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ID PMID Title PublicationDate abstract
27142240 Impact of methotrexate dose on efficacy of adalimumab in Japanese patients with rheumatoid 2017 Jan OBJECTIVE: Upper limit of methotrexate (MTX) for patients with rheumatoid arthritis (RA) was recently increased from 8 to 16 mg/week in Japan. We therefore examined the effect of concomitant MTX dose on the efficacy of adalimumab (ADA) in clinical practice. METHOD: Sixty-one consecutive RA patients treated with ADA were followed for minimum 52 weeks and retrospectively compared by MTX dose; patients receiving concomitant MTX of 10 mg/week or more (MTX ≥10 mg group) and <10 mg/week (MTX <10 mg group). Disease activity and remission were evaluated by the disease activity score 28 (DAS28) criteria. RESULTS: The MTX ≥10 mg group consistently showed better improvement in DAS28 and resulted in more patients (52.8%) with DAS28-remission compared with the MTX <10 mg group (26.1%). Multivariate analysis showed that MTX ≥10 mg had a significant effect on DAS28 remission with odds ratio of 5.12. ADA retention rate was 72.2% in MTX ≥10 mg group compared with 52.0% in MTX <10 mg group. Discontinuation of ADA due to adverse events were comparable in the MTX ≥10 mg and MTX <10 mg groups (11.1% vs. 12.0%). CONCLUSIONS: These findings support the critical role of concomitant MTX in the efficacy of ADA, and recommend use of MTX ≥10 mg in Japanese RA patients.
24265411 Personalised treatment using serum drug levels of adalimumab in patients with rheumatoid a 2015 Feb OBJECTIVE: To evaluate the cost-effectiveness of personalised treatment for rheumatoid arthritis (RA) using clinical response and serum adalimumab levels. METHODS: A personalised treatment algorithm defined, based on clinical (European League Against Rheumatism) response and drug levels at 6 months, whether adalimumab treatment should be continued in a specific dose or discontinued and/or switched to a next biological. Outcomes were simulated using a patient level Markov model, with 3 months cycles, based on a cohort of 272 adalimumab-treated patients with RA for 3 years and data of patients from the Utrecht Rheumatoid Arthritis Cohort. Costs, clinical effectiveness and quality adjusted life years (QALYs) were compared with outcomes as observed in usual care and incremental cost-effectiveness ratios were calculated. Analyses were performed probabilistically. RESULTS: Clinical effectiveness was higher for the cohort simulated to receive personalised care compared with usual care; the average difference in QALYs was 3.84 (95 percentile range -8.39 to 16.20). Costs were saved on drugs: €2 314 354. Testing costs amounted to €10 872. Mean total savings were €2 561 648 (95 percentile range -3 252 529 to -1 898 087), resulting in an incremental cost-effectiveness ratio of €666 500 or €646 266 saved per QALY gained from a societal or healthcare perspective, respectively. In 72% of simulations personalised care saved costs and resulted in more QALYs, in 28% it was cost saving with lower QALYs. Scenario analyses showed cost saving along with QALYs gain or limited loss. CONCLUSIONS: Tailoring biological treatment to individual patients with RA starting adalimumab using drug levels and short-term outcome is cost-effective. Results underscore the potential merit of personalised biological treatment in RA.
27900853 An Injectable, Click-Cross-Linked Small Intestinal Submucosa Drug Depot for the Treatment 2016 Dec Here, a click-cross-linked small intestine submucosa (SIS) drug depot is described for the treatment of rheumatoid arthritis (RA). To the best of the knowledge, there have been no studies related to the intra-articular injection of methotrexate (Met)-loaded click-cross-linkable SIS (Met-loaded Cx-SIS) for RA treatment. As the key objective of this work, injectable formulations of tetrazine-modified SIS (TE-SIS) and transcyclooctene-modified SIS (TC-SIS) are employed as drug depots. Within a few seconds, the simple mixing of equal amounts of TE-SIS and TC-SIS suspensions forms a gelatinous click-cross-linked SIS (Cx-SIS) drug depot in vitro and in vivo. The formed Cx-SIS depot is maintained in the articular joint over an extended period, while SIS alone rapidly disappears. Injectable formulations of Met-loaded Cx-SIS and Met-loaded SIS are prepared and then injected into articular joints to form drug depots. Compared to animals treated with Met-loaded SIS, RA animals treated with Met-loaded Cx-SIS show effective RA repair, as well as extensive regeneration of chondrocytes and glycosaminoglycan deposits. Collectively, these results indicate that the Met-loaded Cx-SIS depot is successfully formed after intra-articular injection of click-cross-linkable SIS, and that this formulation induces long-lasting Met release and allows Met to act effectively in the articular joint, resulting in RA repair.
