Rheumatoid Arthritis Cohort Research Articles

Waning humoral immunity of SARS-CoV-2 vaccination in a rheumatoid arthritis cohort and the benefits of a vaccine booster dose.

We aimed to assess SARS-CoV-2 spike-specific antibody kinetics postvaccination and the benefit of a mRNA vaccine booster dose in rheumatoid arthritis (RA) patients treated with immunosuppressive drugs. Consecutive RA patients on immunosuppressive therapies, with no known history of SARS-CoV-2 infection or high-risk contact, vaccinated with 2 doses SARS-CoV-2 mRNA, BNT162b2 or mRNA-1273, or viral vectored ChAdOx1 nCoV-19 vaccine were recruited during their routine rheumatology consultation. Anti-SARS-CoV-2 IgG spike-specific antibodies were quantified at 1, 3 and 6 months respectively following the second vaccine dose. The incidence of SARS-CoV-2 infection post-vaccination during this 6-month longitudinal study was also assessed. Of the 104 RA patients included, 79 patients completed the 6-month trial follow-up. A significant decrease in anti-SARS-CoV-2 spike-specific IgG titres was observed between 1-month and 3-month postvaccination (p<0.01). Among the 46 patients (46/79) receiving a booster dose, all developed detectable anti-SARS-CoV-2 spike-specific IgG antibodies at the 6-month follow-up with significantly higher titres compared to 1-month (p<0.001) and 3-month (p<0.0001) post-vaccination. Conversely, the antibody titres among the 33 patients (33/79) not receiving a booster dose decreased significantly at the 6-month follow-up compared to 1-month (p<0.0001) and 3-month (p<0.01) post-vaccination. The incidence of COVID-19 disease postvaccination was 8.9% without severe forms. To our knowledge, this is the first study to report on anti-SARS-CoV-2 spike-specific antibody kinetics postvaccination and the effect of a booster dose in a cohort of RA patients. The latter is essential given the waning humoral immunity observed in vaccinated RA patients and the increased incidence of COVID-19 diseases postvaccination in this 6-month longitudinal study.

Glycerophospholipid metabolism is involved in rheumatoid arthritis pathogenesis by regulating the IL-6/JAK signaling pathway

To explore the metabolic mechanism of differential plasma interleukin (IL)-6 expression in patients with rheumatoid arthritis (RA). A total of 240 RA patients were enrolled in the non-target metabolomics study cohort and 69 healthy volunteers were included as healthy controls (HCs). Plasma IL-6 levels were detected by electrochemiluminescence assay. Plasma metabolites were detected by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Patients with active RA (n = 20) and remissive RA (n = 20) and 20 HCs were enrolled in the targeted validation cohort. Metabolites identified by non-target metabolomics were quantitatively analyzed by ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry. Effects of 1-oleoyl-sn-glycero-3-phosphocholine (OGPC) associated with IL-6 on MH7A cells were assessed. After 24-h or 48-h induction by TNF-α, the supernatants were collected for IL-6 quantification by enzyme-linked immunosorbent assay. Furthermore, Western blot was performed to investigate the relative JAK2 and p-JAK2 expressions. With an increasing IL-6 level, OGPC shown to be related to the glycerophospholipid metabolism pathway by Kyoto Encyclopedia of Genes and Genomes analysis displayed a significant decrease. In the validating RA cohort, the OGPC concentrations in remissive RA group and active RA group decreased compared with HC group. OGPC down-regulated IL-6 secretion and p-JAK2 expression in TNF-α-induced MH7A cells in vitro. In conclusion, glycerophospholipid metabolism is the main metabolic pathway associated with the differential IL-6 expression in RA patients. The down-regulated OGPC is a promoting factor for the increased IL-6 plasma level in RA patients, which further affects the downstream JAK signaling pathway.

