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ID PMID Title PublicationDate abstract
24659149 [Inpatient rheumatology treatment in Germany]. 2014 Mar Acute inpatient treatment plays an important role in the care of patients with rheumatic diseases in Germany. Inpatient facilities are usually departments in general hospitals or highly specialized clinics. The introduction of the diagnosis-related groups (DRG) system has led to a change in form which is most obviously characterized by more homogeneous structures and shorter hospital stays. Many rheumatic patients are, however, treated in general hospitals due to a lack of specialized clinics. The presence of a department of rheumatology in medical schools is deficient which therefore leads to only a small number of specialists in rheumatology. The rheumatologists in inpatient facilities are also involved in the care of outpatients, whereby the number of licensed internal medical rheumatologists is declining. Further possibilities in outpatient treatment in hospitals were created with new governmental regulations (§116b). Changes are expected with the implementation of the new outpatient specialist medical care (ASV).
25498119 Familial aggregation of arthritis-related diseases in seropositive and seronegative rheuma 2016 Jan OBJECTIVES: Our objective was to estimate the risk of developing rheumatoid arthritis (RA) associated with a family history of non-RA arthritis-related diseases. This familial co-aggregation is of clinical interest since it is often encountered when assessing family history of RA specifically, but also informative on the genetic overlap between these diseases. Since anticitrullinated peptide antibodies/rheumatoid factor (RF)-positive and RF-negative RA have both specific and shared genetic factors, the familial co-aggregation was assessed separately for seropositive and seronegative disease. METHODS: Nested case-control study in prospectively recorded Swedish total population data. The Multi-Generation Register identified first-degree relatives. RA and arthritis-related diseases were ascertained through the nationwide patient register. RA serology was based on International Classification of Diseases tenth revision coded diagnoses, mainly reflecting RF. Familial risks were calculated using conditional logistic regression. Results were replicated using the Swedish rheumatology register. RESULTS: Familial co-aggregation was found between RA and every studied arthritis-related disease, but the magnitude varied widely, from juvenile idiopathic arthritis (JIA) (seropositive RA OR=3.98 (3.01 to 5.26); seronegative RA OR=5.70 (3.47 to 9.36)) to osteoarthritis (seropositive RA OR=1.03 (1.00 to 1.06); seronegative RA OR=1.05 (1.00 to 1.09)). The familial co-aggregation pattern of non-RA arthritis-related diseases was overall similar for seropositive and seronegative RA. Among those with family history of RA, relatives' other arthritis-related diseases conferred little or no additional risk. CONCLUSIONS: Although family history of several arthritis-related diseases may be useful to predict RA (eg, lupus and JIA), others (eg, osteoarthritis and arthralgia) are less useful. Seropositive and seronegative RA had rather similar familial co-aggregation patterns with arthritis-related diseases, suggesting that the two RA subsets are similar in the genetic factors that overlap with these diseases.
24983407 Inhibition of radiographic joint damage in rheumatoid arthritis patients in DAS28 remissio 2015 Jan OBJECTIVE: We retrospectively investigated the inhibitory effect on radiographic joint damage (RJD) for non-biological disease-modifying antirheumatic drug (non-bioDMARD) monotherapy or methotrexate (MTX) combination therapy for rheumatoid arthritis (RA) in the disease activity score with 28 joint counts with erythrocyte sedimentation rate (DAS28) remission. METHODS: Eighty-four patients (55 cases of monotherapy, 29 cases of MTX-combination therapy) in DAS28 remission (DAS28 ≤ 2.6) were investigated from 538 RA patients newly registered between February 2007 and August 2010. The patients were analyzed for radiological assessments using the modified total Sharp score/year (mTSS/y). RESULTS: The remission rates and ΔmTSS/y for each agent using monotherapy were 7.1% and 0.17 for sulfasalazine; 11.9% and 0.49 for bucillamine (BUC); and 23.9% and 2.06 for MTX. Those using combination therapy were 6.8% and 1.39 for MTX + BUC; 23.5% and -1.64 for MTX + leflunomide; and 8.0% and 0.31 for MTX + tacrolimus. The cumulative distribution in the single and combination therapy groups showed improvement of percentages in structural remission from baseline to 1-year treatment, 34.1% to 60.9% (P < 0.05) and from 0% to 56.7%(P < 0.0001), respectively. Baseline mTSS (r = 0.67, P < 0.0001), disease duration (r = 0.40, P < 0.01), swollen joint counts (r = 0.33, P < 0.05), and anti-cyclic citrullinated peptide antibody (r = 0.31, P < 0.05) were useful predictors of RJD for non-bioDMARD monotherapy, but not for combination therapy. CONCLUSION: Satisfactory inhibition of RJD was observed in the DAS28 remission cases of monotherapy or MTX combination therapy with a non-bioDMARD.