26979104 Association between rheumatoid arthritis disease activity, progression of functional limit 2016 Dec OBJECTIVES: To examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes. METHODS: Health Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA inception cohorts in routine care; Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network from 1986 to 2012. The incidence of major and intermediate orthopaedic surgical episodes over 25 years was collected from national data sets. Disease activity was categorised by mean disease activity score (DAS28) annually between years 1 and 5; remission (RDAS≤2.6), low (LDAS>2.6-3.2), low-moderate (LMDAS≥3.2-4.19), high-moderate (HMDAS 4.2-5.1) and high (HDAS>5.1). RESULTS: Data from 2045 patients were analysed. Patients in RDAS showed no HAQ progression over 5 years, whereas there was a significant relationship between rising DAS28 category and HAQ at 1 year, and the rate of HAQ progression between years 1 and 5. During 27 986 person-years follow-up, 392 intermediate and 591 major surgeries were observed. Compared with the RDAS category, there was a significantly increased cumulative incidence of intermediate surgery in HDAS (OR 2.59 CI 1.49 to 4.52) and HMDAS (OR 1.8 CI 1.05 to 3.11) categories, and for major surgery in HDAS (OR 2.48 CI 1.5 to 4.11), HMDAS (OR 2.16 CI 1.32 to 3.52) and LMDAS (OR 2.07 CI 1.28 to 3.33) categories. There was no significant difference in HAQ progression or orthopaedic episodes between RDAS and LDAS categories. CONCLUSIONS: There is an association between disease activity and both poor function and long-term orthopaedic episodes. This illustrates the far from benign consequences of persistent moderate disease activity, and supports European League Against Rheumatism treat to target recommendations to secure low disease activity or remission in all patients.
26693619 Deforming Arthropathy in Thai Patients With Systemic Lupus Erythematosus. 2016 Jan OBJECTIVE: The aim of this study was to determine the prevalence, spectrum, and clinical, radiological, and serologic findings as well as hand functions among Thai systemic lupus erythematosus (SLE) patients with deforming arthropathy. METHODS: All SLE patients attending the rheumatology clinic between January and December 2012 were interviewed, with their complete history and a physical examination being taken. Those with hand deformities were invited to join the study. RESULTS: Forty (8.7%) of 458 SLE patients had deforming arthropathy, with 13 (2.8%) of them having erosive arthritis (EA group) and 27 nonerosive arthropathy (NEA group) (8 [1.8%] with Jaccoud arthropathy [JA subgroup] and 19 [4.1%] with mild deforming arthropathy [MDA subgroup]). Three of 13 EA patients (0.7% of all SLE patients) had high titer of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies that might represent true overlapping between rheumatoid arthritis and SLE. There were no statistically significant differences in autoantibodies, RF, or anti-CCP between the EA and NEA groups or the JA and MDA subgroups, except for discoid rash that was seen more commonly in the MDA subgroup. Rheumatoid factor and anti-CCP were not present in the JA subgroup. Hand joint destruction and deformities were seen more commonly in the EA group and JA subgroup. The hand grip and palmar pinch strength decreased moderately, with hand functions quite well preserved in all groups. CONCLUSIONS: Deforming arthropathy was not uncommon in Thai SLE patients, but true overlapping between rheumatoid arthritis and SLE was rare. Despite significant hand joint deformities and moderately decreased hand grip and palmar pinch strength, preservation of hand functions was generally apparent.