Low cumulative disease activity is associated with higher bone mineral density in a majority Latinx and Asian US rheumatoid arthritis cohort

ObjectivePrior studies have found conflicting results when evaluating the association between rheumatoid arthritis (RA) disease activity and bone mineral density (BMD). Whether or not cumulative RA disease activity is associated with BMD remains unanswered. MethodsData were from the University of California San Francisco RA Cohort from years 2006–2018. Those with BMD measures and at least two study visits prior to BMD measure were included in the study. The association between low cumulative disease activity, as measured by DAS28ESR, with the primary outcome of femoral neck BMD was assessed using multivariable linear regression. Sensitivity analyses were performed substituting CDAI for the disease activity measure as well as total hip and lumbar spine BMD as outcomes. Results161 participants with RA were studied. The cohort was 62.4 ± 10.2 years old and 88% female. Hispanic/Latino (N = 73, 45%) and Asian (N = 59, 37%) were the most common racial/ethnic groups in our cohort. Mean RA duration was 10.5 ± 7.3 years and 83% were ACPA positive. Low disease activity was independently associated with higher femoral neck BMD compared to the moderate/high disease activity group (β= 0.071 [95%CI: 0.021 to 0.122], p = 0.020). The relationship between low cumulative disease activity was similar when CDAI and other BMD sites were substituted in the multivariable models. ConclusionLow cumulative disease activity as measured by DAS28ESR was associated with higher femoral neck BMD, independent of traditional osteoporosis risk factors (e.g., age, sex, BMI) in a unique RA cohort. Results were similar when evaluating cumulative low CDAI and other BMD sites.

Comprehensive assessment of multimorbidity burden in a population-based cohort of patients with rheumatoid arthritis

ObjectiveTo comprehensively assess multimorbidity burden in patients with rheumatoid arthritis (RA) in order to unify the multimorbidity definition for RA research and clinical practice.MethodsIn this population-based study, residents of eight...

Disease Knowledge and Functional Disability of a Cohort of Rheumatoid Arthritis in a Tertiary Government Hospital in Manila, Philippines

Background. Rheumatoid arthritis (RA) is a chronic and progressive disease resulting in disability and poor quality of life. Patients’ knowledge (PxK) of disease can contribute to better disease control, reduced disability, and improved quality of life. Objective. The objective of this study was to determine the disease knowledge and functional disability of a cohort of patients with RA. Methods. We conducted a cross-sectional study among patients with RA at the University of the Philippines -&nbsp; Philippine General Hospital Arthritis Clinic. The subjects were recruited using convenience sampling over three months in 2019. We obtained demographic and disease characteristics, clinic attendance, patient knowledge, and functional status through chart review, a questionnaire, and a disability index. Descriptive statistics, 2-sample T-test, Pearson’s correlation, analysis of variance (ANOVA), and multiple linear regression analysis were used for data analysis. Informed consent was obtained before participation in the study. Results. Eighty percent (57/71) of recruited patients participated in the study. All were female, and the mean age was 51.6 years (±12.9). Most participants completed secondary education, were employed, had an average duration of RA of 8 (±6.8) years, had been consulting at the Arthritis Clinic for an average of 4.8 years (±3.8), and had moderate disease activity (49.1%). Most patients had American College of Rheumatology (ACR) class I or II functional status (50/57, 88%). The usual source of the patients' knowledge about RA was their physician. The mean knowledge score was 5.10 (±0.93) out of a perfect score of 9. Most patients were aware of their disease diagnosis and the non-communicable nature of RA. There was low awareness of the need for self-monitoring for disease flares or treatment adverse events and the extra-articular involvement in RA. The mean functional disability score was 6.65 ± 5.33, and the mean functional disability index (FDI) was 0.83 (±0.66). These correspond to mild functional disability (FD). There was no significant relationship between the total knowledge score and age, duration of disease, number of consultations in the past year, level of education, employment status, perceived level of disease knowledge, or the practice of asking their physician about illness. Perception of overall health status was associated with functional disability (p=0.001). Conclusion. Most of the patients in our cohort of RA patients had a mild functional disability and low knowledge scores. The study identified the gaps in our patients’ knowledge of disease and its management. A re-evaluation of existing educational and treatment strategies will be beneficial to enhance disease knowledge and improve health outcomes.

