Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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19467899 | Increased prevalence of allergic sensitisation in rheumatoid arthritis patients treated wi | 2009 Oct | INTRODUCTION: Tumour necrosis factor alpha (TNFalpha) has emerged as a therapeutic target in chronic inflammatory disorders characterised by a Th1 type immune response, such as rheumatoid arthritis (RA). The presence of allergic disease in these patients could be influenced both by the presence of RA and anti-TNFalpha therapy. Our aim was to evaluate the prevalence of sensitisation to airborne allergens and allergic disease in RA patients, with and without anti-TNFalpha treatment. METHODS: RA patients with (N=20) and without (N=20) anti-TNFalpha therapy (groups T and R) were enrolled. Healthy controls (N=60, group C) were randomly selected from the general population. All participants answered a standardised questionnaire to assess the prevalence of allergic disease and had skin prick tests (SPT) with a standard panel of airborne allergen extracts. RESULTS: Significant differences were found in the prevalence of positive SPT between groups T and R (70% vs 35%, p=0.027) and groups T and C (70% vs 36.7%, p=0.009), but not between groups R and C. The prevalence of allergic disease was similar in the three groups. Groups T and R had similar gender and age distribution, disease duration, disease activity score (DAS28), erythrocyte sedimentation rate and serum C-reactive protein. CONCLUSIONS: Increased prevalence of sensitisation to airborne allergens in RA patients treated with anti-TNFalpha was found. The clinical impact of the positive SPT following anti-TNFalpha initiation has now to be assessed. | |
19440813 | Effects of low-dose mizoribine pulse therapy in combination with methotrexate in rheumatoi | 2009 | The aim was to determine the efficacy of low-dose intermittent pulse administration of mizoribine (MZR), a purine synthesis inhibitor, in combination with methotrexate (MTX) to control the symptoms of rheumatoid arthritis (RA) in patients with an insufficient clinical response to MTX alone. Twenty-seven patients with active RA, despite treatment with MTX, were enrolled and given MZR in combination with MTX and continued for 24 weeks. The primary endpoint was assessment of clinical improvements using the European League against Rheumatism (EULAR) criteria. Administering MZR to RA patients with an insufficient response to MTX produced significant improvements in the Disease Activity Score 28 (DAS28) after 8-24 weeks. In addition, after 24 weeks, 60.0% and 8.0% of patients had achieved moderate and good responses, respectively, and there were significant reductions in Modified Health Assessment Questionnaire and serum matrix metalloproteinase-3 levels. The present preliminary study suggests that low-dose MZR in combination with MTX is well tolerated and provides both clinical and economic benefits. | |
21221070 | Clinical impact of radiolabeled anti-CD4 antibodies in the diagnosis of rheumatoid arthrit | 2010 Dec | Human rheumatoid arthritis (RA) is characterized by severe chronic synovitis with abundance of CD4-positive T-cells and macrophages in the inflamed synovial tissue. These cells likely play a central pathogenetic role in RA and experimental models of arthritis. CD4 is a surface molecule present on the helper/inducer subset of T lymphocytes and macrophages, although with a lower density on the latter. CD4+ T-cells/macrophages and their cytokine products, therefore, represent potential therapeutic and diagnostic targets in RA. CD4, a 55 kDa monomeric glycoprotein, binds as a T-cell coreceptor to conserved areas of the major histocompatibility complex II on antigen-presenting cells, and thereby participates in the formation of the immunological synapse and the provision of the so-called "second signal" required for full activation of T-helper cells. A specific diagnostic or therapeutic approach is the direct targeting of CD4+ T-cells by anti-CD4 monoclonal antibodies (mAbs). In addition to therapeutic clinical trials with anti-CD4 mAbs in RA, which have yielded only ambiguous results, anti-CD4 mAbs have also been developed and applied for diagnostic purposes. The studies thus far conducted in RA have focused on the following aspects: 1) comparison of anti-CD4 mAb imaging to the