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ID PMID Title PublicationDate abstract
24933628 New laboratory markers for the management of rheumatoid arthritis patients. 2014 Dec Rheumatoid arthritis, the most prominent of systemic autoimmune rheumatic diseases, represents an important social health problem. Recent insights into the immunopathogenic mechanism of this complex and multiform illness might open new perspectives for a more appropriate laboratory approach. In this review we focus on the most relevant pathogenetic mechanism; indicating the laboratory biomarkers specifically linked to early diagnosis, prognosis, evolutive aspects of the disease, and therapeutic efficacy. Evidence based on laboratory medicine could provide the best outcome for patients.
23515142 Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthriti 2013 May 4 BACKGROUND: Roughly a third of patients with rheumatoid arthritis treated with biological treatments receive them as monotherapy. Tocilizumab--an inhibitor of interleukin 6 receptor signalling--has been studied as monotherapy in several clinical trials. We assessed the efficacy and safety of tocilizumab monotherapy compared with adalimumab monotherapy for patients with rheumatoid arthritis. METHODS: We did this randomised, double-blind, parallel-group, phase 4 superiority study in 76 centres in 15 countries in North and South America, Australasia, and Europe. We enrolled patients who were aged at least 18 years, had severe rheumatoid arthritis for 6 months or more, and were intolerant to methotrexate or were inappropriate for continued methotrexate treatment. Patients were randomly assigned (1:1; block size of four) to receive tocilizumab 8 mg per kg bodyweight intravenously every 4 weeks plus placebo subcutaneously every 2 weeks or adalimumab 40 mg subcutaneously every 2 weeks plus placebo intravenously every 4 weeks for 24 weeks. Investigators, patients, and sponsor personnel were masked to assignment. The primary endpoint was change in disease activity score using 28 joints (DAS28) from baseline to week 24. This trial is registered with ClinicalTrials.gov, number NCT01119859. FINDINGS: We screened 452 patients and enrolled 326 patients. The intention-to-treat population contained 325 patients (163 assigned to tocilizumab, 162 assigned to adalimumab). Week 24 mean change from baseline in DAS28 was significantly greater in the tocilizumab group (-3·3) than in the adalimumab group (-1·8) patients (difference -1·5, 95% CI -1·8 to -1·1; p<0·0001). 16 of 162 (10%) patients in the adalimumab group versus 19 of 162 (12%) in the tocilizumab group had serious adverse events. More patients in the tocilizumab group than in the adalimumab group had increased LDL-cholesterol, increased alanine aminotransferase concentrations, and reduced platelet and neutrophil counts. INTERPRETATION: Tocilizumab monotherapy was superior to adalimumab monotherapy for reduction of signs and symptoms of rheumatoid arthritis in patients for whom methotrexate was deemed inappropriate. The adverse event profiles of tocilizumab and adalimumab were consistent with previous findings. FUNDING: F Hoffmann-La Roche.