Differences in trajectory of disease activity according to biologic and targeted synthetic disease-modifying anti-rheumatic drug treatment in patients with rheumatoid arthritis

BackgroundThe purpose of this study was to stratify patients with rheumatoid arthritis (RA) according to the trend of disease activity by trajectory-based clustering and to identify contributing factors for treatment response to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) according to trajectory groups.MethodsWe analyzed the data from a nationwide RA cohort from the Korean College of Rheumatology Biologics and Targeted Therapy registry. Patients treated with second-line biologic and targeted synthetic DMARDs were included. Trajectory modeling for clustering was used to group the disease activity trend. The contributing factors using the machine learning model of SHAP (SHapley Additive exPlanations) values for each trajectory were investigated.ResultsThe trends in the disease activity of 688 RA patients were clustered into 4 groups: rapid decrease and stable disease activity (group 1, n = 319), rapid decrease followed by an increase (group 2, n = 36), slow and continued decrease (group 3, n = 290), and no decrease in disease activity (group 4, n = 43). SHAP plots indicated that the most important features of group 2 compared to group 1 were the baseline erythrocyte sedimentation rate (ESR), prednisolone dose, and disease activity score with 28-joint assessment (DAS28) (SHAP value 0.308, 0.157, and 0.103, respectively). The most important features of group 3 compared to group 1 were the baseline ESR, DAS28, and estimated glomerular filtration rate (eGFR) (SHAP value 0.175, 0.164, 0.042, respectively). The most important features of group 4 compared to group 1 were the baseline DAS28, ESR, and blood urea nitrogen (BUN) (SHAP value 0.387, 0.153, 0.144, respectively).ConclusionsThe trajectory-based approach was useful for clustering the treatment response of biologic and targeted synthetic DMARDs in patients with RA. In addition, baseline DAS28, ESR, prednisolone dose, eGFR, and BUN were important contributing factors for 4-year trajectories.

Traditional and disease-related non-computed variables affect algorithms for cardiovascular risk estimation in Sjögren's syndrome and rheumatoid arthritis.

Several cardiovascular (CV) risk algorithms are available to predict CV events in the general population. Their performance and validity in rheumatic disease patients is suboptimal as some disease-specific variables which strongly contribute to the pathogenesis of CV disease are not included in these CV algorithms. We aimed to evaluate the performance of two CV algorithms and investigate which variables not included in the score contribute to CV risk score in a cohort of rheumatoid arthritis (RA) and Sjögren's syndrome (SS) patients. A consecutive cohort of 77 RA and 68 SS patients without prior CV events was included. Clinical and serological features and traditional CV risk factors were collected. The 10-year CV risk was assessed by Reynold Risk Score (RSS) and "Progetto Cuore" algorithms. Prevalence of traditional CV risk factors and 10-year risk of fatal and non-fatal CV events assessed by RSS and "Progetto Cuore" were similar between the two cohorts. Multiple linear regression model showed that, among variables not included in both algorithms, body mass index (BMI) and disease activity were predictors of "Progetto Cuore" while BMI and bone erosions of RSS in RA. In SS, C-reactive protein was predictor of "Progetto Cuore" while hypertension, ESSDAI and LDL-cholesterol of RSS. The 10-year risk of fatal and non-fatal CV events is similar in RA and SS. Traditional CV risk factors, as hypertension, strongly contribute to CV risk in these patients. Inflammatory parameters and disease activity are two disease-specific variables which should be included in CV algorithm assessment in rheumatic disease patients.

Could potentially calprotectin be a promising biomarker to oracle biologic therapy response in rheumatoid arthritis?

BackgroundThe advent of novel biologic agents for the treatment of rheumatoid arthritis (RA) has proven to be highly productive. Nonetheless, high cost, side effects, and unresponsiveness to these agents dictates the assignment of biomarkers that can foretell treatment response. Currently, calprotectin (a member of the S100 protein family) is amongst the enormously studied candidates in this perspective. Yet, conflicting results have been published. The main purpose of this study was to explore the role of serum concentration of calprotectin to predict the response to biological therapy in RA patients, so as to customize RA treatment.ResultsBaseline serum calprotectin levels were significantly higher in RA patients compared to the control subjects (P value < 0.001). After receiving biologic therapy, a remarkable reduction (P < 0.001) in serum calprotectin was noted in RA cohort. Moreover, no correlation was found between the 28 joint count disease activity score (DAS28) and serum calprotectin levels neither before or after biologics. Intriguingly, no statistically significant association was detected between circulating calprotectin level and response to biological therapy.ConclusionSerum calprotectin concentrations could not be used as a biomarker to forecast clinical response to biological therapy in RA patients. However, further studies involving larger cohort of RA patients should be carried out to deliver more insight in this regard.

