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34630419 Tofacitinib Suppresses Several JAK-STAT Pathways in Rheumatoid Arthritis In Vivo and Basel 2021 OBJECTIVE: Current knowledge on the actions of tofacitinib on cytokine signaling pathways in rheumatoid arthritis (RA) is based on in vitro studies. Our study is the first to examine the effects of tofacitinib treatment on Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathways in vivo in patients with RA. METHODS: Sixteen patients with active RA, despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), received tofacitinib 5 mg twice daily for three months. Levels of constitutive and cytokine-induced phosphorylated STATs in peripheral blood monocytes, T cells and B cells were measured by flow cytometry at baseline and three-month visits. mRNA expression of JAKs, STATs and suppressors of cytokine signaling (SOCS) were measured from peripheral blood mononuclear cells (PBMCs) by quantitative PCR. Association of baseline signaling profile with treatment response was also investigated. RESULTS: Tofacitinib, in csDMARDs background, decreased median disease activity score (DAS28) from 4.4 to 2.6 (p < 0.001). Tofacitinib treatment significantly decreased cytokine-induced phosphorylation of all JAK-STAT pathways studied. However, the magnitude of the inhibitory effect depended on the cytokine and cell type studied, varying from 10% to 73% inhibition following 3-month treatment with tofacitinib. In general, strongest inhibition by tofacitinib was observed with STAT phosphorylations induced by cytokines signaling through the common-γ-chain cytokine receptor in T cells, while lowest inhibition was demonstrated for IL-10 -induced STAT3 phosphorylation in monocytes. Constitutive STAT1, STAT3, STAT4 and STAT5 phosphorylation in monocytes and/or T cells was also downregulated by tofacitinib. Tofacitinib treatment downregulated the expression of several JAK-STAT pathway components in PBMCs, SOCSs showing the strongest downregulation. Baseline STAT phosphorylation levels in T cells and monocytes and SOCS3 expression in PBMCs correlated with treatment response. CONCLUSIONS: Tofacitinib suppresses multiple JAK-STAT pathways in cytokine and cell population specific manner in RA patients in vivo. Besides directly inhibiting JAK activation, tofacitinib downregulates the expression of JAK-STAT pathway components. This may modulate the effects of tofacitinib on JAK-STAT pathway activation in vivo and explain some of the differential findings between the current study and previous in vitro studies. Finally, baseline immunological markers associate with the treatment response to tofacitinib.
34267753 Influence of Seasonal Vitamin D Changes on Clinical Manifestations of Rheumatoid Arthritis 2021 Vitamin D [1,25(OH)(2)D-calcitriol] is basically a steroid hormone with pleiotropic biologic effects, and its impact on the regulation of immune system may influence several clinical conditions. Calcidiol (25OHD), as precursor of calcitriol, derives, for the most part (80%), from cutaneous cholesterol (7-dehydrocholesterol) under the action of UV-B (sunlight). Consequently, serum concentrations fluctuate during the year following the circannual rhythm of sun exposition. We will update about the available evidence regarding the complex influence of seasonal vitamin D changes on two different chronic connective tissue diseases, namely rheumatoid arthritis (RA) and systemic sclerosis (SSc). Notably, RA is an emblematic model of autoimmune disease with prevalent joint inflammatory features, while SSc is mainly an autoimmune progressive pro-fibrotic disease. However, in both conditions, low serum concentrations of 25OHD are involved in the pathogenesis of the diseases, and emerging data report their impact on clinical manifestations.
