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ID PMID Title PublicationDate abstract
31143951 Biomarkers identified by serum metabolomic analysis to predict biologic treatment response 2019 Dec 1 OBJECTIVES: Biologic treatment has recently revolutionized the management of RA. Despite this success, ∼30-40% of the patients undergoing biologic treatment respond insufficiently. The aim of this study was to identify several specific reliable metabolites for predicting the response of RA patients to TNF-α inhibitors (TNFi) and abatacept (ABT), using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). METHODS: We collected serum from RA patients with moderate or high disease activity prior to biologic treatment, and obtained the serum metabolomic profiles of these samples using CE-TOFMS. The patients' response was determined 12 weeks after starting biologic treatment, according to the EULAR response criteria. We compared the metabolites between the response and non-response patient groups and analysed their discriminative ability. RESULTS: Among 43 total patients, 14 of 26 patients in the TNFi group and 6 of 17 patients in the ABT group responded to the biologic treatment. Of the metabolites separated by CE-TOFMS, 196 were identified as known substances. Using an orthogonal partial least-squares discriminant analysis, we identified five metabolites as potential predictors of TNFi responders and three as predictors of ABT responders. Receiver operating characteristic analyses for multiple biomarkers revealed an area under the curve (AUC) of 0.941, with a sensitivity of 85.7% and specificity of 100% for TNFi, and an AUC of 0.985, with a sensitivity of 100% and specificity of 90.9% for ABT. CONCLUSION: By metabolomic analysis, we identified serum biomarkers that have a high ability to predict the response of RA patients to TNFi or ABT treatment.
30911944 Clinical characteristics of rheumatoid arthritis patients with peripheral neuropathy and p 2019 Aug OBJECTIVES: To investigate potential risk factors of peripheral neuropathy (PN) in rheumatoid arthritis patients (RA). METHODS: Eighty-eight patients with RA were enrolled in this study, including patients with PN (n = 44; 28 patients with multiple nerves (MN) involvement and 16 patients with single nerve (SN) involvement) and without (n = 44) peripheral neuropathy were enrolled. Their clinical features were comprehensively collected including symptoms/signs, lab results, electromyogram data. T test or chi-squared test and further binary regression analysis were used to explore risk factors based on analyzing these clinical features. RESULTS: There was no difference as regards patients' age (59.50 ± 8.11 vs 58.68 ± 11.44 years), gender ratio (female/male, 29:15 vs 29:15), and disease duration (6.34 ± 7.87 vs 8.13 ± 9.52 months) between patients with and without PN. RA patients with PN had lower total protein (61.13 ± 7.06 vs 66.06 ± 6.44 g/L), anti-CCP levels (239.13 ± 203.77 vs 361.41 ± 168.09 U/ml) compared with control patients, while patients with MN had higher inflammatory parameters (white blood cells, platelet, C-reactive protein (CRP), erythrocyte sedimentation rate, rheumatoid factor) than patients with SN (p < 0.05). Low total protein (< 63 g/L, 30/44 vs. 12/44) and anti-CCP (< 285.7 U/ml, 27/44 vs. 11/44) were risk factors for patients with PN, while CRP (> 6 mg/L, 26/28 vs. 6/16) and PLT (> 243 × 10(9)/L, 25/28 vs.5/16) were related to the development of MN. CONCLUSIONS: RA patients with PN, especially MN can present various clinical symptoms, which will aggravate patients' anxiety and depression status. The increase of blood platelet, and CRP levels and decrease of blood albumin are probable risk factors for PN in RA patients.
31104217 Diacerein for the treatment of rheumatoid arthritis in patients with inadequate response t 2019 Sep OBJECTIVE: To evaluate the efficacy and safety of diacerein in patients with rheumatoid arthritis (RA) who are methotrexate inadequate responders (MTX-IR). METHOD: In this pilot, multicenter, double-blind, placebo-controlled trial, MTX-IR RA patients were randomized to either diacerein or matching placebo as add-on treatment to MTX for 24 weeks. Efficacy and safety were evaluated every 4 weeks until week 28. Primary and secondary efficacy endpoints were the percentage of patients achieving the ACR20 criteria and a moderate EULAR response at week 24, respectively. RESULTS: Forty patients were equally randomized to both study treatments; 16 and 19 participants completed the study in the diacerein and the placebo arms, respectively. Baseline characteristics were similar in both groups, except that tender joint count, DAS28-ESR score, and non-steroidal anti-inflammatory drug consumption were higher in the placebo arm. The ACR20 response at week 24 was similar in the diacerein and placebo groups (65% vs 45%, P = .20). However, treatment response according to the EULAR criteria was better in patients taking diacerein (75% vs 25% of moderate response, P = .002). In the 35 patients with assessments through week 28, diacerein was superior to placebo in ACR20 at weeks 24 and 28 (both 81% vs 47%, P = .04). Incidence of adverse events was comparable in both arms, with only chromaturia being more common with diacerein than placebo (40% vs 10%, P = .03). CONCLUSIONS: These preliminary results show the potential benefits of diacerein on pain, joint function, and disease activity in MTX-IR RA patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01264211 Key Points • Diacerein has shown positive effects on rheumatoid arthritis symptoms. • A good safety profile of diacerein has been observed when it was administered as add-on therapy to methotrexate in patients with rheumatoid arthritis.