Comparison of chronic widespread pain prevalence with different criteria in two cohorts of rheumatoid arthritis

ObjectiveThis study aims to investigate chronic widespread pain with the 1990 (CWP1990) and 2019 (CWP2019) definitions 6 years after the onset of rheumatoid arthritis (RA), in one patient cohort with tight controls and one conventional cohort, and factors associated with reporting CWP1990 and CWP2019, respectively.MethodsA cohort of 80 RA patients with monthly visits to the physician the first 6 months was compared to a cohort of 101 patients from the same clinic with conventional follow-up. Both cohorts had early RA (< 13 months). The prevalence of CWP1990 and the more stringent CWP2019 were in a 6-year follow-up investigated with a questionnaire, including a pain mannequin and a fear-avoidance beliefs questionnaire.ResultsIn the tight control cohort, 10% reported CWP2019 after 6 years compared to 23% in the conventional cohort (p = 0.026). There was no difference when using the CWP1990 definition (27% vs 31%, p = 0.546). When adjusted for important baseline data, the odds ratio for having CWP2019 was 2.57 (95% CI 1.02–6.50), in the conventional group compared to the tight control group (p = 0.046). A high level of fear-avoidance behaviour towards physical activity was associated with CWP2019, OR 10.66 (95% CI 1.01–112.14), but not with CWP1990 in the tight control cohort.ConclusionA more stringent definition of CWP identifies patients with a more serious pain condition, which potentially could be prevented by an initial tight control management. Besides tight control, caregivers should pay attention to fear-avoidance behaviour and tailor treatment.Key Points• CWP2019 is a more stringent definition of chronic widespread pain and identifies patients with a more serious pain condition.• Patients with a serious pain condition could be helped by frequent follow-ups.• This study suggests that a special attention of fear-avoidance behaviour towards physical activity in patients with RA is needed.

Impact of concomitant chronic kidney disease on hospitalised infections and remission in patients with rheumatoid arthritis: results from the IORRA cohort.

To investigate the impact of concomitant chronic kidney disease (CKD) on unfavourable clinical events and remission in Japanese patients with rheumatoid arthritis (RA). We included 5103 patients with RA and CKD from the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort in 2012. CKD stages were classified into four groups: CKD with normal eGFR ≥60 ml/min/1.73 m2 and proteinuria; mild CKD, eGFR ≥45 to < 60; moderate CKD, eGFR ≥30 to < 45; and severe CKD, eGFR <30. We assessed the association between concomitant CKD and the occurrence of unfavourable clinical events or achieving remission during a 5-year observational period. Of the 5103 patients with RA, 686 (86.6%) had CKD. Concomitant CKD was associated with hospitalised infections [adjusted hazard ratio (aHR) 1.52, 95% confidence interval (CI) 1.07-2.13, p = .02], especially in the moderate to severe CKD group (aHR 1.93, 95% CI 1.12-3.13, p = .02). Of all subjects, 2407 (47.2%) had active RA at baseline and 401 (16.7%) had CKD. Concomitant CKD was also associated with the failure of achieving remission (aHR 0.82, 95% CI 0.68-0.99, p = .04). Concomitant CKD was a risk factor for hospitalised infections in Japanese patients with RA and failure of achieving remission in patients with active RA.

Hydroxychloroquine use is not associated with QTc length in a large cohort of SLE and RA patients

BackgroundHydroxychloroquine (HCQ) is a cornerstone therapy for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, reports of its use and subsequent fatal arrhythmias in patients with coronavirus disease 19 (COVID-19) have raised concern regarding its cardiovascular (CV) safety. Therefore, we examined the relationship between HCQ use and corrected QT (QTc) length in SLE and RA patients without clinical CV disease (CVD).MethodsSLE patients from the Columbia University Lupus Cohort registry (n = 352) and two RA cohorts (n = 178; ESCAPE-RA and RHYTHM-RA) with electrocardiograms (ECGs) collected as part of study data were analyzed. RA cohort participants were recruited from tertiary referral centers with additional referrals from community rheumatologists, while SLE subjects originated from the Columbia University Lupus Cohort. All patients met American College of Rheumatology (ACR) classification criteria for SLE or RA and lacked known CVD. The exposure of interest was HCQ use and main outcome measure was QTc length [continuous or categorical (≥ 440 ms and ≥ 500 ms)].ResultsOf the combined SLE and RA cohorts (n = 530), 70% were HCQ users and 44% had a QTc ≥ 440 ms. The adjusted mean QTc length was comparable between HCQ users vs non-users (438 ms vs 437 ms). In multivariable logistic models, HCQ use was not a significant predictor of a QTc ≥ 440 ms for the entire cohort (OR 0.77; 95% CI 0.48–1.23; p = 0.27). Importantly, a QTc ≥ 500 ms was inversely associated with HCQ use and not associated with arrhythmias or deaths. A significant interaction was found between HCQ use and use of anti-psychotics. Ultimately, the use of HCQ combined with any QTc prolonging medication as a group was associated with a QTc length (434 ms; 95% CI 430, 439) which was comparable to that of use of HCQ alone (433 ms; 95% CI 429-437).ConclusionIn a combined cohort of SLE and RA patients without clinical CVD, adjusted QTc length was comparable between HCQ and non-HCQ users, supporting its CV safety in patients with rheumatic diseases.