33307206 Effects of Yoga in Daily Life program in rheumatoid arthritis: A randomized controlled tri 2021 Mar OBJECTIVES: To explore the feasibility and effectiveness of a yoga program in improving health-related quality of life (HQOL), physical and psychological functioning in rheumatoid arthritis (RA) patients. DESIGN: Single-centre parallel-arms randomized controlled trial comparing yoga (n = 30) and education control group (n = 27). SETTING: Tertiary care University hospital. INTERVENTION: A 12-week yoga program, based on the Yoga in Daily Life system, included 2x weekly/90-minute sessions. The control group had 1xweekly/60-minute educational lectures on arthritis-related topics. MAIN OUTCOME MEASURES: Assessments were performed at baseline, 12 (post-intervention) and 24 weeks (follow-up). The primary outcome was change in The Short Form-36 (SF-36) HQOL at 12 weeks. Linear regression analysis was adjusted for baseline scores. RESULTS: No significant between-group differences were found for SF-36 (all p > 0.05). At 12 weeks the adjusted mean difference between groups favoured yoga for Functional Assessment of Chronic Illness Therapy-fatigue (5.08 CI 1.29 to 8.86; p = 0.009) and Hospital Anxiety and Depression Scale (HADS)-depression (-1.37 CI -2.38 to -0.36); p = 0.008) and at 24 weeks for HADS-anxiety (-1.79 CI -3.34 to - 0.23; p = 0.025), while the impact on fatigue was sustained (5.43 CI 1.33 to 9.54, p = 0.01). The program had no impact on RA disease activity. Feasibility outcomes included recruitment rate 16 %, retention 80.7 %, and adherence to yoga 87.5 vs 82.7 % for control. No serious adverse events were recorded. CONCLUSIONS: Yoga in Daily Life program was not associated with change in health-related quality of life of RA patients. Significant improvements in fatigue and mood were observed at postintervention and follow-up. This yoga program was found feasible and safe for patients and may complement standard RA treat-to-target strategy.
34684536 Improvement of Inflammation and Pain after Three Months' Exclusion Diet in Rheumatoid Arth 2021 Oct 9 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease affecting the synovial joints and causing severe disability. Environmental and lifestyle factors, including diet, have been proposed to play a role in the onset and severity of RA. Dietary manipulation may help to manage the symptoms of RA by lowering inflammation and potentially decreasing pain. METHODS: In 40 patients with long-standing RA with stable symptoms and treated with conventional (c-) and biological (b-) disease modifying anti-rheumatic drugs (DMARDs), the effect of a 3-month diet avoiding meat, gluten, and lactose (and all dairy products; privative diet) was evaluated in comparison with a control balanced diet including those foods. Both diets were designed to reduce weight since all patients were overweight or obese. Patients were randomly assigned to one of the diets, and RA was clinically assessed at Time 0 (T0), through the Visual Analogue Scale (VAS), for pain, and the Disease Activity Score of 28 joints (DAS 28) for RA activity. Patients were also administered the Short Form Health survey (SF-36) and the Health Assessment Questionnaire (HAQ). At T0, a blood sample was collected for laboratory tests and adipokines measurements, and anthropometric measurements were compared. These evaluations were repeated at the end of the 3 months' dietary regimens. RESULTS: A significant decrease in VAS and the improvement of the overall state of physical and mental health, assessed through SF-36, was observed in patients assigned to the privative diet. Both dietary regimens resulted in the improvement of quality of life compared to baseline values; however, the change was significant only for the privative diet. With either diet, patients showed significant decreases in body weight and body mass index, with a reduction in waist and hips circumference and lower basal glucose and circulating leptin levels. A privative diet was also able to significantly reduce systolic (p = 0.003) and diastolic (p = 0.025) arterial pressure. The number of circulating leukocytes and neutrophils, and the level of hs-C-Reactive Protein also decreased after 3 months of the meat-, lactose-, and gluten-free diet. CONCLUSIONS: Our results suggest that a privative diet can result in a better control of inflammation in RA patients under stable optimized drug treatment.
32950628 Outcomes of abdominal aortic aneurysm repair among patients with rheumatoid arthritis. 2021 Apr OBJECTIVE: In the present study, we compared the outcomes of elective abdominal aortic aneurysm (AAA) repair in patients with and without rheumatoid arthritis (RA) stratified by the type of surgery. METHODS: A retrospective population-based cohort study was conducted from 2003 to 2016. Linked administrative health data from Ontario, Canada were used to identify all patients aged ≥65 years who had undergone elective open or endovascular AAA repair during the study period. Patients were identified using validated procedure and billing codes and matching using propensity scores. The primary outcome was survival. The secondary outcomes were major adverse cardiovascular events (MACE)-free survival (defined as freedom from death, myocardial infarction, and stroke), reintervention, and secondary rupture. RESULTS: Of 14,816 patients undergoing elective AAA repair, a diagnosis of RA was present for 309 (2.0%). The propensity-matched cohort included 234 pairs of RA and control patients. The matched cohort was followed up for a mean ± standard deviation of 4.93 ± 3.35 years, and the median survival was 6.76 and 7.31 years for the RA and control groups, respectively. Cox regression analysis demonstrated no statistically significant differences in the hazards for death, MACE, reintervention, or secondary rupture. Analysis of the differences in outcomes stratified by repair approach also showed no statistically significant differences in the hazards for death, MACE, reintervention, or secondary rupture. CONCLUSIONS: We found no statistically significant differences in survival, MACE, reintervention, or secondary rupture among patients with RA undergoing elective AAA repair compared with controls. Further studies are required to evaluate the impact of comorbidities and antirheumatic medications on the outcomes of elective AAA repair.