25707686 Association of joint erosion with SLC22A4 gene polymorphisms inconsistently associated wit 2015 Two single-nucleotide polymorphisms (SNPs) in SLC22A4 encoding an organic cation/zwitterion transporter protein, rs2073838 (commonly called slc2F1) and rs3792876 (slc2F2), had been associated with susceptibility to rheumatoid arthritis (RA) in two Japanese and one recent Chinese studies but not in other two Japanese and six Caucasian studies. In this study, the two SNPs were genotyped for 2313 Korean participants and their associations with RA susceptibility and severity were examined. SNP association with RA susceptibility was tested among 1304 RA patients and 1009 healthy controls, and association with joint erosion among 1063 erosive and 241 non-erosive RA patients. Meta-analysis for RA susceptibility association was additionally performed using 10 previous studies and the current one. The two SNPs were almost perfectly correlated with each other (r(2 )= 0.98), and therefore only slc2F1 was tested for association. RA susceptibility association was not found in Koreans (p = 0.93), but still significant in meta-analysis of six Asian studies including this Korean study (p = 0.00036, odds ratio = 1.1) or all 11 studies additionally including five Caucasian studies (p = 0.00021, odds ratio = 1.1). In contrast, an association was found for RA severity in Koreans. The minor allele A was marginally associated with 1.5-fold increased risk of joint erosion among RA patients afflicted for ≤11 years (p = 0.025) or ≤7 years (p = 0.029), though not among patients with longer-standing RA. Accordingly, SLC22A4 was associated with joint erosion in not-very-longstanding RA, although RA susceptibility association was weak and its clinical significance was uncertain.
26429369 Effect of Long-Term TNF-α Inhibition with Infliximab on Left Ventricular Torsion in Patie 2015 Sep INTRODUCTION: We evaluated the impact of tumor necrosis factor alpha (TNF-α) inhibition on left ventricular torsion (LVtor) in patients with rheumatoid arthritis (RA) using speckle-tracking echocardiography (STE). METHODS: Thirty-eight RA patients without cardiovascular disease and 30 healthy subjects were enrolled in the study. Twenty patients received infliximab, a monoclonal antibody against TNF-α, and 18 patients received increasing doses of prednisolone for 180 days. Global systolic longitudinal strain (G-LS), global systolic radial strain (G-RS) and global systolic circumferential strain (G-CS) were determined by STE. LV basal and apical rotations from the base and apex were obtained and used for calculation of LVtor. Pre-treatment LVtor levels were compared with LVtor levels after therapy in both treatment groups. RESULTS: RA patients had lower G-LS (-16.5 ± 2.9; p<0.01), G-RS (37.6 ± 1.5; p<0.01) and higher GCS (-23.6 ± 3.5; p=0.04) compared with control subjects (-20.0 ± 2.8, 40.7 ± 4.8, -22.4 ± 2.5, respectively; p<0.01). LVtor levels were significantly higher in RA patients compared to controls (16.4 ± 2.7 vs. 15.1 ± 2.5; p=0.04), which might be attributed to higher values of apical rotation (9.7 ± 2.4 vs. 8.8 ± 2.3; p=0.01). Patients treated with infliximab experienced a significant decrease in LVtor (p=0.04), and a significant increase in G-LS (p<0.01) and G-RS (p<0.01). No significant changes were observed among patients treated with prednisolone. Percentage changes in LVtor were correlated with percent changes in C-reactive protein CRP (r=0.58; p<0.01), disease activity score (r=0.78; p<0.01), and G-LS (r=-0.40; p=0.04) in patients treated with infliximab. CONCLUSIONS: RA is characterized by increased LVtor. Long term TNF-α inhibition improves LV longitudinal and radial systolic deformation and decreases LVtor.
24618272 Zymographic analysis using gelatin-coated film of the effect of etanercept on the extracel 2016 Apr AIM: Rheumatoid arthritis (RA) is a chronic inflammatory disease. Most RA patients develop cartilage and bone destruction, and various proteinases are involved in the destruction of extracellular matrix of cartilage and bone. The aim of this study is to evaluate the utility of our newly developed method to measure total gelatinolytic activity. We adopted this method for measurement in synovial fluid from RA patients treated by the anti-rheumatic drug etanercept (ETN), a recombinant human soluble tumor necrosis factor receptor fusion protein, and compared the findings with clinical and laboratory data. METHODS: Enzymatic activity of synovial fluid was analyzed by zymography using gelatin-coated film, and compared with the index of Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP), CRP and matrix metalloproteinase (MMP)-3 level before and after ETN therapy. RESULTS: Synovial fluids of 19 patients were collected before and after administration of ETN therapy. In nine of 19 patients, who showed a decrease in gelatin-degrading activity in synovial fluid, the index of DAS28-CRP (4.85-2.85, ΔDAS = -2.00) and CRP (3.30-0.94 mg/dL, ΔCRP = -2.36) was alleviated after ETN therapy, while cases with no change or an increase in gelatin-degrading activity showed a modest improvement in clinical data: DAS28-CRP (4.23-3.38, ΔDAS = -0.85) and CRP (1.70-0.74 mg/dL, ΔCRP = -0.96). CONCLUSION: Our newly developed method for measurement of gelatin-degrading activity in synovial fluid from RA patients is highly practicable and useful for predicting the effect of ETN therapy.