established early methylene diphosphonate (MDP) scan; 2) biodistribution/ pharmacokinetics studies; and 3) specificity of joint imaging with anti-CD4 mAbs in comparison to control immunoglobulins with irrelevant specificity. The available results in RA and arthritis models show that 99mTc-anti-CD4 mAbs are well-suited to actively image diseased joints, and clearly allow more specific imaging than 99mTc-MDP or control immunoglobulins. Because effective treatment is known to reduce the density of CD4+ cells in the inflamed synovial membrane, diagnostic methods targeted to CD4 warrant further attention, also for early diagnosis of clinically silent joints, precise description of the cellular infiltrates, and monitoring of anti-rheumatic therapy. | |
19888503 | [Rheumatoid factor positivity rather than anti-CCP positivity, a lower disability and a lo | 2009 Jul | OBJECTIVE: Predictors of response to biologics in rheumatoid arthritis (RA) is an important issue in the current era. Rituximab (RTX) has been demonstrated effective and safe in active RA, resistant to traditional or biologic DMARDs. METHODS: Fifty-seven patients with active longstanding RA were treated with RTX after traditional DMARD or anti-TNF alpha therapy failure. RESULTS: Number of anti-TNF treatment previously failed (p=0.005), HAQ (p=0.013), rheumatoid factor (RF) (p=0.0002) and anti-CCP (p=0.006) were associated with an ACR response > or =50 at the end of 6th month by univariate analysis. Multivariate analysis confirmed that the number of anti-TNF previously failed, baseline HAQ and RF, but not anti-CCP were associated with an ACR response > or =50. EULAR moderate/good response was associated with ESR value (p=0.036), HAQ (p=0.032), and RF (p=0.01) by univariate analysis, while only RF positivity was associated with EULAR moderate/good response by multivariate analysis. CONCLUSIONS: RF positivity rather than anti-CCP positivity is a predictor of response to RTX, suggesting that RF-positive patients with low disability may obtain a clinical response when treated to RTX after the first anti-TNF agent failure or after traditional DMARD therapies. Larger studies are required to confirm these results. | |
19363607 | A comparative study of the effects of bucillamine and salazosulfapyridine in the treatment | 2009 | Bucillamine (Buc), developed in Japan, is a disease-modifying antirheumatic drug (DMARD) which has been used to treat numerous patients with rheumatoid arthritis (RA) in Japan and Korea with favorable results. However, it has not been used globally. In the present study, we compared the timing of onset of efficacy and the usefulness of this drug with that of the globally accepted agent salazosulfapyridine (SASP). There were 26 patients in the Buc group and 23 in the SASP group. We compared changes in the number of swollen joints, number of painful joints, duration of morning stiffness, grip strength, levels of inflammatory marker [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)], rheumatoid factor (RF), physician's rating by visual analogue scale (VAS), patient's rating of pain, patient's overall rating (VAS), and improvement according to European League against Rheumatism (EULAR) criteria (DAS28-CRP, DAS28-ESR) in these two groups of patients. Both Buc and SASP were shown to be efficacious within 3 months after the start of treatment. Both drugs were found to be suitable as first-line treatment of early RA. Signs of efficacy tended to occur earlier with Buc than with SASP, and Buc also tended to have higher efficacy than SASP. | |
20069330 | The relation of serum vascular endothelial growth factor level with disease duration and a | 2010 May | Vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of rheumatoid arthritis (RA). In order to elucidate the association between VEGF levels and RA disease activity, VEGF concentrations were measured in RA patients at different phases and severity levels. Thirty-eight healthy subjects and 40 patients with RA were prospectively included in the study. Subjects were further categorized into four subgroups (high, moderate, low, or remission) using the disease activity score-28 (DAS28) scoring system. VEGF levels were significantly higher in patients than controls (p < 0.001). VEGF levels differed significantly in controls, early and late-phase RA patients (p = 0.002). A significant difference was found between controls and patients with high RA disease activity scores (p < 0.0001). VEGF levels were not correlated with age (r = -0.016; p = 0.921) or sex (r = 0.209; p = 0.921). VEGF values were correlated with erythrocyte sedimentation rate (r = 0.445; p = 0.004), but was not correlated with serum rheumatoid factor levels (r = -0.130; p = 0.424) in the patient group. In conclusion, higher VEGF levels are associated with late phase and high disease activity in RA, independent of age and sex. | |
