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.

SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the Chinese population.

OBJECTIVES: A recently published genome-wide association study identified six novel loci associated with rheumatoid arthritis (RA) in Korean population. We aimed to investigate whether these newly reported RA-risk loci are associated with RA in the Chinese population and to further characterize the functional role of the susceptible gene. METHODS: The susceptible variants of RA were genotyped in 600 RA patients and 800 healthy controls, including rs148363003 of SLAMF6, rs117605225 of CXCL13, rs360136 of SWAP70, rs111597524 of NFKBIA, rs194757 of ZFP36L1 and rs1547233 of LINC00158. Synovial tissues were collected from the knee joint of 50 RA patients and 40 controls without osteoarthritis for the gene expression analysis. Inter-group comparisons were performed with the Chi-square test for genotyping data or with Student's t-test for gene expression analysis. RESULT: For rs148363003 of SLAMF6, RA patients were observed to have a significantly lower frequency of genotype CC (4.5% vs. 0.9%, p = 0.004) as compared with the controls. The frequency of allele C was remarkably higher in the patients than in the controls (11.5% vs. 8.0%, p = 0.002), with an odds ratio of 1.49 (95% CI = 1.16-1.92). There was no significant difference between the patients and the controls regarding genotype or allele frequency of the other 5 variants. The mRNA expression of SLAMF6 was 1.6 folds higher in the RA patients than in the controls. Moreover, SLAMF6 expression was 1.5 folds higher in patients with genotype CC than in the patients with genotype TT. CONCLUSIONS: SLAMF6 was associated with both the susceptibility and severity of RA in the Chinese population. Moreover, rs148363003 could be a functional variant regulating the tissue expression of SLAMF6 in RA patients. It is advisable to conduct further functional analysis for a comprehensive knowledge on the contribution of this variant to the development of RA.

Staying moving, staying strong: Protocol for developing culturally appropriate information for Aboriginal people with osteoarthritis, rheumatoid arthritis, lupus and gout.

INTRODUCTION: Addressing disparities in arthritis care is an important yet unmet health need for Aboriginal and Torres Strait Islander people in Australia (respectfully Aboriginal people herewith). Despite the significant prevalence and burden of arthritis within Aboriginal communities, access to care for arthritis is low. One means to reduce existing disparities in health care is to address current challenges relating to the appropriateness and acceptability of health care information resources for Aboriginal people. Health information sources can help to empower patients and their families to have greater involvement in their care and to engage in self-management of their condition. Despite an extensive range of arthritis information resources being available, currently no resources have been culturally adapted and developed in collaboration with Aboriginal consumers with arthritis. This paper outlines the processes that will be undertaken within the Staying Moving, Staying Strong project. This project aims to develop culturally secure arthritis information for Aboriginal people with osteoarthritis, rheumatoid arthritis, lupus and gout. METHODS AND ANALYSIS: The overarching principle guiding this project is cultural security, referring to the incorporation of processes such that the research will not compromise the cultural rights, values and expectations of Aboriginal people. This project will prioritise partnerships, community engagement, community benefit, sustainability, transferability, and capacity building and therefore uphold the cultural rights and values of Aboriginal people. In this six-phase project we will; 1) Establish a community reference group and advisory committee; 2) Explore the health information needs and preferences of Aboriginal people with arthritis; 3) Synthesise the existing key recommendations in high quality clinical practice guidelines on arthritis care; 4) Culturally adapt key clinical recommendations; 5) Develop culturally appropriate arthritis resources and; 6) Qualitatively evaluate the developed resources.