24365380 The effect of B-cell depletion therapy on serological evidence of B-cell and plasmablast a 2014 May B-cell depletion therapy (BCDT) based on rituximab (RTX) induces clinical remission in a majority of seropositive patients with Rheumatoid arthritis (RA). However, all patients eventually relapse. The aim of this study was to determine whether dynamic changes in combinations of serological measures of B-cell activation were associated over up to three cycles of BCDT. We included only RA patients who gave an adequate clinical response, as measured by DAS28. Twenty three patients were studied over 1 cycle, 21 over 2, and 15 over 3 cycles of BCDT. Serum analytes including isotypes of Rheumatoid factors (RhF) and anti-citrullinated protein/peptide antibodies (ACPA), B-cell activating factor (BAFF), serum free light chains (SFLC), soluble CD23 (sCD23), antibodies to tetanus toxoid (TT) and to pneumococcal capsular polysaccharide (PCP) were measured by ELISA at 4 key points in each cycle, namely: Baseline (pre-RTX in each cycle); when B-cell depleted (CD19+B-cells < 5/μl); at B-cell return (CD19+B-cells ≥ 5/μl); and at clinical relapse (ΔDAS28 > 1.2). SFLC were used as a measure of plasmablast activity. As sCD23 is cleaved from naïve B-cells coincident with attaining CD27 expression, levels were used as a novel measure of maturation of B-cells to CD27+. The most consistent changes between baseline and B-cell depletion within all 3 cycles were in SFLC, sCD23 and IgM-RhF which fell and in BAFF levels which rose. After 3 complete cycles of BCDT, both IgM autoantibodies and IgG-CCP had decreased, BAFF levels were higher (all p < 0.05); other analytes remained unchanged compared with baseline. Dynamic changes in λSFLC, sCD23, IgM-RhF and BAFF were also consistently associated with relapse in patients with longer clinical responses after B-cell return. Incremental rises in sCD23 levels in cycles 2 and 3 were correlated with time to relapse. Repopulation of the periphery after BCDT is initiated by naïve B-cells and precedes relapse. Our study showed that differentiation into plasmablasts, attended by sCD23 and SFLC production and IgM-RhF specificity may be required to precipitate relapse in patients experiencing longer responses after RTX. These studies also provide novel information related to the resumption of autoimmune responses and their association with B-cell kinetics following BCDT.
25475240 Constitutively altered frequencies of circulating follicullar helper T cell counterparts a 2014 Dec 5 INTRODUCTION: Circulating CD4 T cells expressing CXCR5, ICOS and/or PD-1 are counterparts of follicular helper T cells (Tfh). There are three subpopulations of circulating Tfh (cTfh): CXCR5 + CXCR3 + CCR6- (Tfh-Th1), CXCR5 + CXCR3-CCR6- (Tfh-Th2) and CXCR5 + CXCR3-CCR6+ (Tfh-Th17). Our objective was to study the B cell helping capacity of cTfh subsets, and examine their frequency in Rheumatoid Arthritis (RA) patients, together with the frequency of circulating plasmablasts (CD19 + CD20-CD38high). METHODS: Peripheral blood was drawn from RA patients with active disease (RA-a, DAS28 >2.6) (n = 17), RA in remission (RA-r, DAS28 <2.6) (n = 17) and healthy controls (HC) (n = 34). cTfh and plasmablast frequencies were determined by flow cytometry. Cocultures of sorted CD4 + CXCR5+ T cell subpopulations were established with autologous CD19 + CD27- naïve B cells of HC, and concentrations of IgG, A and M were measured in supernatants. RESULTS: Isolated Tfh-Th2 and Tfh-Th17 but not Tfh-Th1 cells, induced naïve B cells to secrete IgG and IgA. The frequency of CXCR5+ cells gated for CD4+ T cells was not different among HC, RA-a and RA-r. In contrast, both RA-a and RA-r patients demonstrated an increased frequency of CD4 + CXCR5 + ICOS+ T cells and augmented (%Tfh-Th2 + %Tfh-Th17)/%Tfh-Th1 ratio as compared with HC. In addition, RA-a but not RA-r patients, showed an increased frequency of circulating plasmablasts. CONCLUSION: Both RA-a and RA-r patients demonstrate an increased frequency of cTfh and overrepresentation of cTfh subsets bearing a B cell helper phenotype, suggesting that altered germinal center dynamics play a role in RA pathogenesis. In contrast, only RA-a patients show an increased proportion of circulating plasmablasts.