20499061 | Hip resurfacing for rheumatoid arthritis: independent assessment of 11-year results from a | 2011 Jun | Total hip replacement has shown good outcomes for patients with rheumatoid arthritis. Can hip resurfacing give similar results for patients with rheumatoid arthritis? Using an international hip resurfacing register, 47 patients with rheumatoid arthritis were identified and age and gender matched to a group of 131 randomly selected patients with osteoarthritis of the hip joint. Patients completed a questionnaire to record function and implant revision. Hierarchical regression, Cox regression and Kaplan-Meier method were used for analysis. There was a significant increase in post operative hip score in both groups (p < 0.001) with rheumatoid group scoring higher as compared to the osteoarthritis group (p = 0.23). The post operative score was not significantly influenced by pre-operative score and age (p = 0.15 and 0.84, respectively) but the pre-operative score was a predictor of implant failure (p = 0.02). Patient mobility was affected by age with younger patients scoring high on mobility as compared to older patients (p = 0.01). The Kaplan-Meier analysis showed a survival rate of 96.3% in the rheumatoid group and 97.8% in the osteoarthritis group. This difference was not significant (Log rank test, p = 0.45). Our results from an independent and international register show that hip resurfacing provides good post-operative hip function and excellent implant survival for patients with rheumatoid arthritis of the hip joint. This procedure can be considered as a viable option for management of rheumatoid arthritis of the hip joint. | |
21109516 | Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular even | 2011 Apr | OBJECTIVE: To examine the association of cardiovascular events with tumour necrosis factor (TNF) α antagonist use compared with non-biological disease-modifying antirheumatic drug (DMARD) utilisation in patients with rheumatoid arthritis (RA). METHODS: The study population included 10 156 patients enrolled in the Consortium of Rheumatology Researchers of North America RA registry. Three study cohorts were defined based on three mutually exclusive drug use categories, including TNF antagonists, methotrexate and other non-biological DMARDs. HR were calculated adjusting for cardiovascular risk factors, RA disease characteristics and prednisone use. The primary study outcome was a composite of non-fatal myocardial infarction (MI), transient ischaemic attack (TIA) or stroke and cardiovascular-related death. RESULTS: There were 88 cardiovascular events, including 26 MI, 45 TIA/strokes and 17 cardiovascular-related deaths. After adjusting for age, gender, cardiovascular risk factors and RA disease characteristics, patients using a TNF antagonist experienced a reduced risk of the primary composite cardiovascular endpoint (HR 0.39, 95% CI 0.19 to 0.82) compared with users of non-biological DMARDs. Methotrexate was not associated with a reduced risk (HR 0.94, 95% CI 0.49 to 1.80). Prednisone use was associated with a dose-dependent increased risk (p=0.04). The risk reduction associated with TNF antagonists was also observed for non-fatal cardiovascular events (HR 0.35, 95% CI 0.16 to 0.74). CONCLUSION: TNF antagonist use was associated with a reduced risk of cardiovascular events in patients with RA. | |
20711094 | From a neutrophilic synovial tissue infiltrate to a challenging case of rheumatoid arthrit | 2010 Apr | The herein report illustrates how a synovial tissue heavily infiltrated by neutrophils in the first weeks of arthritis, can evolve in few months to a synovial infiltration by lymphocytes with a characteristic pattern of rheumatoid arthritis (RA). This observation suggests a critical initial role of neutrophils in RA onset, which is eventually surpassed by the activation of the adaptive immune system. In addition, this patient, despite the absence of rheumatoid factors and anti-cyclic citrullinated peptide antibodies, progressed to a highly destructive and disabling disease, that was only controlled adequately with rituximab, due to the lack of response to methotrexate and serious adverse effects with TNF blockers therapy. | |