23741349 Detection of subclinical synovial inflammation by microwave radiometry. 2013 OBJECTIVE: Microwave Radiometry is a non-invasive method which determines within seconds the in vivo temperature of internal tissues at a depth of 3-7 cm with an accuracy of ±0.2°C. In this proof-of-concept study, we tested the hypothesis that, in absence of relevant clinical signs, increased local temperature detected by microwave radiometry reflects subclinical synovial inflammation, using ultrasound as reference method. METHODS: Knees of healthy controls, subjects with recent knee trauma and symptom-free patients with rheumatoid arthritis (RA) or osteoarthritis were examined by placing the microwave radiometry sensor, a) at the upper one third of the anterior surface of the thigh (control-point), and b) over the suprapatellar recess. Ultrasound was performed immediately after and the possible presence of fluid and/or synovitis was correlated with microwave radiometry findings. RESULTS: In 30 healthy and 10 injured knees the temperature was always lower than thigh (32.3±1.1 and 31.8±1.4 versus 34.1±0.9 and 33.6±1.2°C with a difference (ΔΤ) of -1.8±0.2 and -1.9±0.4°C respectively). Of 40 RA and 20 osteoarthritis knees examined, ultrasound findings indicative of subclinical inflammation (fluid effusion and/or Doppler signal) were found in 24 and 12, respectively, in which the temperature was higher than healthy knees and ΔΤ was lower (-0.9±0.7 in RA and -1.0±0.5 in osteoarthritis versus -1.8±0.2°C, p<0.001). The 5 RA knees with power Doppler findings indicative of grade 2 inflammation had a ΔΤ 3 times lower compared to healthy (-0.6±0.6, p = 0.007), whereas the 9 RA and the 7 osteoarthritis knees with additionally fluid effusion, had even lower ΔΤ (-0.4±0.7, p<0.001). CONCLUSION: Using a safe, rapid and easy-to-perform method, such as microwave radiometry, thermal changes within the knee joint may reflect non-clinically apparent joint inflammation. Refinement of this method, including production of sensors for small joints, could result to the development of the ideal objective tool to detect subclinical synovitis in clinical practice.
24574210 Features of the synovium of individuals at risk of developing rheumatoid arthritis: implic 2014 Mar OBJECTIVE: Findings from previous studies have suggested that subclinical inflammation of the synovium does not coincide with the appearance of rheumatoid arthritis (RA)-specific autoantibodies. This study was undertaken to examine the relationship between the presence of autoantibodies, changes in the synovium, and development of arthritis over time in a markedly larger, prospective study. METHODS: Fifty-five individuals who were IgM rheumatoid factor positive and/or anti-citrullinated protein antibody (ACPA) positive (detected by the anti-cyclic citrullinated peptide antibody test) and who were without any evidence of arthritis upon physical examination were included in the study. ACPAs were subsequently also detected using a multiplex chip-based assay. All individuals underwent magnetic resonance imaging and mini-arthroscopic synovial biopsy sampling of a knee joint at inclusion and were prospectively followed up. Proportional hazards regression analysis was performed to investigate whether changes in the synovium were associated with the onset of arthritis. RESULTS: Fifteen individuals (27%) developed arthritis after a median followup time of 13 months (interquartile range 6-27 months; range 1-47 months). No overt synovial inflammation was observed, but CD3+ T cell numbers in the biopsy tissue showed a borderline association with subsequent development of clinically manifest arthritis (hazard ratio 2.8, 95% confidence interval [95% CI] 0.9-9.1; P = 0.088). In addition, the presence of CD8+ T cells was associated with ACPA positivity (odds ratio [OR] 16.0, 95% CI 1.7-151.1) and with the total number of ACPAs present (OR 1.4, 95% CI 1.0-1.8). CONCLUSION: These findings confirm and extend previous results showing the absence of clearcut synovial inflammation in individuals having systemic autoimmunity associated with RA. However, subtle infiltration by synovial T cells may precede the signs and symptoms of arthritis in preclinical RA.