30396592 Added value of combining methotrexate with a biological agent compared to biological monot 2019 Jun OBJECTIVES: To assess the efficacy and safety of methotrexate (MTX) in combination with an approved biological agent compared to biological monotherapy, in the management of patients with rheumatoid arthritis (RA). METHODS: MEDLINE, EMBASE, CENTRAL and other sources were searched for randomised trials evaluating a biological agent plus MTX versus the same biological agent in monotherapy. Co-primary outcomes were ACR50 and the number of patients who discontinued due to adverse events (AEs). Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals and the GRADE approach was used to assess confidence in the estimates. RESULTS: The analysis comprised 16 trials (4965 patients), including all biological agents approved for RA except anakinra and certolizumab. The overall likelihood of responding to therapy (i.e. ACR50) after 6 months was 32% better when MTX was given concomitantly with biological agents (1.32 [1.20-1.45]; P < 0.001) corresponding to 11 more out of 100 patients (7-16 more); Moderate Quality Evidence. Discontinuing due to AEs from concomitant use of MTX was potentially 20% increased (1.21 [0.97-1.50]; P = 0.09) compared to biological monotherapy corresponding to 1 more out of 100 patients (0-3 more); Moderate Quality Evidence. CONCLUSIONS: Randomised trials provide Moderate Quality Evidence for a favourable benefit-harm balance supporting concomitant use of MTX rather than monotherapy when prescribing a biological agent in patients with RA although in absolute terms only 7-16 more out of 100 patients will achieve an ACR50 response after 6 months of this combination therapy.
30630756 Reversible Cerebral Vasoconstriction Syndrome after Administering Etanercept during Puerpe 2019 Apr Our objective is to clarify relationship between reversible cerebral vasoconstriction syndrome and administrating etanercept during puerperium. Several lines of evidence have suggested tumor necrosis factor (TNF) as a mediator of vascular dysfunction associated with estrogen deficiency. A 32-year-old woman resumed etanercept (25 mg/week), a TNF inhibitor, which had been discontinued during pregnancy, because of the deterioration of rheumatoid arthritis. She was admitted to our hospital with upper right quadrant blindness and mild right hemiparesis accompanied by pulsating left occipital pain, which had appeared 4 hours after restarting etanercept (25 mg/week). Magnetic resonance imaging and angiography revealed acute left hippocampal infarction with multiple segmental stenoses of the main intracranial arteries. Reversible cerebral vasoconstriction syndrome was diagnosed based on improvement of the multiple stenoses on magnetic resonance angiography on hospital day 17. A causal relationship was considered to exist between TNF inhibition by etanercept and multiple cerebral vasoconstrictions with brain infarct in this puerperant.
