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ID PMID Title PublicationDate abstract
29953748 Limited Health Literacy and Patient Confusion About Rheumatoid Arthritis Patient Global As 2019 May OBJECTIVE: Patient global assessment visual analog scales (PGA-VAS) are widely used in rheumatoid arthritis (RA) practice and research, and low PGA-VAS scores are required for remission. Vulnerable patients with RA may have difficulty completing the PGA-VAS. There is limited information about both patients' perceptions of PGA-VAS and how patients score VAS model disease states. The objective of this study was to understand the perspectives of vulnerable patients regarding PGA-VAS and model disease states. METHODS: We enrolled patients with RA at Denver Health (n = 300). Subjects completed the PGA-VAS in the Disease Activity Score in 28 joints and the Multidimensional Health Assessment Questionnaire and completed a questionnaire regarding these PGA-VAS. Subjects also scored remission, mild, moderate, and severe model disease states by VAS. We performed analyses by linear and logistic regression and by using summary statistics. Outcomes included whether subjects found the PGA-VAS confusing, whether subjects' responses to the model disease states followed a natural progression (remission
31267533 Role of microRNA-26a in cartilage injury and chondrocyte proliferation and apoptosis in rh 2020 Feb This study is carried out to investigate the role of microRNA-26a (miR-26a) in cartilage injury and chondrocyte proliferation and apoptosis in rats with rheumatoid arthritis (RA) by regulating expression of CTGF. A rat model of RA induced by type II collagen was established. The rats were assigned into normal, RA, RA + mimics negative control (NC), and RA + miR-26a mimics groups, and the cells were classified into blank, mimics NC, and miR-26a mimics groups. The degree of secondary joint swelling and arthritis index, expression of miR-26a, pathological changes, proliferation and apoptosis of chondrocytes, and expression of CTGF, interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, Bax, and Bcl-2 were also determined through a series of experiments. The targeting relationship between miR-26a and CTGF was verified. Initially, downregulated miR-26a was found in cartilage tissues and inflammatory articular chondrocytes of RA rats. In addition, CTGF was determined as a direct target gene of miR-26a, and upregulation of miR-26a inhibited CTGF expression in cartilage tissues of RA rats. Furthermore, upregulation of miR-26a reduced swelling and inflammation of joints, inhibited cartilage damage, apoptosis of chondrocytes, inflammatory injury, promotes proliferation, and inhibited apoptosis of inflammatory articular chondrocytes, which may be correlated with the targeting inhibition of CTGF expression. Collectively, the results demonstrate that upregulating the expression of miR-26a could attenuate cartilage injury, stimulate the proliferation, and inhibit apoptosis of chondrocytes in RA rats.
31300847 Re-conceptualizing functional status through experiences of young adults with inflammatory 2020 Feb The objective of this study is to assess the impact of inflammatory arthritis on young adults' activity participation using quantitative and qualitative methods to advance the field's conceptualization of functional status. Young adults diagnosed with juvenile idiopathic arthritis or rheumatoid arthritis completed (1) the Health Assessment Questionnaire-Disability Index to determine functional status and (2) the day reconstruction method to explore experiential dimensions of function, including functional performance, functional satisfaction, and severity of arthritis symptoms during activities on the previous day. Bivariate analyses were conducted to examine relationships between functional status, experiential variables, and demographic variables. Open-ended questions were provided for participants to report ways that arthritis affected their participation that were not otherwise reflected within survey questions; responses were numerically coded using summative content analysis. Among 37 participants (24.8 ± 3.3 years old), 70% reported moderate-to-severe disability. On average, participants experienced pain, stiffness, or fatigue for more than 50% of their waking hours. Functional status significantly correlated with functional performance (r = - 0.39, p = 0.02) and satisfaction (r = - 0.39, p = 0.02), yet did not correlate with stiffness or fatigue severity or duration of symptoms throughout the day. Participants described strategies that improved their ability to participate in certain activities but reduced their overall quality of activity engagement and caused emotional distress. Young adults with arthritis may experience more significant functional limitations than previously reported. Traditional measures of functional assessment may not capture experiential components of activity that affect participation, such as severity of stiffness or fatigue or the duration of symptoms throughout the day.