23460124 Metabolic profiling predicts response to anti-tumor necrosis factor α therapy in patients 2013 Jun OBJECTIVE: Anti-tumor necrosis factor (anti-TNF) therapies are highly effective in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), but a significant number of patients exhibit only a partial or no therapeutic response. Inflammation alters local and systemic metabolism, and TNF plays a role in this. We undertook this study to determine if the patient's metabolic fingerprint prior to therapy could predict responses to anti-TNF agents. METHODS: Urine was collected from 16 RA patients and 20 PsA patients before and during therapy with infliximab or etanercept. Urine metabolic profiles were assessed using nuclear magnetic resonance spectroscopy. Discriminating metabolites were identified, and the relationship between metabolic profiles and clinical outcomes was assessed. RESULTS: Baseline urine metabolic profiles discriminated between RA patients who did or did not have a good response to anti-TNF therapy according to European League Against Rheumatism criteria, with a sensitivity of 88.9% and a specificity of 85.7%, with several metabolites contributing (in particular histamine, glutamine, xanthurenic acid, and ethanolamine). There was a correlation between baseline metabolic profiles and the magnitude of change in the Disease Activity Score in 28 joints from baseline to 12 months in RA patients (P = 0.04). In both RA and PsA, urinary metabolic profiles changed between baseline and 12 weeks of anti-TNF therapy. Within the responders, urinary metabolite changes distinguished between etanercept and infliximab treatment. CONCLUSION: The clear relationship between urine metabolic profiles of RA patients at baseline and their response to anti-TNF therapy may allow development of novel approaches to the optimization of therapy. Differences in metabolic profiles during treatment with infliximab and etanercept in RA and PsA may reflect distinct mechanisms of action.
24692576 Increased risk of rheumatoid arthritis in women with pregnancy complications and poor self 2014 Aug OBJECTIVE: This study assessed the suggested association between pregnancy-associated hypertensive disorders, hyperemesis and subsequent risk of RA using a cohort with information about pre-pregnancy health. METHODS: Self-reported information on pre-pregnancy health, pregnancy course, gestational hypertension, pre-eclampsia and hyperemesis was available from 55 752 pregnant women included in the Danish National Birth Cohort. Information about pregnancy-related factors and lifestyle was obtained by interviews twice during pregnancy and at 6 months post-partum. Women were followed for RA hospitalizations identified in the Danish National Patient Register. Hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards models. Women with RA and non-specific musculoskeletal problems at the time of pregnancy were excluded. RESULTS: On average, women were followed for 11 years after childbirth and 169 cases of RA were identified. The risk of RA was increased in women with pre-eclampsia (n = 11, HR = 1.96, 95% CI 1.06, 3.63), a poor self-rated pregnancy course (n = 32, HR = 1.63, 95% CI 1.11, 2.39) and fair or poor self-rated pre-pregnancy health (fair health: n = 86, HR = 1.52, 95% CI 1.11, 2.09; poor health: n = 14, HR = 3.24, 95% CI 1.82, 5.76). Hyperemesis was not associated with risk of RA. CONCLUSION: We confirmed the previously suggested increased risk of RA in women with pre-eclampsia and also found an inverse association between self-rated pre-pregnancy health and risk of RA. These results suggest that the clinical onset of RA is preceded by a prolonged subclinical phase that may interfere with women's general well-being and pregnancy course or that some women carry a shared predisposition to pre-eclampsia and RA.