34819386 Validation of a machine learning approach to estimate Clinical Disease Activity Index Scor 2021 Nov OBJECTIVE: Disease activity measures, such as the Clinical Disease Activity Index (CDAI), are important tools for informing treatment decisions and monitoring patient outcomes in rheumatoid arthritis (RA). Yet, documentation of CDAI scores in electronic medical records and other real-world data sources is inconsistent, making it challenging to use these data for research. The purpose of this study was to validate a machine learning model to estimate CDAI scores for patients with RA using clinical notes. METHODS: A machine learning model was developed to estimate CDAI score values using clinical notes from a specific rheumatology visit. Data from the OM1 RA Registry were used to create a training cohort of 56 177 encounters and a separate validation cohort of 18 726 encounters, 11 985 of which passed a model-derived confidence filter; all included encounters had both a clinician-recorded CDAI score and a clinical note. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), positive predictive value (PPV) and negative predictive value (NPV), calculated using a binarised version of the outcome. The Spearman's R and Pearson's R values were also calculated. RESULTS: The model had a PPV of 0.80, NPV of 0.84 and AUC of 0.88 when evaluating performance using the binarised version of the outcome. The model had a Spearman's R value of 0.72 and a Pearson's R value of 0.69 when evaluating performance using the continuous CDAI numeric scores. CONCLUSION: A machine learning model estimates CDAI scores from clinical notes with good performance. Application of the model to real-world data sets may allow estimated CDAI scores to be used for research purposes.
33913032 Fatty Acids and Oxylipins in Osteoarthritis and Rheumatoid Arthritis-a Complex Field with 2021 Apr 28 PURPOSE OF REVIEW: Osteoarthritis (OA) and rheumatoid arthritis (RA) are characterized by abnormal lipid metabolism manifested as altered fatty acid (FA) profiles of synovial fluid and tissues and in the way dietary FA supplements can influence the symptoms of especially RA. In addition to classic eicosanoids, the potential roles of polyunsaturated FA (PUFA)-derived specialized pro-resolving lipid mediators (SPM) have become the focus of intensive research. Here, we summarize the current state of knowledge of the roles of FA and oxylipins in the degradation or protection of synovial joints. RECENT FINDINGS: There exists discordance between the large body of literature from cell culture and animal experiments on the adverse and beneficial effects of individual FA and the lack of effective treatments for joint destruction in OA and RA patients. Saturated 16:0 and 18:0 induce mostly deleterious effects, while long-chain n-3 PUFA, especially 20:5n-3, have positive influence on joint health. The situation can be more complex for n-6 PUFA, such as 18:2n-6, 20:4n-6, and its derivative prostaglandin E(2), with a combination of potentially adverse and beneficial effects. SPM analogs have future potential as analgesics for arthritic pain. Alterations in FA profiles and their potential implications in SPM production may affect joint lubrication, synovial inflammation, pannus formation, as well as cartilage and bone degradation and contribute to the pathogeneses of inflammatory joint diseases. Further research directions include high-quality randomized controlled trials on dietary FA supplements and investigations on the significance of lipid composition of microvesicle membrane and cargo in joint diseases.