30959862 Association between Exposure to Ambient Air Pollution and Rheumatoid Arthritis in Adults. 2019 Apr 6 Environmental factors may play roles in the development of rheumatoid arthritis (RA), and some studies have shown that air pollution was associated with the development of autoimmune disease. This study was designed to investigate the effect of air pollutants on the development of adult RA. A nested case-control cohort study was performed using the National Health Insurance Service-National Sample Cohort during 2002⁻2014 in Korea. Air pollution data were collected from the National Ambient Air Monitoring System (NAMIS), and exposure levels were extrapolated using geographic information systems. The group with RA (n = 444) was compared with a propensity score-matched control group (n = 1776), and one-year average concentrations of air pollution were predicted at each patient's residence. The adjusted binary logistic regression analysis showed a positive association between O₃ exposure and the incidence risk of RA for the third (odds ratios (OR) = 1.45, 95% confidence intervals (CI): 1.08⁻1.96) and fourth (OR = 1.35, 95% CI: 1.00⁻1.83) quartiles in adults over 20 years of age. The third quartile CO exposure was also associated with an increased risk of RA (OR = 1.57, 95% CI: 1.16⁻2.12). The results of this nationwide population-based study showed that a one-year exposure to CO and O₃ in adults was associated with an increased risk of RA.
30320973 Correlation of the Multi-Biomarker Disease Activity Score With Rheumatoid Arthritis Diseas 2019 Nov OBJECTIVE: There are conflicting reports on the validity of the multi-biomarker disease activity (MBDA) score for assessing rheumatoid arthritis (RA) disease activity. Our aim was to perform a systematic review of the MBDA and a meta-analysis of the correlation between the MBDA and other RA disease activity measures. METHODS: A systematic review was performed by searching Medline, Embase, Scopus, Google Scholar, and the Cochrane Library from inception to March 7, 2017. Study details, MBDA performance, and study quality were assessed by independent reviewers. Correlations of the MBDA with composite RA disease activity measures were pooled using random-effects meta-analyses. RESULTS: A total of 22 studies were identified in the systematic review, of which 8 (n = 3,242 assays) reported correlations of the MBDA with RA disease activity measures. Pooling results from these 8 studies in the meta-analysis, the MBDA demonstrated modest correlations with the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP; r = 0.41, 95% confidence interval [95% CI] 0.36-0.46) and the Disease Activity Score using the erythrocyte sedimentation rate (DAS28-ESR; r = 0.48, 95% CI 0.38-0.58), with weaker correlations observed with the Simplified Disease Activity Index (SDAI; r = 0.35, 95% CI 0.26-0.43), Clinical Disease Activity Index (CDAI; r = 0.26, 95% CI 0.19-0.33), and Routine Assessment of Patient Index Data 3 (RAPID3; r = 0.23, 95% CI 0.19-0.27). Correlations between change in MBDA and change in disease activity measures ranged from r = 0.53 for the DAS28-ESR to r = 0.26 for the CDAI. CONCLUSION: The MBDA demonstrates moderate convergent validity with the DAS28-CRP and the DAS28-ESR but weaker correlations with the SDAI, CDAI, and RAPID3. While it appears to complement existing RA disease activity measures, further assessment of the performance characteristics of the MBDA is warranted.
