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ID PMID Title PublicationDate abstract
21985834 [Higher prevalence of depression in patients with rheumatoid arthritis--a systematic revie 2011 Oct 10 Chronic pain patients frequently suffer from depression. This systematic review finds that patients suffering from rheumatoid arthritis (RA) have a higher prevalence of depression than controls without RA. Depression is related to pain intensity, passive coping strategies and disability. For patients this may result in a decreased quality of life and a shorter lifespan. For society it results in increased health costs.
22325923 Simultaneous evaluation of long-lasting knee synovitis in patients undergoing arthroplasty 2012 Jan OBJECTIVES: We simultaneously assessed ultrasonography (US) and magnetic resonance imaging (MRI) in comparison with histopathological changes in the knee joints of long-lasting arthritis patients. METHODS: We studied 15 patients with rheumatoid arthritis and 5 patients with osteoarthritis, who underwent total knee arthroplasty. On the day before surgery, the joints were examined by US and contrast-enhanced MRI. In US, synovitis was graded with 0-3 grey scale (GSUS) and power Doppler (PDUS). In MRI, synovitis was graded according to OMERACT-RAMRIS (grade 0-3). Synovial tissue samples were obtained during arthroplasty and evaluated on the basis of inflammatory cell infiltrates (grade 0-3), synovial lining layer thickness (grade 0-3) and vascularity (grade 0-3). RESULTS: Positive findings of PDUS and contrast-enhanced MRI were 45% and 85% of 20 operated joints, respectively. GSUS, PDUS and MRI synovitis were well correlated with overall histopathological grades of synovitis (Spearman correlation coefficients 0.48, 0.84 and 0.48, p<0.05, p<0.01 and p<0.05, respectively). Moreover, positive PDUS findings were closely associated with all pathological comportments of synovitis including inflammatory cell infiltrates, synovial lining layer thickness and vascularity. CONCLUSIONS: The present study revealed that positive PDUS findings more faithfully illustrated active synovitis than MRI, whereas contrast-enhanced MRI was more sensitive in detecting synovitis in patients with long-lasting arthritis. It is important to understand distinct features of the both modalities for clinical assessment of chronic joint diseases.
22855346 What RA patients expect of their treatment--discussion over the result of our survey. 2012 Nov We conducted a survey among Japanese rheumatoid arthritis (RA) patients to better understand what they expect from treatment and whether there is a difference between expectations of biologics-treated and disease-modifying antirheumatic drugs (DMARDs)-treated patients. An anonymous survey was conducted with 165 outpatients from our clinic (with informed written consent). On the survey, they wrote their age, gender, medical history, and commented on: (1) expectations for treatment, (2) disappointment with treatment, (3) experience of, and thoughts about switching treatments, (4) information wanted before starting a new treatment, (5) expectations before administration and noticeable differences after treatment, (6) level of satisfaction with current treatment, and (7) expectations of possible treatments. Patients who had never been treated with DMARDs were excluded from the survey. For "treatment goals before administration," 86 % responded with "assured efficacy," while 73 % responded "suppress joint destruction" or "recover from joint destruction." Also, more patients hoped for "long-lasting efficacy" (67 %) over "fast acting" (41 %), which suggests significance of the long-term improvement of QOL. Related to "disappointment with treatment," patients also felt anxiety over switching treatment for possibilities of not responding enough, or side effects. RA patients have high expectations for medication in terms of assured improvement of conditions and long-lasting efficacy of drugs, while the biggest concern was if they would have side effects or not, and if so, what type. The results suggest patients hope to have worries over switching medications dispelled. The results also verified those who have used biologics before have higher treatment goals than those who have not.