33040232 Clinical conditions needed to acquire sustained functional remission in rheumatoid arthrit 2021 May OBJECTIVES: Treatments aimed at maintaining sustained clinical remission in rheumatoid arthritis (RA) patients have been recommended by several groups. Improvement and maintenance of functional status are also important for RA patients. The purpose of this study was to investigate the factors for maintaining long-term functional remission. METHODS: RA patients with usual care without specific protocols were included. Disease activity score using 28-joint count C-reactive protein (DAS28-CRP), simplified disease activity index (SDAI) score, and Health Assessment Questionnaire Disability Index (HAQ-DI) score was calculated every 3 months for 1 year. Patients were divided into the HAQ-DI remission (REM) group and the HAQ-DI non-remission (NO-REM) group; time-averaged values of these parameters were compared between groups. RESULTS: Of the 205 patients, 154 fulfilled the remission criteria. Time-averaged DAS28-CRP and SDAI score were significantly lower in the REM group than in the NO-REM group (1.66 vs 2.59, 3.54 vs 10.68, respectively; p < 0.001). Subsequent receiver-operating characteristic (ROC) analysis for estimation of remission indicated a cut-off value of 1.65 for time-averaged DAS28-CRP and 2.85 for time-averaged SDAI score. CONCLUSIONS: Previous reports showed that fulfillment of clinical remission increases the possibility of functional remission; the probability of which is higher in patients with sustained clinical remission. Sustained clinical remission is required to achieve sustained functional remission; the criteria for clinical remission may be more stringent. Key Points • Sustained deep clinical remission was required to achieve sustained functional remission.
34417705 The role of renin angiotensin system in the pathophysiology of rheumatoid arthritis. 2021 Sep BACKGROUND: In rheumatoid arthritis (RA) and osteoarthritis (OA), chronic inflammatory processes lead to progresive joint destruction. The renin-angiotensin system (RAS) is involved in the pathogenesis of RA and OA. The aim of this mini-review article is to summarize evidence on the role of RAS in RA and OA. METHODS: A non-systematic search in Pubmed included terms as "rheumatoid arthritis", "renin angiotensin system", "osteopenia", "RANKL", "DKK-1", "MMP", "inflammation", "angiogenesis", "local renin-angiotensin system", "angiotensin converting enzyme", "AT2 receptor", "Ang-(1-7)", "VEGF", "angiotensine receptor blocker", "angiotensin converting enzyme inhibitors", "renin inhibitors". RESULTS: Both RAS axes, the classical one, formed by angiotensin converting enzyme (ACE), angiotensin (Ang) II and AT1 receptor (AT1R) and the counter-regulatory one, composed by ACE2, Ang-(1-7) and the Mas receptor, modulate inflammation and tissue damage. Ang II activates pro-inflammatory mediators and oxidative stress. Conversely, Ang-(1-7) exerts anti-inflammatory actions, decreasing cytokine release, leukocyte attraction, density of vessels, tissue damage and fibrosis. Angiogenesis facilitates inflammatory cells invasion, while osteopenia causes joint dysfunction. Up-regulated osteoclastogenisis and down-regulated osteoblastogeneses were associaed with the activation of the classical RAS axis. Three different pathways, RANKL, DKK-1 and MMPs are enhanced by classical RAS activation. The treatment of RA included methotrexate and corticosteroids, which can cause side effects. Studies with angiotensin receptor blockers (ARBs), angiotensin converting enzyme inhibitors (ACEi) and renin inhibitors have been conducted in experimental and clinical RA with promising results. CONCLUSION: The classical RAS activation is an important mechanism in RA pathogenesis and the benefit of ARB and ACEi administration should be further investigated.
33771759 Inflammation-targeted therapies and cancer. 2021 Jul OBJECTIVE: To review and analyze the current knowledge on the risk of malignancy associated with inflammation-targeted therapies in rheumatic diseases. METHODS: We performed a non-systematic literature review on PubMEd MEDLINE by screening randomized controlled trials, meta-analyses, reviews, and observational studies focusing on malignancies and inflammation-targeted therapies including TNF inhibitors, other biologics and JAK inhibitors in rheumatic diseases. RESULTS: Data from literature are reassuring regarding the overall risk of incident and recurrent cancer with TNF inhibitors. The risk of lymphoma is more difficult to analyze and data are controversial; however, in most of the studies, this risk does not seem to be significanlty increased. By contrast, there is probably an increased risk of non-melanoma skin cancer associated with TNF inhibitors, as with other immunosuppressants. There is no signal for an increased risk of malignancies with other biological DMARDs, but additional data are needed. A recent post-marketing surveillance study found out an increased risk of malignancies for tofacitinib compared with TNFi; additional data are, therefore, urgently needed to confirm or not these results. CONCLUSION: Data are presently reassuring regarding the overall risk of cancer, whatever the inflammation-targeted treatment. However, additional data are needed for non-TNF biologics and JAK-inhibitors.