31859424 Singapore Chapter of Rheumatologists updated consensus statement on the eligibility for go 2020 Feb INTRODUCTION: Approximately 30% of patients with rheumatoid arthritis (RA) respond inadequately to conventional-synthetic disease-modifying anti-rheumatic drugs (csDMARDs). However, widespread use of biologic DMARDs (bDMARDs) and targeted-synthetic (tsDMARDs) is limited by cost. We formulated updated recommendations for eligibility criteria for government-assisted funding of bDMARDs/tsDMARDs for RA patients in Singapore. MATERIALS AND METHODS: Published guidelines regarding use of bDMARD and tsDMARDs were reviewed. We excluded those without a systematic literature review, formal consensus process or evidence grading. Separately, unpublished national reimbursement guidelines were included. RESULTS: Eleven recommendations regarding choice of disease activity measure, initiation, order of selection and continuation of bDMARD/tsDMARDs were formulated. A bDMARD/tsDMARD is indicated if a patient has: (a) at least moderately active RA with a Disease Activity Score in 28 joints/erythrocyte sedimentation rate (DAS28-ESR) score of ≥3.2; (b) failed ≥2 csDMARD strategies, 1 of which must be a combination; (c) received an adequate dose regimen of ≥3 months for each strategy. For the first-line bDMARD/tsDMARD, either tumor necrosis factor inhibitors (TNFi), non-TNFi (abatacept, tocilizumab, rituximab), or tsDMARDs, may be considered. If a first-line TNFi fails, options include another TNFi, non-TNFi biologic or tsDMARDs. If a first-line non-TNFi biologic or tsDMARD fails, options include TNFi or another non-TNF biologic or tsDMARD. For continued bDMARD/tsDMARD subsidization, a patient must have a documented DAS28-ESR every 3 months and at least a moderate European League Against Rheumatism response by 6 months. CONCLUSION: These recommendations are useful for guiding funding decisions, making bDMARD/tsDMARDs usage accessible and equitable in RA patients who fail csDMARDs.
30647443 A single nucleotide polymorphism of IL6-receptor is associated with response to tocilizuma 2019 Aug Biological disease-modifying anti-rheumatic drugs (bDMARDs) have changed care of patients with rheumatoid arthritis (RA). However, bDMARDs are costly, can lead to serious infections, and induce a sustained remission in only 30% of RA patients. In this study, we sought to determine if the clinical response to treatment with Tocilizumab (TCZ), an IL-6 inhibitor, varied with genetic background. The efficacy of TCZ was assessed using the European League Against Rheumatism (EULAR) response criteria, measured after 3 months of treatment in two samples of French RA patients (TOCI and ROC studies). Single nucleotide polymorphisms (SNPs) in 21 candidate genes were genotyped using KasPar method (LGC-genomics, UK) and then analyzed to determine their contribution to variation in the response to treatment. One hundred twenty-three patients in the TOCI group (79.8%) and 48 patients in the ROC group (80%) experienced good or moderate EULAR response. The clinical response to treatment was associated with SNP genotype in the gene IL6R, with patients with the homozygous AA-genotype for rs12083537 (IL6R) showing a significantly better response than homozygous or heterozygous patients with the G allele [TOCI: 87.5% of responders for AA genotype vs. 72.2% for AG or GG genotype (p = 0.018); ROC patients: 89.2% of responders for AA genotype vs. 65.2% for AG or GG genotype, p = 0.044]. A meta-analysis combining data from the two cohorts confirmed the lower response rate in patients carrying a copy of the G allele (OR (95% CI) = 0.35 (0.16-0.61), p = 0.001). No association was found with any of the other SNPs tested.
30978322 Structure-based design and in vivo anti-arthritic activity evaluation of a potent dipeptid 2019 Jun Cathepsin C (CatC) is a dipeptidyl-exopeptidase which activates neutrophil serine protease precursors (elastase, proteinase 3, cathepsin G and NSP4) by removing their N-terminal propeptide in bone marrow cells at the promyelocytic stage of neutrophil differentiation. The resulting active proteases are implicated in chronic inflammatory and autoimmune diseases. Hence, inhibition of CatC represents a therapeutic strategy to suppress excessive protease activities in various neutrophil mediated diseases. We designed and synthesized a series of dipeptidyl cyclopropyl nitrile compounds as putative CatC inhibitors. One compound, IcatC(XPZ-01) ((S)-2-amino-N-((1R,2R)-1-cyano-2-(4'-(4-methylpiperazin-1-ylsulfonyl)biphenyl-4-yl)cyclopropyl)butanamide)) was identified as a potent inhibitor of both human and rodent CatC. In mice, pharmacokinetic studies revealed that IcatC(XPZ-01) accumulated in the bone marrow reaching levels suitable for CatC inhibition. Subcutaneous administration of IcatC(XPZ-01) in a monoclonal anti-collagen antibody induced mouse model of rheumatoid arthritis resulted in statistically significant anti-arthritic activity with persistent decrease in arthritis scores and paw thickness.
