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ID PMID Title PublicationDate abstract
22218637 The effect of isometric exercise of the hand on the synovial blood flow in patients with r 2013 Jan In 90% of patients with rheumatoid arthritis (RA), the joints of the hand are affected. Studies of grip strength training have not indicated a negative effect on disease activity after training. Introduction of ultrasound Doppler (USD) to measure increased blood flow induced by inflammation has made it possible to investigate the direct effect on blood supply in the synovium after training. In this case-control study, 24 patients with RA with USD activity in the wrist joint participated. The USD activity was measured by the color fraction (CF) (CF = colored pixels/total number of pixels in ROI). Twenty-four patients were assigned to an 8-week grip strength training program. At baseline and after 8 weeks of training, an USD examination of the wrist joint was performed. In the training group, we measured grip strength and pain in the wrist joint. Six patients withdrew from the training because of pain or change in medication. Eighteen patients served as control group. There was a modest, not significant, decrease in the CF in response to training (1.86%; P = 0.08). Grip strength increased 8.8% after training (P = 0.055). Pain in motion deceased after training (P = 0.04). No difference in the CF was seen between the training and control groups, neither at baseline nor at follow-up (P = 0.82 and P = 0.48). Patients withdrawing from training had a significantly higher CF than the other patients (P > 0.001). The results in this study might indicate that the flow in the synovium assessed by USD is not affected by grip strength training.
21530103 Hand appearance as a patient motivation for surgery and a determinant of satisfaction with 2011 Jun PURPOSE: To determine patient motivations for surgery and satisfaction with outcomes for metacarpophalangeal (MCP) joint arthroplasty in 3 domains (appearance, function, and pain) and whether patient-reported satisfaction correlates with standard outcome measures. METHODS: In a randomized controlled trial of MCP joint implants, 33 patients with rheumatoid arthritis had primary MCP joint arthroplasty: 15 hands received Swanson implants, and 18 received NeuFlex implants. Range of motion, ulnar drift, grip strength, Sollerman hand function test, and the Michigan Hand Questionnaire were collected before surgery and 1 year after surgery. Preoperative patient motivations for and expectations of MCP joint arthroplasty were assessed for function, pain, and appearance. Patient-perceived improvement and satisfaction within the 3 domains and global satisfaction were assessed after surgery. RESULTS: Function was rated the most important motivator for surgery by 31 patients, pain by 22, and appearance by 15. Twenty-six patients rated 2 or more motivators equally high. Michigan Hand Questionnaire subscores were moderately correlated or weakly correlated with patient-reported satisfaction. The Sollerman score was weakly correlated with patient-reported satisfaction. Range of motion, ulnar drift, and grip strength were not correlated with patient-reported satisfaction. More patients stated that a much better improvement was obtained for appearance than for function or pain relief. CONCLUSIONS: Patient expectations of MCP joint arthroplasty were uniformly high. The greatest motivation for surgery was functional improvement. Pain was highly ranked, and 25 patients rated hand appearance as the first or second motivator. Patient satisfaction correlated poorly with traditional outcome measures and moderately with patient-reported outcomes. We conclude that appearance should be considered an important motivator for surgery and determinant of satisfaction. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.
21873267 (99m)Tc-anti-TNF-α scintigraphy in RA: a comparison pilot study with MRI and clinical exa 2011 Nov OBJECTIVE: To compare the use of radiolabelled human monoclonal anti-TNF-α scintigraphy with clinical examination and MRI of hands and wrists joints in patients with active RA. METHODS: Eight patients with active RA, 28-joint DAS (DAS-28) ≥ 3.2 and a healthy volunteer underwent whole body and hand/wrist scintigraphy after the administration of anti-human TNF-α labelled with technetium-99m ((99m)Tc). One hundred and ninety-eight joints were examined. Patients were also given clinical examinations in addition to MRI of the hands and wrists. RESULTS: Of the 198 joints examined, signs of inflammation were detected by MRI in 49 (24.7%) and by scintigraphy in 48 (24.2%) joints, with agreement between the two methods in 44 joints. In five joints, MRI was positive and scintigraphy negative. In another four joints, scintigraphy was positive and MRI negative for signs of inflammation. MRI and scintigraphy were in agreement for negative results for 145 joints. The sensitivity and specificity of scintigraphy was 89.8 and 97.3%, respectively. When clinical parameters (presence of swelling and tenderness of joints) were compared with the MRI findings, lower correlation coefficients were observed (sensitivity of 59.2% and 65.3%, respectively). CONCLUSIONS: Scintigraphy using (99m)Tc-anti-TNF-α showed high correlation with the presence of inflammatory signs detected by MRI in the hands and wrists of patients with active RA, and demonstrated a greater sensitivity than clinical examination. These results can assist in better understanding of anti-cytokine therapy and support the achievement of evidence-based biologic therapy.