33434531 Down-regulation of A(3)AR signaling by IL-6-induced GRK2 activation contributes to Th17 c 2021 Feb 15 IL-6-triggered Th17 cell expansion is responsible for the pathogenesis of many immune diseases including rheumatoid arthritis (RA). Traditionally, IL-6 induces Th17 cell differentiation through JAK-STAT3 signaling. In the present work, PKA inhibition reduces in vitro induction of Th17 cells, while IL-6 stimulation of T cells facilitates the internalization of A(3)AR and increased cAMP production in a GRK2 dependent manner. Inhibition of GRK2 by paroxetine (PAR) or genetic depletion of GRK2 restored A(3)AR distribution and prevented Th17 cell differentiation. Furthermore, in vivo PAR treatment effectively reduced the splenic Th17 cell proportion in a rat model of collagen-induced arthritis (CIA) which was accompanied by a significant improvement in clinical manifestations. These results indicate that IL-6-induced Th17 cell differentiation not only occurs through JAK-STAT3-RORγt but is also mediated through GRK2-A(3)AR-cAMP-PKA-CREB/ICER-RORγt. This elucidates the significance of GRK2-controlled cAMP signaling in the differentiation of Th17 cells and its potential application in treating Th17-driven immune diseases such as RA.
34770980 Polyphenols Targeting MAPK Mediated Oxidative Stress and Inflammation in Rheumatoid Arthri 2021 Oct 30 Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disorder, predominantly symmetric, which causes joint inflammation, cartilage degeneration and bone erosion, resulting in deformity and the loss of physical function. Although the management of RA has steadily improved, the pathophysiological mechanism is incompletely elucidated, and therapeutic options are still limited. Due to shortcomings in the efficacy or safety profiles of conventional RA therapies, therapeutic alternatives have been considered. Therefore, natural extracts containing polyphenolic compounds can become promising adjuvant agents for RA global management, due to their antioxidant, anti-inflammatory and apoptotic properties. Polyphenols can regulate intracellular signaling pathways in RA and can generate different immune responses through some key factors (i.e., MAPK, interleukins (ILs 1 and 6), tumor necrosis factor (TNF), nuclear factor light k chain promoter of activated receptor (NF-κB), and c-Jun N-terminal kinases (JNK)). The critical function of the Toll like-receptor (TLR)-dependent mitogen-activating protein kinase (MAPK) signaling pathway in mediating the pathogenic characteristics of RA has been briefly discussed. Oxidative stress can trigger a change in transcription factors, which leads to the different expression of some genes involved in the inflammatory process. This review aims to provide a comprehensive perspective on the efficacy of polyphenols in mitigating RA by inhibiting signaling pathways, suggesting future research perspectives in order to validate their use.
34609663 Factors affecting quality of life in patients with rheumatoid arthritis in South Korea: a 2022 Feb INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease that significantly reduces the quality of life (QOL) of affected patients. Many studies have emphasized the deterioration of QOL during the treatment of patients with RA, but factors that affect this phenomenon in Koreans with RA remain unclear. METHODS: In this cross-sectional study, 166 Korean patients with RA were enrolled, and their general characteristics, disease-related characteristics, fatigue, feelings of depression, self-efficacy, social support, and QOL were assessed. RESULTS: The overall mean score for RA-specific QOL was 5.8 out of 10. Fatigue, depression, self-efficacy, and social support were found to be significantly associated with the QOL of patients with RA. Notably, self-efficacy was found to be the most significant predictor of QOL. CONCLUSIONS: Compared to patients with RA in Western countries, Korean patients with RA, even those with better physical function, seem to have a lower QOL. Identification of the relevant physical, psychological, and social factors affecting QOL in Koreans with RA is beneficial for clinical practice. Incorporation of strategies to address these factors, such as cognitive behavioral therapy, should be considered for the holistic management of RA. Key Points • Korean patients with RA report lower levels of QOL. • Factors associated with the QOL of patients with RA were fatigue, depression, self-efficacy, and social support. • Self-efficacy was the strongest factor affecting QOL in this population; thus, it would be beneficial for clinical practitioners to incorporate cognitive-behavioral approaches into patient education to enhance self-management. • Our findings suggest that QOL and psychological factors should also be regularly evaluated for the holistic management of patients with RA.