«Vivir con artritis reumatoide» en una población indígena qom en la Argentina. Un estudio cualitativo / «Living with Rheumatoid Arthritis» in an Indigenous Qom Population in Argentina. A Qualitative Study

Introducción: La artritis reumatoide (AR) es una enfermedad crónica que impacta la vida de los pacientes. La prevalencia de AR en la población qom fue de 2,4% y representó una enfermedad agresiva y limitante. El objetivo del estudio fue describir la experiencia de los individuos de la comunidad indígena qom que sufrían de AR y su experiencia con el sistema de salud local en la ciudad de Rosario, Santa Fe, Argentina. Materiales y métodos: Estudio cualitativo, de corte etnográfico, utilizando técnicas de observación de los participantes y entrevistas semiestructuradas; siguiendo una guía desarrollada por un grupo multidisciplinario de antropólogos, reumatólogos, enfermeras y psicólogos. Se realizó un análisis temático basado en las narrativas reconstruidas y una estrategia de triangulación entre investigadores. Resultados: Se realizaron 33 entrevistas a 29 individuos con AR. Los resultados mostraron una «normalización» de los síntomas y de sus limitaciones al realizar tareas diarias. La relación entre los individuos y el sistema de salud local fue complejo y limitado en diferentes aspectos (p. ej., acceso al sistema de salud, continuidad del tratamiento, complejidad en las vías de acceso a la asistencia médica y falta de competencia cultural). Conclusiones: La AR es una enfermedad que tiene un impacto negativo en la vida diaria de la población qom que vive en Rosario. Mejorar la relación entre esta población y el sistema de salud, así como implementar un trabajo multidisciplinario debe ser una prioridad.(AU)

Introduction: Rheumatoid arthritis (RA) is a chronic disease which impacts patients’ quality of life. The prevalence of RA in the qom population was 2.4% and represented an aggressive and disabling disease. The study goal was to describe the experience of the indigenous qom community individual suffering from RA, along with their experience with the local health care system in the city of Rosario, Santa Fe, Argentina. Methods: Qualitative Study using techniques of participant observation and semi-structured interviews; following a guideline developed by a multidisciplinary research group comprising anthropologists, rheumatologists, nurses, and psychologists. A triangulation strategy was implemented for the analysis. Results: A total of 33 interviews were conducted in 29 individuals with RA. The results showed a «normalization» of their symptoms and of their limitations in performing daily tasks. The individual relationships with the local health care system was complex and limited in several aspects (e.g. access to health care, continuity of treatment, complexity of medical care pathway and lack of cultural competence). Conclusions: RA is a disease that has a negative impact on the daily lives of the qom people living in Rosario. Improving the relationship between this population and the local health care system as well as the implementation of multidisciplinary work should be priorities.(AU)

Predictors of Smoking Cessation in Patients With Rheumatoid Arthritis in Two Cohorts: Most Predictive Health Care Factors.

OBJECTIVE: Recognizing smoking as a risk factor for rheumatoid arthritis (RA) severity, the present study was undertaken to evaluate patient- and health care-level predictors of smoking cessation in patients with RA to guide implementation of smoking cessation interventions. METHODS: Electronic health record data from 2 health systems were abstracted for patients with at least 2 International Classification of Disease diagnosis codes for RA between 2005 and 2016. Patients missing smoking statuses or with <6 months of follow-up were excluded. Multivariable logistic regression was used to determine predictors of smoking cessation. RESULTS: Among 3,577 patients with RA, 507 smoked at baseline, and 29% quit over a median of 4.75 years. Black male patients, ages 40-59 years and enrolled in Medicaid, were significantly more likely to be baseline smokers; however, none of these factors predicted cessation. Instead, patients new to rheumatology care were 60% more likely to quit (adjusted odds ratio [ORadj ] 1.60 [95% confidence interval (95% CI) 1.02-2.50]), and patients in the rural community health system were 66% more likely to quit (ORadj 1.66 [95% CI 1.03-2.69]). Seropositive patients were 43% less likely to quit smoking (ORadj 0.57 [95% CI 0.35-0.91]). CONCLUSION: Health care factors, including health system and being new to rheumatology care, were more predictive of smoking cessation in patients with RA than patient sociodemographic factors, suggesting an important role for health system cessation efforts for patients with RA. Seropositive patients were less likely to quit and may particularly benefit from cessation support. Emphasizing smoking cessation with new or seropositive RA patients and leveraging health system interventions could improve smoking cessation and outcomes in RA.

Interleukin-17 Gene Polymorphism (Rs2275913 G/A, Rs763780 C/T) in Rheumatoid arthritis：Meta-analysis Based on Ethnicity.