22237045 Work disability rates in RA. Results from an inception cohort with 24 years follow-up. 2012 Feb OBJECTIVE: To explore rates of and reasons for work disability in an early RA cohort with median 10 years follow-up. METHODS: One thousand four hundred and sixty patients with early RA (<2 years symptom duration) and no prior DMARD therapy were recruited from nine rheumatology outpatient departments across the UK between 1986 and 1998. Standard clinical, laboratory and radiological assessments were recorded at 6-monthly and yearly intervals. Assessment of employment included details of type and hours of paid work. The main outcomes investigated were rates of and main reasons for work cessation, analysed by age of onset of RA (<45, 45-60 years) and year of recruitment to the study (before or after 1992). RESULTS: Maximum follow-up was 24 years, median 10 years. Of 647 patients in paid work at baseline, the majority were <60 years old (91%). The estimated probability of stopping work due to RA was highest in patients with older age of onset (45-60 years) who were recruited before 1992, but improved in those recruited from 1992 to 1998 (P < 0.01). There was no difference seen over the study recruitment years in younger age of onset patients. CONCLUSION: Work loss related to RA occurred much earlier than for other reasons, especially in the first 5 years of RA, but improved in the later recruitment period. Work disability is multifactorial, and the gradual changes in therapies used over time in this cohort may be one explanation for the secular differences seen.
23101665 Altered sequence of the ETS1 transcription factor may predispose to rheumatoid arthritis s 2013 OBJECTIVE: ETS1 belongs to the ETS family of transcription factors that regulate the expression of various immune-related genes. The aim of this study was to identify whether the ETS1 single nucleotide polymorphism (SNP) rs11221332, described in Caucasian subjects, plays a role in rheumatoid arthritis (RA) susceptibility. METHODS: We genotyped this polymorphism in 136 unrelated patients with RA and 147 healthy individuals with no history of autoimmune disease. Genotyping was performed with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and the data were analysed using SPSS statistical software. RESULTS: A statistically significant difference was observed in the distribution of the rs11221332 genotypes between RA patients and controls (p = 0.041). Comparing the distribution of rs11221332 alleles between the groups studied, a greater difference was found [odds ratio (OR) 1.504, 95% confidence interval (CI) 1.036-2.183; p = 0.039]. CONCLUSIONS: The present study revealed, for first time, the positive association of a polymorphism in the sequence of the ETS1 transcription factor with RA susceptibility. Further studies in other ethnic groups of patients are needed to confirm the results of the present genetic association study related to ETS1, a widely used transcription factor in the regulation of the expression of various genes.
