Relationship between time-integrated C-reactive protein levels and radiologic progression in patients with rheumatoid arthritis

OBJECTIVE: An elevated acute-phase response is associated with increased radiologic damage in rheumatoid arthritis (RA), but development of damage in previously normal joints ("new joint involvement") has not previously been investigated. This study was undertaken to investigate the hypothesis that when there is suppression of disease activity as judged by the C-reactive protein level, new joint involvement is reduced to a greater extent than is progression in already damaged joints ("damaged joint progression"). METHODS: Three hundred fifty-nine patients with active RA were studied as part of a 5-year randomized, prospective, open-label study of disease-modifying antirheumatic drug therapy. Time-averaged CRP was calculated from samples obtained every 6 months, and patients were divided into groups with CRP values of <6, 6-<12, 12-<25, and > or =25 mg/liter. Radiographs of the hands and feet were scored by the Larsen method; a damaged joint was defined as one with a score of > or =2. RESULTS: The rank correlation between time-integrated CRP and increase in Larsen score was 0.50; the correlation increased to 0.59 for patients entering the study with disease duration of < or =2 years. The percentage of new joint involvement over 5 years varied markedly with time-integrated CRP, from 7.3% in the CRP <6 mg/liter group to 39.1% in the CRP > or =25 mg/liter group (5.4-fold increase). The percentage of damaged joint progression increased from 26.1% in the CRP <6 mg/liter group to 41.6% in the CRP > or =25 mg/liter group (1.6-fold increase). CONCLUSION: The results of this study provide further confirmation that high CRP levels over time are associated with greater radiologic progression. Although radiologic progression still occurred in both previously normal and damaged joints despite the presence of normal CRP levels, this consisted of proportionately less new joint involvement compared with damaged joint progression. These findings support the idea that disease-suppressive therapy should be instituted at an early stage in patients with RA, before erosive damage has occurred.     

High serum and synovial fluid granulocyte colony stimulating factor (G-CSF) concentrations in patients with rheumatoid arthritis

OBJECTIVE: To determine the relationship between serum G-CSF, RA disease activity and the levels of inflammatory cytokines. METHODS: Sixty-one patients (5 men and 56 women; mean age; 56.1 +/- 11.4 [+/- SD] years, range, 22-70 years) who were selected at random and met the American College of Rheumatology criteria for RA were examined. Granulocyte-colony stimulating factor (G-CSF) levels in sera and synovial fluid were measured by solid-phase radioimmunoassay (RIA). We also measured various indices of RA disease activity and serum levels of IL-1 beta, IL-6 and TNF-alpha by ELISA. RESULTS: The morning stiffness, number of tender or swollen joints, ESR, Lansbury index and serum G-CSF levels in patients with active RA were significantly higher than the corresponding levels in patients with inactive RA. Serum G-CSF levels correlated significantly with morning stiffness, the number of tender or swollen joints and the Lansbury index. However, there was no correlation between serum G-CSF and ESR. High levels of IL-1 beta, IL-6 and TNF-alpha were detected in RA patients. The number of tender or swollen joints, ESR, Lansbury index, and IL-1 beta were significantly higher in G-CSF-positive RA patients than in G-CSF-negative RA patients. CONCLUSION: Our results suggest that G-CSF produced by synovial cells stimulated by inflammatory cytokines might contribute to inflammatory arthritis in RA patients.     

Clinically apparent atherosclerotic disease in diabetes is associated with an increase in platelet microparticle levels.