31855971 Immunotherapy for the rheumatoid arthritis-associated coronary artery disease: promise and 2019 Dec 20 OBJECTIVE: To review the latest progress on the pathogenic mechanism and management of rheumatoid arthritis (RA)-associated coronary artery disease (CAD), and propose advice on future management optimization as well as prospects for research and development of new therapeutic regimen. DATA SOURCES: This study was based on data obtained from PubMed up to May 2019 using various search terms and their combinations, including coronary artery disease, myocardial ischemia, cardiovascular diseases, RA, rheumatic diseases, treatment, therapy, strategies, immunotherapy, inflammation, and anti-inflammation. STUDY SELECTION: All retrieved literature was scrutinized, most relevant articles about the pathogenic mechanism and clinical management, especially anti-inflammatory therapy of RA-associated CAD were reviewed. RESULTS: RA is an immune-mediated chronic inflammatory disease which has a great social disease burden. In addition to typical arthritic manifestations, RA also affects extra-articular tissues and organs, within which the involvement of the cardiovascular system, especially incorporating CAD, is the leading cause of death for patients with RA. Recently, numerous basic and clinical studies have been carried out on the mechanism of CAD development and progression under the inflammatory cascade of RA. The effect of traditional RA drugs on CAD risk management has been gradually clarified, and more emerging biologic agents are being explored and studied, which have also achieved satisfactory outcomes. Furthermore, with the success of the CANTOS clinical trial, novel anti-inflammatory therapy for the prevention of cardiovascular disease is believed to have a broad prospect. CONCLUSIONS: RA is an independent risk factor for CAD, which mainly results from the underlying inflammatory cascade; therefore, anti-inflammatory therapy, especially the emerging novel biologic drugs, is important for CAD management in patients with RA and may also be a promising approach among the general population.
30229926 Population Pharmacokinetics and Exposure-Response Relationship of Intravenous and Subcutan 2019 Feb Abatacept population pharmacokinetics (PK) and exposure-response (E-R) models for selective efficacy end points were developed using phase 2 and 3 study data in patients with rheumatoid arthritis treated with abatacept (intravenous [IV] or subcutaneous [SC]), followed by simulations. Two efficacy end points were assessed in the E-R analyses: Disease Activity Score in 28 joints (DAS28) and American College of Rheumatology response criteria for 20/50/70% improvement (ACR20/50/70). The analyses were performed with data from 11 clinical studies for the population PK analysis and from 3 clinical studies for the E-R analyses (DAS28 and ACR20/50/70). The PK of abatacept were time invariant and can be described by a linear 2-compartment model with first-order elimination and with zero-order IV infusion or first-order absorption for SC abatacept. Baseline body weight was the only clinically meaningful covariate; that is, abatacept clearance and volume of central compartment increased with increasing baseline body weight. Steady-state trough concentration (C(minss) ) of abatacept was identified as the best exposure predictor of DAS28 response compared with other exposure measures. In addition, the E-R relationship was the same for IV and SC abatacept. Similar results were confirmed in the ACR20/50/70 E-R analyses. Efficacy responses increased with increasing C(minss) and a near-maximal response was associated with C(minss) ≥10 μg/mL. The model-based analyses confirmed that the weight-tiered ∼10 mg/kg IV and fixed 125 mg SC abatacept dosing regimens are comparable and achieved plateau responses, by delivering C(minss) ≥10 μg/mL in RA patients across all body weights.
30971120 Forefoot Reconstruction Following Metatarsal Head Resection Arthroplasty With a Plantar Ap 2019 Jul BACKGROUND: Rheumatoid arthritis (RA) can cause significant forefoot disorders. If forefoot deformity and pain are severe, surgical treatment can be considered. The aim of this study was to analyze the long-term outcomes of surgical forefoot correction per Tillmann, which involves resection of the metatarsal heads through a transverse plantar approach for the lesser toes and a dorsomedial approach to the great toe. METHODS: This retrospective study used patient-based questionnaires to analyze the revision rate, pain, use of orthoses, walking ability, forefoot function, and patient satisfaction of patients with RA who had undergone a complete forefoot correction of metatarsophalangeal (MTP) I to V. The study only included participants with RA before the era of biological agents and who were at least 20 years postoperatively. A total of 60 patients who had undergone 100 complete forefoot operations according to Tillmann 24.6 ± 3.5 years ago were included in this study. RESULTS: The data collected showed that 35 reoperations were performed on 26 of the patients. Deformity relapses were often documented for the hallux valgus. More than 60% of the patients were able to wear conventional shoes. The distances the participants were able to walk were significantly increased by wearing shoes when compared with walking barefoot (P < .01). CONCLUSION: While forefoot function remained difficult to assess, the majority of patients were able to use conventional shoes. This long-term follow-up study of patient-reported questionnaires completed more than 20 years after the Tillmann procedure showed that more than 80% of the patients remained satisfied with the outcome. LEVEL OF EVIDENCE: Level IV, retrospective cohort study.