34077778 Polymorphisms in the TP53-MDM2-MDM4-axis in patients with rheumatoid arthritis. 2021 Aug 15 BACKGROUND: In addition to being a tumour suppressor, TP53 is a suppressor of inflammation, and dysfunction of this gene has been related to autoimmune diseases. Patients with autoimmunity, such as rheumatoid arthritis (RA) have an increased risk of certain cancers, like lymphomas, indicating that some underlying mechanisms may modulate risk of both cancers and autoimmunity. METHODS: We genotyped 5 common genetic variants in TP53 and its main regulators MDM2 and MDM4 in a sample of 942 RA patients and 3,747 healthy controls, and mined previously published GWAS-data, to assess the potential impact of these variants on risk of RA. RESULTS: For the TP53 Arg72Pro polymorphism (rs1042522), MDM4 SNP34091 (rs4245739) and MDM2 SNP285C (rs117039649), we found no association to risk of RA. For MDM2 SNP309 (rs2279744), the minor G-allele was associated with a reduced risk of RA (OR: 0.87; CI: 0.79-0.97). This association was also seen in genotype models (OR: 0.86; CI: 0.74-0.99 and OR: 0.79; CI 0.63-0.99; dominant and recessive model, respectively), but was not validated in a large GWAS data set. For MDM2 del1518 (rs3730485), the minor del-allele was associated with an increased risk of RA in the dominant model (OR: 1.18; CI: 1.02-1.38). Stratifying RA cases and controls into phylogenetic subgroups according to the combined genotypes of all three MDM2 polymorphism, we found individuals with the del158-285-309 genotype del/ins-G/G-T/T to have an increased risk of RA as compared to those with the ins/ins-G/G-G/G genotype (OR: 1.56; CI: 1.18-2.06) indicating opposite effects of the del1518 del-allele and the SNP309 G-allele. CONCLUSION: We find a potential association between the MDM2 del1518 variant and RA, and indications that combinatorial genotypes and haplotypes in the MDM2 locus may be related to RA.
34299970 A Novel Radiographic Measurement Method for the Evaluation of Metatarsophalangeal Joint Di 2021 Jul 15 Dorsal dislocation of metatarsophalangeal (MTP) joints of the lesser toe frequently occurs in patients with rheumatoid arthritis (RA), and may cause painful and uncomfortable plantar callosities and ulceration. The current study examined the reliability and clinical relevance of a novel radiographic parameter (the MTP overlap distance [MOD]) in evaluating the severity of MTP joint dislocation. The subjects of the current study were 147 RA patients (276 feet; 1104 toes). MOD, defined as the overlap distance of the metatarsal head and the proximal end of the phalanx, was measured on plain radiographs. The relationship between the MOD and clinical complaints (forefoot pain and/or callosity formation) was analyzed to create a severity grading system. As a result, toes with callosities had a significantly larger MOD. ROC analysis revealed that the MOD had a high AUC for predicting an asymptomatic foot (-0.70) and callosities (0.89). MOD grades were defined as follows: grade 1, 0 ≤ MOD < 5 mm; grade 2, 5 ≤ MOD < 10 mm; and grade 3, MOD ≥ 10 mm. The intra- and inter-observer reliability of the MOD grade had high reproducibility. Furthermore, the MOD and MOD grade improved significantly after joint-preserving surgeries for lesser toe deformities. Our results suggest that MOD and MOD grade might be useful tools for the evaluation of deformities of the lesser toe and the effect of surgical intervention for MTP joints in patients with RA.
