrate the potential of the developed nanoemulgel containing combination of GOR and LGE for the management of RA.

Assessment of interactions and dosage recommendations of synthetic DMARDs-Evidence-based and consensus-based recommendations based on a systematic literature search.

Conventional synthetic (cs) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) have potential interactions with a multitude of drugs. Furthermore, they sometimes have a lower therapeutic index, particularly in cases of limited organ functions. The aim of this work was to establish evidence-based recommendations on the therapeutic use of DMARDs in the context of drug interactions and dosage recommendations. A systematic literature search was carried out on the issue of drug interactions and dosages in cases of patients with limited kidney function and higher age and suffering from rheumatoid arthritis. A total of 2756 scientific publications were screened and 154 selected of which 68 were scrutinized in detail. Furthermore, the respective product information was also analyzed. A multitude of possible interactions of synthetic DMARDs with different drugs were detected, which were then assessed with respect to the clinical significance and consequences. A consensus process led to making recommendations with which the interactions were classified: A: dangerous combination, B: avoid combination (if possible, pausing DMARD treatment), C: possible combination requiring increased monitoring and potential adjustments in dosage and D: pharmacological interaction without relevance in DMARD standard doses. Apart from that dosage recommendations were established for each csDMARD and tsDMARD depending on kidney function and age. There are 3 primary recommendations and 11 core recommendations on interactions and dosages of csDMARDs and tsDMARDs meant as a practical help for therapeutic decision making and to improve safety in the treatment of rheumatoid arthritis.