Increased radiographic progression of distal hand osteoarthritis occurring during biologic DMARD monotherapy for concomitant rheumatoid arthritis

ObjectivesA considerable proportion of patients with rheumatoid arthritis (RA) also suffer from hand osteoarthritis (OA). We here assess the association between conventional synthetic (cs) and biological (b) disease-modifying antirheumatic drugs (DMARDs) and radiographic distal interphalangeal-(DIP) OA in patients with RA.MethodsAdult RA patients from a longitudinal Swiss registry of rheumatic diseases who had ≥ 2 hand radiographs were included at the first radiograph and followed until the outcome or the last radiograph. Patients were grouped into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for the severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. KLS ≥ 2 in ≥ 1 DIP joint indicated incident or existing OA, and increase of ≥ 1 in KLS in ≥ 1 DIP joint indicated progression in existing DIP OA. Time-varying Cox regression and generalized estimating equation (GEE) analyses were performed. We estimated hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) of DIP OA incidence (cohort 2), or progression (cohort 1), in bDMARD monotherapy, bDMARD/csDMARD combination therapy, and past or never DMARD use, when compared to csDMARD use. In post hoc analyses, we descriptively and analytically assessed the individual KLS features in cohort 1.ResultsAmong 2234 RA patients with 5928 radiographs, 1340 patients had DIP OA at baseline (cohort 1). Radiographic progression of DIP OA was characterized by new or progressive osteophyte formation (666, 52.4%), joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), or erosions (62, 4.3%). bDMARD monotherapy had an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34 [95% CI 1.07–1.69]). The risk was not significant in csDMARD/bDMARD combination users (HR 1.12 [95% CI 0.96–1.31]), absent in past DMARD users (HR 0.96 [95% CI 0.66–1.41]), and significantly lower among never DMARD users (HR 0.54 [95% CI 0.33–0.90]). Osteophyte progression (HR 1.74 [95% CI 1.11–2.74]) was the most significantly increased OA feature with bDMARD use compared to csDMARD use. In 894 patients without initial DIP OA (cohort 2), the risk of incident OA did not differ between the treatment groups. The results from GEE analyses corroborated all findings.ConclusionsThese real-world RA cohort data indicate that monotherapy with bDMARDs is associated with increased radiographic progression of existing DIP OA, but not with incident DIP OA.

Identification of Novel, Immunogenic HLA-DR-Presented Prevotella copri Peptides in Patients With Rheumatoid Arthritis.

We previously identified HLA-DR-presented epitopes from a 27-kd protein of Prevotella copri (Pc) obtained from peripheral blood mononuclear cells (PBMCs) from 1 rheumatoid arthritis (RA) patient. Herein, we sought to identify other HLA-DR-presented Pc peptides and source proteins in PBMCs from additional patients to better understand Pc immune responses and RA disease pathogenesis. Using tandem mass spectrometry, we searched for HLA-DR-presented Pc peptides in PBMCs from RA and Lyme arthritis (LA) patients. The identified peptides and source proteins were tested for reactivity in RA patients, those with other arthritides, and the general population. These results were assessed for correlation with clinical findings. Including Pc-p27, we identified 5 HLA-DR-presented Pc peptides, each derived from a different Pc protein, in 3 of 4 RA patients, but none in 2 LA patients. When tested in our RA cohort, 14 of 19 patients (74%) had T cell responses, and 47 of 89 patients (53%) had IgG or IgA responses to ≥1 of the 5 Pc peptides or proteins, most commonly IgA reactivity with Pc-p27. Additionally, 74% of RA patients with IgA antibodies to ≥1 Pc protein had anti-citrullinated protein antibodies (ACPAs) compared with 49% of patients who lacked IgA Pc antibody responses (P = 0.05), and IgA Pc antibody levels correlated with ACPA values. The majority of the RA patients had Pc immune responses. The correlation of IgA Pc antibody responses, particularly to Pc-p27, with ACPA supports the hypothesis that specific microbial antigens in the mucosa have a role in shaping or amplifying immune responses in RA joints.