31601357 Group cognitive-behavioural programme to reduce the impact of rheumatoid arthritis fatigue 2019 Oct BACKGROUND: Fatigue is a major problem in rheumatoid arthritis (RA). There is evidence for the clinical effectiveness of cognitive-behavioural therapy (CBT) delivered by clinical psychologists, but few rheumatology units have psychologists. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of a group CBT programme for RA fatigue [named RAFT, i.e. Reducing Arthritis Fatigue by clinical Teams using cognitive-behavioural (CB) approaches], delivered by the rheumatology team in addition to usual care (intervention), with usual care alone (control); and to evaluate tutors' experiences of the RAFT programme. DESIGN: A randomised controlled trial. Central trials unit computerised randomisation in four consecutive cohorts within each of the seven centres. A nested qualitative evaluation was undertaken. SETTING: Seven hospital rheumatology units in England and Wales. PARTICIPANTS: Adults with RA and fatigue severity of ≥ 6 [out of 10, as measured by the Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scale (BRAF-NRS)] who had no recent changes in major RA medication/glucocorticoids. INTERVENTIONS: RAFT - group CBT programme delivered by rheumatology tutor pairs (nurses/occupational therapists). Usual care - brief discussion of a RA fatigue self-management booklet with the research nurse. MAIN OUTCOME MEASURES: Primary - fatigue impact (as measured by the BRAF-NRS) at 26 weeks. Secondary - fatigue severity/coping (as measured by the BRAF-NRS); broader fatigue impact [as measured by the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ)]; self-reported clinical status; quality of life; mood; self-efficacy; and satisfaction. All data were collected at weeks 0, 6, 26, 52, 78 and 104. In addition, fatigue data were collected at weeks 10 and 18. The intention-to-treat analysis conducted was blind to treatment allocation, and adjusted for baseline scores and centre. Cost-effectiveness was explored through the intervention and RA-related health and social care costs, allowing the calculation of quality-adjusted life-years (QALYs) with the EuroQol-5 Dimensions, five-level version (EQ-5D-5L). Tutor and focus group interviews were analysed using inductive thematic analysis. RESULTS: A total of 308 out of 333 patients completed 26 weeks (RAFT, n/N = 156/175; control, n/N = 152/158). At 26 weeks, the mean BRAF-NRS impact was reduced for the RAFT programme (-1.36 units; p < 0.001) and the control interventions (-0.88 units; p < 0.004). Regression analysis showed a difference between treatment arms in favour of the RAFT programme [adjusted mean difference -0.59 units, 95% confidence interval (CI) -1.11 to -0.06 units; p = 0.03, effect size 0.36], and this was sustained over 2 years (-0.49 units, 95% CI -0.83 to -0.14 units; p = 0.01). At 26 weeks, further fatigue differences favoured the RAFT programme (BRAF-MDQ fatigue impact: adjusted mean difference -3.42 units, 95% CI -6.44 to - 0.39 units, p = 0.03; living with fatigue: adjusted mean difference -1.19 units, 95% CI -2.17 to -0.21 units, p = 0.02; and emotional fatigue: adjusted mean difference -0.91 units, 95% CI -1.58 to -0.23 units, p = 0.01), and these fatigue differences were sustained over 2 years. Self-efficacy favoured the RAFT programme at 26 weeks (Rheumatoid Arthritis Self-Efficacy Scale: adjusted mean difference 3.05 units, 95% CI 0.43 to 5.6 units; p = 0.02), as did BRAF-NRS coping over 2 years (adjusted mean difference 0.42 units, 95% CI 0.08 to 0.77 units; p = 0.02). Fatigue severity and other clinical outcomes were not different between trial arms and no harms were reported. Satisfaction with the RAFT programme was high, with 89% of patients scoring ≥ 8 out of 10, compared with 54% of patients in the control arm rating the booklet (p < 0.0001); and 96% of patients and 68% of patients recommending the RAFT programme and the booklet, respectively, to others (p < 0.001). There was no significant difference between arms for total societal costs including the RAFT programme training and delivery (mean difference £434, 95% CI -£389 to £1258), nor QALYs gained (mean difference 0.008, 95% CI -0.008 to 0.023). The probability of the RAFT programme being cost-effective was 28-35% at the National Institute for Health and Care Excellence's thresholds of £20,000-30,000 per QALY. Tutors felt that the RAFT programme's CB approaches challenged their usual problem-solving style, helped patients make life changes and improved tutors' wider clinical practice. LIMITATIONS: Primary outcome data were missing for 25 patients; the EQ-5D-5L might not capture fatigue change; and 30% of the 2-year economic data were missing. CONCLUSIONS: The RAFT programme improves RA fatigue impact beyond usual care alone; this was sustained for 2 years with high patient satisfaction, enhanced team skills and no harms. The RAFT programme is < 50% likely to be cost-effective; however, NHS costs were similar between treatment arms. FUTURE WORK: Given the paucity of RA fatigue interventions, rheumatology teams might investigate the pragmatic implementation of the RAFT programme, which is low cost. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52709998. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 57. See the NIHR Journals Library website for further project information.