INTRODUCTION: The association between interleukin(IL)-17A and IL-17 F gene polymorphism with rheumatoid arthritis (RA) were inconsistent among previous studies. This meta-analysis aimed to determine the association between IL-17A and IL-17 F gene polymorphism with RA. METHODS: We searched Medline up to February 2020. Meta-analyses were performed for the comparisons of allele and multiple genetic models, including dominant, recessive, heterozygous, and homozygous models using fixed or random effects models. Odds ratios (OR) with 95% confidence intervals (95%CI) were utilized to assess the potential relationship. RESULTS: A total of 2315 confirmed cases and 2342 controls were included from eligible 10 case-controls studies. Meta analysis suggested that rs2275913 G allele increased the risk of RA in Caucasians (G vs A: OR = 1.14, 95% CI = 1.00-1.29, P = .044), but not in Mongolians (P > .05). Pooled analysis suggested that a significant associations between rs763780 C allele with RA susceptibility (C vs T: OR = 1.83, 95% CI = 1.13-2.97, P = .014). Subgroup analysis by ethnicity indicated that rs763780 C allele was closely related to RA risk in two races (P < .001). TSA plot revealed that the present study sufficient to draw a conclusion. CONCLUSIONS: This meta-analysis demonstrates IL-17A and IL-17 F genes play a significant role in RA, but its role in Mongolian populations needs further exploration.

A pooled safety analysis of peficitinib (ASP015K) in Asian patients with rheumatoid arthritis treated over a median of 2 years.

OBJECTIVE: To evaluate the safety of peficitinib for the treatment of rheumatoid arthritis (RA) in Asian patients. METHODS: Safety data from one Phase 2b, two Phase 3, and one open-label long-term extension study [data cut-off 31 May 2018] were pooled into Phase 3 studies (peficitinib 100 and 150 mg/day, and placebo) and Phase 2/3 studies (all peficitinib-treated patients). Incidence rates per 100 patient-years (PY) of adverse events (AEs) of special interest were calculated. RESULTS: Overall, 1052 patients received peficitinib for 2336.3 PY of exposure (median 2.1 years); four deaths occurred, including one death after the studies. AE incidence was similar across peficitinib 100 and 150 mg/day groups (Phase 3 studies). Respective peficitinib and placebo incidence rates (95% confidence interval) per 100 PY were 2.9 (1.9, 4.6) and 0.0 for serious infections, 5.7 (4.2, 7.9) and 2.3 (0.6, 9.4) for herpes zoster-related disease, and 0.6 (0.2, 1.6) and 1.2 (0.2, 8.3) for malignancies (excluding non-melanoma skin cancer) (Phase 3 studies), and 0.1 (0.0, 0.3) for venous thromboembolism in all peficitinib-treated patients (Phase 2/3 studies). CONCLUSION: Peficitinib was well tolerated in Asian patients with RA over a median of 2 years, with no observed dose or temporal dependency for AEs with prolonged administration.

Reweighting to address nonparticipation and missing data bias in a longitudinal electronic health record study.

PURPOSE: We examined whether weighting techniques could account for longitudinal differences in disease activity by race/ethnicity between research participants and nonparticipants with rheumatoid arthritis (RA). METHODS: We included 377 patients with RA from a public hospital in San Francisco, CA. We estimated the probability of not enrolling in a research study by constructing weights using inverse probability weighting. Disease activity over time by race/ethnicity was analyzed across the entire patient population and among research participants only using multivariable mixed-effects models. RESULTS: There were no differences in RA disease activity scores between research participants and nonparticipants at baseline; however, longitudinal differences in disease activity between research participants and nonparticipants were found by race/ethnicity. Weighting research participants in accordance with sociodemographic and clinical characteristics of the nonparticipant population did not result in any meaningful changes in disease activity by race/ethnicity over time. CONCLUSIONS: In our study of patients with RA, inverse probability weighting using select sociodemographic and clinical variables was not sufficient to account for longitudinal disease activity differences by race/ethnicity between research participants and nonparticipants.