20481050 | [Use of life quality indices in the rehabilitation therapy of inflammatory and degenerativ | 2009 | AIM: To study whether life quality (LQ) indices may be used to evaluate the efficiency of structural resonance electromagnetic therapy (SREMT) and its correction in patients with rheumatoid arthritis (RA) and in those with osteoarthrosis (OA). SUBJECTS AND METHODS: One hundred and twenty patients with significant RA and 94 patients diagnosed as having OA were followed up. The SF-36 questionnaire was used to detect and assess objective data on health problems and changes. The patients with RA and those with OA were randomized to the groups matched for gender, age, and disease duration: a study group (n = 80) and a control one (n = 40) for RA; a study group (n = 56) and a control one (n = 38) for OA. Both group patients received the same medical and physiotherapeutic treatment (within each nosological entity, respectively). Furthermore, in the study groups, the patients with RA and those with OA had additionally 10-12 daily (43-min) sessions of SREMT on a Rematerp apparatus. RESULTS: The inclusion of SREMT into the multimodality treatment of patients with RA and those with OA has shown significant benefits. A wide spectrum of therapeutic action of SREMT exerts a positive impact on the basic LQ indices (the indicators of physical and role physical performance, somatic pain, general condition, and social and role emotional performance). CONCLUSION: SREMT may be recommended for use in rheumatological care as a technique that enhances the efficiency of performed therapy and medical rehabilitative measures in inflammatory and degenerative rheumatic diseases. | |
19531759 | A followup study of asymptomatic carriers of Pneumocystis jiroveci during immunosuppressiv | 2009 Aug | OBJECTIVE: To examine the preventive effects of prophylaxis against Pneumocystis jiroveci-induced pneumonia (PCP) in patients receiving immunosuppressive therapy for rheumatoid arthritis (RA) who are colonized by this organism. METHODS: We performed molecular testing by polymerase chain reaction (PCR) for P. jiroveci on induced sputum or bronchoalveolar lavage fluids of 82 patients with RA. During primary prophylaxis, asymptomatic carriers of this organism were examined by high-resolution computed tomography and PCR every 2 weeks. RA patients who had developed PCP received PCR tests every week. Once negative results were obtained, PCR testing was scheduled at Months 1, 3, and 6, followed by reexaminations every 6 months. RESULTS: We found 9 cases of asymptomatic carriage of P. jiroveci. All the carriers had received low doses of methotrexate. Upon introduction of PCP prophylaxis, 5 cases tested negative for PCR within 1 month. Three carriers developed PCP before starting prophylaxis, but these tested negative for PCR after short periods (1-2 weeks) of PCP treatment. Once P. jiroveci was eradicated, all cases maintained negative PCR results during followup without prophylactic intervention, even after resuming immunosuppressive therapy. One patient refused PCP prophylaxis, but no PCP developed. CONCLUSION: RA patients with asymptomatic carriage of P. jiroveci benefited from short-term prophylaxis against PCP. Positive PCR results appeared to be predictive of future development of PCP in RA patients. Identification of P. jiroveci carriers will encourage prompt introduction of PCP prophylaxis when rheumatologists consider immunosuppressive therapy for RA. | |