30874879 ERAMRS: a new MR scoring system for early rheumatoid arthritis of the wrist. 2019 Oct PURPOSE: To (i) devise a new semi-quantitative scoring system known as Early Rheumatoid Arthritis Magnetic Resonance Score (ERAMRS) to assess inflammation of the wrist on magnetic resonance imaging in early rheumatoid arthritis and to (ii) test ERAMRS and other MR scoring systems against everyday used clinical scorings. MATERIALS AND METHODS: One hundred six treatment-naïve patients (81 females, 25 males, mean age 53 ± 12 years) with early rheumatoid arthritis (ERA) underwent clinical/serological testing as well as 3-T MRI examination of the most symptomatic wrist. Clinical assessment included Disease Activity Score-28 and Health Assessment Questionnaire; erythrocyte sedimentation rate and C-reactive protein were measured. MR imaging data was scored in all patients using three devised MR semi-quantitative scoring systems, namely, the (a) ERAMRS system, (b) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) system, and the (c) McQueen Score system. RESULTS: Synovitis was present in 106 (100%), tenosynovitis in 98 (92%), and bone marrow edema in 84 (79%) of 106 ERA wrists. ERAMRS had the highest correlation with clinical disease activity scores (r = 0.476, p < 0.001) and serological parameters (r = 0.562, p < 0.001). RAMRIS system had the lowest correlation (r = 0.369, p < 0.001 for clinical disease activity; r = 0.436, p < 0.001 for serological parameters). RAMRIS synovitis subscore had a lower correlation than ERAMRS for clinical disease activity (r = 0.410, p < 0.001) and for serological parameters (r = 0.456, p < 0.001). CONCLUSION: The ERAMRS system, designed to grade inflammation on wrist MRI in ERA, provided the best correlation with all clinical scoring systems and serological parameters, indicating its improved clinical relevance over other MR scoring systems. KEY POINTS: • We devised a clinically relevant, easy-to-use semi-quantitative scoring system for scoring inflammation on MRI of the wrist in patients with early rheumatoid arthritis. • ERAMRS system showed better correlation with all clinical and serological assessment of inflammation in patients with early rheumatoid arthritis indicating its improved clinical relevance over other MR scoring systems.
31385441 Risk Factors for Major Adverse Cardiovascular Events in Phase III and Long-Term Extension 2019 Sep OBJECTIVE: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). This study was undertaken to evaluate the risk of major adverse cardiovascular events (MACE) in patients with RA receiving tofacitinib. METHODS: Data were pooled from patients with moderately to severely active RA receiving ≥1 tofacitinib dose in 6 phase III and 2 long-term extension studies over 7 years. MACE (myocardial infarction, stroke, cardiovascular death) were independently adjudicated. Cox regression models were used to evaluate associations between baseline variables and time to first MACE. Following 24 weeks of tofacitinib, changes in variables and time to future MACE were evaluated after adjusment for age, baseline values, and time-varying tofacitinib dose. Hazard ratios and 95% confidence intervals were calculated. RESULTS: Fifty-two MACE occurred in 4,076 patients over 12,873 patient-years of exposure (incidence rate 0.4 patients with events per 100 patient-years). In univariable analyses of baseline variables, traditional cardiovascular risk factors and glucocorticoid and statin use were associated with MACE risk; disease activity and inflammation measures were not. In subsequent multivariable analyses, baseline age, hypertension, and the total cholesterol to high-density lipoprotein (HDL) cholesterol ratio remained significantly associated with risk of MACE. After 24 weeks of treatment, an increase in HDL cholesterol and a decrease in the total to HDL cholesterol were associated with decreased MACE risk; changes in total cholesterol, low-density lipoprotein (LDL) cholesterol, and disease activity measures were not. Increased erythrocyte sedimentation rates trended with increased future MACE risk. CONCLUSION: In this post hoc analysis, after 24 weeks of tofacitinib treatment, increased HDL cholesterol, but not increased LDL cholesterol or total cholesterol, appeared to be associated with lower future MACE risk. Further data are needed to test the cardiovascular safety of tofacitinib.