22765047 Anti-tumour necrosis factor alpha therapy improves insulin sensitivity in normal-weight bu 2012 Jul 5 INTRODUCTION: Insulin resistance (IR), a risk factor for the development of cardiovascular disease, is common among patients with rheumatoid arthritis (RA). Inflammation, and especially tumour necrosis factor alpha (TNFα), has been associated with IR, and the administration of anti-TNFα agents is suggested to improve insulin sensitivity. However obesity, a potent contributor to IR, may limit the beneficial effects of anti-TNFα medication on IR. The aim of this study is to compare the effects of anti-TNFα therapy on IR between normal-weight and obese patients with RA. METHODS: Patients who were normal-weight with IR (N+IR) or obese with IR (O+IR) and had embarked on anti-TNFα treatment, participated. Assessments included body mass index (BMI), insulin sensitivity (Homeostasis Model Assessment of insulin resistance, HOMA and the Quantitative Insulin sensitivity Check Index, QUICKI), and RA disease characteristics before and following six months of anti-TNFα treatment. Their results were compared to matched (for age, gender, BMI, disease duration and smoking status) normal-weight patients without IR (N-IR) and obese without IR (N-IR), respectively. In total, 32 patients were assessed for this study, with 8 in each group. RESULTS: Following six months of treatment, disease activity was significantly reduced in all groups (P < 0.05) to a similar extent (P for differences between groups > 0.05 in all cases). In the total population, changes in HOMA (mean reduction at 6 m = -0.2 ± 0.1; P = 0.088) and QUICKI (mean increase at 6 m = 0.03 ± 0.022; P = 0.092) after treatment were not statistically significant, though a trend towards improvement was observed. However, N+IR patients showed a significant decrease in HOMA (mean reduction at 6 m = -0.54 ± 0.2; P = 0.002) and increase in QUICKI (mean increase at 6 m = 0.046 ± 0.02; P = 0.011). These changes were significantly different compared to the other groups (P < 0.05 in all cases). Multivariable analyses showed that the change in Erythrocyte Sedimentation Rate (ESR), and the change in C-Reactive Protein (CRP) associated with the improvement in HOMA (ESR: F₁₋₇ = 5.143, P = 0.019; CRP: F₁₋₇ = 3.122, P = 0.022) and QUICKI (ESR: F₁₋₇ = 3.814, P = 0.021; CRP: F₁₋₇ = 2.67; P = 0.041) only in the N+IR group. CONCLUSIONS: Anti-TNFα therapy, through controlling inflammation, seems to improve insulin sensitivity in normal-weight RA patients with insulin resistance, but is not sufficient to achieving the same beneficial effect in obese RA patients with insulin resistance.
21898062 Medical costs for Korean patients with rheumatoid arthritis based on the national claims d 2012 Sep The purposes of this study are to investigate medical resource utilization and medical costs of Korean rheumatoid arthritis (RA) patients and to analyze predictors in relation to medical costs. National claims data on medical treatment were analyzed for the 151,472 RA patients in 2009. For outpatients, the mean annual number of visits was 32.5, and the mean annual total outpatient care costs were 2.0 million KRW (US$1,594) per patient. On the other hand, the mean annual length of stay of inpatients was 22.2 days, and the mean annual total inpatient care costs were 3.8 million KRW (US$3,013). Average annual total medical costs per patient for all of the RA patients were 2.9 million KRW (US$2,310). Total medical costs consisted of 26.1% outpatients' costs, 25.4% inpatient, and 48.6% medication costs, making medication costs a predominant cost driver. In the multiple regression analysis, biologic use was an important cost factor in relation to the annual total medical costs. This study provides information on the cost of illness of RA with the population-based representative RA patients in Korea, which had not been reported until now.
21961794 Use of osteoporosis drugs in patients with recent-onset rheumatoid arthritis in Finland. 2011 Sep OBJECTIVES: We investigated the implementation of pharmaceutical osteoporosis (OP) prevention in early rheumatoid arthritis (RA) in Finland. METHODS: All incident RA cases from 2000 to 2007 were identified using the national register of the Social Insurance Institution (SII) as the sole source. The use of calcium and vitamin D preparations and OP drugs during the first year was evaluated. RESULTS: A total of 14,878 incident RA patients were found. They had a mean age of 56 (SD 15) and 68% were female. Nine per cent of the total number, which equated to 11% for women and to 5% men, had purchased OP drugs. The use of OP drugs increased over time: in the 2006-2007 period, relative risk (RR) for purchase was 1.62 (95% CI 1.38-1.92) for women and 2.1 (1.34-3.30) for men compared to the 2000-2001 period. Over the 2000-2005 period, 49% of females and 52% of males used glucocorticoids (GCs) during the first year. Among the GC-users, 38% of women and 24% of men also received calcium and vitamin D preparations by prescription, and 14% of women and 6% of men also used OP drugs. For GC users, the female sex, and older age increased the risk for OP use: the respective RRs were 1.45 (95% CI 1.31-1.61), 2.54 (95% CI 2.21-2.91), and 1.060 (95% CI 1.057-1.065). CONCLUSIONS: Patients with early RA are increasingly receiving OP drugs, and the use is more frequent among patients with known risk factors.