Does Use of Acupuncture Reduce the Risk of Type 2 Diabetes Mellitus in Patients With Rheumatoid Arthritis? Evidence From a Universal Coverage Health Care System.

Objectives: Although acupuncture is often advocated for patients with rheumatoid arthritis (RA), its efficacy for type 2 diabetes mellitus (T2DM), a common metabolic disease among RA cohorts, has not yet been established. This retrospective cohort study aimed to determine the association between acupuncture use and the development of T2DM among them.Methods: Data were collected from 1999 through 2008 for individuals aged 20–70 years in the nationwide insurance database of Taiwan. From them, we extracted 4,941 subjects within newly diagnosed RA and being T2DM free at baseline. A total of 2,237 patients had ever received acupuncture, and 2,704 patients without receiving acupuncture were designated as a control group. All of them were followed to the end of 2013 to identify T2DM incidence. The Cox proportional hazards regression model was utilized to obtain the adjusted hazard ratio (HR) for acupuncture use.Results: Compared with the RA subjects without use of acupuncture, the incidence of T2DM was lower for those who received acupuncture, with the incidence rates of 24.50 and 18.00 per 1,000 person-years (PYs), respectively. After adjusting for potential confounders, use of acupuncture was significantly related to the lower T2DM risk, with the adjusted HR of 0.73 [95% confidence interval (CI) 0.65–0.86]. Those who used acupuncture for more than five sessions had the greatest benefit in lowering the susceptibility to T2DM.Conclusion: Adding acupuncture into conventional treatment for RA was found to be related to lower risk of T2DM among RA patients. Further clinical and mechanistic studies are warranted.

Metabolic syndrome and its effect on the outcomes of rheumatoid arthritis in a multi-ethnic cohort in Singapore.

Over-expression of common inflammatory mediators in the metabolic syndrome (MetS) and in rheumatoid arthritis (RA) may lead to mutually adverse outcomes. We investigate the prevalence of MetS in a multi-ethnic population of RA patients and its effect on clinical and patient-reported outcomes. Six hundred sixty RA (561 women) patients from a public-sector specialist clinic in a hospital in Singapore were assessed for MetS according to the 2009 Joint Consensus (JC) and the 2004 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definitions. Univariable and multivariable regression modelling were used to investigate the associations between patients' demographics with MetS and MetS with RA outcomes. The prevalence of MetS in our RA cohort was 49.4% and 44.9% according to the JC and NCEP ATP III definitions, respectively. The diagnosis of MetS was largely due to hypertriglyceridemia, hypertension, and obesity. MetS was associated with older age (OR1.06 [95% CI 1.04-1.08]), Malay ethnicity (OR 1.78 [95% CI 1.02-3.09]), or Indian ethnicity (OR3.07 [95% CI 1.68-5.59]). No significant associations between MetS and RA outcomes were observed. RA patients with MetS are more likely to suffer from stroke and ischemic heart disease. The prevalence of MetS in RA patients in Singapore was almost double that in the general population. MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease. RA patients, especially those older and of Indian and Malay ethnicities, should be routinely screened for MetS. Any MetS-defining condition should be actively controlled. Key Points • Approximately half of the RA sample from the Singapore RA population can be diagnosed with MetS. • Older patients, and patients of Malay and Indian ethnicities have higher odds of MetS. • MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease.