22875903 Periodontal disease is significantly higher in non-smoking treatment-naive rheumatoid arth 2012 Sep OBJECTIVE: To find the strength of association between periodontal disease (PD) and rheumatoid arthritis (RA) in non-smoking, disease modifying antirheumatic drug (DMARD)-naive RA patients in a case-control design. METHODS: Patients of RA (DMARD-naive, non-smokers) satisfying the American college of Rheumatology 1987 criteria and healthy controls were included. PD was defined as present if the mean pocket depth (MPD) is ≥3 mm. Demographic data and disease specific variables were recorded for RA patients and healthy controls. Titres of immunoglobulin M-rheumatoid factor (IgM-RF) and anticitrullinated peptide antibodies (ACPAs) were measured using ELISA. RESULTS: Patients with RA (n=91) had a 4.28 (CI 2.35 to 7.38) higher odds of PD (64.8% vs 28%, p<0.001) compared with healthy controls (n=93). The MPD was 3.61±1.22 mm in cases and 2.46±0.74 mm in controls (p<0.001). IgM-RF titres (110.56±95.81 vs 66.53±70.29; p=0.02) and ACPA titres (753.05±1088.27 vs 145.15±613.16, p=0.001) were significantly higher in RA patients with PD than those without PD. The MPD positively correlated with titres of ACPAs in RA patients (r=0.24; p=0.02). CONCLUSIONS: PD is more frequent and severe in non-smoking DMARD-naive RA patients compared with healthy controls. PD in RA is associated with high titres of ACPAs.
22948123 Validity and responsiveness of the Measure of Activity Performance of the Hand (MAP-Hand) 2012 Oct BACKGROUND: The Measure of Activity Performance of the Hand (MAP-Hand) is reliable and valid in patients with rheumatoid arthritis. OBJECTIVE: To assess the validity and responsiveness of the MAP-Hand in patients with hand osteoarthritis. METHODS: Patients were recruited from 2 rheumatology centres. The internal consistency of the MAP-Hand was assessed by Cronbach's α. Content validity was evaluated based on patient interviews. Construct validity and responsiveness were based on predefined hypotheses of correlation between the MAP-Hand and concurrent measures. RESULTS: Ten men and 201 women, mean age 62.8 years (standard deviation (SD) 6.8) and disease duration 12.5 (SD 7.5) years were included. A Cronbach's α of 0.86 was determined. All 18 items in the MAP-Hand were described in the interviews. Sixty-seven percent of the correlation coefficients for baseline scores and 75% for change scores were in correspondence with the predefined hypotheses. A high correlation was found between the MAP-Hand and the Australian/Canadian Hand Osteoarthritis Index function score at baseline (rho = 0.76). A moderate correlation was found for change scores (rho = 0.52). CONCLUSION: The content of the MAP-Hand adequately reflects described activity limitations in patients with hand osteoarthritis. The results suggest that the MAP-Hand has adequate internal consistency and responsiveness. Before the MAP-Hand is used in patients with hand osteoarthritis, evaluations of reliability and further construct validity are warranted.
22753649 Variants within STAT genes reveal association with anticitrullinated protein antibody-nega 2012 Aug OBJECTIVE: STAT3 and 4 are, among other factors, critical for the interleukin 12 (IL-12)-mediated Th1 response, for transfer of IL-23 signals, and for survival and expansion of Th17 cells. We investigated the association of STAT3 and STAT4 polymorphisms with serologically distinct subgroups of rheumatoid arthritis (RA). METHODS: A total of 41 single-nucleotide polymorphisms (SNP) within STAT3 and STAT1-STAT4 loci were investigated in a Swedish cohort of 2043 RA cases and 1115 controls. Nine of the associated SNP were tested in a Spanish cohort of 1223 RA cases and 1090 controls. RESULTS: Fourteen SNP in the STAT3 and STAT1-STAT4 loci were associated with anticitrullinated protein antibody (ACPA)-negative RA in the Swedish cohort. Three of the SNP in STAT4 and 2 SNP in STAT3 remained associated with ACPA-negative RA after considering the Spanish results. In addition, rs7574865 and rs10181656, in STAT4, were associated with ACPA-positive RA in the Swedish study. One of these SNP, rs7574865, showed a similar pattern of the association in serologically distinct subgroups of RA in a metaanalysis of all 7 published studies. CONCLUSION: Our findings suggest that variants in STAT genes may contribute differentially to susceptibility to RA in seropositive and in seronegative patients.