22504829 Dyslipidemia and changes in lipid profiles associated with rheumatoid arthritis and initia 2012 Sep OBJECTIVE: To investigate the frequency of lipid testing in clinical practice and to explore the relationship between rheumatoid arthritis (RA), dyslipidemia, and other cardiovascular (CV) risk factors with RA treatment. METHODS: Patients in this retrospective database study were ages ≥18 years and had ≥2 physician diagnoses for RA or osteoarthritis (OA; comparator group) between March 2004 and March 2008. Outcomes of interest included the percentage of RA and OA patients receiving lipid tests, lipid profiles (total cholesterol, low-density lipoprotein [LDL] cholesterol, and high-density lipoprotein [HDL] cholesterol) of RA versus OA patients, and lipid profiles of RA patients before and after initiation with a tumor necrosis factor (TNF) inhibitor. We used multivariable regression to control potential confounders between the cohorts. RESULTS: Over a median ≥2-year followup, fewer RA patients than OA patients had ≥1 lipid test (62.0% [95% confidence interval (95% CI) 61.5-62.5] versus 69.8% [95% CI 69.5-70.1]). Mean total cholesterol and LDL cholesterol were each 4 mg/dl lower in the RA cohort (P < 0.0001); HDL cholesterol was similar between the cohorts. Across the RA cohort, 25.2% of patients had suboptimal LDL cholesterol levels (≥130 mg/dl). Among RA patients not receiving lipid-lowering therapy who initiated TNF inhibitor therapy (n = 96), mean total cholesterol and LDL cholesterol increased by 5.4 and 4.0 mg/dl, respectively. CONCLUSION: Patients with RA were less likely to be tested for hyperlipidemia and had more favorable lipid profiles than patients with OA. TNF inhibitor therapy modestly increased all lipid parameters. Additional studies are needed to determine the effect of traditional CV risk factors and inflammation and the impact of biologic agents on CV outcomes in RA patients.
21824477 Differential effect of drug interference in immunogenicity assays. 2011 Sep 30 The presence of anti-drug antibodies (ADA) in adalimumab-treated patients is associated with reduced serum adalimumab levels and a lower clinical response. Currently, there is no standard for measurement of anti-drug antibodies and many factors influence the results. Consequently, the incidence of ADA as reported in different studies varies considerably. Here we investigated the differential effect of drug interference in two common types of assays used to measure anti-adalimumab: an antigen binding test (ABT) and a more often-used bridging elisa. We measured ADA to adalimumab in a cohort of 216 rheumatoid arthritis patients treated with adalimumab for 28 weeks. Only 15 samples (7%) were positive in the bridging elisa, compared to 29 (13%) in the ABT, despite the fact that the bridging elisa was the most sensitive assay. Furthermore, in an ABT specific for IgG4, 48 samples (22%) were found positive. The bridging elisa was found to detect only the bivalent form of (drug-specific) IgG4, resulting in an underestimation of ADA levels. However, the predominant reason for the different outcomes of these assays was a differential susceptibility to drug interference. In particular, the bridging elisa only detected ADA in the absence of detectable amounts of circulating adalimumab and is therefore not suited for measurement of ADA in complex with the drug. In summary, we showed that a bridging elisa is susceptible to drug interference and typically measures ADA only in absence of detectable drug levels.
22137923 B-cell therapies in established rheumatoid arthritis. 2011 Aug B-cell depletion therapy based on rituximab is effective and relatively safe in established rheumatoid arthritis. Rituximab is licensed for the treatment of rheumatoid arthritis in combination with methotrexate and in patients who did not respond or cannot tolerate tumour necrosis factor antagonists. Sustained control of disease activity can be achieved by repeated courses of treatment. The optimal dose and schedule of retreatment are still not established. Nevertheless, data are now available that provide a good base for current clinical practice and a good starting point for further research. In general, rituximab has a good safety profile with most studies showing similar incidences of serious adverse events and infections to placebo. However, reasonable and well-funded doubts remain over the safety of long-term strategies of treatment of rheumatoid arthritis with rituximab, in particular, in relation to the risk of secondary hypogammaglobulinaemia and potential increased risk of infections.