Estimated 10-year cardiovascular risk in a large Italian cohort of rheumatoid arthritis patients: Data from the Cardiovascular Obesity and Rheumatic DISease (CORDIS) Study Group

BackgroundSeveral cardiovascular (CV) risk algorithms are available to predict CV events in the general population. However, their performance in patients with rheumatoid arthritis (RA) might differ from the general population. This cross-sectional multicentre study aimed to estimate the 10-year CV risk using two different algorithms in a large RA cohort and in patients with osteoarthritis (OA). MethodsIn a consecutive series of RA patients and matched OA controls without prior CV events, clinical and serologic data and traditional CV risk factors were recorded. The 10-year CV risk was assessed with the Systematic COronary Risk Evaluation (SCORE) and the “Progetto Cuore” algorithms. Results1,467 RA patients and 342 OA subjects were included. RA patients were more frequently diabetic (9.9% vs 6.4%; p=0.04) and smokers (20.4% vs 12.5%; p=0.002) but had lower prevalence of obesity (15% vs 21%; p=0.003). Dyslipidaemia was more prevalent in OA (32.5% vs 21.7%; p<0.0001). The 10-year estimated CV risk was 1.6% (95%CI 1.3-1.9) in RA and 1.4% (95%CI 1.3-1.6) in OA (p=0.002) according to SCORE and 6.5% (95%CI 6.1-6.9) in RA and 4.4% (95%CI 3.9-5.1) in OA (p<0.001) according to “Progetto Cuore”. Regardless of the score used, RA patients had a 3- to-4-fold increased 10-year risk of CV events compared to OA subjects. ConclusionRA patients have a significantly higher 10-year risk of CV events than OA subjects. In addition to effective disease control and joint damage prevention, specific protective measures targeting modifiable traditional CV risk factors should be implemented in RA.

Molecular Changes in the Adipose Tissue Induced by Rheumatoid Arthritis: Effects of Disease-Modifying Anti-Rheumatic Drugs

Disease severity, progression and response to therapy might be worse in obese rheumatoid arthritis (RA) patients, but paradoxically, obesity also might protect from radiographic joint damage. Thus, the intricate relationship between obesity and RA needs urgent clarification. The aim of this study was to assess the influence of obesity on the onset and development of RA and to determine whether arthritis could modify the adipose tissue biology and whether conventional Disease Modifying Anti-Rheumatic Drugs (cDMARDs) can modulate these alterations. Two strategies were followed: (1) clinical profiling of two cohorts of RA: non-obese and obese patients; and (2) mechanistic studies carried out in both a collagen-induced arthritis (CIA) in an obese mouse model and 3T3-L1 adipocytes treated with cDMARDs (leflunomide, methotrexate, and hydroxychloroquine). In our cohort of RA patients with low-moderate disease activity, the presence of obesity was not related to a higher activity of the disease; actually, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) was reduced in the obese RA patients. However, the induction of arthritis promoted transcriptomic changes in the adipose tissue under obesity condition in the obese CIA model. Treatment with hydroxychloroquine reduced weight and insulin resistance, accompanied by beneficial metabolic effects in the adipose tissue. These molecular changes in adipose tissue were also observed after methotrexate administration. In sum, arthritis might affect directly the inflammatory burden and metabolic alterations associated with obesity in adipose tissue. Clinicians should be cautious measuring the activity of the disease in obesity and managing the best therapeutic options for the metabolic comorbidities of these patients, where the combination of hydroxychloroquine and methotrexate should be considered to improve adipose tissue dysfunction in obese RA.

Rheumatoid Arthritis and Cardiovascular Risk: Retrospective Matched-Cohort Analysis Based on the RECORD Study of the Italian Society for Rheumatology.

Background: Rheumatoid arthritis (RA) is associated with an increase in cardiovascular (CV) risk. This issue maybe not only explained by a genetic component, as well as by the traditional CV risk factors, but also by an underestimation and undertreatment of concomitant CV comorbidities.Method: This was a retrospective matched-cohort analysis in the Italian RA real-world population based on the healthcare-administrative databases to assess the CV risk factors and incidence of CV events in comparison with the general population. Persistence and adherence to the CV therapy were also evaluated in both groups.Results: In a RA cohort (N = 21,201), there was a greater prevalence of hypertension and diabetes with respect to the non-RA subjects (N = 249,156) (36.9 vs. 33.4% and 10.2 vs. 9.6%, respectively), while dyslipidemia was more frequent in the non-RA group (15.4 vs. 16.5%). Compared with a non-RA cohort, the patients with RA had a higher incidence of atrial fibrillation (incidence rate ratio, IRR 1.28), heart failure (IRR 1.53), stroke (IRR 1.19), and myocardial infarction (IRR 1.48). The patients with RA presented a significantly lower persistence rate to glucose-lowering and lipid-lowering therapies than the controls (odds ratio, OR 0.73 [95% CI 0.6–0.8] and OR 0.82 [0.8–0.9], respectively). The difference in the adherence to glucose-lowering therapy was significant (OR 0.7 [0.6–0.8]), conversely no statistically significant differences emerged regarding the adherence to lipid-lowering therapy (OR 0.89 [95% CI 0.8–1.0]) and anti-hypertensive therapy (OR 0.96 [95% CI 0.9–1.0]).Conclusion: The patients with RA have a higher risk of developing CV events compared with the general population, partially explained by the excess and undertreatment of CV risk factors.