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.
21187211 Predictors of stenosing tenosynovitis in the hand and hand-related activity limitations in 2011 Jan OBJECTIVES: To identify early predictors of stenosing tenosynovitis in the hand and hand-related activity limitations in patients with rheumatoid arthritis (RA). DESIGN: A longitudinal study of an inception cohort. SETTING: A large outpatient clinic. PARTICIPANTS: Consecutive patients who attended the Early Arthritis Clinic for at least 2 years and fulfilled the American College of Rheumatology criteria for RA at baseline and/or at the 1-year follow-up were invited to participate until 200 patients were included. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Stenosing tenosynovitis, assessed by means of a standardized physical examination. Hand-related activity limitations, assessed with the Disabilities of Arm, Shoulder and Hand questionnaire (DASH). A DASH score above the upper limit of the 95% range of the normative score was defined as abnormal. Prognostic factors: demographic and disease activity-related variables, radiographic damage, the Health Assessment Questionnaire (HAQ) total score and category scores at the 2-year follow-up. RESULTS: The mean age ± SD of the patients was 59.7±10.7 years (75% female). The mean time ± SD between the 2-year follow-up and the assessment of the dependent variables was 3.9±2.7 years. Stenosing tenosynovitis was present in 33%. The median (interquartile range) DASH score was 26.7 (10.8-42.5); 30% were abnormal. Stenosing tenosynovitis was predicted by the HAQ subscale regarding the use of hands (HAQ-hand) at the 2-year follow-up (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2-4.2). Hand-related activity limitations were predicted by the Disease Activity Score in 28 joints (OR, 1.8; 95% CI, 1.3-2.4) and HAQ-hand (OR, 2.4; 95% CI, 1.3-5.8) at the 2-year follow-up. CONCLUSIONS: Stenosing tenosynovitis in patients with RA was predicted by HAQ-hand at the 2-year follow-up, and hand-related activity limitations were predicted by disease activity and HAQ-hand at the 2-year follow-up.
23412262 Lateral approach is advantageous in total knee arthroplasty for valgus deformed knee. 2014 Jan INTRODUCTION: For the total knee arthroplasty in valgus deformed knee, superiority of the medial or lateral approach is still controversial. We compared the short-term result of two approach groups. MATERIALS AND METHODS: Forty-seven knees in rheumatoid arthritis with valgus deformity from 6° to 24° were randomly divided into two group; medial approach (24 knees) and lateral approach (24 knees). We used Scorpio NRG PS for all knees. Median postoperative periods were 43 months in both groups. We compared the surgical time, and alignment on standing radiograph, range of motion (ROM) pre/postoperatively, and degrees of soft-tissue release procedure, and lateral laxity measured by stress radiograph immediately after operation and at final follow-up. RESULT: Pre/postoperative alignment, surgical time, lateral laxity, and preoperative ROM had no significant in two groups; however, postoperative flexion was superior in lateral approach group 123.8°, 109° in medial approach group. All cases required iliotibial band (ITB) release at Gerdy's tubercle, 83 % ITB at joint level, 21 % lateral collateral ligament (LCL), 17 % popliteus tendon (PT) in medial approach group, and 88 % ITB at Gerdy's tubercle, 46 % ITB at joint level, 13 % LCL, 4 % PT in lateral approach group. DISCUSSION: In the valgus knee, lateral structures are tight. Lateral approach can directly adjust the tight structure, and also less vascular compromise to the patella than medial approach with lateral patellar release. Less invasiveness to the quadriceps muscle in lateral approach could result into better range of motion after the surgery.