22586441 Association of human leukocyte antigen with interstitial lung disease in rheumatoid arthri 2012 INTRODUCTION: Interstitial Lung Disease (ILD) is frequently associated with Rheumatoid Arthritis (RA) as one of extra-articular manifestations. Many studies for Human Leukocyte Antigen (HLA) allelic association with RA have been reported, but few have been validated in an RA subpopulation with ILD. In this study, we investigated the association of HLA class II alleles with ILD in RA. METHODS: An association study was conducted on HLA-DRB1, DQB1, and DPB1 in 450 Japanese RA patients that were or were not diagnosed with ILD, based on the findings of computed tomography images of the chest. RESULTS: Unexpectedly, HLA-DRB1*04 (corrected P [Pc] = 0.0054, odds ratio [OR] 0.57), shared epitope (SE) (P = 0.0055, OR 0.66) and DQB1*04 (Pc = 0.0036, OR 0.57) were associated with significantly decreased risk of ILD. In contrast, DRB1*16 (Pc = 0.0372, OR 15.21), DR2 serological group (DRB1*15 and *16 alleles) (P = 0.0020, OR 1.75) and DQB1*06 (Pc = 0.0333, OR 1.57, respectively) were significantly associated with risk of ILD. CONCLUSION: HLA-DRB1 SE was associated with reduced, while DR2 serological group (DRB1*15 and *16) with increased, risk for ILD in Japanese patients with RA.
22504565 Is there a sex bias in prescribing anti-tumour necrosis factor medications to patients wit 2012 Jul OBJECTIVES: To determine whether men and women with rheumatoid arthritis are prescribed anti-tumour necrosis factor (anti-TNF) treatment at different levels of disease activity. METHODS: Data from the Swedish national biologics registry ARTIS were used to analyse characteristics of patients' disease at the start of the first anti-TNF treatment. Means for men and women were compared using t-tests, and non-normally distributed covariates were compared using the Wilcoxon rank-sum test. Linear regression models, adjusted for age and calendar year, were used to investigate the association between sex and each disease activity measurement. RESULTS: Women were younger and had longer disease duration at treatment start than men. Tender joint count, erythrocyte sedimentation rate, patient's global assessment, patient-reported pain and health assessment questionnaire scores were significantly higher in women, whereas men had a higher level of C-reactive protein (p<0.05 for all comparisons). Swollen joint count and physician's global assessment did not differ by sex. CONCLUSIONS: For women with rheumatoid arthritis, treatment with anti-TNF therapy was initiated at a higher level of subjective disease activity than for men, but at the same level of physician-reported disease activity. These data imply that patients' subjectively experienced disease activity may be discounted in the treatment decision.
21515604 Expression and function of EZH2 in synovial fibroblasts: epigenetic repression of the Wnt 2011 Aug OBJECTIVES: To study the expression, regulation and function of the histone methyltransferase enhancer of zeste homologue 2 (EZH2) in synovial fibroblasts (SF) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: SF were obtained from RA and OA patients undergoing joint surgery. Expression levels were assessed by quantitative real-time PCR and western blot. Kinase inhibitors and reporter gene assays were employed to study signalling pathways. Functional analyses included EZH2 overexpression by plasmid transfection and gene silencing by small interfering RNA. Chromatin immunoprecipitation assay was used to analyse histone methylation within distinct promoter regions. RESULTS: By studying the expression and function of EZH2 in SF the authors found that EZH2 is overexpressed in rheumatoid arthritis synovial fibroblasts (RASF) and further induced by tumour necrosis factor alpha through the nuclear factor kappa B and Jun kinase pathways. As a target gene of EZH2 the authors identified secreted frizzled-related protein 1 (SFRP1), an inhibitor of Wnt signalling, which is associated with the activation of RASF, and show that SFRP1 expression correlates with the occupation of its promoter with activating and silencing histone marks. CONCLUSIONS: These data strongly suggest that the chronic inflammatory environment of the RA joint induces EZH2 and thus might cause changes in the epigenetic programmes of SF.