25227967 Initial high-dose prednisolone combination therapy using COBRA and COBRA-light in early rh 2015 Treatment with initial high-dose prednisolone and a combination of methotrexate (MTX) and sulfasalazine (SSZ) according to the COBRA regimen (Dutch acronym for combinatietherapie bij reumatoide artritis, 'combination therapy for rheumatoid arthritis'), has repeatedly been demonstrated to be very effective in early rheumatoid arthritis (RA). COBRA combination therapy is superior to initial monotherapy of SSZ and MTX, is also associated with a good long-term outcome, is as safe as other treatment regimes, and performs as well as the combination of high-dose MTX and the tumor necrosis factor antagonist infliximab. A pilot study with an intensified version of the COBRA combination therapy showed that strict monitoring and aggressive treatment intensification based on the Disease Activity Score can result in a remission rate of 90% in patients with active early RA. Also, the first results indicate that an attenuated variation on COBRA combination therapy, called 'COBRA-light', is effective in decreasing disease activity and is generally well tolerated. Based on these results, we conclude that initial high-dose prednisolone in combination with MTX and SSZ could or should be the first choice in early active RA since it is effective and safe, and the cost price of the drugs is low.
25037187 Rheumatoid nodule in the lower lip of a patient with rheumatoid arthritis: a novel case re 2014 Aug PURPOSE: Rheumatoid nodules are a well-characterized common extra-articular manifestation of rheumatoid arthritis. However, the occurrence of a rheumatoid nodule in the oral mucosa is extremely rare. PATIENTS AND METHODS: We present the case of a rheumatoid nodule in the lower lip, which rarely presents with variations in the clinical manifestation, that occurred in a 48-year-old female patient with rheumatoid arthritis. The nodule was totally excised under the clinical diagnosis of either a fibroma or salivary gland lesion. RESULTS: On histopathologic examination, within the deep mucosa, a necrobiotic nodule surrounded by elongated histiocytic cells with a focal palisaded arrangement. The lesion was diagnosed postoperatively as a rheumatoid nodule from the histopathologic and clinical findings. CONCLUSIONS: Few studies have been performed of oral rheumatoid lesions; however, a review of the published data showed that this is the first case of a rheumatoid nodule in the lower lip of a patient with rheumatoid arthritis.
25082556 Comparison of the effect of 18-month daily teriparatide administration on patients with rh 2014 Dec Patients with rheumatoid arthritis showed greater response to 18-month administration of daily teriparatide especially in the increase of bone formation markers at 1 month and femoral neck bone mineral density at 18 months compared to postmenopausal osteoporosis patients. INTRODUCTION: The aim of this study was to evaluate the effects of 18-month administration of daily teriparatide (TPTD) in osteoporosis patients with rheumatoid arthritis (RA) by comparing that of postmenopausal osteoporosis patients (Porosis). METHODS: The effects of TPTD were examined between RA (n = 70; age 68.4 years; disease activity score assessing 28 joints with CRP [DAS28-CRP] 2.8; rheumatoid factor [RF] positivity 75.5 %) with 77.1 % of prior bisphosphonate (BP), 84.3 % of oral prednisolone (PSL) (4.4 mg/day at baseline), 25.7 % of biologics, and Porosis (n = 62; age 71.3 years) with 77.4 % of prior BP. RESULTS: Femoral neck (FN) bone mineral density (BMD) increase at 18 months was significantly greater in RA compared to Porosis (4.7 vs. 0.7 %, P = 0.038), whereas it was 9.7 versus 7.9 % (P = 0.736) in the lumbar spine (LS). The increase of bone formation markers (bone alkaline phosphatase [bone ALP] and N-terminal type I procollagen propeptide [PINP]) at 1 month were all significantly greater in RA compared to Porosis. A multivariate logistic regression analysis revealed that the significant indicator of 18-month BMD increase in RA was a 3-month increase of under-carboxylated osteocalcin (ucOC) for LS (β = 0.446, P = 0.005) and baseline ucOC for FN (β = 0.554, P = 0.001), in which both showed significant negative correlation with baseline PSL dose. CONCLUSIONS: RA showed greater response to daily TPTD administration, especially in the increase of bone formation markers at 1 month and FN BMD increase at 18 months compared to Porosis.