BACKGROUND: The commonest cause of mortality in patients with Type 2 diabetes is atherothrombosis, which can be related to abnormalities in the coagulation and fibrinolytic pathways, as well as in platelet function. Platelet microparticles (PMPs) may contribute to the prothrombotic state and may promote the progression of atherosclerosis. We hypothesized that PMPs are elevated in Type 2 diabetes and that patients with Type 2 diabetes and clinically apparent atherosclerosis would have the highest levels. Similarly, we hypothesized that soluble plasma P-selectin (sPsel) and CD40L (both molecules which are released by activated platelets), as well as %CD62P (P-selectin) and %CD63 positivity on platelets quantified by flow cytometry, would be highest in patients with Type 2 diabetes and clinically apparent atherosclerotic disease, and might be correlated to PMP levels. METHODS: Venous blood was obtained from 21 Type 2 diabetic patients without atherosclerotic complications, 18 diabetic patients with clinically apparent atherosclerotic disease and 21 non-diabetic control subjects. PMPs, as well as %CD62P and %CD63 positivity on platelets, were quantified by flow cytometry. sPsel and CD40L were measured using ELISA. RESULTS: Patients with Type 2 diabetes and clinically apparent atherosclerotic disease had the highest PMP (P=0.045) and sPsel (P=0.046) levels, compared with patients without complications (who had intermediate PMP levels) and control subjects. Control subjects had the lowest CD40L levels (P<0.001) when compared with patients with Type 2 diabetes, with no difference in sCD40L levels between the two diabetic subgroups. %CD62P and %CD63 positivity did not differ between the groups. PMP levels correlated with %CD62P positivity (P=0.026) but not to %CD63 positivity (P=0.089), sCD40L (P=0.407) or sP-sel (P=0.163); sCD40L levels did not correlate with any other marker of platelet activation. CONCLUSION: PMPs are elevated in Type 2 diabetes. In addition, patients with clinically apparent atherosclerosis had the highest levels of PMPs and sPsel. Thus, PMPs may be a marker of symptomatic atherosclerotic vascular disease in Type 2 diabetes, and may both represent a useful risk stratification tool as well as a novel therapeutic target for anti-thrombotic drugs.     

The Swedish early psoriatic arthritis register-- 2-year followup: a comparison with early rheumatoid arthritis

OBJECTIVE :Patients with symptoms and signs compatible with psoriatic arthritis (PsA), with or without psoriasis, have been documented in the Swedish Early Psoriatic Arthritis (SwePsA) register. Our aim was to find markers for disease progression and to evaluate treatments for PsA using these data. METHODS: Patients referred to rheumatology outpatient clinics within 2 years of onset were assessed on inclusion and at followup 2 years later. Data collection was performed according to the program for SwePsA, and classification was as described by Moll and Wright and the ClASsification Criteria for Psoriatic ARthritis (CASPAR). Remission was recorded if the patient had no tender or swollen joints and if erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were within the reference range. Patients with early rheumatoid arthritis (RA) recruited from the Swedish Early Rheumatoid Arthritis Register (Ramona) provided comparison data. RESULTS: One hundred thirty-five patients with PsA according to CASPAR were assessed; 44% were classified as having mono/oligoarthritis and 47% as polyarthritis. Two patients (1%) were in remission initially, and 23 (17%) at followup. Patients with polyarticular disease had the highest inflammatory activity, measured by swollen and tender joint counts, ESR, Health Assessment Questionnaire, and self-assessment by visual analog scale of pain and global disease activity. Dactylitis was associated with radiological findings. Compared with RA patients, they had significantly lower CRP, ESR, and number of swollen joints (p = 0.0003, p = 0.0026, p = 0.0380, respectively) at inclusion, but equal numbers of tender joints and self-assessment of pain and disease activity. CONCLUSION: About half the patients had polyarthritis and the other half had mono/oligoarthritis at followup after 2 years. Patients with polyarthritis had the highest inflammatory activity. Apart from ESR, CRP, and swollen joint count, there were no significant differences in activity between RA and polyarticular PsA.     

Plasma TNF binding capacity profiles during treatment with etanercept in rheumatoid arthritis