24584927 Establishing a core domain set to measure rheumatoid arthritis flares: report of the OMERA 2014 Apr OBJECTIVE: The OMERACT Rheumatoid Arthritis (RA) Flare Group (FG) is developing a data-driven, patient-inclusive, consensus-based RA flare definition for use in clinical trials, longterm observational studies, and clinical practice. At OMERACT 11, we sought endorsement of a proposed core domain set to measure RA flare. METHODS: Patient and healthcare professional (HCP) qualitative studies, focus groups, and literature review, followed by patient and HCP Delphi exercises including combined Delphi consensus at Outcome Measures in Rheumatology 10 (OMERACT 10), identified potential domains to measure flare. At OMERACT 11, breakout groups discussed key domains and instruments to measure them, and proposed a research agenda. Patients were active research partners in all focus groups and domain identification activities. Processes for domain selection and patient partner involvement were case studies for OMERACT Filter 2.0 methodology. RESULTS: A pre-meeting combined Delphi exercise for defining flare identified 9 domains as important (>70% consensus from patients or HCP). Four new patient-reported domains beyond those included in the RA disease activity core set were proposed for inclusion (fatigue, participation, stiffness, and self-management). The RA FG developed preliminary flare questions (PFQ) to measure domains. In combined plenary voting sessions, OMERACT 11 attendees endorsed the proposed RA core set to measure flare with ≥78% consensus and the addition of 3 additional domains to the research agenda for OMERACT 12. CONCLUSION: At OMERACT 11, a core domain set to measure RA flare was ratified and endorsed by attendees. Domain validation aligning with Filter 2.0 is ongoing in new randomized controlled clinical trials and longitudinal observational studies using existing and new instruments including a set of PFQ.
23429352 Extraarticular manifestations of rheumatoid arthritis in a multiethnic cohort of predomina 2013 Mar We conducted a study to determine the prevalence of extraarticular manifestations (ExRA) in a cohort of predominantly Hispanic and Asian patients with rheumatoid arthritis (RA), to identify factors associated with the development of ExRA, and to compare the prevalence of ExRA between Hispanic and Asian patients. Patients with RA followed in the outpatient rheumatology clinics of a public hospital were included if they were aged ≥18 years and met the 1987 American College of Rheumatology criteria for the diagnosis of RA. We performed a cross-sectional analysis in which patients with ExRA were identified based on predefined criteria. We compared sociodemographic and clinical characteristics in patients with and without ExRA. Multivariate logistic regression was used to examine the association between sociodemographic variables, clinical characteristics, and the presence of ExRA. The prevalence of ExRA was 21.5%, and the most common manifestations were subcutaneous nodules (17.2%) and interstitial lung disease (3.6%). Hispanic patients were significantly more likely to develop ExRA than Asian patients (odds ratio, 2.53; 95% confidence interval, 1.26-5.09). The development of ExRA was also associated with disease duration, male sex, and seropositivity for serum rheumatoid factor.