34347058 Socioeconomic Disparities in Functional Status in a National Sample of Patients With Rheum 2021 Aug 2 IMPORTANCE: Little is known about the association of poverty with functional status (FS) in patients with rheumatoid arthritis (RA) who use rheumatology care. OBJECTIVES: To examine the association between socioeconomic status (SES) and FS among patients with RA and to evaluate the association between SES and functional declines over time in patients who received at least some rheumatology care. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry between January 1, 2016, and December 31, 2018. Analyses included all adult patients with a confirmed RA diagnosis (ie, had ≥2 encounters associated with RA International Classification of Diseases codes ≥30 days apart) and at least 1 FS score documented between 2016 and 2018 seen at participating rheumatology practices. Data analysis was conducted from April to December 2020. EXPOSURES: The Area Deprivation Index (ADI), a zip code-based indicator of neighborhood poverty, was used as a proxy for SES. ADI scores were categorized into quintiles. MAIN OUTCOMES AND MEASURES: FS measures included Multidimensional Health Assessment Questionnaire (MDHAQ), Health Assessment Questionnaire Disability index, and Health Assessment Questionnaire-II. Cross-sectionally, mean FS scores were compared across ADI quintiles. Longitudinally, among patients with at least 2 FS scores, multilevel multivariate regression computed the probability of functional decline, defined as a change greater than the minimum clinically important difference, across ADI quintiles. In a subgroup analysis, whether disease activity mediated the association between SES and functional decline was examined. RESULTS: Of the 83 965 patients included in the study, 66 649 (77%) were women, and 60 037 (72%) were non-Hispanic White. Mean (SD) age was 63.4 (13.7) years. MDHAQ was the most reported FS measure (56 928 patients [67.8%]). For all measures, mean (SD) FS score was worse at lower SES levels (eg, for MDHAQ quintile 1: 1.79 [1.87]; quintile 5: 2.43 [2.17]). In longitudinal analyses, the probability of functional decline was 14.1% (95% CI, 12.5%-15.7%) in the highest SES quintile and 18.9% (95% CI, 17.1%-20.7%) in the lowest SES quintile. The association between SES and functional decline was partially mediated (7%; 95% CI, 4%-22%) by disease activity. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with RA, worse FS and faster declines in functioning over time were observed in patients with lower SES. These findings provide a framework for monitoring disparities in RA and for generating evidence to spur action toward achieving health equity.
33360371 Associations between an expanded autoantibody profile and treatment responses to biologic 2021 Feb BACKGROUND: Although biologics represent a major advance in rheumatoid arthritis (RA), many patients fail to achieve adequate responses to these agents. We examined whether combined positivity to three well-characterized autoantibodies predicts treatment response among RA patients initiating biologics. METHODS: The study included biologic-naïve patients initiating anti-TNF treatment, biologic-exposed patients switching to rituximab or tocilizumab, and patients (biologic naïve or exposed) initiating abatacept. Rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody, and IgG antibodies to malondialdehyde-acetaldehyde (MAA) were measured using banked enrollment serum. The relationship between the number of autoantibodies positive (0-3) and treatment response (absolute improvement in 28-joint Disease Activity Score [DAS28-CRP] or improvement > 1.2) at 6 months was examined using multivariable linear and logistic regression. RESULTS: Of 1,229 patients initiating biologics, 79% were women; 89% were Caucasian. The number of baseline RA-related autoantibodies positive was associated with improved treatment response in a dose-dependent fashion. Compared to patients seronegative for all autoantibodies, adjusting for covariates, those positive for all three were more than twice (OR 2.35; 95% CI 1.57-3.51) as likely to achieve DAS28 improvement > 1.2 units. Associations of autoantibody positivity with biologic treatment response were strongest for anti-CCP antibody, persisted in analyses limited to biologic naïve patients, and did not appear to differ markedly among different agents examined. CONCLUSION: An expanded autoantibody profile appears to significantly predict RA treatment response to biologic treatment in a dose-dependent fashion. Incorporating these serologic profiles with additional biomarkers or other informative patient characteristics could provide an opportunity to personalize RA management.
34559374 Tofacitinib for the treatment of rheumatoid arthritis: a real-world study in China. 2022 Apr Tofacitinib has only been available in China for 2 years to treat rheumatoid arthritis (RA). Our purpose was to compare real-world effectiveness of tofacitinib with that of disease-modifying anti-rheumatic drugs (DMARDs) in Chinese patients with RA. The records of patients with RA treated at Guangdong Provincial People's Hospital between July 2017 and September 2019 were retrospectively reviewed. Patients were divided into those treated with tofacitinib, biological DMARDs (bDMARDs), and conventional synthetic DMARDs (csDMARDs). Clinical disease activity index (CDAI), simplified disease activity index (SDAI), health assessment questionnaire-disability index (HAQ-DI), visual analog scale (VAS) pain score, patient global assessment of disease activity (PtGA), physician global assessment of disease activity (PhGA), and swollen joint and tender joint count were compared among the groups up to 12 months of treatment. A total of 150 patients were included: 63 were treated with tofacitinib, 48 with bDMARDs, and 39 with csDMARDs. Tofacitinib was first-line treatment in 26.98% of patients, second-line treatment in 49.21%, and third-line treatment in 26.98%. Patients in the tofacitinib group had significantly higher disease duration (6.11 ± 6.97 years) than those in the other groups. All disease indices in the three groups decreased with time, indicating improvement of symptoms, with no differences among the groups at 12 months. Tofacitinib appeared to improve symptoms more rapidly than other treatments; however, differences in disease indices were not significant. This real-world study suggests that tofacitinib is rapidly effective and that the effects are sustained after 12 months in Chinese patients with RA.
