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ID PMID Title PublicationDate abstract
19482847 Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoi 2009 Sep OBJECTIVE: Inhibition of interleukin-1 activity improves nitro-oxidative stress, endothelial and coronary function. The authors investigated (a) the association of nitro-oxidative stress and endothelial function with myocardial deformation, (b) the effects of anakinra, an interleukin-1a receptor antagonist on myocardial deformation in patients with rheumatoid arthritis (RA). METHODS: The authors compared 46 RA patients to 23 normal controls. 23 patients received anakinra (150 mg subcutaneously once daily) and 23 patients a 5-mg increase of prednisolone dose for 30 days. At baseline and post-treatment this study assessed (a) the left ventricular (LV) longitudinal, circumferential and radial strain and strain rate, using speckle tracking echocardiography, (b) the coronary flow reserve (CFR), (c) the flow-mediated endothelial-dependent dilation of the brachial artery (FMD) and (d) nitrotyrosine (NT) and malondialdehyde blood levels. RESULTS: Patients had impaired baseline myocardial deformation indices compared to controls (p<0.05). CFR and NT levels were related to longitudinal strain, systolic and diastolic strain rate, circumferential strain and systolic strain rate (p<0.05). FMD was related to longitudinal and circumferential diastolic strain rate (p<0.01). Compared to baseline, anakinra-treated patients increased the longitudinal strain (-17.8% (3.7%) vs -22.1% (3.5%)), systolic (-1.02 (0.23) l/s vs -1.25 (0.23) l/s) and diastolic (0.96 (0.37) l/s vs 1.20 (0.39) l/s) longitudinal strain rate, circumferential strain and strain rate (p<0.05 for all comparisons). No significant changes were observed among prednisolone-treated patients CONCLUSIONS: Myocardial deformation is impaired in RA patients and is related to nitro-oxidative stress and endothelial dysfunction. Chronic inhibition of IL-1 improves LV deformation in parallel with endothelial function and nitro-oxidative stress.
21186172 The power Doppler ultrasonography score from 24 synovial sites or 6 simplified synovial si 2011 May OBJECTIVE: We evaluated the significance of the power Doppler ultrasonography (PDUS) score by comparing it with serum biomarkers and clinical disease activity. METHODS: We measured the PDUS scores of 24 synovial sites in 12 joints in 22 RA patients. For convenience, the PDUS scores of six synovial sites in six joints were also examined. Each joint was scored for a power Doppler (PD) signal on a scale from 0 to 3. The PDUS scores are the sums of the PD signal scores for the 24 synovial sites or the 6 synovial sites. On the same day, serum variables as well as clinical disease activity were evaluated. RESULTS: The PDUS scores from the 24 joint sites were significantly positively correlated with DAS of 28 joints (DAS-28), simplified disease activity index (SDAI), clinical disease activity index (CDAI) and serum biomarkers including MMP-3, VEGF and tissue inhibitor of metalloproteinases-1 (TIMP-1). Accordingly, the PDUS scores from the six synovial sites greatly correlated with those from the 24 joint sites. Clinical disease activities as well as serum variables were also clearly correlated with the PDUS scores from the six synovial sites. CONCLUSION: The standard as well as the simplified PDUS scores well reflected clinical disease activity and serum variables, including angiogenic factors. Our data reaffirm the utility of ultrasonography for monitoring disease activity in patients with RA.
21196130 Rituximab in rheumatoid arthritis and the risk of malignancies: report from a French cohor 2011 Oct OBJECTIVE: To determine in real-life conditions the safety of treatment with rituximab (RTX) in patients with rheumatoid arthritis (RA) regarding malignancies. METHODS: Analysis of safety data from a cohort of RA patients who received at least one course of RTX. RA patients with previous malignancies were followed-up and compared to the group of patients with no history of malignancy. RESULTS: One hundred and eighty-six RA patients, 33 (17.7%) males, the mean age and disease duration were 55.8 ± 13.0 and 14.5 ± 11.1 years, respectively. The mean follow-up was 22.3 ± 15.1 months, corresponding to a follow-up of 346 pt-years of RTX exposure. Among these, 24 (12.9%) patients had a history of a prior malignancy. Five cancers were diagnosed during follow-up with four new malignancies (1 prostate, 1 breast, 1 colon and 1 cervical cancers) and one recurrence of a known breast cancer. The overall cancer rate was 1.45/100 pt-years (95%CI: 0.19 to 2.70), which is comparable to previously studied DMARD-treated cohorts. No new hematopoietic neoplasms were reported and the six lymphomas that have been in remission prior to RTX-therapy remained under follow-up. The baseline demographic and disease characteristics and the cancer-risk of the 24 patients who presented with a prior malignancy were similar to those with no cancer history (162 patients). CONCLUSIONS: Although based on a modest number of observed cancers, and despite selection bias (12.9% of prior malignancies in our RTX treated RA), this observational study suggests that RTX does not increase the cancer risk in RA patients.