23887879 Quantitative in vivo HR-pQCT imaging of 3D wrist and metacarpophalangeal joint space width 2013 Dec In this technique development study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was applied to non-invasively image and quantify 3D joint space morphology of the wrist and metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA). HR-pQCT imaging (82 μm voxel-size) of the dominant hand was performed in patients with diagnosed rheumatoid arthritis (RA, N = 16, age: 52.6 ± 12.8) and healthy controls (CTRL, N = 7, age: 50.1 ± 15.0). An automated computer algorithm was developed to segment wrist and MCP joint spaces. The 3D distance transformation method was applied to spatially map joint space width, and summarized by the mean joint space width (JSW), minimal and maximal JSW (JSW.MIN, JSW.MAX), asymmetry (JSW.AS), and distribution (JSW.SD)-a measure of joint space heterogeneity. In vivo precision was determined for each measure by calculating the smallest detectable difference (SDD) and root mean square coefficient of variation (RMSCV%) of repeat scans. Qualitatively, HR-pQCT images and pseudo-color JSW maps showed global joint space narrowing, as well as regional and focal abnormalities in RA patients. In patients with radiographic JSN at an MCP, JSW.SD was two-fold greater vs. CTRL (p < 0.01), and JSW.MIN was more than two-fold lower (p < 0.001). Similarly, JSW.SD was significantly greater in the wrist of RA patients vs. CTRL (p < 0.05). In vivo precision was highest for JSW (SDD: 100 μm, RMSCV: 2.1%) while the SDD for JSW.MIN and JSW.SD were 370 and 110 μm, respectively. This study suggests that in vivo quantification of 3D joint space morphology from HR-pQCT, could improve early detection of joint damage in rheumatological diseases.
23826623 Co-morbidities in Finnish patients with rheumatoid arthritis: 15-year follow-up. 2013 OBJECTIVES: To study the prevalence and importance of co-morbidities in patients with rheumatoid arthritis (RA) at the time of the diagnosis and after a 15-year follow-up, focusing on the relationship between co-morbidity and disease activity. METHOD: The study population comprised 87 patients with early RA (mean age 44 years, 79% female, and 65% rheumatoid factor positive) collected from the Helsinki area between 1986 and 1989. Data for co-morbidities were collected at baseline and at a 15-year examination or at the time of death, and the age-weighted Charlson co-morbidity index (CCIa) at baseline was calculated for each patient. The disease activity score based on 28 joints (DAS28) was assessed with three parameters at baseline and during the first year (DAS28 AUC0-12). The relationship between co-morbidity and activity of RA was studied in groups CCIa 0, CCIa 1-2, and CCIa ≥ 3. RESULTS: Adequate data were available in 80 patients with a mean age of 60 years and a mean disease duration of 15.4 years. At baseline, 20% of patients had at least one co-morbid condition (CC). At endpoint, 60% of the patients had some co-morbidity: 34% had one CC, 19% two, 5% three, and 2% four CCs. The most common end-point CCs were hypertension (30%), cardiovascular diseases (14%), and malignancies (11%). DAS28 AUC0-12 and DAS28 at end-point were higher in groups CCIa1-2 and CCIa ≥ 3 than in CCIa 0. CONCLUSIONS: Co-morbidities increased during the 15 years of RA and the patients with high baseline CCIa showed higher disease activity both in early disease and at end-point.
24763541 Immunomodulation in human and experimental arthritis: including vitamin D, helminths and h 2014 May Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that is mainly directed to the joints, affecting the synovial membrane, the cartilage and also the bone. This disease affects 1% to 2% of the world population and is associated with significant morbidity and increased mortality. RA experimental models have allowed a great deal of information to be translated to the corresponding human disease. This review summarizes some of the most relevant findings targeting immunomodulation in arthritis. Some general guidelines to choose an adequate experimental model and also our experience with arthritis are supplied.