20061956 | Outcomes of hand surgery in the patient with rheumatoid arthritis. | 2010 May | PURPOSE OF REVIEW: Surgeons have long been striving to develop new surgical procedures to improve functional outcomes for a variety of hand and wrist deformities resulting from rheumatoid arthritis (RA). The purpose of this review is to assess the latest surgical outcomes related to hand and wrist surgery in the patient with RA. RECENT FINDINGS: There is a lack of outcome studies in RA hand and wrist surgery to justify many of the surgical procedures proposed for the treatment of the rheumatoid hand. However, advances made by the silicone metacarpophalangeal arthroplasty (SMPA) group regarding hand reconstruction for RA patients have improved patient care for this widely used procedure. Prophylactic versus therapeutic procedures are also discussed. SUMMARY: Rheumatoid hand is one of the earliest presentations of RA, and the progression of rheumatoid hand disease can be unpredictable. There are a number of surgical treatments for the rheumatoid hand and careful sequential planning of the surgical procedures can maintain patients' hand function and in many cases should enhance outcomes of the rheumatoid hand by correcting existing deformities. An early introduction to a hand surgeon can inform patients of available options and allow longitudinal assessment of structural and functional changes that could be treatable by future surgical interventions. | |
20569500 | Immediate determination of ACPA and rheumatoid factor--a novel point of care test for dete | 2010 | INTRODUCTION: Autoantibodies against mutated and citrullinated vimentin (MCV) represent a novel diagnostic marker for rheumatoid arthritis (RA). Recently, an increased sensitivity for anti-MCV compared to autoantibodies against cyclic citrullinated peptides (anti-CCP2) was shown in cohorts of patients with early RA and established disease.The aim of this study was to develop and evaluate a point of care test (POCT) for detection of anti-MCV antibodies immediately at the first visit or at the bed side. METHODS: A lateral-flow immunoassay was developed for simultaneous detection of anti-MCV antibodies and rheumatoid factor (RF-IgG) and evaluated in a prospective setting. Analyses were performed from whole blood samples of patients with seropositive RA (n=108), seronegative RA as well as other rheumatic disorders (n=122), and healthy blood donors (n=200) and compared to detection via ELISA. RESULTS: Using the POCT, anti-MCV antibodies were detected in 54.6% and RF-IgG in 56.5% of patients with RA. Specificity was 99.1% for anti-MCV antibodies and 91.2% for RF-IgG. Compared to ELISA's results, POCT sensitivity was 69.3% for anti-MCV and 55.6% for RF-IgG, specificity was 99.7% and 97.2%, respectively. CONCLUSIONS: This POCT for detection of anti-MCV antibodies and RF-IgG provides high specificity for the diagnosis of RA and is useful in clinical practice due to its simplicity and its reliable performance. This test can greatly improve a timely management of RA and may help in screening patients with suspected RA in non-specialized settings prompting early referrals. | |
19252245 | [Three-tesla MR imaging of rheumatoid arthritis: implications for the mechanism of bone de | 2009 Mar | 3T MRI can visualize synovium, cartilaginous, bone, and soft tissue more clearly than 1.5T MRI due to the enhanced SNR and the higher spatial resolution. The ability to delineate synovitis with high sensitivity can contribute to discriminating and managing early-stage RA patients. The constant coil development and technical solutions at 3T MRI would elucidate the mechanism of bone destruction in rheumatoid arthritis in more detail. | |
21078713 | Low body mass index is adversely associated with radiographic joint damage in Indian patie | 2011 Mar | OBJECTIVE: Various factors affect joint damage in rheumatoid arthritis (RA). The influence of body mass index (BMI) is not adequately known. As BMI is potentially modifiable, we studied its influence on radiological joint damage in patients with RA. METHODS: Treatment-naive patients with early RA (< 24 mo) were included. Demographic data were collected along with swollen joint count (SJC), tender joint count (TJC), erythrocyte sedimentation rate (ESR), and IgM-rheumatoid factor (IgM-RF). Radiographs of hands and feet were obtained. BMI and Disease Activity Score for 28-joint count (DAS28-ESR) were calculated. Joint damage was assessed using the Simplified Erosions Narrowing Score (SENS). RESULTS: A total of 101 patients were studied (81 women; mean age 41.91 ± 11.99 yrs). Mean disease duration was 10.77 ± 6.73 months; 55 patients (54.5%) were IgM-RF-positive. Mean BMI was 22.82 ± 4.66 kg/m(2) with 24 (23.8%) patients having low, 42 (41.6%) normal, and 35 (34.7%) high BMI. Mean SENS score was 16.81 ± 11.10; mean DAS28 was 6.23 ± 0.96. Significant correlation