30681031 Nonopioid versus opioid agents for chronic neuropathic pain, rheumatoid arthritis pain, ca 2019 Mar 1 Chronic pain continues to be a major health issue throughout the world and a huge economic burden for nations around the world. While the use of opioids does have risks, they are still widely used by clinicians as a treatment option for various chronic pain conditions. This review explores and compares the efficacy and safety of opioid and nonopioid agents for the following commonly encountered chronic pain conditions: neuropathic pain, rheumatoid arthritis joint pain, cancer pain and low back pain. Our findings demonstrate that while there are several nonopioid pharmacologic options that are clinically effective, opioids maintain a role in the treatment of certain chronic pain conditions and should continue to have an important place in the armamentarium of clinicians.
30637604 PTPN22 +788 G>A (R263Q) Polymorphism is Associated with mRNA Expression but it is not a 2019 Jun PTPN22 represents an important non-HLA gene that has been strongly associated with rheumatoid arthritis (RA) pathogenesis. Several studies have reported a specific genetic variant for PTPN22 (+788 G>A; rs33996649) that might be associated with decreased RA risk in Caucasian population; nevertheless, its specific role in western Mexican population has not been yet described. A case-control study with 443 RA patients and 317 control subjects (CS) was conducted. The genotyping was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique and the PTPN22 mRNA expression was determined by SYBR Green-based real-time quantitative-PCR assay. No association between the PTPN22 +788 G>A polymorphism and RA susceptibility in western Mexican population was found when comparing genotype and allelic frequencies between RA patients and CS (G/G vs. G/A: OR 0.55, p = 0.14, 95% CI 0.22-1.32; G vs. A: OR 0.56, p = 0.14, 95% CI 0.23-1.36). The PTPN22 mRNA expression increased 4.6-fold more in RA patients than in CS, and RA patients, carriers of PTPN22 +788 G/A genotype, expressed 15.6-fold more than RA patients carrying the homozygous G/G genotype. Overall, these results showed that the PTPN22 +788 G>A polymorphism is not associated with RA susceptibility in western Mexican population, whereas the presence of G/A genotype is associated with increased PTPN22 mRNA expression in RA patients.
30863410 Inflammation and Lymphatic Function. 2019 The lymphatic vasculature plays a crucial role in regulating the inflammatory response by influencing drainage of extravasated fluid, inflammatory mediators, and leukocytes. Lymphatic vessels undergo pronounced enlargement in inflamed tissue and display increased leakiness, indicating reduced functionality. Interfering with lymphatic expansion by blocking the vascular endothelial growth factor C (VEGF-C)/vascular endothelial growth factor receptor 3 (VEGFR-3) signaling axis exacerbates inflammation in a variety of disease models, including inflammatory bowel disease (IBD), rheumatoid arthritis and skin inflammation. In contrast, stimulation of the lymphatic vasculature, e.g., by transgenic or viral overexpression as well as local injections of VEGF-C, has been shown to reduce inflammation severity in models of rheumatoid arthritis, skin inflammation, and IBD. Strikingly, the induced expansion of the lymphatic vasculature improves lymphatic function as assessed by the drainage of dyes, fluorescent tracers or inflammatory cells and labeled antigens. The drainage performance of lymphatic vessels is influenced by vascular permeability and pumping activity, which are influenced by VEGF-C/VEGFR-3 signaling as well as several inflammatory mediators, including TNF-α, IL-1β, and nitric oxide. Considering the beneficial effects of lymphatic activation in inflammation, administration of pro-lymphangiogenic factors like VEGF-C, preferably in a targeted, inflammation site-specific fashion, represents a promising therapeutic approach in the setting of inflammatory pathologies.