BACKGROUND: Etanercept (Enbrel) induces a rapid and sustained decline in disease activity in the majority of patients with refractory rheumatoid arthritis (RA). In these patients neutralization of TNFalpha and lymphotoxin (LT), previously termed TNFbeta is mediated by etanercept itself, as well as by naturally occurring soluble TNF receptors. However, the clinical response to treatment with etanercept may vary. Previously, pharmacokinetic studies have focused on the molar concentrations of etanercept, but very little is known about the kinetics of bioactive etanercept in patients treated with etanercept. The purpose of this study was to evaluate kinetics, including inter- and intraindividual variations of the total TNF binding capacity, in RA patients who were on a standard treatment schedule with etanercept. METHODS: Plasma samples were collected daily from 16 RA patients who were in the steady-state phase during treatment with etanercept 25 mg subcutaneous once (n = 2) or twice (n = 14) weekly. The inflammatory activity, including Health Assessment Questionnaire (HAQ) score, numbers of painful and swollen joints, and ESR, was assessed at inclusion; CRP was measured on a daily basis. The samples were incubated with human recombinant LT to a concentration of 1000 pg/mL and the levels of detectable LT were measured by ELISA specific for free LT. The LT binding capacity (LTBC) was expressed in arbitrary units (AU) as the percentage value of bound LT to added LT. RESULTS: The median LTBC values measured during the treatment schedule from Day 1 (before the injection) to Day 4 (before the next injection) were 47 AU. The LTBC values in each individual patient generally remained fairly stable through the treatment schedule, and there were no significant differences in LTBC levels in samples obtained on a daily basis during the treatment schedule. However, a pronounced variation between the patients was noticed with LTBC values ranging from 10-82 AU (coefficient of variation=38%). No significant association was found between LTBC levels and clinical measures of disease activity, including HAQ and numbers of swollen or painful joints. However, among patients with high LTBC levels (> or =65 AU), elevated levels of ESR and CRP were less frequent (0%) compared with patients who had lower LTBC levels, in which the frequencies of elevated ESR and CRP were 53% and 37%, respectively. Soluble TNF receptor 1 (sTNFR1) remained stable between the injections and correlated with the number of swollen joints, but did not correlate with LTBC values. CONCLUSION: LTBC levels appeared stable in each individual RA patient who was on the standard treatment schedule with weekly injections of etanercept, but the inter-individual variations were considerable.     

血清骨桥蛋白水平与类风湿关节炎活动性的关系及在伴肺间质病变中的意义

目的 检测类风湿关节炎(RA)患者血清骨桥蛋白(OPN)水平,分析血清OPN水平与RA疾病活动的相关性,初步探讨OPN在RA合并肺间质病变(ILD)发病机制中的作用.方法 收集临床确诊的65例RA患者血清.其中活动期RA患者43例,缓解期RA患者22例;其中合并ILD者24例,未合并ILD者41例.以20名健康体检者血清为健康对照组.采用酶联免疫吸附法(ELISA)检测血清OPN水平,并与RA患者的临床及实验室指标进行相关性分析.结果 ①RA组血清OPN水平(中位数18.0 ng/ml),高于健康对照组(中位数14.0 ng/ml,P<0.01);活动期RA组血清OPN水平(中位数20.0 ng/ml),高于缓解期RA组(中位数1.5 ng/ml,P<0.01).②RA组血清OPN水平与病程、关节压痛数、红细胞沉降率(ESR)、C反应蛋白(CRP)等呈显著正相关,与关节肿胀数无相关性.③RA合并ILD组血清OPN水平(中位数20.0 ng/ml),高于RA未合并ILD组(中位数17.0 ng/ml,P<0.05);且与动脉氧分压(PaO2)呈负相关;与肺功能(肺活量、一氧化碳弥散吸收率)无相关性.④RA合并ILD组关节压痛数,关节肿胀数、ESR、CRP等与RA未合并ILD组相比差异具有统计学意义(P均<0.01);RA合并ILD组血清类风湿因子(RF)(IgM)高于RA未合并ILD组(P<0.05).结论 OPN在RA发病机制中具有一定意义且与RA活动性有关,可作为评价疾病活动度的炎性指标;OPN参与了RA合并ILD的发生及进展,并与肺损害严重程度有关.     

Most patients receiving routine care for rheumatoid arthritis in 2001 did not meet inclusion criteria for most recent clinical trials or american college of rheumatology criteria for remission