27354688 Ultrasound-detected tenosynovitis independently associates with patient-reported flare in 2016 Oct OBJECTIVES: This study aimed to estimate the prevalence of US-detected tenosynovitis in RA patients in clinical remission and to explore its clinical correlates. METHODS: A total of 427 RA patients in clinical remission were consecutively enrolled from 25 Italian rheumatology centres. Tenosynovitis and synovitis were scored by US grey scale (GS) and power Doppler (PD) semi-quantitative scoring systems at wrist and hand joints. Complete clinical assessment was performed by rheumatologists blinded to the US results. A flare questionnaire was used to assess unstable remission (primary outcome), HAQ for functional disability and radiographic erosions for damage (secondary outcomes). Cross-sectional relationships between the presence of each US finding and outcome variables are presented as odds ratios (ORs) and 95% CIs, both crude and adjusted for pre-specified confounders. RESULTS: The prevalence of tenosynovitis in clinical remission was 52.5% (95% CI 0.48, 0.57) for GS and 22.7% (95% CI 0.19, 0.27) for PD, while the prevalence of synovitis was 71.6% (95% CI 0.67, 0.76) for GS and 42% (95% CI 0.37, 0.47) for PD. Among clinical correlates, PD tenosynovitis associated with lower remission duration and morning stiffness while PD synovitis did not. Only PD tenosynovitis showed a significant association with the flare questionnaire [OR 1.95 (95% CI 1.17, 3.26)]. No cross-sectional associations were found with the HAQ. The presence of radiographic erosions associated with GS and PD synovitis but not with tenosynovitis. CONCLUSIONS: US-detected tenosynovitis is a frequent finding in RA patients in clinical remission and associates with unstable remission.
28121529 The Disease Burden of the Most Common Autoimmune Diseases. 2016 Jul By some measures, the financial and health toll from inflammatory bowel disease, rheumatoid arthritis, and psoriasis is comparable to stroke and lower back pain. Collectively, they affect about 10 million patients in the United States. They are chronic conditions characterized by immune-mediated inflammation of unknown etiology and for which there is no cure.
28460767 Predictors of endothelial dysfunction and atherosclerosis in rheumatoid arthritis in India 2017 Mar OBJECTIVE: Cardiovascular (CV) disease is leading cause of mortality in rheumatoid arthritis (RA). Dysfunction of the vascular endothelium is a hallmark of most conditions that are associated with atherosclerosis and is therefore an early feature in atherogenesis. Biomarkers for rapid evolution of CV complications would be highly desirable for risk stratification. Finally, predictive biomarkers for cardiovascular risk would allow tailoring therapy to the individual. We assessed endothelial function and atherosclerosis utilizing carotid intima-media thickness (CIMT) in RA in context of clinical and laboratory markers in Indian RA population. METHODS: We performed a prospective study of 35 consecutive RA patients and 25 age- and sex matched healthy controls. Patients with traditional CV risk factors were excluded. Flow mediated dilatation (FMD) as measures of endothelial function and CIMT as measures of atherosclerosis were assessed. Disease-specific measures, inflammatory measures, serum cytokines, serum nitrite, lipids and endothelial progenitor cells (EPCs) were estimated. RESULTS: FMD was significantly lower in RA (6.53%±1.81%) compared to controls (10.77%±0.53%; p<0.001). CIMT (mm) was significantly increased in RA (0.62±0.17) vs. controls (0.043±0.07; p=0.003). In RA patients, FMD% inversely correlated with CIMT, CRP, DAS-28, TNF-α, serum nitrite and positively correlated with EPC. CIMT correlated with age, DAS-28, IL-6, HDL, LDL, and inversely correlated with EPC. CONCLUSIONS: In the present study, FMD and CIMT were impaired in RA, indicating endothelial dysfunction and accelerated atherosclerosis respectively. CRP, TNF-α, serum nitrite, DAS-28 and depleted EPC population predicted endothelial dysfunction. Age, IL-6, HDL, LDL and depleted EPC population predicted accelerated atherosclerosis.