30663460 The economic burden of depression among adults with rheumatoid arthritis in the United Sta 2019 Apr AIMS: Depression is the most frequent comorbidity reported among patients with rheumatoid arthritis (RA). Comorbid depression negatively impacts RA patients' health-related quality-of-life, physical function, mental function, mortality, and experience of pain and symptom severity. The objective of this study was to assess healthcare utilization, expenditures, and work productivity among patients with RA with or without depression. MATERIALS AND METHODS: Data from adult patients who had at least two visits each related to RA and depression over a 1-year period were extracted from the Truven Health MarketScan research databases. Outcomes comprised healthcare resource utilization, work productivity loss, and direct healthcare costs comparing patients with RA with depression (n = 3,478) vs patients with RA without depression (n = 43,222). RESULTS: Patients with RA and depression had a significantly greater relative risk of hospitalization and number of all-cause and RA-related hospitalizations, utilization of emergency services, days spent in the hospital, physician visits, and RA-related surgeries compared with RA patients without depression. Patients with RA and depression had a higher risk of and experienced more events and days of short-term disability compared with patients without depression. The incremental adjusted annual all-cause and RA-related direct costs were $8,488 (95% CI = $6,793-$10,223) and $578 (95% CI = -$98-$1,243), respectively, when comparing patients with RA and depression vs RA only. LIMITATIONS: The current analysis is subject to the known limitations of retrospective studies based on administrative claims data. CONCLUSIONS: This study suggested increased healthcare utilization, work productivity loss, and economic burden among RA patients due to comorbid depression. These findings emphasize the importance of managing depression and including depression as a factor when devising treatment algorithms for patients with RA.
30767875 Neutrophil-derived lactoferrin induces the inflammatory responses of rheumatoid arthritis 2019 Sep OBJECTIVES: Damage-associated molecular patterns (DAMPs) are proposed to drive aberrant stimulation of Toll-like receptors (TLRs) in rheumatoid arthritis (RA) inflamed joints. In the current study we investigated the role of the neutrophil-derived lactoferrin (LTF), as an endogenous ligand for TLR4 in the inflammatory response of RA synovial fibroblasts (RASFs). METHODS: RASFs were stimulated with LTF, and the expressions of inflammatory cytokines in RASFs were measured. To clarify the TLR4 signalling pathway associated with LTF stimulation, a small molecular inhibitor of TLR4 (TAK242) and NF-κB inhibitor were used. The role of nuclear factor of activated T cells 5 (NFAT5) was identified using small interfering RNA. To reveal the interaction between NF-κB and NFAT5, cerulenin, which disrupts their interaction, was used. RESULTS: Stimulation of RASFs with LTF significantly increased the expressions of inflammatory cytokines and chemokines, such as IL-6, CCL20 and IL-8, in RASFs. LTF enhanced the mRNA expressions of these cytokines in RASFs stimulated by TNF-α. TAK242 almost completely inhibited the expressions of inflammatory cytokines and chemokines in RASFs stimulated by LTF. The NF-κB inhibitor partially repressed the expressions of IL-6 and IL-8 mRNAs induced by LTF, but not CCL20 mRNA expression. On the other hand, NFAT5 silencing decreased the expressions of CCL20 and IL-8 mRNAs induced by LTF, but not IL-6 mRNA expression. Cerulenin repressed the expressions of IL-6, CCL20 and IL-8 in RASFs stimulated by LTF. CONCLUSIONS: Neutrophil-derived LTF may play a role as an endogenous ligand for TLR4 expressed on RASFs. NFAT5-NF-κB enhanceosome might regulate the expressions of LTF-TLR4-responsive genes in RASFs.