was noted between SENS and DAS28 (r = 0.28; p < 0.005). There was significant negative correlation between BMI and SENS (r = -0.509; p < 0.0005). In patients with low BMI, mean SENS (26.62 ± 13.45) was significantly higher than in patients with normal (15.88 ± 8.38; p < 0.001) and high BMI (11.20 ± 7.32; p < 0.001). Patients with normal BMI also had significantly higher SENS scores than those with high BMI (p < 0.05). One-way ANOVA did not reveal significant differences in DAS28 between groups. SENS was significantly higher in the IgM-RF-positive group (19.55 ± 11.36) than in the IgM-RF-negative group (13.54 ± 9.94; p < 0.01); DAS28 was not different between the 2 groups (6.22 ± 0.98 vs 6.26 ± 0.96, respectively). Within the 2 IgM-RF groups, a significant negative correlation was seen between BMI and SENS. Multiple regression analysis revealed RF, DAS28, and BMI were independently associated with SENS. BMI accounted for 23.04% of the variance in SENS independent of DAS28 and IgM-RF. CONCLUSION: Low BMI is adversely associated with joint damage in patients with early RA. | |
18712459 | Quality of life evaluated by Short Form-8 in patients with rheumatoid arthritis who were r | 2009 | In this study, influences of infliximab to health-related quality of life (HRQOL) and active status of RA were assessed. Between 2003 and 2006, 22 patients with rheumatoid arthritis (RA) began receiving infusion of infliximab. Of all the patients, 17 patients who were followed for at least 30 weeks (102 weeks at maximum) after the start of infliximab were included in this study. The mean age was 54.6+/-10 years. HRQOL was evaluated with use of the SF-8trade mark, which is a simple version of the Medical Outcome Study Short Form 36. As an index of active status of RA, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were collected. CRP and ESR significantly improved at the final follow-up, but RF did not. All subscales of the SF-8 were significantly improved after the start of infliximab. However, there were three patients whose laboratory data were improved, but HRQOL was not. We should not be prepossessed only with laboratory data in treating patients with RA. We recommend that the SF-8 to evaluate HRQOL of patients with RA in busy outpatient clinics because it is both simple and convenient. | |
19709443 | Comprehensibility, reliability, validity, and responsiveness of the Thai version of the He | 2009 | INTRODUCTION: The Health Assessment Questionnaire Disability Index (HAQ-DI) is a commonly used instrument to assess functional status of patients with rheumatoid arthritis (RA). Translations and adaptations of the HAQ-DI have been carried out for use with RA patients in several countries. The objective of this study was to evaluate the psychometric properties of the Thai version of the HAQ-DI (Thai HAQ) in Thai patients with RA. METHODS: Comprehensibility of the Thai HAQ was assessed by 126 patients with RA from 6 medical centers in Thailand. Another group of 115 patients with active RA was enrolled to test the reliability (internal reliability and 1-week test-retest reliability), construct validity (correlations with other measures of RA disease activity), floor and ceiling effects, and sensitivity to change of the Thai HAQ at 3 months of treatment with disease-modifying antirheumatic drugs. RESULTS: More than 98% of the patients regarded the Thai HAQ as comprehensible. The internal consistency of the Thai HAQ was satisfactory with the overall Cronbach alpha of 0.91. The test-retest reliability of the Thai HAQ was acceptable with the intraclass correlation coefficient of 0.89. Moderate correlations between the Thai HAQ and other outcomes of RA disease activity were observed, except erythrocyte sedimentation rate, with the Spearman correlation coefficients ranging from 0.42 to 0.57. The responsiveness of the Thai HAQ was moderate, with a standardized response mean of 0.75 (95% confidence interval 0.56 to 0.94). CONCLUSIONS: The Thai HAQ is comprehensible, reliable, valid and sensitive to change in the evaluation of functional status of Thai patients with RA. The Thai HAQ is an essential tool to measure treatment effects and progression of disability in RA patients and should be applied in both clinical trials and routine clinical care settings. | |