24827875 The role of interferon-gamma release assays in predicting the emergence of active tubercul 2016 May Conversions and reversions of interferon-gamma (IFN-γ) release assays (IGRAs) were observed when these tests were repeated over time in the same individuals, including those treated with biological agents. In most studies, the variability of IFN-γ plasma levels was not paralleled by clinical change, but a few exceptions exist, in which IGRA conversion predicted the emergence of active tuberculosis (TB). We report the case of a Peruvian patient with rheumatoid arthritis (RA) and Crohn's disease scheduled for treatment with adalimumab. TB screening demonstrated latent TB infection (LTBI), and the patient was started on isoniazid (INH) for 9 months. Adalimumab was initiated after 1 month since INH. QuantiFERON-TB Gold In-Tube, one of the IGRAs currently available, was serially repeated to monitor the status of TB infection during treatment with the biological agent. The patient developed active TB preceded by progressively rising levels of released IFN-γ. We came to know that she had withdrawn INH after 2 months on her own initiative. Considering the low rate of INH completion, serial IGRAs may help in the clinical vigilance during prophylaxis as well as anti-TNF treatment, at least in patients presenting other risk factors aside from the state of immunosuppression.
22999907 Two cases of Takayasu's arteritis occurring under anti-TNF therapy. 2013 Mar Takayasu's arteritis is a granulomatous, large vessel vasculitis that affects the aorta, its major branches and the pulmonary arteries. Compelling evidence exists to support the notion that Takayasu's arteritis is a T-cell mediated process and that tumor necrosis factor alpha (TNFa) is an important factor in the pathogenesis of this disease. Moreover, encouraging results from recent studies support the use of anti-TNFa therapy for relapsing or resistant cases of Takayasu's arteritis. Here, however, we describe the case of two patients: one with seropositive rheumatoid arthritis, the other with HLA-B27 negative spondylarthropathy, who developed Takayasu's arteritis during treatment with TNFa inhibitors (adalimumab and golimumab respectively). This is the first report of Takayasu's arteritis in rheumatic patients under TNFa blocking agents which suggests the presence of different pathogenetic mechanism in a subgroup of patients with Takayasu's arteritis, as well as a potential role of TNFa blockers as triggers of this disease in some cases.
24584485 Perceived injustice in fibromyalgia and rheumatoid arthritis. 2014 This is a pilot study to compare levels of perceived injustice via the Injustice Experience Questionnaire in patients with fibromyalgia or rheumatoid arthritis. Two cohorts of patients, one with fibromyalgia (FM), one with rheumatoid arthritis (RA), completed the Injustice Experience Questionnaire, a visual analogue pain scale, and the Hospital Anxiety and Depression Scale (HADS). Inferential statistics were then used to determine whether participants in the two diagnostic groups had significantly different scores on the Perceived Injustice Questionnaire. This was done univariately using t tests and after adjusting for potential confounders using ANCOVA. We also examined crude associations between the variables using Pearson correlation coefficients, then examined the adjusted association between diagnostic group and perceived injustice using multivariable linear regression. Our final models were built in a blocked fashion by initially entering diagnostic category into the model, then entering other variables simultaneously using a stepwise strategy (p-to-enter ≤.05, p-to-remove ≥.10). A total of 126 participants (64 FM, 62 RA) completed all questionnaires. The FM group had a greater percentage of female participants, more severe pain, more severe anxiety and more severe depression. In unadjusted analysis, the FM group had higher Injustice Experience Questionnaire scores. When the RA and FM group scores for the Injustice Experience Questionnaire are adjusted for pain levels, there is no statistically significant difference between groups. Adjustment for HADS anxiety and HADS depression does not significantly affect the Injustice Experience Questionnaire scores after adjustment for pain. Fibromyalgia is associated with a higher level of perceived injustice than is seen with rheumatoid arthritis. This difference appears to be associated with higher levels of pain reported by fibromyalgia patients, and therefore may not be specific to the diagnosis. Prospective studies may help to resolve this issue.