27307417 Chronic pain experience on depression and physical disability: The importance of acceptanc 2019 Feb The mediating effect of acceptance and mindfulness in the relationship between pain, depression, and physical disability was examined in 55 rheumatoid arthritis patients. Results showed that the relationship between pain and depression was mediated by both nonreact and acceptance. By contrast, the relationship between pain and physical disability was mediated by acceptance but not by nonreact. This study provides evidences that the influence of these processes is different on depression and on physical disability. These findings support models that take both general measures of mindfulness and content-specific measures of acceptance into account when conceptualizing rheumatoid arthritis. Theoretical and clinical implications are discussed.
31270057 [Pannus does not occur only in rheumatoid arthritis: a pathological observation of pannus 2019 Jun 30 OBJECTIVE: To compare the histopathological features of the synovium between rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: We retrospectively analyzed the synovial specimens obtained after synovial surgery in 72 cases of RA and 24 cases of OA. Two independent pathologists reviewed the sections of the synovial tissues with HE staining, quantitatively scored the degree of fibroblast-like synoviocyte (FLS) hyperplasia, vascular hyperplasia, fibroplasia, and lymphocyte infiltration, and examined the presence plasma cell infiltration. The pathological morphology of the synovial tissues was evaluated in relation with the clinical data of the patients. RESULTS: Pannus formation was also detected in the synovium of OA patients, which showed a lesser degree of OA-FLS hyperplasia, fibrosis and lymphocyte infiltration and a significantly lower rate of plasma cell infiltration compared with the pannus in RA patients. Vascular proliferation was also milder in the pannus of OA patients than in RA pannus, but the difference was not statistically significant. In OA patients, the pannus could be observed under a microscope and was difficult to distinguish from that in RA patients. CONCLUSIONS: Pannus formation occurs also in the synovium of OA patients but with milder FLS hyperplasia, fibrosis and lymphocyte infiltration and a lower rate of plasma cell infiltration compared with the pannus in RA patients. These differences in the pannus between OA and RA can be of potential value in the diagnosis and treatment of the patients.
30380152 Relationship between rheumatoid arthritis and periodontal disease in Korean adults: Data f 2019 Apr BACKGROUND: This study aims to investigate the relationship between rheumatoid arthritis and periodontal disease using data from the Sixth Korea National Health and Nutrition Examination Survey (KNHANES, 2013 to 2015). METHODS: Of 22,948 KNHANES participants, 14,264 who were aged ≥19 years and responded to questions pertaining to periodontal disease and rheumatoid arthritis were analyzed. Periodontal status was measured using the Community Periodontal Index. The authors used a complex sampling analysis by applying an individual sampling weighting to maintain the rolling survey sampling method. To determine the prevalence of rheumatoid arthritis and periodontal disease, a Chi-squared test was performed. Logistic regression analysis was performed after controlling for selected variables to determine relevance. RESULTS: The prevalence of rheumatoid arthritis in patients with periodontal disease was 1.6%, which was higher than in individuals without periodontal disease (1.5%). The prevalence of periodontal disease in individuals with rheumatoid arthritis was 28.4%, which was higher than in subjects without rheumatoid arthritis (27.9%). The risk for periodontal disease was 1.64 times higher in individuals with rheumatoid arthritis than in those without rheumatoid arthritis. Regardless of age or sex, the risk for periodontal disease was 1.97 times higher in the presence of rheumatoid arthritis. However, other logistic regression analysis models, when adjusted for socioeconomic-, health-, and oral health-related factors, did not yield statistically significant findings. CONCLUSIONS: The study results suggest a possible relationship between rheumatoid arthritis and periodontal disease. Further large cohort studies investigating causal relationships between rheumatoid arthritis and periodontal disease are needed.
30508136 Clinical significance of Janus Kinase inhibitor selectivity. 2019 Jun 1 Cytokines are key drivers of inflammation in RA, and anti-cytokine therapy has improved the outcome of RA. Janus Kinases (JAK) are intracellular tyrosine kinases linked to intracellular domains of many cytokine receptors. There are four JAK isoforms: JAK1, JAK2, JAK3 and TYK2. Different cytokine receptor families utilize specific JAK isoforms for signal transduction. Phosphorylation of JAK when cytokine binds to its cognate receptor leads to phosphorylation of other intracellular molecules that eventually leads to gene transcription. Oral JAK inhibitors (JAKi) have been developed as anti-cytokine therapy in RA. Two JAKi, tofacitinib and baricitinib, have been approved recently for the treatment of RA, and many JAKi are currently in development. JAKi inhibit JAK isoforms with different selectivity. This review discusses the efficacy and safety of JAKi in RA, in particular the potential clinical significance of JAKi selectivity.