24891289 Treg cell function in rheumatoid arthritis is compromised by ctla-4 promoter methylation r 2014 Sep OBJECTIVE: Functionally impaired Treg cells expressing abnormally low levels of CTLA-4 have been well documented in rheumatoid arthritis (RA). However, the molecular defect underlying this reduced expression is unknown. The aims of this study were to assess the role of DNA methylation in regulating CTLA-4 expression in Treg cells isolated from RA patients and to elucidate the mechanism of their reduced suppressor function. METHODS: CTLA-4 expression in Treg cells from RA patients and healthy controls was measured by quantitative polymerase chain reaction (PCR) and flow cytometry. Methylation of the CTLA-4 gene promoter was analyzed by bisulfite-specific PCR, followed by sequencing. Methylation-dependent transcriptional activity of the CTLA-4 gene promoter was measured by luciferase assay, and NF-AT binding to the CTLA-4 gene promoter was determined by chromatin immunoprecipitation. The role of CTLA-4 expression in controlling Teff cells was analyzed using an autologous mixed lymphocyte reaction. RESULTS: Down-regulation of CTLA-4 expression in Treg cells from RA patients was caused by methylation of a previously unidentified NF-AT binding site within the CTLA-4 gene promoter. As a consequence, Treg cells were unable to induce expression and activation of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO), which in turn resulted in a failure to activate the immunomodulatory kynurenine pathway. CONCLUSION: We show for the first time that epigenetic modifications contribute to defective Treg cell function in RA through an inability to activate the IDO pathway. Therefore, this study sets a precedent for investigating potential therapeutic strategies aimed at reinforcing the IDO pathway in RA patients.
24882841 Telemedicine applied to kinesiotherapy for hand dysfunction in patients with systemic scle 2014 Jul OBJECTIVE: To describe a feasibility study focused on a telemonitoring approach to self-managed kinesiotherapy sessions for the rehabilitation of hand function in patients with systemic sclerosis (SSc) and rheumatoid arthritis (RA). METHODS: Ten patients with SSc and 10 with RA were enrolled in a 3-month controlled trial (approval no. 9751/2012 - Italian Department of Health) to perform a home kinesiotherapy protocol, consisting of strengthening and mobility exercises, using a newly developed telemedicine system (a portable device and the related telemonitoring infrastructure). A further 10 patients with SSc and 10 with RA were enrolled as controls to perform a similar home kinesiotherapy protocol with the aid of common daily-life objects. Both groups were evaluated at baseline and at followup, after 6 and 12 weeks. The primary outcome of the trial was hand function measured by Dreiser's index (Functional Index for Hand OA, FIHOA), Health Assessment Questionnaire (HAQ), and the Hand Mobility in Scleroderma (HAMIS) test (only for SSc). RESULTS: Patients with SSc showed an improvement of FIHOA in both arms (p < 0.01) but the HAQ (p = 0.016) and the HAMIS test (right hand p = 0.016, left hand p = 0.075) improved significantly only in the experimental arm. Patients with RA showed a statistically significant improvement of FIHOA (p = 0.013) and HAQ (p = 0.015) in the experimental arm, while patients in the control arm did not significantly improve. However, no statistically significant differences in outcome measures between treatment methods were observed. Withdrawals were higher in control arms (SSc 20%; RA 30%) than in experimental arms (SSc 10%; RA 10%). CONCLUSION: Telemonitoring of self-administered kinesiotherapy programs is a promising approach to the rehabilitation of hand functions in patients with rheumatic disease.
25327159 Clinical relevance of monitoring serum levels of adalimumab in patients with rheumatoid ar 2014 Nov OBJECTIVES: The aim of this paper is to assess the usefulness of measuring serum levels of adalimumab (ADL) and anti-ADL antibodies in 57 patients with rheumatoid arthritis (RA) treated with ADL for at least 3 months in daily practice. METHODS: All patients received concomitant disease-modifying anti-rheumatic drug (DMARD). Receiver-operator characteristics (ROC) analysis was used to obtain the cut-off value of ADL for low disease activity (DAS28-ESR ≤3.2). RESULTS: Anti-ADL antibodies were detected in 4 (7%) patients with a mean (SD) DAS28 score of 4.6 (0.9). Patients with positive anti-ADL antibodies had significantly lower levels of ADL and higher DAS28 scores than those with negative antibodies. Patients with DAS28 ≤3.2 as compared with patients with DAS28 >3.2 showed significantly better SDAI score, higher serum concentrations of ADL and none of them showed anti-ADL antibodies. The cut-off of serum level of ADL for DAS28 <3.2 was 4.3 mg/L. According to serum levels of ADL, patients were grouped into group 1 (low level) <5.5 mg/L, group 2 (medium level) 5.5-11.3 mg/L and group 3 (high level) >11.3 mg/L. Patients in the medium group were closed to clinical remission (median DAS28 2.7) and patients in the high group were on clinical remission (DAS28 2.1). CONCLUSIONS: Serum levels of ADL should be maintained >4.3 mg/L. In patients with ADL levels >11.3 mg/L, a decrease of the dose of ADL or an increase in the interval between doses may be planned. The presence of anti-ADL antibodies was associated with a loss of clinical efficacy of ADL.