24062057 Expression of programmed death-1 (PD-1) on CD4+ and CD8+ T cells in rheumatoid arthritis. 2014 Feb Rheumatoid arthritis (RA) is characterized by chronic inflammatory process that targets the synovial lining of diarthrodial joints. Programmed death 1 (PD-1) plays a key role in the negative regulation of the immune response. In the current study, we investigated the expression of PD-1 on peripheral CD4+ and CD8+ T cells in RA patients. Percentage of PD-1+ cells was measured by flow cytometry in 82 RA cases and 90 healthy controls. Results showed that PD-1 expression was significantly decreased in both peripheral CD4+ and CD8+ T cells in RA (p = 0.002 and p < 0.001, respectively). Similarly, serum levels of soluble PD-1 were also downregulated in RA cases. When comparing PD-1 level in RA patients with different clinical parameters, patients with positive C-reactive protein (CRP) revealed lower proportion of PD-1 on CD4+ and CD8+ T cells than those with negative CRP. Also, disease activity score of RA patients was inversely correlated with PD-1 expression on peripheral CD4+ and CD8+ T cells. These data suggested that PD-1 may act as a negative regulator in the pathogenesis and progression of RA.
23949659 The association between n-3 polyunsaturated fatty acid levels in erythrocytes and the risk 2013 BACKGROUND: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases that result in chronic inflammation of the joints. n-3 polyunsaturated fatty acids (PUFAs) have been suggested to play a role in the pathogenesis and clinical course of RA. The purpose of the present study was to investigate whether erythrocyte levels of n-3 PUFA are associated with an increased risk of RA and whether this could potentially serve as an indicator of RA disease activity in Korean women. METHODS: A total of 100 female RA patients and 100 healthy women were enrolled into this study. Erythrocyte fatty acid composition and RA disease activity were evaluated in all patients. RESULTS: Erythrocyte levels of α-linolenic acid (ALA; 18:3n3), eicosapentaenoic acid (EPA; 20:5n3), and the omega-3 index [EPA + docosahexaenoic acid (DHA)] were significantly lower in RA patients than in healthy controls. Multivariable-adjusted regression analysis showed that the levels of ALA, EPA, and the ratio of EPA to arachidonic acid were negatively associated with the risk of RA after adjusting for body weight and smoking status. Additionally, the concentration of prostaglandin E2 was significantly decreased with increased levels of erythrocyte DHA among RA patients. CONCLUSIONS: Erythrocyte levels of EPA and ALA were negatively associated with the risk of RA in Korean women, which may be related to eicosanoid metabolism.
23087184 Why the findings of published multiple treatment comparison meta-analyses of biologic trea 2013 Sep 1 OBJECTIVES: To evaluate the quality of published multiple treatment comparison (MTC) meta-analyses on biologic disease modifying antirheumatic drugs (bDMARDs) for rheumatoid arthritis (RA), and to identify methodological issues that can explain the discrepancies in the findings of these MTCs. METHODS: We searched MEDLINE for MTCs of bDMARDs for RA. Following the PRISMA guidelines, we extracted a large set of methodological items. These comprised of inclusion/exclusion criteria, information sources, reported results and outcomes measures, approaches to dealing with differing response profiles to available treatments, monotherapies versus combination therapies, and potential sources of heterogeneity. RESULTS: We identified 13 published MTCs, of which nine were published since 2009. Despite similar stated eligibility criteria and objectives across MTCs, we identified major discrepancies in the estimated treatment effects, the inclusion of trials and analytic approaches. The number of included trials was typically much smaller than the number of eligible trials at the time of publication. Three out of six MTCs including patients of differing response profiles inappropriately combined DMARD-naive and DMARD-inadequate responder patients in the analyses. Four out of eight MTCs that considered both monotherapy and combination therapy (ie, concomitant DMARD) did not adjust for the potential effect modification. Half of the identified MTCs did not explore potential sources of heterogeneity, and the explored sources varied considerably. Last, most MTCs only included one or two efficacy outcomes (eg, ACR50) and only two considered health related quality of life outcomes (eg, HAQ). CONCLUSIONS: The identified methodological shortcomings and inconsistencies most likely explain the observed discrepancies in findings across MTCs.