The genetics of rheumatoid arthritis.

RA is a chronic systemic inflammatory disease that primarily affects the small joints of the hands and feet, and results in a mean reduction in life expectancy of 3-10 years. RA is a multigene disorder with a substantial genetic component and a heritability estimate of 60%. Large-scale Genome-Wide Association Studies (GWAS) and meta-analyses have revealed common disease-associated variants in the population that may contribute cumulatively to RA pathogenesis. This review identifies the most significant genetic variants associated with RA susceptibility to date, with particular focus on the contribution of the HLA class II genes across different ethnic groups. Also discussed are the potential applications of pharmacogenomics to RA management by identifying polymorphisms associated with variation in treatment response or toxicity. The use of genetic variants to guide treatment strategy has the potential to not only reduce National Health Service costs, but also drastically improve patient experience and quality of life.

Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial.

BACKGROUND: Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. METHODS: The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5-15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints-erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4-6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov, NCT02573012. FINDINGS: Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35-0·73) with tapered prednisone and -0·08 (-0·27 to 0·12) with continued prednisone (difference 0·61 [0·35-0·88]; p<0·0001), favouring continuing prednisone 5 mg per day for 24 weeks. Treatment was regarded as successful (defined as low disease activity at week 24, plus absence of rheumatoid arthritis flare for 24 weeks and no confirmed adrenal insufficiency) in 99 (77%) patients in the continued-prednisone group versus 85 (65%) patients in the tapered-prednisone group (relative risk 0·83; 95% CI 0·71-0·97). Serious adverse events occurred in seven (5%) patients in the tapered-prednisone group and four (3%) patients in the continued-prednisone group; no patients had symptomatic adrenal insufficiency. INTERPRETATION: In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. FUNDING: F Hoffmann-La Roche.

Cross-culture adaptation and validation of English version of Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS) in patients with rheumatoid arthritis.

AIM: To carry out cross-culture adaptation and validation of the English version of Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS) in patients with rheumatoid arthritis (RA). METHODS: A cross-sectional study was conducted for 2 months in 2 tertiary care hospitals in Karachi, Pakistan. Sample size was calculated based on item-subject ratio. The translation was carried out using standard procedures for translation and cross-culture adaptation. The validation process included estimation of discrimination power, item difficulty index, factorial, convergent, construct and known group validities and reliability. Reliability of the scale was estimated using Kuder-Richardson Formula 20 and a value of σ2  ≥ 0.6 was acceptable. SPSS v23, Remark Classic OMR v6 software and MedCalc Statistical Software v16.4.3, were used to analyze the data. The study was approved by the relevant ethics committee (IRB#NOV:15). RESULTS: The mean score was 7.68 ± 2.52 (95% CI: 7.31-8.05) for 177 patients. The σ2  = 0.601, that is, >0.6, test-retest reliability ρ = .753, P < .05. The average discrimination power = 47.27, average Item Difficulty Index = 0.557. The fit indices were acceptable in a range that established its factorial validity and average factor loading was ≥0.7 which established convergent validity. A significant association (χ2  = 33.074, P < .01) between score interpretation and previous counseling by pharmacists established its construct validity. A significant association (χ2  = 19.113, P < .05) between score interpretation and patient occupation established known group validity. CONCLUSION: The English version of RAKAS was deemed a reliable and validated tool to measure knowledge about disease in Pakistani patients with RA.

Fatigue and associated factors in a multi-ethnic cohort of rheumatoid arthritis patients.