22117383 [A case of pulmonary nontuberculous mycobacteriosis induced by tocilizumab treatment for r 2011 Sep A 65-year-old woman whose rheumatoid arthritis was treated with tocilizumab (TCZ) was found in chest radiography to have a new consolidation in the right lower lung field. Positive Mycobacterium intracellulare and Mycobacterium avium cultures in sputum and bronchial secretions yielded a diagnosis of pulmonary nontuberculous mycobacteriosis. The most common adverse TCZ effect is infection. This case highlights the fact that those treated with TCZ should be considered at elevated risk for developing nontuberculous mycobacteriosis.
21863469 [Magnetic resonance imaging in rheumatology]. 2011 Aug Imaging plays a major role in the diagnosis and meanwhile also in the therapy control of rheumatic diseases. Besides the commonly used X-ray technique and musculoskeletal ultrasound, magnetic resonance imaging (MRI) is able to provide a three-dimensional view of musculature, ligaments, tendons, capsules, synovial membranes, bones and cartilage with high resolution quality. Therefore, MRI is being employed more and more in the early diagnosis of inflammatory joint and spinal diseases. Contrast-enhanced MRI enables an assessment of disease activity and a differentiation between active and chronic joint manifestation. The technical examinations by MRI are these days standardized and invariably reproducible. This makes it possible to document the course of a disease and allows subsequent treatment decisions. In addition to midfield (>0.5<1.0 T) and high field MRI (>1.0 T), low field MRI (<0.5 T) is used in rheumatology as a patient-friendly office-based technique.
23070807 Activities of enzymes that hydrolyze adenine nucleotides in lymphocytes from patients with 2013 Jul The purpose of this study was to investigate the activities of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase; EC 3.6.1.5; CD39) and adenosine deaminase (E-ADA; EC 3.5.4.4) in lymphocytes from patients with rheumatoid arthritis (RA). Thirty patients diagnosed with RA through American College of Rheumatology criteria as well as 30 healthy patients were selected. Peripheral blood lymphocytes were isolated, and E-NTPDase and E-ADA activities were assayed. The results demonstrated an increased E-NTPDase activity (both ATP and ADP as substrates) and a decreased E-ADA activity in RA patients. These data suggest an organic effort to preserve the adenosine level, which is known to have anti-inflammatory and analgesic properties, working as a potent suppressor of immune response.
23036591 Dendritic cells provide a potential link between smoking and inflammation in rheumatoid ar 2012 Oct 4 INTRODUCTION: Smoking increases the risk of developing rheumatoid arthritis (RA) and affects the severity of established RA. Smoking can impact on Th17 lymphocyte differentiation and function through activation of the aryl hydrocarbon receptor (AHR), a process with implications for the pathogenic mechanisms in RA that involve the cytokine, interleukin (IL)-17A. The objective of this study was to establish any effect of smoking on the inflammatory tissue lesions of rheumatoid arthritis via the AHR and IL-17A. METHODS: Twenty synovial and eighteen subcutaneous nodule tissue samples from 31 patients with RA were studied. Patient smoking status at the time of tissue collection was established. Expression of AHR, CYP1A1, AHRR, IL6, IL17A, IL17F, IL22, IL23, IL23R, IFNG, TBX21, IDO1 and FOXP3 genes were assessed in tissues and cultured cells using real-time PCR. Two-colour immunofluorescence was used to co-localise AHR and CYP1A1 protein in synovial tissues. The response of monocytes and monocyte-derived dendritic cells (mo-DCs) to the AHR agonist, benzo(a)pyrene (BaP) was compared in vitro. RESULTS: AHR gene expression was demonstrated in rheumatoid synovial tissues and nodules with significantly greater expression in synovia. Expression was not influenced by smoking in either tissue. Evidence of AHR activation, indicated by CYP1A1 and AHRR gene expression, was found only in synovia from patients who smoked. However, IL17A gene expression was lower in synovia from smokers. TBX21 and FOXP3 expression was not affected by smoking. Within the synovial tissues of smokers the principal cell type with evidence of AHR activation was a subset of synovial DCs. This observation was consistent with the sensitivity of human mo-DCs to BaP stimulation demonstrated in vitro. Exposure to BaP affected mo-DC function as demonstrated by decreased IL6 expression induced by PolyI:C, without affecting indoleamine 2,3 dioxygenase (IDO)1 expression. CONCLUSION: Our findings show that one effect of smoking on inflamed rheumatoid synovial tissue involves activation of the AHR pathway. A subset of synovial DCs is important in the response to cigarette smoke. The potential for smoking to affect DC behaviour in joint tissues has relevance to both early and late phases of RA pathogenesis and warrants further investigation.