Factors associated with frailty in Japanese patients with rheumatoid arthritis: results from the Institute of Rheumatology Rheumatoid Arthritis cohort study.

This study aimed to evaluate the prevalence of, and the factors associated with, frailty in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort completed self-administered questionnaires, which included the 5-item frailty screening index. Patients were classified as frail, prefrail, or robust based on the 5 components of the frailty screening index. Logistic regression analyses were used to evaluate associations between clinical variables and frailty. Among 3,290 Japanese patients with RA (86.7% female, mean age 62.4years) who participated this frailty study, 549 (16.7%) patients were categorized as frailty, 2,063 (62.7%) as prefrailty, and 678 (20.6%) as robust. In multivariable models, body mass index (BMI) ≥ 25kg/m2 (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.41 to 2.47), BMI < 18.5kg/m2 (OR 1.31, 95% CI 1.00 to 1.71), disease activity scores in 28 joints (DAS28) (OR 1.32, 95% CI 1.18 to 1.47), Japanese version of Health Assessment Questionnaire disability index (J-HAQ) (OR 1.26, 95% CI 1.04 to 1.52), the European Quality of Life-5 Dimensions (EQ-5D) (OR 0.80, 95% CI 0.74 to 0.85), non-steroidal anti-inflammatory drug (NSAID) use (OR 1.59, 95% CI 1.23 to 1.98), and methotrexate (MTX) use (OR 0.75, 95% CI 0.60 to 0.94) were significantly (P < 0.05) associated with frailty. BMI (both overweight and underweight), DAS28, J-HAQ, EQ-5D, NSAID use, and MTX nonuse appear to be associated with frailty in Japanese patients with RA. Key Points • This is the largest study showing the prevalence and the associated factors of frailty in patients with RA. • Maintaining normal BMI appears to be important for preventing frailty in patients with RA. • We confirmed the significant associations of frailty with high disease activity, high degree of disability, and poor health related QOL in Japanese patients with RA. • NSAID use and MTX nonuse were associated with the frailty in Japanese patients with RA, which could be explained by patients' background.

Prevalence and Risk Factors of Substance Use Disorder in Rheumatoid Arthritis.

ObjectiveIn this study, we aimed to determine the lifetime prevalence of substance use disorder (SUD) in a Canadian rheumatoid arthritis (RA) cohort and factors associated with SUD in RA.MethodsParticipants with RA (N = 154) were recruited via rheumatology clinics as part of a larger cohort study of psychiatric comorbidity in immune‐mediated inflammatory diseases. SUD is defined as the uncontrolled use of a substance despite the harmful consequences of its use. To identify lifetime SUD, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition was administered to participants. Participants’ sociodemographic and RA clinical characteristics were also assessed. We examined factors associated with lifetime SUD using unadjusted and adjusted logistic regression modeling.ResultsTwenty‐three (14.9%) of 154 participants with RA met the criteria for a lifetime diagnosis of SUD. The majority of the participants were women, were White, had postsecondary education, and were on a disease‐modifying antirheumatic drug. Factors associated with increased odds of SUD were male sex (adjusted odds ratio [aOR]: 3.63, 95% confidence interval [CI]: 1.03‐12.73), younger age (aOR: 0.94, 95% CI: 0.90‐0.98), and ever smoking (aOR: 6.44, 95% CI: 1.53‐27.07).ConclusionWe found that approximately 1 in 7 individuals with RA had a lifetime diagnosis of SUD, highlighting the importance of identifying and treating SUD in those with RA. In particular, the following factors were associated with higher odds of SUD: male sex, younger age, and smoking behaviors.