21979101 Complementary and alternative medicine for rheumatoid arthritis and osteoarthritis: an ove 2011 Dec This review critically evaluates the literature on complementary and alternative medicine (CAM) as treatment options for rheumatoid arthritis and osteoarthritis. DESIGN: Electronic databases were searched to identify all relevant systematic reviews of the effectiveness of CAM in rheumatoid arthritis and osteoarthritis published between January 2010 and January 2011. Reviews were defined as systematic if they included explicit and repeatable inclusion and exclusion criteria for studies. Their methodological quality was assessed using the Oxman criteria for systematic reviews. RESULTS: Five systematic reviews met our inclusion criteria. They all arrived at cautious conclusions. Four reviews were of high quality and one was burdened with high risk of bias. The evidence to support the effectiveness of CAM as a treatment option for rheumatoid arthritis and osteoarthritis is ambiguous.
22595643 Risk of significant infection in rheumatoid arthritis patients switching anti-tumor necros 2012 Oct OBJECTIVES: To describe rates of first significant infection of rheumatoid arthritis patients who switch between anti-tumor necrosis factor (aTNF) drugs. METHODS: Subjects with rheumatoid arthritis who received only aTNF drugs were observed in an insurance claims database from January 2001 to December 2007. Nonswitchers (NS) remained on one aTNF throughout the study period (date of the first aTNF claim was the index date); switchers (S) received at least one other aTNF (claim date for the 2nd agent was the index date). Significant infections included those that required intravenous antibiotics or hospitalization. Two attributable risk periods were used: (1) an infection occurring ≤90 days following a claim for an aTNF (90-day) and (2) an infection occurring after the index date (ever-treated). Follow-up was censored at the first occurrence of a significant infection event, end of eligibility, or end of study period. Data were analyzed using Cox regression. RESULTS: In 13,752 NS and 2293 S patients, time-stratified rates declined 2- to 3-fold between the first year versus ≥2 years. Risk of significant infection was not different for either attribution model [90-day hazard ratio (HR) = 0.93, 95CI: 0.74 to 1.17, P = 0.55; ever treated HR = 0.94, 95CI: 0.78 to 1.15, P = 0.57]. First and second year rates were similar. Predictors included age ≥50 years; history of significant or opportunistic infection, diabetes, respiratory disease; Charlson score ≥2; or prior hospitalizations. CONCLUSIONS: The risk of a significant infection was not different between NS and S patients. Regardless of switching status, the rate of infection was greater in the first year. This study was limited by the lack of clinical data to determine the reason for switching.
21285116 The influence of systemic glucocorticoid therapy upon the risk of non-serious infection in 2011 Jun BACKGROUND: Glucocorticoid therapy is strongly associated with an elevated risk of serious infections in patients with rheumatoid arthritis (RA). The association between glucocorticoids and common non-serious infections (NSI) is not well studied. METHODS: A cohort of 16 207 patients with RA aged over 65 years was assembled using administrative data from Quebec. Glucocorticoid and disease-modifying antirheumatic drug (DMARD) therapy were identified from drug dispensing records. NSI cases were defined as first occurrence of a community physician billing code for infection or community-dispensed anti-infectives. A nested case-control analysis was performed considering drugs dispensed within 45 days of the index date, adjusting for age, sex, markers of disease severity, DMARD and comorbidity. RESULTS: For 13 634 subjects, a NSI occurred during 28 695 person-years of follow-up, generating an incidence rate of 47.5/100 person-years. The crude rate of NSI in glucocorticoid-exposed and unexposed person time was 52.4 and 38.8/100 person-years, respectively. Glucocorticoid therapy was associated with an adjusted RR of 1.20 (95% CI 1.15 to 1.25). A dose response was seen, the adjusted RR increasing from 1.10 (<5 mg prednisolone/day) to 1.85 for doses greater than 20 mg/day. All glucocorticoid risk estimates (including <5 mg/day) were higher than that seen for methotrexate (adjusted RR 1.00; 0.95 to 1.04). CONCLUSION: Glucocorticoid therapy is associated with an increased risk of NSI. The magnitude of risk increases with dose, and is higher than that seen with methotrexate, although residual confounding may exist. While the RR is low at 1.20, the absolute risk is high with one additional infection seen for every 13 patients treated with glucocorticoids for 1 year.