20687367 | [Standardisation of the MRI and US images evaluation in the diagnostics of rheumatoid arth | 2010 | In Rheumatoid arthritis (RA) it is very important to recognize pathologic condition and to start proper treatment as early as possible to lessen its consequences. Currently, magnetic resonance imaging and ultrasonography are the best imaging modalities because they depict early stages of this disease and allows to control response to treatment. MRI depicts also bone oedema, which is a strong predictor of further progression. The process of standardization is needed in assessing both MR and US pictures. Standardization allows to compared both examinations of the same patient in different time and examinations of different patients. An aim of this article is to present: MR protocols of hand and wrist MR examinations for rheumatologic demand and standards of results, according to worldwide OMERAC RAMRIS 2002 and supplemented by tenosynovitis system; proposals for US examination of hands in rheumatoid patients. | |
20190641 | Sequential use of biologic therapy in rheumatoid arthritis. | 2010 May | PURPOSE OF REVIEW: With an increasing range of biological therapies available in the management of rheumatoid arthritis, sequencing of such therapies is becoming more frequent, particularly with more ambitious treatment aims. This review will address the evidence to date on use of successive targeted agents. RECENT FINDINGS: Double-blind, randomized controlled trials have confirmed the role of alternative tumour necrosis factor (TNF) inhibitors (TNFi), rituximab, abatacept and tocilizumab, following TNFi failure with no comparative studies to date. Registry data have demonstrated efficacy of switching from a first to a second TNFi. Observational experience has confirmed benefits of switching from TNFi to TNFi and TNFi to rituximab. Within available randomized controlled trial data, tocilizumab appears effective in TNFi failure group, irrespective of number of TNFi previously failed. Such data are not available for the other agents. No safety signals have been identified thus far with biologic sequencing. Although formal comparative, controlled studies do not exist, type of previous failure to TNFi and disease characteristics (serology, comorbidity, concomitant therapy) can provide a good platform for choosing the next biologic treatment. SUMMARY: Although biological sequencing is well established, optimal approach represents a significant knowledge gap; well designed clinical studies with associated mechanistic investigation are necessary to identify disease subgroups that would benefit from one sequence over another. | |
20658292 | Cold and heat pattern of rheumatoid arthritis in traditional Chinese medicine: distinct mo | 2012 Jan | The research is aimed to explore the distinct molecular signatures in discriminating the rheumatoid arthritis patients with traditional Chinese medicine (TCM) cold pattern and heat pattern. Twenty patients with typical TCM cold pattern and heat pattern were included. Microarray technology was used to reveal gene expression profiles in CD4+ T cells. The signal intensity of each expressed gene was globally normalized using the R statistics program. The ratio of cold pattern to heat pattern in patients with RA at more or less than 1:2 was taken as the differential gene expression criteria. Protein-protein interaction information for these genes from databases was searched, and the highly connected regions were detected by IPCA algorithm. The significant pathways were extracted from these subnetworks by Biological Network Gene Ontology tool. Twenty-nine genes differentially regulated between cold pattern and heat pattern were found. Among them, 7 genes were expressed significantly more in cold pattern. Biological network of protein-protein interaction information for these significant genes were searched and four highly connected regions were detected by IPCA algorithm to infer significant complexes or pathways in the biological network. Particularly, the cold pattern was related to Toll-like receptor signaling pathway. The following related pathways in heat pattern were included: Calcium signaling pathway; cell adhesion molecules; PPAR signaling pathway; fatty acid metabolism. These results suggest that better knowledge of the main biological processes involved at a given pattern in TCM might help to choose the most appropriate treatment. |