27911913 Effect of Osteoprotegerin and Dickkopf-Related Protein 1 on Radiological Progression in Ti 2016 OBJECTIVE: To analyze the association between circulating osteoprotegerin (OPG) and Dickkopf-related protein 1 (DKK-1) and radiological progression in patients with tightly controlled rheumatoid arthritis (RA). METHODS: Serum levels of OPG and DKK-1 were measured in 97 RA patients who were treated according to a treat-to-target strategy (T2T) aimed at remission (DAS28<2.6). Radiologic joint damage progression was assessed by changes in the total Sharp-van der Heijde score (SHS) on serial radiographs of the hands and feet. The independent association between these biomarker levels and the structural damage endpoint was examined using regression analysis. RESULTS: The mean age of the 97 RA patients (68 women) at the time of the study was 54 ± 14 years, and the median disease duration was 1.6 ± 1.5 years. Most patients were seropositive for either RF or ACPA, and the large majority (76%) were in remission or had low disease activity. After a median follow-up time of 3.3 ± 1.5 years (range, 1-7.5 yrs.), the mean total SHS annual progression was 0.88 ± 2.20 units. Fifty-two percent of the patients had no progression (defined as a total SHS of zero). The mean serum OPG level did not change significantly over the study period (from 3.9 ± 1.8 to 4.07 ± 2.23 pmol/L), whereas the mean serum DKK-1 level decreased, although not significantly (from 29.9 ± 10.9 to 23.6 ± 18.8 pmol/L). In the multivariate analysis, the predictive factors increasing the likelihood of total SHS progression were age (OR per year = 1.10; p = 0.003) and a high mean C-reactive protein level over the study period (OR = 1.29; p = 0.005). Circulating OPG showed a protective effect reducing the likelihood of joint space narrowing by 60% (95% CI: 0.38-0.94) and the total SHS progression by 48% (95% CI: 0.28-0.83). The DKK-1 levels were not associated with radiological progression. CONCLUSION: In patients with tightly controlled RA, serum OPG was inversely associated with progression of joint destruction. This biomarker may be useful in combination with other risk factors to improve prediction in patients in clinical remission or low disease activity state.
27597652 Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator o 2017 Mar OBJECTIVES: Tristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway mediates the inactivation of TTP via phosphorylation of two serine residues. We wished to test the hypothesis that these phosphorylations contribute to the development of inflammatory arthritis, and that, conversely, joint inflammation may be inhibited by promoting the dephosphorylation and activation of TTP. METHODS: The expression of TTP and its relationship with MAPK p38 activity were examined in non-inflamed and rheumatoid arthritis (RA) synovial tissue. Experimental arthritis was induced in a genetically modified mouse strain, in which endogenous TTP cannot be phosphorylated and inactivated. In vitro and in vivo experiments were performed to test anti-inflammatory effects of compounds that activate the protein phosphatase 2A (PP2A) and promote dephosphorylation of TTP. RESULTS: TTP expression was significantly higher in RA than non-inflamed synovium, detected in macrophages, vascular endothelial cells and some fibroblasts and co-localised with MAPK p38 activation. Substitution of TTP phosphorylation sites conferred dramatic protection against inflammatory arthritis in mice. Two distinct PP2A agonists also reduced inflammation and prevented bone erosion. In vitro anti-inflammatory effects of PP2A agonism were mediated by TTP activation. CONCLUSIONS: The phosphorylation state of TTP is a critical determinant of inflammatory responses, and a tractable target for novel anti-inflammatory treatments.
26177216 Evaluation of a specific diagnostic marker for rheumatoid arthritis based on cyclic citrul 2015 Nov 10 A specific peptide marker for diagnosing rheumatoid arthritis (RA) was found based on cyclic citrullinated peptide (CCP) using the following three steps: (1) analysis of the binding epitope of autoimmune antibodies using ϵ-aminocaproic acid-modified peptides; (2) RA diagnosis using sequence-modified peptides; and (3) evaluation of the peptides' diagnostic performance for RA diagnosis. Ninety-five serum samples were analyzed by ELISA and compared using MedCalc (version 15.2.1). Microplate binding ϵ-aminocaproic acid was added to the N- or C-terminal of the CCP sequence. The N-terminal anchoring peptide assay showed 15% higher specificity compared with the C-terminal anchoring peptide assay. Based on this result, the hydrophilic C-terminal sequence of CCP was substituted with a hydrophobic amino acid. Among the sequence-modified peptides, CCP11A (in which alanine was substituted for the 11th amino acid of CCP) assay showed the highest sensitivity (87%) and specificity (100%) for RA diagnosis. Thus, CCP11A was selected as a possible specific marker peptide for RA diagnosis and further analyzed. The results of this analysis indicated that CCP11A showed better specificity than the CCP assay in both healthy individuals (11% better) and OA cohort (20% better). From these results, CCP11A was evaluated as a specific marker for diagnosing RA with higher diagnostic performance.