34301525 Adherence to treatment with tofacitinib in patients with rheumatoid arthritis in daily cli 2022 Mar OBJECTIVES: To evaluate the adherence to treatment with Tofacitinib in patients with Rheumatoid Arthritis (RA) using two versions of the self-questionnaire Compliance Questionnaire Rheumatology, CQR19 and CQR5, to determine the variables associated with adherence to Tofacitinib and to compare the performance of both questionnaires. MATERIAL AND METHODS: A cross-sectional study was carried out. We included patients ≥18 years old, with RA (ACR/EULAR criteria 2010) under treatment with Tofacitinib. Sociodemographic data, clinical characteristics, treatment and data on patient evaluation. All the patients completed self-questionnaires CQR19 and CQR5. STATISTICAL ANALYSIS: Descriptive statistics. t-Test or Mann Whitney to compare the continuous variables, Chi(2) test or Fisher's exact test for the categorical ones. Kappa concordance index. Multiple logistic regression. RESULTS: We included 52 patients, 82.7% women, with a median (m) age of 57.7 years, disease duration m 16 years, 63.5% had comorbidities. Of the patients, 86.5% were treated with Tofacitinib (5 mg BID) and 48% received Tofacitinib as monotherapy. The median time of Tofacitinib treatment was 13 months, 42.3% suspended treatment, and only one patient permanently stopped treatment due to lack of provision. Median CQR19 was 89.5% and 84.6% had an adherence ≥ 80%. The variables significantly associated with adherence ≥ 80% were the presence of comorbidities (p = .014) and older age (p = .033). Considering the CQR5, a similar percentage of patients (82.7%) were adherents to treatment, however, the concordance with CQR19 was low. In the multivariate analysis, older age was the only variable independently associated with good adherence to treatment. CONCLUSIONS: Treatment adherence to Tofacitinib was very good for both presentations. Older age was associated with higher adherence. The agreement between the questionnaires CQR19 and CQR5 was low.
32880228 Significance of anti-Ro/SSA antibodies in the response and retention of abatacept in patie 2021 Jan Objective: To determine whether the positivity of baseline anti-Ro/Sjögren's syndrome antigen A (SSA) antibodies influences the response to abatacept, we compared therapeutic responses between anti-Ro/SSA antibody-negative and -positive patients with rheumatoid arthritis (RA) using a multicentre RA ultrasonography prospective cohort. Method: We reviewed Japanese patients with RA who started abatacept as the first biological disease-modifying anti-rheumatic drug between June 2013 and April 2018. We assessed 28-joint Disease Activity Score-erythrocyte sedimentation rate (DAS28-ESR) change between baseline and 6 or 12 months after treatment in RA patients treated with abatacept, and European League Against Rheumatism (EULAR) response at 6 and 12 months. The Global OMERACT-EULAR Synovitis Score (GLOESS) was calculated at baseline and at 6 and 12 months. Results: Overall, 51 patients were enrolled and divided into anti-Ro/SSA antibody-negative and -positive groups of 35 and 16, respectively. Median age at baseline was significantly higher in the anti-Ro/SSA antibody-negative group (p = 0.04). The retention rate and percentage of EULAR good responders at 12 months were significantly higher in the anti-Ro/SSA antibody-negative group (both p = 0.02). Anti-Ro/SSA antibody-negative patients exhibited larger decreases in both DAS28-ESR and DAS28-C-reactive protein at 12 months than anti-Ro/SSA antibody-positive patients (p = 0.02 and 0.04, respectively). GLOESS decreased significantly at 6 months in anti-Ro/SSA antibody-negative patients (p = 0.03). Multivariate analyses showed that anti-Ro/SSA antibody positivity was an independent factor associated with change in the DAS28-ESR at 6 months (p < 0.05). Conclusion: Anti-Ro/SSA antibody positivity predicts a poor response to abatacept and low retention rate.