21962388 Rheumatoid meningitis occurring during adalimumab and methotrexate treatment. 2012 Jan Rheumatoid arthritis is well known for multiple extra-articular manifestations. Here, we present a case of chronic rheumatoid meningitis occurring during treatment with methotrexate and the tumour necrosis factor (TNF) alpha antibody adalimumab. Nine and seven months, respectively, into the course of these two treatments, a 59-year-old Caucasian lady with mild, early, seropositive rheumatoid arthritis developed headaches and psychomotor retardation followed by seizures. The diagnosis was confirmed by a brain biopsy showing a necrotizing granulomatous meningitis. Withdrawal of both drugs and high dose corticosteroids led to marked improvement. The addition of the anti-CD20 antibody rituximab allowed discontinuation of the corticosteroids. This is the fifth published case describing the occurrence of rheumatoid meningitis during treatment with TNF blockers. TNF blockers and methotrexate thus do not appear to prevent this complication, and may even contribute to its development.
23124086 [A case of rheumatoid arthritis complicated with deteriorated interstitial pneumonia after 2012 We report a case of rheumatoid arthritis (RA) complicated with interstitial pneumonia that deteriorated after the administration of abatacept. A 55-year-old man developed RA and interstitial pneumonia. Although interstitial pneumonia was improved by high-dose glucocorticoids, various disease-modifying antirheumatic drugs including infliximab were ineffective for his arthritis. Tacrolimus was effective but was discontinued due to refractory itching and diarrhea. After 2 months, he was registered on the Phase III trial of abatacept in Japan because of worsening of arthritis. From 2 days after the abatacept administration, frothy sputum frequently appeared, but sputum culture was negative. On 13 days after the administration, the interstitial shadow was deteriorated by chest CT as compared with that of 2 months before, and he was dropped out from the trial. On 27 days after the administration, the dose of prednisolone was increased from 2 to 10 mg/day for his arthritis. On 44 days after the administration, the interstitial pneumonia improved. Abatacpet might be the cause of the deterioration of the interstitial pneumonia, but other possibilities such as discontinuation of tacrolimus, flare-up of RA itself or viral infection should be considered. This is the first report of deteriorated interstitial pneumonia after the abatacept administration in the literature. Further cases are needed to identify the relation between abatacept and interstitial pneumonia, however this possibility should be always kept in mind when we use abatacept.
22072115 Second generation automated anti-CCP test better predicts the clinical diagnosis of rheuma 2012 Feb Rheumatoid arthritis (RA) is one of the most common systemic autoimmune diseases. The presence of antibodies to cyclic citrullinated peptide (CCP) is better at discriminating RA patients and is also associated with significantly more disease activity compared to serum rheumatoid factor. In this study, we assessed two new automated second generation tests to detect the presence of anti-CCP antibodies in 226 serum samples submitted to the Clinical Immunology Laboratory for anti-CCP antibody testing. We compared CCP antibody results on these samples obtained using the ImmunoCAP 250 (Phadia) and the Architect i2000SR (Abbott Laboratories) instruments to our currently used CCP IgG third generation manual ELISA (Inova Diagnostics). One hundred and fifty-four samples were negative while 52 were positive by all three tests. Eighteen samples were negative by the automated tests but weakly/moderately positive by manual ELISA yielding an overall concordance of 79%. When we compared the discordant test results to patient diagnosis, we observed a better correlation with clinical RA diagnosis for the new automated tests compared to the manual ELISA. These two new anti-CCP antibody tests have the benefit of automation and may have better positive predictive value for the diagnosis of RA than our current manual ELISA.
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.