OBJECTIVE: To determine the proportion of 2 cohorts of patients with rheumatoid arthritis (RA) in Nashville, Tennessee, who met 4 common criteria for inclusion in clinical trials: > or = 6 swollen joints, > or = 6 tender joints, erythrocyte sedimentation rate > or = 28 mm/h, and/or morning stiffness > or = 45 min. METHODS: Two cohorts of patients with RA, all of whom had met American Rheumatism Association (ARA) [now American College of Rheumatology (ACR)] criteria for RA at some time, were studied. Cohort L (late) included 146 consecutive patients whose mean disease duration was 14.0 years and who had been under care at a weekly academic rheumatology clinic for a mean of 6.2 years when seen in 1998-2001. Cohort E (early) included 232 patients of 5 private practice rheumatologists whose symptoms began in 1998 or later and whose mean disease duration was 1.8 years when seen in 2001. Patients were reviewed for the 4 inclusion criteria as well as 6 ARA remission criteria. RESULTS: In Cohort L, on a 28 joint count, 42.5% of patients had > or = 6 swollen joints, 25.3% had > or = 6 tender joints, 19.9% had both > or = 6 swollen and > or = 6 tender joints, 25.0% had ESR > or = 28, and 45.9% had morning stiffness > or = 45 min. In Cohort E, on a 42 joint count, 63.4% of patients had > or = 6 swollen joints, 50.4% had > or = 6 tender joints, 38.8% had both > or = 6 swollen and > or = 6 tender joints, 49.3% had ESR > or = 28, and 50.9% had morning stiffness > or = 45 min. Overall, 15.3% of Cohort L and 34.1% of Cohort E patients had > or = 6 swollen and tender joints, as well as an ESR > or = 28 or morning stiffness > or = 45 min. Only 4.1% of Cohort L and no patient in Cohort E met ARA criteria for remission. CONCLUSION: The majority of patients seen in routine care in these 2 cohorts did not meet criteria for inclusion in most contemporary RA clinical trials, including clinical trials sponsored by pharmaceutical companies to introduce new drugs or biological agents. Few of these patients met ARA criteria for remission. Controlled trial data are not available concerning results of treatment with new biological agents or disease modifying antirheumatic drugs in a large proportion, if not a majority, of patients with RA at this time.     

Serum matrix metalloproteinase 3 levels in comparison to C-reactive protein in periods with and without progression of radiological damage in patients with early rheumatoid arthritis

OBJECTIVE: To evaluate serum matrix metalloproteinase 3 (MMP-3) levels in comparison to C-reactive protein (CRP) in periods with and without progression of radiological damage in patients with early rheumatoid arthritis (RA). METHODS: Thirty-two patients with RA and radiological progression (> or = 5 points according to the Sharp/van der Heijde method) during 6 months followed by a 6-month period without radiological progression (< or = 1 point) were selected from a prospective follow-up study of early RA patients. Serum MMP-3 levels, CRP, the erythrocyte sedimentation rate (ESR), disease activity index (DAS), swollen joint count (SJC), tender joint count (TJC), and Ritchie articular index (RAI) were measured monthly and results were transformed into mean values for the 6-month periods. RESULTS: During the period with radiological progression the mean serum MMP-3 correlated significantly with the mean CRP (r = 0.68, p < 0.001), ESR (r = 0.54, p = 0.001) and swollen joint count (r = 0.48, p = 0.006). In the period without radiological progression the mean serum MMP-3 only correlated with the mean CRP (r = 0.44, p = 0.012). Individual changes--expressed in percentages (%)--between the two periods showed a decrease in both the mean serum MMP-3 and CRP in 19 and an increase in 3 patients, in parallel with other markers of disease activity in these patients (69% of cases). The individual change (%) in mean serum MMP-3 or CRP did not correlate with the difference in radiological progression between the two periods. CONCLUSIONS: Serum MMP-3 and CRP are closely related and there seems to be no difference between serum MMP-3 and CRP with regard to the monitoring of the progression of radiological damage.     

Plasma monocyte chemoattractant protein 1 is a marker for joint inflammation in rheumatoid arthritis

OBJECTIVE: Monocyte chemoattractant protein 1 (MCP-1) level in plasma is described as a marker for joint inflammation in rheumatoid arthritis (RA). METHODS: MCP-1 in plasma and synovial fluid (SF) was quantified by ELISA in 36 RA patients with synovitis of the knee at Day 1 and 30. Disease activity was assessed by the swollen joint count, Ritchie Articular Index (RAI), global assessment, pain on visual analog scale, Health Assessment Questionnaire, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). RESULTS: By linear regression analysis plasma MCP-1 levels correlated significantly with the swollen joint count (Day 1: R = 0.47, p = 0.005; Day 30: R = 0.53, p < 0.001) and the RAI (Day 1: R = 0.37, p = 0.03; Day 30: R = 0.41, p = 0.01). The correlations of swollen joint count and RAI with ESR and CRP were significant only on Day 30 for the ESR (R = 0.40, p = 0.02). No association was found between plasma MCP-1 levels and the ESR/CRP levels. MCP-1 levels in plasma in RA patients were elevated compared to controls (p < 0.001) and MCP-I levels in SF were higher than in plasma (p < 0.001). No correlation was found between SF MCP-1 levels and in vitro migration of mononuclear cells towards SF. MCP-1 appears to participate in the disease process in RA, and plasma MCP-1 may be useful in monitoring joint inflammation.     