31050750 Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients Durin 2019 May 1 BACKGROUND: A frequent observation in inflammatory conditions, including rheumatoid arthritis (RA), is low circulating amounts of pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B-6. Recently, a functional marker of vitamin B-6 status, the ratio of 3-hydroxykynurenine (HK): xanthurenic acid (XA) in plasma (HK: XA), was proposed. OBJECTIVE: We investigated vitamin B-6 status in patients with RA before and after established treatment with TNFα inhibitors. METHODS: We performed a longitudinal study of RA patients (n = 106, 36% men, median age 54 y) starting first treatment with a TNFα inhibitor (infliximab, etanercept, adalimumab, golimumab, or certolizumab). Clinical assessment (Disease Activity Score for 28 standard joints, DAS28), joint ultrasonography, and blood draw were performed at baseline and after 3 mo treatment. Plasma concentrations of PLP, HK, and XA were measured by liquid chromatography-tandem mass spectrometry. Associations of changes in vitamin B-6 markers with change in DAS28 were assessed by generalized additive models regression and with European League Against Rheumatism (EULAR) response categories by linear regression. RESULTS: At baseline PLP was inversely correlated with CRP (ρ = -0.27, P = 0.007), whereas HK: XA correlated with DAS28 (ρ = 0.46, P < 0.001), CRP (ρ = 0.36, P < 0.001), and ultrasonography scores (ρ = 0.29-0.35, P ≤ 0.003). After 3 mo treatment, the change (a 33% overall reduction) in DAS28 was related to changes in both PLP (ß = -0.28, P = 0.01) and HK: XA (ß = 0.33, P < 0.001). Good responders (45%) according to EULAR criteria experienced a 31% increase in PLP (P = 0.003) and an 11% decrease in HK: XA (P = 0.1), whereas nonresponders (24%) experienced a 25% increase in HK: XA (P = 0.02). CONCLUSION: Two independent measures of vitamin B-6 status confirm an association with disease activity in RA patients. The association of HK: XA with disease activity may also imply perturbations in kynurenine metabolism in RA. This trial was registered at helseforskning.etikkom.no as 2011/490.
31445793 Prevalence of anterior knee pain after patellar retention total knee arthroplasty: Compari 2019 Nov OBJECTIVE: The aim of this study was to investigate whether there is an increased risk of anterior knee pain (AKP) after total knee arthroplasty (TKA) without patellar resurfacing in patients with rheumatoid arthritis (RA) versus primary osteoarthritis (OA). METHODS: This study was a retrospective review of 388 patients (577 knees) who underwent TKA without patellar resurfacing between 2003 and 2011, with a minimum of 5 years of follow-up. Patients were divided into two groups: Group OA (273 knees of 206 patients; 83 males, 123 females; mean age: 64.4 (47-87) years) and Group RA (304 knees of 182 patients; 92 males, 90 females; mean age: 50.7 (21-72) years). In the clinical evaluation, the knee range of motion (ROM) and several outcome measures such as The Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and International Knee Documentation Committee (IKDC) scores were used preoperatively and at the final follow-up visit. The quality of life was measured using Short Form (SF)-36 MCS and PCS scores. The primary outcome was the frequency and severity of patient-reported AKP. The AKP Scale was used to determine the severity of AKP. RESULTS: The IKDC raised from 21.62 (range, 13-29.9) preoperatively to 85.1 (range, 80-88) for group OA and from 21.8 (range, 13-29.9) to 85.2 (range, 81-88) for group RA (p < 0.001). The mean KSS improved from 28.35 (range, 22-38) preoperatively to 90.04 (range, 88-95) for group OA and from 21.9 (range, 18-35) preoperatively to 89.7 (range, 86-95) for group RA. The mean WOMAC increased from 20.61 (range, 17.4-24.2) preoperatively to 95.7 (range, 90.9-97.7) for group OA (p < 0.001) and from 20.2 (range, 16.7-24.2) preoperatively to 95.8 (range, 90.9-98.5) for group RA (p < 0.001). The mean ROM improved from 80.14° (range, 55°-130°) preoperatively to 113.17° (range, 95°-140°) in group OA (P = 0.003) and from 73.4° (range, 10°-130°) to 112.8° (range 90°-140°) in group RA (P = 0.003) postoperatively. The frequency of AKP was 8% in Group OA and 7% in Group RA (p = 0.27). For patients with AKP, the mean AKP Scale was 92.74 (range, 84-98) in Group OA and 93.39 (range, 82-98) in Group RA (p = 0.3). CONCLUSION: After TKA without resurfacing the patella, patients with RA were determined to have a similar risk for AKP as those with OA. LEVEL OF EVIDENCE: Level III, Therapeutic Study.