30566899 Forefoot pathology in relation to plantar pressure distribution in patients with rheumatoi 2019 Feb BACKGROUND: In patients with rheumatoid arthritis (RA), both high and low forefoot plantar pressures have been reported. Better understanding of pathology in the forefoot associated with altered pressure distribution in patients with RA could help to better formulate and specify goals for treatment with foot orthoses or therapeutic footwear. OBJECTIVES: To investigate the association of plantar pressure with disease activity and deformity in the forefoot in patients with rheumatoid arthritis and forefoot symptoms. METHODS: A cross sectional study, using data of 172 patients with rheumatoid arthritis and forefoot symptoms, was conducted. Peak pressure (PP) and pressure time integral (PTI) in the forefoot were measured with a pressure platform. Forefoot deformity was assessed using the Platto score. Forefoot disease activity was defined as swelling and/or pain assessed by palpation of the metatarsophalangeal joints. The forefoot was divided in a medial, central and lateral region, in which the following conditions could be present: 1) no pathology, 2) disease activity, 3) deformity or 4) disease activity and deformity. A multilevel analysis was performed using condition per forefoot region as independent variable and PP or PTI in the corresponding region as dependent variable. RESULTS: Statistically significant higher plantar pressures were found in forefoot regions with deformities (RR 1.2, CI 1.1-1.3, P<0.0001), compared to forefoot regions without forefoot pathology. No significant differences in plantar pressures were found when solely forefoot disease activity was present in forefoot regions. SIGNIFICANCE: Forefoot deformities are related to higher plantar pressures measured in the corresponding forefoot regions. The absence of an association between local disease activity and plantar pressure might be explained by the low prevalence of metatarsophalangeal joint pain or swelling. Future research with sensitive imaging measures to detect disease activity is recommended to reveal the effect of forefoot disease activity on plantar pressure.
31142786 Herbo-mineral formulation 'Ashwashila' attenuates rheumatoid arthritis symptoms in collage 2019 May 29 Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that affects joints of hands and feet and introduces injury in secondary organs such as cardiac tissue. In the present study, we induced RA in male Balb/c mice (CAIA) using collagen-antibody cocktail (C-Ab) and lipopolysaccharide intraperitoneal injections. Induction of RA in the animals was detected through the loss of body weight, food, and water consumption, pedal edema, increased arthritis score of the paw and ankle, increase in radiological and histological lesion score of ankle and knee joints and enhanced pain perception in the C-Ab induced RA animals. Ashwashila is a herbo-mineral medicine from Indian Ayurvedic system. Human equivalent doses of Ashwashila (ASHW) and standard of care, Methotrexate were given to the CAIA animals for two weeks. ASHW treatment significantly reversed the effect of C-Ab with reduced pedal edema, arthritis score, radiological and histological lesion scores in ankle-joint, knee-joint and articular cartilage, reduced pain perception. These effects were comparable with the Methotrexate treatment. In human monocytic (THP-1) cells, ASHW was found to be biocompatible at in-vitro test doses. The anti-arthritis mechanism of action for ASHW was established through the suppression of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α; and upstream regulator, NF-κB. Taken together, we show the pre-clinical efficacy of ASHW in reducing RA associated symptoms by controlling inflammation and suggest it as a potential therapeutic candidate for rheumatoid arthritis.
30907366 [Late-onset rheumatoid arthritis: clinical, biological, and therapeutic features About a r 2019 Mar 1 Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatism in adults. The objective of our study was to analyze the clinical, biological and therapeutic characteristics in subjects over 60 years old. PATIENTS AND METHODS: We performed a retrospective, monocentric, descriptive study on medical records consultations. The data collection concerned subjects over 60 years of age who had been diagnosed with "rheumatoid arthritis" in the rheumatology and internal medicine departments of CHU Reims over a period stretching from 2010 to 2015. RESULTS: Thirty-two patients were included in our study for this period. The mean age of diagnosis was 66.6 years, for a median age of 67.5 years (min: 60 years, max: 88 years). There were 22 female (69%) and 10 male (31%) patients, with a sex ratio H/F of 2.2. The mean duration of symptom progression before diagnosis was 33.2 months. What dominates our series is the inaugural involvement of the interphalangeal proximal, wrists, shoulders and metacarpophalangeal for the vast majority of cases. Oral corticosteroids were used in 27 patients and were the only treatment in 3 patients. Methotrexate (MTX) was introduced in 27 patients. Nine patients received biotherapy: it was tocilizumab (Roactemra®) for 5 patients, adalimumab (Humira®) for 2 patients, abatacept (Orencia®) for 2 patients, etanercept (Enbrel®) for 2 patients, golimumab (Simponi®) for 1 patient and infliximab (Remicade®) for one patient. In our series, 7 patients are over 75 years old at the time of diagnosis of RA. CONCLUSION: The rheumatoid arthritis of the elderly remains a common condition and constitutes a diagnostic and therapeutic challenge. Because of the co-morbidities, the clinician's perception of the patient's overall condition and the inaccuracies in the use of certain molecules in these patients, under-treatment may, on the contrary, weaken a patient whose remission will be postponed. This was not the case in our series, with a methodical use of methotrexate as well as effective dose biotherapies.