24950169 Obstacles to the implementation of the treat-to-target strategy for rheumatoid arthritis i 2015 Jan OBJECTIVE: To clarify the obstacles preventing the implementation of the treat-to-target (T2T) strategy for rheumatoid arthritis (RA) in clinical practice. METHODS: A total of 301 rheumatologists in Japan completed a questionnaire. In the first section, participants were indirectly questioned on the implementation of basic components of T2T, and in the second section, participants were directly questioned on their level of agreement and application. RESULTS: Although nearly all participants set treatment targets for the majority of RA patients with moderate to high disease activity, the proportion who set clinical remission as their target was 59%, with only 45% of these using composite measures. The proportion of participants who monitored X-rays and Health Assessment Questionnaires for all their patients was 44% and 14%, respectively. The proportion of participants who did not discuss treatment strategies was 44%, with approximately half of these reasoning that this was due to a proportion of patients having a lack of understanding of the treatment strategy or inability to make decisions. When participants were directly questioned, there was a high level of agreement with the T2T recommendations. CONCLUSION: Although there was a high level of agreement with the T2T recommendations, major obstacles preventing its full implementation still remain.
23725568 Emerging therapies for rheumatoid arthritis. 2013 Jun INTRODUCTION: With the introduction of biologic therapies, tremendous progress has been made in the treatment of rheumatoid arthritis (RA). However, up to 40% of patients do not respond to these treatments. AREAS COVERED: Several new treatment strategies are discussed, with brief overview of currently performed clinical trials. The development of molecules targeting cytokines other than TNF is discussed, as well as chemokine-directed drugs. Finally, the area of small molecular inhibitors is explored. EXPERT OPINION: Since RA is a life-long disease often evolving into disability, development of new treatment strategies remains crucial. Especially small molecules targeting JAK, Syk and PDE4 may provide novel therapeutic options.
23512675 Lack of association of IL-2RA and IL-2RB polymorphisms with rheumatoid arthritis in a Han 2013 Feb 27 Polymorphisms in IL-2RA and IL-2RB genes have been reported to confer susceptibility to rheumatoid arthritis (RA) in European populations. We investigated a possilbe association between SNPs in IL-2RA and IL-2RB genes and RA in a Han Chinese population. rs2104286 in IL-2RA and rs743777 in IL-2RB genes were genotyped in a Han Chinese cohort composed of 500 patients with RA and 600 controls. The levels of anti-cyclic citrullinated peptide antibodies (CCP) and rheumatoid factor were determined in all patients and controls. The genotype and allele frequencies of the two SNPs were compared in patients and controls. Additionally, serum concentrations of anti-CCP and rheumatoid factor were analyzed in the three genotype groups of IL-2RA and IL-2RB genes. There was no overall difference in the genotype and allele frequencies of the two SNPs, rs2104286 in IL-2RA and rs743777 in IL-2RB, between the patients with RA and controls. In addition, none of the subgroups showed any significant association with RA risk after stratification by CCP and rheumatoid factor levels. We conclude that the two genetic variants within IL-2RA and IL-2RB are not associated with genetic susceptibility to RA in Han Chinese. Also, the rs2104286 and rs743777 genotypes were not significantly associated with the concentrations of anti-CCP antibodies or rheumatoid factor.