31474600 Outcomes and Findings of the International Rheumatoid Arthritis (RA) BIODAM Cohort for Val 2020 Jun 1 OBJECTIVE: The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings. METHODS: Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required to adhere to a treat-to-target strategy. Biosamples (serum, urine) were acquired every 3 months, radiography of hands and feet every 6 months, and ultrasound of hands and feet every 3 months in a subset. Primary endpoint was radiographic progression by the Sharp/van der Heijde score. RESULTS: A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. At baseline, the majority was female (76%), mean age 55.7 years, and mean disease duration 6.5 years. Patients had a mean of 8.4 swollen and 13.6 tender joints, 44-joint count Disease Activity Score (DAS44) 3.8, 77.7% rheumatoid factor-positive or anticitrullinated protein antibody-positive. Percentage of patients in DAS and American College of Rheumatology remission at 2 years was 52.2% and 27.1%, respectively. Percentage of patients with radiographic progression (> 0.5) at 1 and 2 years was 38.2% and 59.9%, respectively. CONCLUSION: The RA BIODAM prospective study succeeded in generating an extensive list of clinical, imaging (2343 radiographs), and biosample (4638 sera) resources that will be made available to expedite the identification and validation of biomarkers for radiographic damage endpoints. (Clinicaltrials.gov: NCT01476956, clinicaltrials.gov/ct2/show/NCT01476956).
30327328 How to treat patients with rheumatoid arthritis when methotrexate has failed? The use of a 2019 Jan OBJECTIVES: To compare consecutive disease modifying antirheumatic drug (DMARD)-treatment regimes in daily practice in patients with rheumatoid arthritis (RA) who failed on initial methotrexate, while using a multiple propensity score (PS) method to control for the spurious effects of confounding by indication. METHODS: Patients with newly diagnosed RA who had failed initial treatment with methotrexate were selected from METEOR, an international, observational registry. Subsequent DMARD-treatment regimens were categorised as: (1) conventional synthetic DMARD(s) (csDMARD(s)) only (143 patients), (2) csDMARD(s)+glucocorticoid (278 patients) and (3) biological DMARD (bDMARD)±csDMARD(s) (89 patients). Multiple PS that reflect the likelihood of treatment with each treatment-regime were estimated per patient using multinomial regression. Linear mixed model analyses were performed to analyse treatment responses per category (Disease Activity Score (DAS)) after a maximum follow-up duration of 6 and 12 months, and results were presented with adjustment for the multiple PS. RESULTS: After 6 months, follow-up PS-adjusted treatment responses yielded a change in DAS per year (95%  CI) of -2.00 (-2.65 to -1.36) if patients received a bDMARD; of -0.96 (-1.33 to -0.59) if patients received csDMARD(s)+glucocorticoids and of -0.73 (-1.21 to -0.25) if patients received csDMARDs only. These changes were -0.91 (-1.23 to -0.60); -0.43 (-0.62 to -0.23) and -0.39 (-0.66 to -0.13), respectively after 1  year of follow-up. CONCLUSIONS: In this analysis of worldwide common practice data with adjustment for multiple PS, patients with RA who had failed initial treatment with methotrexate monotherapy had a better DAS-response after a subsequent switch to a bDMARD-containing treatment regimen than to a regimen with csDMARD(s) only, with or without glucocorticoids.
31167870 Efficacy and safety of cannabidiol followed by an open label add-on of tetrahydrocannabino 2019 Jun 4 INTRODUCTION: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic, systemic, inflammatory diseases, primarily in the musculoskeletal system. Pain and fatigue are key symptoms of RA and AS. Treatment presents a clinical challenge for several reasons, including the progressive nature of the diseases and the involvement of multiple pain mechanisms. Moreover, side effects of pain treatment pose an implicit risk. Currently, no well-controlled studies have investigated how medical cannabis affects pain and cognitive functions in RA and AS. The present study aims to evaluate the efficacy and safety of medical cannabis in the treatment of persistent pain in patients with RA and AS with low disease activity. METHODS AND ANALYSIS: A double-blinded, randomised, placebo-controlled study of cannabidiol (CBD), followed by an open label add-on of tetrahydrocannabinol (THC) with collection of clinical data and biological materials in RA and AS patients treated in routine care. The oral treatment with CBD in the experimental group is compared with placebo in a control group for 12 weeks, followed by an observational 12-week period with an open label add-on of THC in the primary CBD non-responders. Disease characteristics, psychological parameters, demographics, comorbidities, lifestyle factors, blood samples and serious adverse events are collected at baseline, after 12 and 24 weeks of treatment, and at a follow-up visit at 36 weeks. Data will be analysed in accordance with a predefined statistical analysis plan. ETHICS AND DISSEMINATION: The Danish Ethics Committee (S-20170217), the Danish Medicines Agency (S-2018010018) and the Danish Data Protection Agency approved the protocol. The project is registered in the European Clinical Trials Database (EudraCT 2017-004226-15). All participants will give written informed consent to participate prior to any study-related procedures. The results will be presented at international conferences and published in peer-reviewed journals.