INTRODUCTION: Fatigue is an important yet infrequently evaluated component in patients with rheumatoid arthritis (RA) and may have a major impact on quality of life. OBJECTIVES: To evaluate fatigue, identify factors associated with fatigue and assess the effect of fatigue on health-related quality of life (HRQoL) in a multi-ethnic cohort of RA patients. METHODS: A cross-sectional study was performed in patients who fulfilled European League Against Rheumatism/ American College of Rheumatology 2010 criteria for RA. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire was used to assess fatigue. Potential factors for fatigue were categorized into RA-related (gender, seropositivity [rheumatoid factor and/or anti-citrullinated protein antibody], disease duration, visual analog scale pain score, Disease Activity Score of 28 joints - erythrocyte sedimentation rate [DAS28-ESR], ESR, hemoglobin level, functional disability [Health Assessment Questionnaire - Disability Index, HAQ-DI score], EQ-5D-3L, concomitant prednisolone use and number of conventional synthetic disease-modifying anti-rheumatic drugs [csDMARDs] used) and non-RA-related (age, body mass index, ethnicity and number of co-morbidities). RESULTS: A total of 214 patients (86.9% female) were included; the median age was 62 (25-91) years and 67.3% were seropositive. Seventy-six (33.5%) patients had moderate disease activity, 12 (5.6%) had high disease activity and 152 (71%) patients had mild difficulties to moderate disability HAQ-DI scores. Median of total FACIT-F score was 113.2 (36.3-160.0). Joint factors of younger age, longer disease duration, higher HAQ score (increased functional disability), and lower EQ-5D (poorer HRQoL) were significantly associated with higher levels of fatigue (all P < .02). CONCLUSION: Fatigue was associated with functional disability and has a significant impact on HRQoL in RA. Fatigue assessment should be considered in routine clinical practice for RA patients.

Association of two polymorphisms Asp299Gly and Thr399Ile in Toll-like receptor 4 with rheumatoid arthritis: A meta-analysis.

Our meta-analysis aims to evaluate the association of Asp299Gly and Thr399Ile with rheumatoid arthritis (RA) susceptibility and severity. By manually searching 3 electronic databases (PubMed, Embase and Web of Science), relevant articles were collected. After checking eligibility for every study, this meta-analysis on eligible studies was performed under 5 genetic models: (1) allelic contrast; (2) heterozygous model; (3) homozygous model; (4) dominant model; (5) recessive model. In Spanish populations, a significantly decreased RA risk was identified in allelic comparison (odds ratio [OR] = 0.73, 95% CI 0.55 ~ 0.96) and dominant model (OR = 0.74, 95% CI 0.56 ~ 0.99) of Asp299Gly polymorphism. A trend of reduced risk was also observed under the heterozygous model (OR = 0.77, 95% CI 0.58 ~ 1.03). As for Thr399Ile, it might also have a protective effect on Spanish populations in allelic comparison (OR = 0.71, 95% CI 0.44 ~ 1.15). In contrast, for both Asp299Gly and Thr399Ile, a higher risk of RA was detected in Chinese Han populations. The frequency of both Asp299Gly and Thr399Ile increased in rheumatoid factor (RF)-positive subjects in Chinese patients (Asp299Gly, RF+:RF- = 0.165:0.145; Thr399Ile, RF+:RF- = 0.170:0.161) and decreased in Spanish patients (Asp299Gly, RF+:RF- = 0.060:0.073; Thr399Ile, RF+:RF- = 0.046:0.056), but not to a statistically significant extent. Our meta-analysis suggested that both Asp299Gly and Thr399Ile might have a protective effect on Spanish populations, but the 2 polymorphisms could act as a susceptible factor in Chinese Han populations. To confirm our results, further investigation concerning the functional impacts of Asp299Gly and Thr399Ile are still needed.

Association analysis in a Latin American population revealed ethnic differences in rheumatoid arthritis-associated SNPs in Caucasian and Asian populations.

Large genome-wide association studies (GWAS) have increased our knowledge of the genetic risk factors of rheumatoid arthritis (RA). However, little is known about genetic susceptibility in populations with a large admixture of Amerindian ancestry. The aim of the present study was to test the generalizability of previously reported RA loci in a Latin American (LA) population with admixed ancestry. We selected 128 single nucleotide polymorphisms (SNPs) in linkage equilibrium, with high association to RA in multiple populations of non-Amerindian origin. Genotyping of 118 SNPs was performed in 313 RA patients/487 healthy control subjects by mid-density arrays of polymerase chain reaction (PCR). Some of the identified associations were validated in an additional cohort (250 cases/290 controls). One marker, the SNP rs2451258, located upstream of T Cell Activation RhoGTPase Activating Protein (TAGAP) gene, showed significant association with RA (p = 5 × 10-3), whereas 18 markers exhibited suggestive associations (p < 0.05). Haplotype testing showed association of some groups of adjacent SNPs around the signal transducer and activator of transcription 4 (STAT4) gene (p = 9.82 × 10-3 to 2.04 × 10-3) with RA. Our major finding was little replication of previously reported genetic associations with RA. These results suggest that performing GWAS and admixture mapping in LA populations has the potential to reveal novel loci associated with RA. This in turn might help to gain insight into the 'pathogenomics' of this disease and to explore trans-population differences for RA in general.