24200065 [Effect of acetazolamide on AQP1 and AQP3 expressions in fibroblast-like synoviocytes of r 2013 Nov OBJECTIVE: To observe the effect of acetazolamide (AZ) on the expressions of aquaporin 1 (AQP1) and AQP3 in fibroblast-like synoviocytes of rheumatoid arthritis (RAFLSs) and explore the roles of AQP1 and AQP3 in the development of rheumatoid arthritis (RA). METHODS: The study included 12 RA with knee hydrarthrosis and 10 osteoarthritis (OA) with knee hydrarthrosis and collected their synovia. From the synovia, FLSs were separated and cultured in vitro. RAFLSs were treated with different concentrations of acetazolamide (10(-4), 10(-6), 10(-8) mol/L) for different time (24, 48, 72 hours). The expressions of AQP1 mRNA and AQP3 mRNA in RAFLSs and OAFLSs were measured by RT-PCR; the expression of AQP1 protein was detected by immunofluorescence in RAFLSs and OAFLSs treated with the same concentration of acetazolamide (10(-4) mol/L) for different time (24, 48, 72 hours). RESULTS: AQP1 mRNA and AQP3 mRNA were both expressed in RAFLSs. The level of AQP1 mRNA in RAFLSs was significantly higher than that in OAFLSs (P<0.05). Different concentrations of acetazolamide (10(-4), 10(-6), 10(-8) mol/L) were able to significantly decrease the expression level of AQP1 mRNA in RAFLSs (P<0.05) in a time- and dose-dependent manner. There was no significant difference in transcription level of AQP3 mRNA between RAFLSs and OAFLSs (P>0.05); Immunofluorescence showed that AQP1 protein was significantly distributed on cell membrane. AQP1 protein expression was very apparent without acetazolamide treatment, whereas the expression was significantly attenuated by acetazolamide in a time-dependent manner. CONCLUSION: Up-regulation of AQP1 expression in RA synovial membrane may be the one of mechanisms of arthroedema. Acetazolamide can reduce the expression of AQP1 rather than AQP3 in RAFLSs.
23509040 Treating to a target in established active rheumatoid arthritis patients receiving a tumor 2013 Sep OBJECTIVE: In early rheumatoid arthritis (RA), treating to a target is more effective than routine care (RC). Our aim was to determine if treating to a target has better outcomes than RC in established active RA. METHODS: We used a real-world, 18-month cluster-randomized trial in established active RA patients treated with adalimumab. Physicians were randomized to RC, treating to a Disease Activity Score in 28 joints (DAS28) of <2.6 (DAS group), or treating to a 0 of 28 swollen joint count (SJC; 0-SJC group). RESULTS: Among the 308 enrolled patients, 109 (35.4%) were randomized to RC, 100 (32.5%) to the DAS group, and 99 (32.1%) to the 0-SJC group. When adjusting for baseline DAS28, a comparable but significant (P < 0.001) improvement in DAS28 was observed at 12 months for all groups (DAS28 mean score 3.1, 3.4, and 3.2, respectively). There were no significant between-group differences in the improvement of clinical parameters and patient-reported outcomes with the exception of the mean change in patient satisfaction over time (P = 0.020), which was highest in the DAS group. Time to achieving good/moderate European League Against Rheumatism (EULAR) response was significantly shorter in the targeted treatment groups compared to RC (adjusted hazard ratio [HR] for the DAS-group 2.99 [95% confidence interval (95% CI) 1.71-5.24] and HR for the 0-SJC group 1.86 [95% CI 1.09-3.13]). The dropout rate was 52.3% in RC, 27% in the DAS group, and 22.2% in the 0-SJC group (P < 0.001). CONCLUSION: All groups experienced significant improvements at 18 months of treatment with adalimumab. Treating to target in established RA did not differ from RC in terms of therapeutic end point achievement for patients remaining on treatment. However, time to achieving good/moderate EULAR response was significantly shorter in the targeted treatment groups compared to RC and, importantly, the dropout rate was significantly lower with targeted treatment.