30778120 Tumour Necrosis Factor-α Inhibition Improves Stroke Outcome in a Mouse Model of Rheumatoi 2019 Feb 18 Rheumatoid Arthritis (RA) is a chronic inflammatory disorder where incidence and severity of myocardial infarction are increased. Data on the incidence and outcome of stroke are conflicting. Thus, we investigated outcome after Ischemia/Reperfusion (I/R) brain injury in a mouse model of RA and assessed for the role of the tumour necrosis factor-α (TNF-α) inhibitor Infliximab herein. We used a TNF-α reliant mouse model of RA. RA and wildtype (WT) animals were treated with vehicle (RA/WT) or Infliximab (RA Infliximab) for 4 weeks, before undergoing I/R brain injury. RA-animals displayed larger strokes and poorer neurological performance. Immunohistochemistry on brain sections revealed increased numbers of resident and peripheral innate immune cells (microglia and macrophages); increased Blood-Brain-Barrier (BBB)-disruption; decreased levels of the tight junction proteins (TJPs) claudin-5 and occludin; increased expression of matrix-metalloproteinases (MMP)-3 and -9 and enhanced lipid peroxidation. Treatment with Infliximab corrected these alterations. We show that RA associates to worse stroke-outcome via exacerbated BBB degradation by decrease of the TJPs claudin-5 and occludin. We identified MMPs-3 and -9 and increased oxidative stress as potential mediators thereof. Increased numbers of resident and peripheral innate immune cells (microglia and macrophages) may in turn contribute to all these effects. Infliximab-treatment restored the phenotype of RA-mice to baseline. Our data provide evidence clearly linking RA to adverse stroke-outcome in mice and indicate an approved TNF-α inhibitor as a potential strategy to reduce stroke-burden in this setting.
31615910 Opioid Use among Patients with Early Inflammatory Arthritides Compared to the General Popu 2020 Aug 1 OBJECTIVE: To assess to what extent the worldwide opioid epidemic affects Finnish patients with early inflammatory arthritis (IA). METHODS: From the nationwide register maintained by the Social Insurance Institution of Finland, we collected all incident adult patients with newly onset seropositive and seronegative rheumatoid arthritis (RA+ and RA-) and undifferentiated arthritis (UA) between 2010 and 2014. For each case, 3 general population (GP) controls were matched according to age, sex, and place of residence. Drug purchases between 2009 and 2015 were evaluated 1 year before and after the index date (date of IA diagnosis), further dividing this time into 3-month periods. RESULTS: A total of 12,115 patients (66% women) were identified. At least 1 opioid purchase was done by 23-27% of the patients 1 year before and 15-20% one year after the index date. Relative risk (RR) of opioid purchases compared to GP was highest during the last 3-month time period before the index date [RR 2.81 (95% CI 2.55-3.09), 3.06 (2.68-3.49), and 4.04 (3.51-4.65) for RA+, RA-, and UA, respectively] but decreased after the index date [RR 1.38 (1.23-1.58), 1.91 (1.63-2.24), and 2.51 (2.15-2.93)]. Up to 4% of the patients were longterm users both before and after the diagnosis. CONCLUSION: During 2009-15 in Finland, opioid use peaked just before the diagnosis of IA but decreased rapidly after that, suggesting effective disease control, especially in seropositive RA. Further, opioids were used to treat arthritis pain of patients with incident RA and UA less often than previously reported from other countries.