24834463 Radial deviation of the finger caused by an occult intramuscular ganglion in a patient wit 2016 Jul Ulnar deviation is a common complication in patients with rheumatoid arthritis (RA). We report a case of an unusual radial deviation of the middle finger caused by an occult intramuscular ganglion of the second interosseous muscle (IOM) in a patient with RA. The resection of the ganglion did not resolve the problem, and the full range of motion of the metacarpophalangeal (MP) joint was achieved through dissection of the tendon of the second dorsal IOM.
23149338 Progranulin antibodies in autoimmune diseases. 2013 May Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis.
24445255 The specificity of ultrasound-detected bone erosions for rheumatoid arthritis. 2015 May BACKGROUND: Bone erosion is one of the hallmarks of rheumatoid arthritis (RA), but also seen in other rheumatic diseases. The objective of this study was to determine the specificity of ultrasound (US)-detected bone erosions (including their size) in the classical 'target' joints for RA. METHODS: Patients fulfilling the diagnostic criteria for RA, psoriatic arthritis, osteoarthritis or gout in addition to healthy volunteers were included. The following areas were examined by US: distal radius and ulna, 2nd, 3rd and 5th metacarpophalangeal (MCP), 2nd and 3rd proximal interphalangeal (PIP) and 1st and 5th metatarsophalangeal (MTP) joints. All joints were scanned in four quadrants using both semiquantitative (0-3) and quantitative (erosion diameter) scoring systems. RESULTS: 310 subjects were recruited. The inter-reader and intrareader agreements were good to excellent. US-detected bone erosions were more frequent but not specific for RA (specificity 32.9% and sensitivity 91.4%). The presence of erosions with semiquantitative score ≥2 in four target joints (2nd, 5rd MCP, 5th MTP joints and distal ulna) was highly specific for RA (specificity 97.9% and sensitivity 41.4%). Size of erosion was found to be associated with RA. Erosions of any size in the 5th MTP joint were both specific and sensitive for RA (specificity 85.4% and sensitivity 68.6%). CONCLUSIONS: The presence of US-detected erosions is not specific for RA. However, larger erosions in selected joints, especially 2nd and 5rd MCP, 5th MTP joints and distal ulna, were highly specific for and predictive of RA.
25299390 Alveolar bone loss is associated with circulating anti-citrullinated protein antibody (ACP 2015 Feb BACKGROUND: This study examines: 1) alveolar bone loss (ABL), a hallmark of periodontitis, in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) patients versus control patients with osteoarthritis (OA); and 2) the association of ABL with RA disease activity and ACPA concentrations, including multiple antigen-specific ACPA. METHODS: This multicenter case-control study includes 617 patients diagnosed with RA (n = 287) or OA (n = 330). Panoramic radiographs were taken; patients were categorized into low, moderate, or high tertiles based on mean percentage ABL. Serum ACPA was measured using second-generation anticyclic citrullinated peptide enzyme-linked immunosorbent assay and a multiplex platform to assess distinct antigen-specific ACPA. A generalized linear mixed model for binary data was used to compare stratified ABL in RA versus OA patients. Associations of moderate and high ABL (versus low) with RA disease activity and severity measures were examined using multivariate regression. Antigen-specific ACPA responses were compared among ABL tertiles using significance analysis of microarrays. RESULTS: ACPA-positive patients with RA had a significantly higher mean percentage of sites with ABL >20% compared with patients with OA (P = 0.03). After multivariate adjustment, greater ABL was significantly associated with higher serum ACPA concentration (P = 0.004), 28-joint Disease Activity Score (P = 0.023), health assessment questionnaire disability (P = 0.05), tender joint count (P = 0.02) and joint space narrowing scores (P = 0.05) among patients with RA. ACPAs targeting citrullinated vimentin and histone were significantly higher in moderate and high ABL groups versus low, regardless of smoking status (q <0.1%). CONCLUSIONS: Greater ABL was associated with higher ACPA, consistent with findings at articular sites. ACPA targeting could provide novel insight into important linkages between RA and periodontitis.