22674853 Minimum clinically important improvement and patient acceptable symptom state in pain and 2012 Nov OBJECTIVE: To estimate the minimum clinically important improvement (MCII) and patient acceptable symptom state (PASS) values for 4 generic outcomes in 5 rheumatic diseases and 7 countries. METHODS: We conducted a multinational (Australia, France, Italy, Lebanon, Morocco, Spain, and The Netherlands) 4-week cohort study involving 1,532 patients who were prescribed nonsteroidal antiinflammatory drugs for ankylosing spondylitis, chronic back pain, hand osteoarthritis, hip and/or knee osteoarthritis, or rheumatoid arthritis. The MCII and PASS values were estimated with the 75th percentile approach for 4 generic outcomes: pain, patient global assessment, functional disability, and physician global assessment, all normalized to a 0-100 score. RESULTS: For the whole sample, the estimated MCII values for absolute change at 4 weeks were -17 (95% confidence interval [95% CI] -18, -15) for pain; -15 (95% CI -16, -14) for patient global assessment; -12 (95% CI -13, -11) for functional disability assessment; and -14 (95% CI -15, -14) for physician global assessment. For the whole sample, the estimated PASS values were 42 (95% CI 40, 44) for pain; 43 (95% CI 41, 45) for patient global assessment; 43 (95% CI 41, 44) for functional disability assessment; and 39 (95% CI 37, 40) for physician global assessment. Estimates were consistent across diseases and countries (for subgroups ≥20 patients). CONCLUSION: This work allows for promoting the use of values of MCII (15 of 100 for absolute improvement, 20% for relative improvement) and PASS (40 of 100) in reporting the results of trials of any of the 5 involved rheumatic diseases with pain, patient global assessment, physical function, or physician global assessment used as outcome criteria.
22409963 Induction of long-term B-cell depletion in refractory rheumatoid arthritis patients prefer 2012 Mar 12 INTRODUCTION: B-cell depletion has become a common treatment strategy in anti-TNF-refractory rheumatoid arthritis (RA). Although the exact mechanism of how B-cell depletion leads to clinical amelioration in RA remains to be elucidated, repetitive treatment with B-cell-depleting agents leading to long-term B-cell depletion has been reported to be beneficial. The latter has led to the hypothesis that the beneficial effects of B-cell depletion might act through their influence on pathogenic autoreactive plasma cells. METHODS: In this study, we investigated the effects of a fixed retreatment regimen with anti-CD20 mAbs on the humoral (auto)immune system in a cohort of therapy-refractory RA patients. RESULTS: Fixed retreatment led to long-term B-cell depletion in peripheral blood, bone marrow and, to a lesser extent, synovium. Also, pathologic autoantibody secretion (that is, anticitrullinated peptide antibodies (ACPAs)) was more profoundly affected by long-term depletion than by physiological protective antibody secretion (that is, against measles, mumps and rubella). This was further illustrated by a significantly shorter estimated life span of ACPA-IgG secretion compared to total IgG secretion as well as protective antibody secretion. CONCLUSION: By studying plasma cell function during an extensive 2-year period of B-cell depletion, autoantibody secretion was significantly shorter-lived than physiologically protective antibody secretion. This suggests that the longevity of autoreactive plasma cells is different from protective long-lived plasma cells and might indicate a therapeutic window for therapies that target plasma cells.