25822883 The role of statins in inflammatory vasculitides. 2015 May While the statins are best known for their cholesterol lowering capabilities, they also appear to have anti-inflammatory, anti-oxidant and endothelial-repairing properties that have raised the question as to whether this class of drugs can be of benefit in non-atherosclerotic, acute and chronic vasculitides. These effects, independent of the lipid-lowering effects, make the statins a class of drugs that are primed for repurposing and being used in disease states where innate and adaptive immunity and endothelial damage play a key role. Thus far, statins have been used in Behcet's, rheumatoid arthritis and Kawasaki disease with some promising results. Further study is needed to better understand the innate and adaptive immunological response to statins in cardiovascular diseases as well as the full potential of statins in acute and chronic inflammatory vasculitides.
27452207 Evidence-based recommendations for the diagnosis and management of rheumatoid arthritis fo 2017 Sep AIM: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease leading to joint damage, functional disability, poor quality of life and shortened life expectancy. Early diagnosis and aggressive treatment are a principal strategy to improve outcomes. To provide best practices in the diagnosis and management of patients with RA, the Thai Rheumatism Association (TRA) developed scientifically sound and clinically relevant evidence-based recommendations for general practitioners, internists, orthopedists, and physiatrists. METHODS: Thirty-seven rheumatologists from across Thailand formulated 18 clinically relevant questions: three for diagnosis, 10 for treatments, four for monitoring, and one for referral. A bibliographic team systematically reviewed the relevant literature on these topics up to December 2013. A set of recommendations was proposed based on the results of systematic reviews combined with expert opinions. Group consensus was achieved for all statements and recommendations using the nominal group technique. RESULTS: A set of recommendations was proposed. For diagnosis, either American College of Rheumatology (ACR) 1987 or ACR/European League Against Rheumatism 2010 classification criteria can be applied. For treatment, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs, including antimalarials, methotrexate and sulfasalazine are recommended. Physiotherapy should be suggested to all patients. Tight control strategy and monitoring for efficacy and side effects of treatments, as well as indications for referral to a rheumatologist are provided. CONCLUSIONS: These evidence-based recommendations provide practical guidance for diagnosis, fundamental management and referral of patients with RA for non-rheumatologists. However, it should be incorporated with clinical judgments and decisions about care for each individual patient.
26245721 The influence of age at disease onset on disease activity and disability: results from the 2016 Mar This study aims to compare characteristics between late-onset rheumatoid arthritis (RA) and young-onset RA and determine the association between age at disease onset and disease severity. We cross-sectionally studied 971 patients at the time of entry into the Ontario Best Practices Research Initiative, a registry of RA patients followed up in routine care. We restricted patients to ≤5 years of disease duration. Late-onset RA was defined as an onset ≥60 years of age and young-onset RA <60 years. Group differences were compared, and multivariate linear regression models were used to test the influence of age at onset on Disease Activity Score in 28 Joints with erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and Health Assessment Questionnaire (HAQ) scores. The swollen joint count (6.2 vs. 5.3), acute phase reactants (C-reactive protein (CRP) 17.4 vs. 11.8 mg/L, ESR 30.6 vs. 21.5 mm/h), and comorbidity burden were higher in late-onset RA compared to young-onset RA (p < 0.01). Mean DAS28-ESR (4.6 vs. 4.3) and HAQ (1.2 vs. 1.1) scores were higher in late-onset RA patients (p < 0.05). Late-onset RA patients received more initial disease-modifying antirheumatic drug (DMARD) monotherapy and corticosteroids in comparison to greater DMARD/biologic combination therapy in young-onset RA patients (p < 0.05). Adjusted multivariate analyses showed that late-onset RA was independently associated with higher mean DAS28-ESR and HAQ scores, but not CDAI. Late-onset RA patients have greater disease activity that may contribute to disability early in the disease course. Despite this, initial treatment consists of less combination DMARD and biologic use in late-onset RA patients. This may have implications for future response to therapy and development of joint damage, disability, and comorbidities in this group.