Elevated platelet microparticle levels in nonvalvular atrial fibrillation: relationship to p-selectin and antithrombotic therapy

BACKGROUND: Platelet microparticles (PMPs), are procoagulant membrane vesicles that are derived from activated platelets, the levels of which are elevated in patients with hypertension, coronary artery disease (CAD), diabetes, and stroke, all of which are conditions that lead to (and are associated with) atrial fibrillation (AF). We hypothesized the following: (1) PMP levels are elevated in patients with AF compared to levels in both healthy control subjects (ie, patients without cardiovascular diseases who are in sinus rhythm) and disease control subjects (ie, patients with hypertension, CAD, diabetes or stroke, but who are in sinus rhythm); (2) PMP levels correlate with levels of soluble P-selectin (sP-selectin) [a marker of platelet activation]; and (3) PMP levels are related to the underlying factors in patients with AF that contribute to the overall risk of stroke secondary to AF. METHODS: We performed a case-control study of 70 AF patients, 46 disease control subjects and 33 healthy control subjects. Peripheral venous levels of PMP and sP-selectin were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: Both AF patients and disease control subjects had significantly higher levels of PMPs (p < 0.001) and sP-selectin (p = 0.001) compared to healthy control subjects, but there was no difference between AF patients and disease control subjects. There was no difference in PMP levels between patients with paroxysmal and permanent AF (p = 0.581), and between those receiving therapy with aspirin and warfarin (p = 0.779). No significant correlation was observed between PMP and sP-selectin levels (p = 0.463), and the clinical characteristics that contribute to increased stroke risk in patients with AF. On stepwise multiple regression analysis in the combined cohort of AF patients plus disease control subjects, the presence/absence of AF was not an independent determinant of PMP and sP-selectin levels. CONCLUSION: There is evidence of platelet activation (ie, high PMP and sP-selectin levels) in AF patients, but this is likely to be due to underlying cardiovascular diseases rather than the arrhythmia per se.     

血清抗角蛋白抗体抗环瓜氨酸肽抗体和类风湿因子在类风湿关节炎中的意义

目的 评价抗角蛋白抗体(AKA)、抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)在类风湿关节炎(RA)中的意义.方法 收集82例RA患者及56例非RA患者,测定其抗CCP抗体、AKA和RF水平,评价对RA诊断的敏感性、特异性,比较RA患者中抗CCP抗体、AKA阳性组和阴性组的压痛关节数、肿胀关节数、红细胞沉降率(ESR)、C反应蛋白(CRP)、疾病活动指数(DAS)、Ritchie's指数(RAI).结果 单独检测AKA、抗CCP抗体、RF及联合检测的曲线下面积都较高(P<0.05).抗CCP抗体、AKA的特异度分别为92.9%、91.1%,联合检测AKA、抗CCP抗体和RF有任何一种及以上阳性的灵敏度最高,为95.1%.抗CCP抗体阳性组与阴性组的关节肿胀数、关节压痛数、ESR、CRP、DAS、RAI差异有统计学意义(P<0.05);AKA阳性组与阴性组的关节肿胀数、ESR、DSA差异均有统计学意义(P<0.05).结论 联合检测抗CCP抗体、RF、AKA对诊断RA有意义,抗CCP抗体、AKA可能与RA的活动度相关.     