Association of adiponectin and adiponectin receptor gene polymorphisms with rheumatoid arthritis in a Chinese population.

PURPOSE: To explore the association of adiponectin (AD) and adiponectin receptor (ADR) gene single-nucleotide polymorphisms (SNPs) with genetic susceptibility to rheumatoid arthritis (RA) in a Chinese population. STUDY DESIGN: Five AD SNPs (rs266729, rs2241766, rs1063537, rs2082940 and rs1063539) and two ADR SNPs (rs7539542 and rs12342) were genotyped in a cohort of 617 patients with RA and 639 healthy controls. Seven SNPs were genotyped using TaqMan genotyping assays on the Fluidigm 192.24 system. The concentration of AD in plasma was examined by ELISA. RESULTS: Patients with RA showed a considerably lower plasma level of AD than healthy controls (p=0.002). No significant differences were observed for the distribution of allele and genotype frequencies of rs266729, rs2241766, rs2082940, rs1063539, rs7539542 and rs12342 SNPs between patients with RA and controls. The genotype effects of recessive and dominant models were also analysed, but no marked evidence for association was found. However, further analysis in female patients with RA showed that the frequency of the AD gene rs1063539 GG genotype was nominally significantly higher in patients who were anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (p=0.040). No significant differences in serum AD level were observed in patients with RA with different genotypes. CONCLUSIONS: rs266729, rs2241766, rs2082940 and rs1063539 in the AD gene and rs7539542 and rs12342 in the ADR gene are possibly not associated with genetic susceptibility to RA, but the A D gene rs1063539 locus was possibly associated with anti-CCP in RA female patients.

First Validation of the Full PROMIS Pain Interference and Pain Behavior Item Banks in Patients With Rheumatoid Arthritis.

OBJECTIVE: Pain interference and pain behavior are highly relevant outcomes in patients with rheumatoid arthritis (RA). The Patient-Reported Outcomes Measurement Information System (PROMIS) is a universally applicable set of item banks measuring patient-reported health, and if applied as computerized adaptive tests (CATs), more efficiently and precisely than current instruments. The objective was to study the psychometric properties of the Dutch-Flemish PROMIS pain interference (PROMIS-PI) and the PROMIS pain behavior (PROMIS-PB) item banks in patients with RA. METHODS: A total of 2,029 patients with RA completed the full PROMIS-PI (version 1.1, 40 items), and 1,554 patients completed the full PROMIS-PB (version 1.1, 39 items). The following psychometric properties were studied: unidimensionality, local dependence, monotonicity and graded response model (GRM) fit, cross-cultural validity (differential item functioning [DIF] for language [Dutch versus Flemish]), other forms of measurement invariance, construct validity, reliability, and floor and ceiling effects. RESULTS: The PROMIS-PI and PROMIS-PB banks were sufficiently unidimensional (Omega-hierarchical [Omega-H] 0.99, 0.95, and explained common variance 0.95, 0.78, respectively), had negligible local dependence (0.3-1.4% of item pairs), good monotonicity (H 0.75, 0.46), and a good GRM model fit (no misfitting items). Furthermore, both item banks showed good cross-cultural validity (no DIF for language), measurement invariance (no DIF for age, sex, administration mode, and disease activity), good construct validity (all hypotheses met), high reliability (>0.90 in the range of patients with RA), and an absence of floor and ceiling effects (0% minimum or maximum score, respectively). CONCLUSION: Both PROMIS-PI and PROMIS-PB banks showed good psychometric properties in patients with RA and can be used as CATs in research and clinical practice.