26232929 [18F]fluorodeoxyglucose uptake as a predictor of large joint destruction in patients with 2016 Jan The present retrospective study investigated the relationship between [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET) findings and subsequent progression of joint destruction on plain X-ray. Nineteen rheumatoid arthritis (RA) patients (59 joints) who underwent FDG-PET and whose joints could be evaluated on plain X-ray 5 years later were included in this retrospective investigation. The relationship between the standardized uptake value (SUV) on FDG-PET and Larsen grade progression on plain X-ray was investigated for each joint. Factors related to progression of joint destruction were also investigated. Joints with advanced joint destruction (Larsen grades IV and V) on X-ray imaging at the time of FDG-PET were excluded. On initial plain X-ray images taken at the time of FDG-PET, a significant correlation was observed between the initial SUV of each joint and the progression of joint destruction 5 years later (R = 0.47, P < 0.01). Significant correlations between the SUV and progression of joint destruction were observed in both load-bearing (R = 0.52, P < 0.01) and non-load-bearing joints (R = 0.52, P < 0.01). On logistic regression analysis, higher SUV and lower prednisolone dose were associated with greater risk of progressive joint destruction (P < 0.05). On receiver operating characteristics curve analysis, the optimum threshold for identifying preceding joint destruction was an SUVmean of 1.33. In RA joints, FDG uptake was seen mostly by inflammatory cells; therefore, FDG uptake reflected joint inflammation. Additionally, the activity seen on FDG-PET might be associated with future radiographic changes in RA patients.
26140472 (18)F-FDG and (18)F-NaF PET/CT demonstrate coupling of inflammation and accelerated bone t 2016 OBJECTIVE: To compare the findings in rheumatoid arthritis (RA)-affected joints between (18)F-fluorodeoxyglucose (FDG) and (18)F-fluoride (NaF) positron emission tomography (PET)/computed tomography (CT). METHODS: We enrolled twelve RA patients who started a new biologic agent (naïve 9 and switch 3). At entry, both hands were examined by (18)F-FDG PET/CT, (18)F-NaF PET/CT, and X-ray. Intensity of PET signals was determined by standardized uptake value max (SUVmax) in metacarpophalangeal (MCP), proximal interphalangeal (PIP), and ulnar, medial, and radial regions of the wrists. Hand X-rays were evaluated according to the Genant-modified Sharp score at baseline and 6 months. RESULTS: Both (18)F-FDG and (18)F-NaF accumulated in RA-affected joints. The SUVmax of (18)F-FDG correlated with that of (18)F-NaF in individual joints (r = 0.65), though detail distribution was different between two tracers. (18)F-NaF and (18)F-FDG signals were mainly located in the bone and the surrounding soft tissues, respectively. The sum of SUVmax of (18)F-NaF correlated with disease activity score in 28 joint (DAS28), modified health assessment questionnaire (MHAQ), and radiographic progression. (18)F-FDG and (18)F-NaF signals were associated with the presence of erosions, particularly progressive ones. CONCLUSION: Our data show that both (18)F-FDG and (18)F-NaF PET signals were associated with RA-affected joints, especially those with ongoing erosive changes.
26272466 Depressive Symptoms and Momentary Mood Predict Momentary Pain Among Rheumatoid Arthritis P 2016 Feb BACKGROUND: Although a relationship between mood and pain has been established cross-sectionally, little research has examined this relationship using momentary within-person data. PURPOSE: We examined whether baseline depressive symptoms and within-person levels of negative and positive mood predicted momentary pain among 31 individuals with rheumatoid arthritis (RA). METHODS: Depressive symptomatology was measured at baseline. Mood and RA symptoms were self-reported via ecological momentary assessment five times a day for seven consecutive days. Analyses controlled for gender, age, weekend day, time of day, and experiences of stress. RESULTS: Greater momentary positive mood was associated with less momentary pain and fewer arthritis-related restrictions; negative mood was associated with more restrictions. Greater depressive symptomatology also predicted more pain and restrictions, an effect which was not accounted for by mood. CONCLUSIONS: Results suggest that both depression and mood are uniquely associated with momentary pain; as such, multi-component interventions may provide optimal disease management.