31473702 Potential mechanisms linking periodontitis to rheumatoid arthritis. 2019 Jul 1 Periodontitis (PD), a chronic inflammatory disease which results in irreversible attachment loss, bone destruction and tooth loss, is a major oral health problem. Rheumatoid arthritis (RA), with a global prevalence of 1%, is an autoimmune disease characterized as a chronic inflammatory disorder leading to synovial inflammation and destruction of cartilage and bone. Studies have reported an association between PD and RA whereby PD is reportedly more severe in patients with established RA. Justification for the plausible link between both conditions is based on shared characteristics and pathogenic similarities with regard to risk factors, immunogenetics and tissue destruction pathways. The search for the possible mechanism linking PD to RA continues as it can play an important role in enabling early intervention in the form of prevention and treatment of infection. This will ultimately improve patients' oral health related quality of life and reduce societal burden related to increased patient discomfort and treatment costs. The current review provides an update on the cellular and molecular events that have thus far explained the link.
31520798 Macrophage M1/M2 polarization and rheumatoid arthritis: A systematic review. 2019 Nov BACKGROUND AND AIM: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease; the clinical manifestations are correlated with continuum multiarticular synovitis, cartilage and bone damage, and defeat of joint function, that causes disability. Involvement of internal organs is also frequent. Between the inflammatory cells involved in RA, macrophages play a key role. These cells can polarize in different phenotype and mediate the immune/inflammatory reaction as well as the reparatory phase when possible. The properties of these cells are mediate by the body's environmental factors. In this systematic review, all English-speaking articles concerning the role of M1 (pro-inflammatory) or M2 (anti-inflammatory) macrophages in RA were systematically reviewed and categorized according to their polarized-function in RA, especially in the synovial tissue. Analyses of the endogenous molecules and the drugs that could modulate M1 and M2 activity in RA were achieved. METHODS: A sensitive search was developed in Pubmed, Web of Science, Ovid Med-Line, Embase Database and Science Direct Database (la both from Elsevier) to identify articles to increase the highlighting on the role of macrophages M1 and M2 in RA using the following terms: ((M1 AND M2) AND Rheumatoid Arthritis). All selected papers were read and discussed by two independent reviewers. The selection process was based on title, abstract and full text level. Relevant data were extracted and analyzed using a standardized template designed for this review. RESULTS: In total 39 resulting articles were selected and categorized according to description of M1/M2's role in RA. Data from humans, mice and rats were subcategorized, thus in every section were highlighted the contribute, in peripheral blood and synovial tissue, of both polarized macrophages; section for endogenous molecules and drugs that favor the switch from M1 to M2 macrophages were carried out. The most evinced relevant results, were that in RA blood and in the synovial tissue, there isn't a clear distinction phase with M1 or M2 macrophages (by membrane marker analysis); rather there is M1 and M2 subset disequilibrium and by deeply analyses of mRNA gene and cytokine produced, it emerged that a non-coherent expression inner marker match with membrane molecules, and also the tissue section can define the marker expressed. CONCLUSION: This systematic review emphasizes that the rigid classical subdivision of M1 and M2 macrophages, as well as the different samples' results comparison, might be questionable. In addition, it is suggested, when taking samples from RA patients, to carefully consider their therapies in order to analyze the M1 and M2 macrophages behavior without drug influence. In line with the advances in M1 and M2 knowledge, and the progression in the single-cell methodologies by identification of individual cell molecular markers, therapeutic approaches seem possible to favor the anti-inflammatory macrophage response in RA (e.g. M2 polarization).