Sociodemographic factors as determinants of disease, disability and quality of life trajectories in early rheumatoid arthritis: A multi-ethnic inception cohort study.

OBJECTIVE: This study aims to describe the association between sociodemographic factors and trajectories of disease, disability and health-related quality of life (HRQoL) in early rheumatoid arthritis (ERA). METHODS: Data were collected prospectively over 3 years in the Singapore Early Arthritis Cohort study. Trajectories were modeled using multi-trajectory group-based trajectory modeling (GBTM) and determinants of trajectory membership were identified using multinomial logistic regression. RESULTS: Two hundred and thirteen patients were included: 58.2% Chinese, 16.4% Malay, 21.6% Indian, mean (SD) age 51.3 (12.6) years and symptom duration 21.8 (15.3) weeks. In the multi-trajectory analysis, three groups of disease trajectories and corresponding disability and HRQoL trajectories were identified: group 1 (moderate disease rapid response, 49.9%), group 2 (high disease rapid response, 31.1%) and group 3 (high disease slow response, 19.1%). Malay patients had higher relative risk ratio (RRR) of being in trajectory groups 2 and 3 compared to group 1 (RRR = 2.30, 95% CI 1.05-3.98 and RRR = 4.02, 95% CI 1.45-6.43, respectively) while patients with tertiary education had lower relative risk (RRR = 0.56, 95% CI 0.45-0.89 and RRR = 0.33, (95% CI 0.14-0.83, respectively). In the analysis of individual outcomes, ethnicity, education level and body mass index were determinants of the heterogeneous disease activity trajectories. Gender and education level were determinants of the disability trajectories. Only gender was a determinant of the HRQoL trajectories. Further, 96.2% of the patients were treated with conventional synthetic disease-modifying antirheumatic drugs. CONCLUSION: Disparities in sociodemographic factors should be taken into consideration in formulating treatment strategies in ERA.

Associations between WNT1-inducible signaling pathway protein-1 (WISP-1) genetic polymorphisms and clinical aspects of rheumatoid arthritis among Chinese Han subjects.

This study genotyped blood samples from 214 patients with rheumatoid arthritis (RA) and 293 healthy controls for single nucleotide polymorphisms (SNPs) rs2977537, rs2929970, rs2929973, rs2977530, rs1689334 and rs62514004. We want to investigate whether the SNPs in the WNT1-inducible signaling pathway protein 1 (WISP-1) gene may increase the risk of developing RA. We showed that RA disease was more likely with the AA genotype compared with the AG genotype of SNP rs2977537 (adjusted odds ratio [AOR]: 0.54; 95% confidence interval [CI]: 0.34-0.84), and with the TT genotype (AOR: 0.24; 95% CI: 0.13-0.39) or the GG genotype (AOR: 0.05; 95% CI: 0.03-0.10) compared with the GT genotype of rs2929973, and with the AA genotype (AOR: 0.34; 95% CI: 0.22-0.54) or GG genotype (AOR: 0.52; 95% CI: 0.31 to 0.87) vs the AG genotype of rs2977530. Rheumatoid factor positivity was more likely with the AA genotype than with the AG genotype of the rs2977537 polymorphism (AOR: 0.16; 95% CI: 0.16-0.94). High CRP (>8 mg/L) was more likely with the non-AG genotype (AA + GG) than the AG genotype of rs2977537 (AOR: 1.84; 95% CI: 1.05-3.21) and with the AA genotype vs the AG genotype of rs2977530 (AOR: 2.62; 95% CI: 1.35-5.09). Compared with the AG genotype, the AA genotype of rs2929970 was more likely to require prednisolone (AOR: 0.49; 95% CI: 0.27-0.88), while the AG genotype was more likely than the AA genotype of SNP rs2977530 to require TNF-α inhibitors (AOR: 2.07; 95% CI: 1.08 to 3.98). WISP-1 may be a diagnostic marker and therapeutic target for RA therapy.