25571733 [Correlation between quantitative results of contrast-enhanced ultrasonography and clinica 2014 Nov OBJECTIVE: To determine the correlation between quantitative results of contrast enhanced ultrasound and clinical and laboratory index for synovium of patients with rheumatoid arthritis (RA). METHODS: Thirty five RA patients participated in this study, with ten normal adults serving as controls. They were given a score of DAS28 and underwent laboratory tests, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Contrast-enhanced ultrasound examinations were performed to detect thickness of synovium (2D and Power Dopple). RESULTS: Peak intensity (PI) and area under the curve (AUC) were positively correlated with ESR, CRP and DAS28 score, respectively (P<0. 01). The rest of ultrasound parameters had no significant correlations with ESR, CRP and DAS28 score (P>0. 05). Synovium thickness identified by contrast enhanced ultrasound had significant correlations with ESR, CRP and DAS28 score (P < 0. 01). CONCLUSION: Synovium thickness determined by contrast enhanced ultrasound, PI and AUC can serve as an index estimating inflammatory activity of RA, and provide evidence for clinical diagnosis and treatment.
24939720 Characterization and evaluation of triamcinolone, raloxifene, and their dual-loaded micros 2014 Aug In this study, injectable microspheres were developed for the local treatment of joint degeneration in rheumatoid arthritis (RA). Microspheres loaded with triamcinolone (TA), a corticosteroid drug, and/or raloxifene (Ral), a cartilage regenerative drug, were prepared with a biodegradable and biocompatible polymer, polycaprolactone (PCL). Microspheres were optimized for particle size, structural properties, drug release, and loading properties. In vitro release of Ral was very slow because of the low solubility of the drug and hydrophobic nature of PCL. However, when coloaded with TA, both drugs were released at higher amounts compared with their single forms. Smallest particle sizes were obtained in dual drug-loaded microspheres. In vitro cytotoxicity tests showed biocompatibility of microspheres. In vivo bioefficacy of these microspheres was also examined in adjuvant-induced arthritis model in rats. In vivo histological studies of control groups showed development of RA with high median lesion score (5.0). Compared with control and intra-articular free drug injections, microsphere treatment groups showed lower lesion scores and better healing outcomes in histological evaluations. Results suggest that a controlled delivery system of TA and RAL by a single injection in inflamed joints holds promise for healing and suppressing inflammation.
24333119 Update of the Mexican College of Rheumatology guidelines for the pharmacologic treatment o 2014 Jul BACKGROUND: The pharmacologic management of rheumatoid arthritis has progressed substantially over the past years. It is therefore desirable that existing information be periodically updated. There are several published international guidelines for the treatment of rheumatoid arthritis that hardly adapt to the Mexican health system because of its limited healthcare resources. Hence, it is imperative to unify the existing recommendations and to incorporate them to a set of clinical, updated recommendations; the Mexican College of Rheumatology developed these recommendations in order to offer an integral management approach of rheumatoid arthritis according to the resources of the Mexican health system. OBJECTIVE: To review, update and improve the available evidence within clinical practice guidelines on the pharmacological management of rheumatoid arthritis and produce a set of recommendations adapted to the Mexican health system, according to evidence available through December 2012. METHODS: The working group was composed of 30 trained and experienced rheumatologists with a high quality of clinical knowledge and judgment. Recommendations were based on the highest quality evidence from the previously established treatment guidelines, meta-analysis and controlled clinical trials for the adult population with rheumatoid arthritis. RESULTS: During the conformation of this document, each working group settled the existing evidence from the different topics according to their experience. Finally, all the evidence and decisions were unified into a single document, treatment algorithm and drug standardization tables. CONCLUSIONS: This update of the Mexican Guidelines for the Pharmacologic Treatment of Rheumatoid Arthritis provides the highest quality information available at the time the working group undertook this review and contextualizes its use for the complex Mexican health system.