Age adjustment corrects for apparent differences in erythrocyte sedimentation rate and C-reactive protein values at the onset of seropositive rheumatoid arthritis in younger and older patients

OBJECTIVE: To evaluate the effect of age adjustment on baseline erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in patients with late-onset rheumatoid arthritis (LORA, age > or = 55 yrs) and younger-onset RA (YORA, age < 55 yrs) in a cohort with early, rheumatoid factor (RF) positive RA that has not received disease modifying antirheumatic drugs (DMARD). METHODS: In an ongoing prospective cohort study of 263 patients with seropositive RA who were enrolled within 14 months of symptom onset, baseline assessments included ESR, CRP, tender and swollen joint counts, and functional status. Westergren ESR determinations were performed in the rheumatologist's office or in a local laboratory using appropriate methods. CRP were performed at the Specialty Laboratories in Santa Monica, CA, using Behring nephelometry. Percentages of patients with greater than the upper limit of normal (ULN) laboratory values using both age-unadjusted and age-adjusted ESR and CRP values were determined. The late-onset and younger-onset RA patients were compared using Wilcoxon rank-sum and chi-square tests. RESULTS: At study entry, both the YORA and LORA patients had comparable symptom duration, disease activity scores, tender and swollen joint counts, and Health Assessment Questionnaire values. RF, CRP, and ESR were significantly higher (p < 0.05) in LORA patients. Although the percentages of patients with age-unadjusted ESR and CRP above ULN were higher in LORA patients, the percentages exceeding the age-adjusted ULN did not differ significantly between the YORA and LORA groups. CONCLUSION: In patients with late-onset and younger-onset RA with similar disease duration and severity, the apparent discrepancy in elevation of both the baseline ESR and CRP disappears after age-adjustment.     

Safety and efficacy of vaccination against hepatitis B in patients with rheumatoid arthritis

BACKGROUND: Hepatitis B infection and vaccination against it have been implicated in the potential triggering or flare of some autoimmune diseases, including rheumatoid arthritis (RA). However, the safety of hepatitis B vaccination in patients with pre-existing RA is not known. OBJECTIVES: To assess the safety and antibody response of immunisation with a recombinant DNA hepatitis B vaccine in patients with RA. PATIENTS AND METHODS: The study comprised 44 patients with RA, of whom 22 received three doses (the second and third dose being given after one and six months) of a recombinant DNA hepatitis B vaccine (study group) and 22 did not receive the vaccine (control group). Both groups had comparable proportions of women and similar mean age (51 years). Clinical assessment before and two and seven months after the first immunisation included evaluation of daytime pain with a 10 cm visual analogue scale, duration of morning stiffness, and number of tender and swollen joints. Erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were measured at each visit. Antibodies to hepatitis B surface antigen (HBsAg) were determined by a commercial enzyme linked immunosorbent assay (ELISA) test kit. RESULTS: Hepatitis B vaccination was not associated with an appreciable deterioration in any clinical or laboratory measure of disease. The measures of disease activity of the patients and controls during the study period did not differ significantly: p=0.76 for daytime pain, p=0.1 for morning stiffness, p=0.24 and p=0.3 for tender and swollen joints respectively, p=0.08 for CRP, and p=0.12 for ESR. Fifteen of the 22 patients responded to vaccination, with an antibody level against HBsAg of 10 IU/l after seven months. Lack of response was associated with older age and higher scores of daytime pain. CONCLUSIONS: Hepatitis B vaccination is safe in RA and produces antibodies in 68% of the patients.     

Elevated platelet microparticles in stable coronary artery disease are unrelated to disease severity or to indices of inflammation

Platelet microparticles (PMPs), procoagulant membrane vesicles derived from activated platelets, are elevated in acute myocardial infarction and unstable angina but their relationship to inflammation and indices of coronary artery disease are unclear. We therefore hypothesised that PMPs are related to scores of coronary atheroma and/or coronary stenosis. Our study was completed by comparing PMP data with other platelet markers and with hs-CRP, marking inflammation. We recruited 54 patients attending for coronary angiography, comparing them to 35 age- and sex-matched controls. Peripheral blood was analysed for PMPs, percent platelets positive for CD62P and CD63 (all flow cytometry), soluble P selectin and hsCRP (both immunoassay). Patients exhibited higher PMPs, increased platelet %CD62P, %CD63 and soluble P selectin (all P < 0.01) and hs-CRP (P = 0.0167) than healthy controls. However, analysing only patients with an unequivocal classification, there were no significant (P 相似文献   