22838954 Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with est 2012 Jul BACKGROUND: The performance of a clinical pharmacogenetic model to predict nonresponse of methotrexate (MTX) monotherapy in patients with established rheumatoid arthritis (RA) and failure of disease-modifying antirheumatic drugs (DMARDs) was studied. METHODS: For 75 RA patients receiving MTX monotherapy for 6 months, DNA and clinical data were available. Risk scores for nonresponse at 6 months (disease activity score >2.4), were calculated using the pharmacogenetic prediction model utilizing four clinical factors and four polymorphisms in the genes MTHFD1, AMPD1, ITPA and ATIC. RESULTS: At 6 months, there were 25 responders and 50 nonresponders. Using the clinical pharmacogenetic prediction model, 75% (56 out of 75) were categorized into predicted responders (risk score ≤ 3.5) and predicted nonresponders (risk score ≥ 6). At 6 months, the negative predictive value was 81% (21 out of 26) and the positive predictive value was 47% (14 out of 30). CONCLUSION: The pharmacogenetic model predicts nonresponse to MTX monotherapy, but performs better in DMARD naive recent-onset RA patients than in patients with preceding DMARD failure.
21298002 Prostaglandin E2 synthesizing enzymes in rheumatoid arthritis B cells and the effects of B 2011 Jan 27 INTRODUCTION: B cells may play an important role in promoting immune activation in the rheumatoid synovium and can produce prostaglandin E(2) (PGE(2)) when activated. In its turn, PGE(2) formed by cyclooxygenase (COX) and microsomal prostaglandin E(2) synthase 1 (MPGES1) contributes to the rheumatoid arthritis (RA) pathological process. Therapeutic depletion of B cells results in important improvement in controlling disease activity in rheumatoid patients. Therefore we investigated the expression of PGE(2) pathway enzymes in RA B cells and evaluated the effects of B cell depleting therapy on their expression in RA tissue. METHODS: B cells expressing MPGES1 and COX-2 were identified by flow cytometry in in vitro stimulated and control mononuclear cells isolated from synovial fluid and peripheral blood of RA patients. Synovial biopsies were obtained from 24 RA patients before and at two consecutive time points after rituximab therapy. Expression of MPGES1, COX-1 and COX-2, as well as interleukin (IL)-1β and IL-6, known inducers of MPGES1, was quantified in immunostained biopsy sections using computerized image analysis. RESULTS: Expression of MPGES1 or COX-2 was significantly upregulated upon stimulation of B cells from blood and synovial fluid while control cells displayed no detectable enzymes. In synovial biopsy sections, the expression of MPGES1, COX-1 or COX-2 was resistant to rituximab therapy at 8 or 16 weeks after start of treatment. Furthermore expression of IL-1β in the synovial tissue remained unchanged, while IL-6 tended to decrease after therapy. CONCLUSIONS: Therapy with B cell depleting agents, although efficient in achieving good clinical and radiographic response in RA patients, leaves important inflammatory pathways in the rheumatoid synovium essentially unaffected.
23129427 Association of TLR4 gene non-missense single nucleotide polymorphisms with rheumatoid arth 2013 May Toll-like receptor4 (TLR4) plays an important role in the induction and regulation of the innate or adaptive immune responses. Thus, the genetic variation in TLR4 gene may influence the development of autoimmune diseases such as rheumatoid arthritis (RA). Several studies have investigated the roles of genetic polymorphisms of TLR4 gene in RA, but most of these studies were restricted to two cosegregating functional missense polymorphisms Asp299Gly and Thr399Ile. To determine whether non-missense genetic polymorphisms located in regulatory region of TLR4 are related to RA in a Chinese Han population, four single nucleotide polymorphisms (SNPs) situated on 3' untranslating region (UTR) and 5' UTR were genotyped in 213 RA patients and 247 unrelated ethnically matched controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing techniques. Significant genetic associations were observed with the 3' UTR SNP rs41426344 and rs7873784. The minor allele C and homozygotic variant genotype CC of rs41426344 and minor allele C of rs7873784 were identified to be risk factors for the development of RA in Chinese Han people. Furthermore, by comparing the variation allele frequencies to other populations, prevalent genetic ethnic specificity was observed in all the four SNPs. Our study suggested that the effect of non-missense polymorphisms located in regulatory region would not be neglected in disease association analysis.