Serum amyloid A in the assessment of early inflammatory arthritis

OBJECTIVE: Acute phase serum amyloid A (A-SAA) has been reported to be more sensitive than C-reactive protein (CRP) as a marker of disease activity. It may function in immune regulation and is linked to the development of secondary amyloidosis. We investigated the profile of A-SAA in early inflammatory arthritis and compared A-SAA with CRP and erythrocyte sedimentation rate (ESR) in relation to diagnosis and disease activity. METHODS: Using a sensitive and specific ELISA, A-SAA was measured in the serum of 140 patients with early arthritis (disease duration 2 weeks to 24 mo, mean 6 mo). CRP was determined using a standard ELISA; ESR and clinical disease activity variables were also recorded. RESULTS: Sixty-four patients had rheumatoid arthritis (RA), 19 psoriatic arthritis (PsA), 28 undifferentiated arthritis (UA), and 29 other forms of arthritis. A-SAA levels correlated with both CRP (r = 0.73, p = 0.0001) and ESR (r = 0.6, p = 0.0001). The magnitude of the A-SAA response was greater than either the CRP or ESR, and very high A-SAA levels were observed in disease as early as 2 weeks. Highest A-SAA concentrations occurred in RA (median 70.3 mg/l, maximum 1542) compared with the other groups (medians, PsA: 33 mg/l; UA: 12.3 mg/l; other arthritis: 11.2 mg/l), with values > 520 mg/l observed exclusively in RA. A-SAA, unlike CRP or ESR, could distinguish patients with a final diagnosis of RA from those who had persistent UA. In RA, A-SAA provided the strongest correlations with clinical measurements of disease activity. Clinical improvement was also best represented by A-SAA, while disease deterioration was associated with a significant increase in A-SAA values, but not CRP or ESR. CONCLUSION: Compared with ESR or CRP, A-SAA correlates best with markers of disease activity, and in patients with recent onset arthritis, very high levels of SAA occur exclusively in RA. As A-SAA is sensitive to change and accurately reflects alterations in disease status, it is the best marker available for the assessment of inflammatory joint disease.     

Effect of age on 3 year outcome in early rheumatoid arthritis

OBJECTIVE: To investigate the effect of age on clinical and radiological outcome and on efficacy and tolerance of antirheumatic therapy in early rheumatoid arthritis (RA). METHODS: In a prospective 3 year study 113 patients (83 women, 30 men) were divided into 2 groups according to age at onset of disease: before (n = 55) and after 55 years of age (n = 58). For clinical outcome, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, Ritchie index, and number of swollen joints were measured. Radiological progression was analyzed by Larsen score. The principles of the "sawtooth" strategy were applied in the treatment of all patients. RESULTS: At baseline, inflammatory activity (ESR, CRP) and the Larsen score for hands were significantly higher in patients with late onset RA (LORA) and they also developed more extraarticular symptoms compared to patients with early onset RA (EORA). However, no differences were found in Ritchie index, number of swollen joints, or CRP values between the groups. Also during the followup there was a trend toward increased inflammatory activity (ESR) among LORA patients. After the initiation of antirheumatic therapy a parallel improvement in clinical activity was observed in the 2 groups. The frequencies of remissions, side effects, and withdrawals due to drug inefficacy did not differ significantly between the 2 groups. The radiological progression was also comparable. CONCLUSION: The onset of RA was more active in patients with LORA. However, the clinical course and the radiological progression were parallel in LORA and EORA patients. The "sawtooth" therapy was equally tolerated in both patient groups.     

Clinical remission and/or minimal disease activity in patients receiving adalimumab treatment in a multinational, open-label, twelve-week study

OBJECTIVE: To evaluate the effect of adalimumab treatment on clinical remission and/or minimal disease activity (MDA) in 6,610 patients with active rheumatoid arthritis (RA) who were enrolled in the Research in Active RA trial, a multinational, open-label, 12-week study with an optional extension period. METHODS: Clinical remission was defined as a Disease Activity Score in 28 joints (DAS28)<2.6, Simplified Disease Activity Index (SDAI) score相似文献   

Ultrasound Evaluation of the Effects of Leukocytapheresis on Rheumatoid Arthritis

Leukocytapheresis (LCAP) is effective in treating rheumatoid arthritis (RA). Ultrasound (US) examination of joints is useful for evaluating disease activity and therapeutic effects in RA, but the clinical assessment of LCAP therapy with US has been little reported. We investigated the usefulness of US for evaluating the effects of LCAP in patients with RA. US examination was performed in six patients (total of seven cases) who underwent LCAP. Twenty‐eight joints (bilateral shoulders, elbows, wrists, 1st to 5th metacarpophalangeal joints, 1st to 5th proximal interphalangeal joints, and knee joints) were evaluated by a systematic multiplanar grey‐scale and power Doppler (PD) examination. Disease activity of RA was evaluated using the 28‐joint Disease Activity Score with erythrocyte sedimentation rate (DAS28‐ESR). Moderate or good responses to LCAP based on the DAS28‐ESR were observed in four of the seven cases although C‐reactive protein (CRP) and ESR did not decrease. LCAP significantly reduced the mean total PD score 17.3 ± 11.6 to 13.0 ± 10.5 (P = 0.0469). The total PD score decreased in six of the seven cases, and the number of joints with PD score ≥2 decreased in five of the seven cases. The rate of decrease in the number of joints with PD score ≥2 correlated strongly with the DAS28‐ESR and its components, especially swollen joint counts and evaluator's global assessment, but not with the rate of decrease in CRP and ESR. US imaging of joints may be useful for evaluating the therapeutic effects of LCAP on RA compared to other inflammatory parameters.     

Clinical effects of actarit in rheumatoid arthritis: improvement of early disease activity mediated by reduction of serum concentrations of nitric oxide

OBJECTIVE: We previously reported the presence of high serum concentrations of nitric oxide (NO) in patients with rheumatoid arthritis (RA). In this study we evaluated the effect of actarit on patients with early and advanced stages of RA and the relationship between RA activity and serum NO levels. METHODS: Thirty-seven RA patients who were undergoing care at Sasebo Chuo Hospital were entered into the study. Patients were divided into two groups based on the severity of their disease: group I (stages I and II) and group II (stages III and IV). NO concentrations in serum samples were measured by the chemiluminescence method. RESULTS: Morning stiffness, the number of tender and swollen joints, grip strength, pain score, modified Health Assessment Questionnaire score (mHAQ), ESR, CRP and the Lansbury index significantly improved during 24 weeks of treatment in group I. Patients in group II did not show improvement in morning stiffness, pain score, ESR or CRP during treatment. The concentrations of NO in group I were significantly reduced at 8 weeks after administration of actarit. Those in group II showed a delayed response; a significant decrease in NO occurred at 20 weeks. The improvement in the number of tender and swollen joints, grip strength, pain score, mHAQ and Lansbury index noted in group I preceded the fall in NO concentrations. CONCLUSION: Our results demonstrate that actarit improves disease activity in early phase RA by suppressing serum NO levels. The results suggest that NO is a useful marker for monitoring improvement in the early stages of RA.     

The effect of infliximab on bone metabolism markers in patients with rheumatoid arthritis

OBJECTIVE: The aim of this study was to evaluate urinary excretion of N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD), markers of bone resorption, and serum bone alkaline phosphatase (BAP) level, a marker of bone formation and an early marker of osteoblast differentiation, in patients with rheumatoid arthritis (RA) treated with infliximab. METHODS: Seventeen male and female patients (age 60.7+/-2.53 yr; mean disease duration 12.9+/-3.01 yr; Steinbrocker's class II-IV) with RA, diagnosed according to the criteria of the American College of Rheumatology (ACR), took part in the study between March 2003 and January 2005. None of the patients had a history of oestrogen replacement therapy. All patients were treated with infliximab combined with methotrexate. Infliximab was infused intravenously at 3 mg/kg at baseline, 2 and 6 weeks, then every 8 weeks. To evaluate disease activity, ESR, CRP, the numbers of swollen and tender joints, modified Stanford Health Assessment Questionnaire (mHAQ) score and ACR score were measured. Levels of NTX and DPD in urine and BAP in serum were measured in all patients. RESULTS: ESR, CRP, the number of swollen joints and tender joints, and mHAQ score had decreased significantly 6 weeks after initial treatment and were still low 6 months after initial treatment. NTX levels had decreased significantly 6 weeks after the initial treatment and were still low 6 months after initial treatment. DPD levels had decreased 6 months after initial infusion. Mean serum BAP level did not differ significantly among the three time points. NTX levels were statistically corresponding with the number of swollen joints and mHAQ scores. DPD levels were statistically lower corresponding with ESR. CONCLUSION: Infliximab therapy may inhibit generalized bone loss in patients with RA. NTX is a more sensitive marker than DPD.