20383550 A systematic review of the effect of TNF-alpha antagonists on lipid profiles in patients w 2010 Sep Atherosclerosis plays a key role in cardiovascular disease in patients with rheumatoid arthritis (RA). Although therapy with TNF-alpha antagonists has resulted in dramatic improvement in the prognosis of RA, its effects on circulatory lipids are unclear. We conducted a systematic review of the literature to summarize the available evidence on lipid profile modification in patients with RA treated with TNF-alpha antagonists, with extensive searches in PubMed, the Cochrane Collaboration database (Central), and SCOPUS. Twenty-four observational studies met the inclusion criteria; 12 included only patients with RA treated with infliximab and three, patients with RA treated with adalimumab. The other nine included a mix of patients with various rheumatic diseases, or receiving one of several TNF-alpha antagonists. Eleven studies found a statistically significant increase in total cholesterol (TC) and high-density lipoprotein (HDL); six of 20 found significant increases in triglycerides (TG). Four of 13 studies found a statistical increase in low-density lipoprotein. No major changes were observed for ApoB/ApoA1 ratios. A small trend to increased TC was observed in patients receiving TNF-alpha antagonists, mostly due to an increase in HDL. There was a small trend to increased TG, and no changes in ApoB/ApoA1 ratio. The clinical impact of these findings is unclear, and further studies are needed to clarify the role of these lipid changes on cardiovascular morbidity in RA.
19104753 Radiographic progression in weight-bearing joints of patients with rheumatoid arthritis af 2009 Apr The aim of the present study was to assess the influence of tumor necrosis factor (TNF)-blocking therapies on weight-bearing joints in patients with rheumatoid arthritis. Changes in clinical variables and radiological findings in 213 weight-bearing joints (69 hip joints, 63 knee joints, and 81 ankle joints) of 42 consecutive patients were investigated at baseline and at 1 year of TNF-blocking therapies. Structural damage to the weight-bearing joints was assessed using the Larsen scoring method. Detailed comparisons of the sizes and locations of erosions were performed for each set of radiographs of the respective joints. Assessment of radiographs of the 213 weight-bearing joints indicated progression of the Larsen grade in eight joints. Another five joints without Larsen grade progression showed apparent radiographic progression of joint damage based on increases in bony erosions. Overall, 13 joints (6%) of eight patients (19%) showed progression of joint damage after 1 year of TNF-blocking therapies. Analysis of each baseline grade indicated that radiographic progression of joint damage was inhibited in most grade 0-II joints. On the other hand, all hip and knee joints with pre-existing damage of grade III/IV showed apparent progression even in patients with good response. The results further suggested that radiographic progression may occur in less damaged joints when the patients were non-responders to the therapy. Among the weight-bearing joints, ankle joints showed different radiographic behavior and four ankle joints displayed improvement of radiographic damage. Early initiation of anti-TNF therapy should be necessary especially when the patients are starting to show early structural damage in weight-bearing joints.
19491302 High-resolution ultrasound confirms reduced synovial hyperplasia following rituximab treat 2009 Aug OBJECTIVE: To assess the response of RA patients to rituximab (RTX) treatment using a sensitive imaging technique for synovitis. METHODS: Twenty-three RA patients were treated with two 1000-mg infusions of the B-cell depleting antibody, RTX, in an observational protocol. Clinical response was assessed by the European League Against Rheumatism (EULAR) response criteria. High-resolution grey-scale and colour-coded power Doppler (PD) ultrasonography was performed at baseline and 6 months after RTX. The second to fifth MCP and PIP joints were bilaterally examined with joints in a neutral 0 position from a palmar view and scored from 0 to 3. RESULTS: Median disease activity score (DAS28) improved from 5.03 to 3.56 (P = 0.001), which corresponded to a EULAR moderate response in 11 of 23 patients and a EULAR good response in another 6 patients. Improved control of disease activity by RTX was also indicated by tapering of median daily corticosteroid doses from 10 to 5 mg, without flare ups. Mean grey-scale scores correlated with the swollen joint count at baseline (r = 0.484, P = 0.022) and month 6 (r = 0.519, P = 0.011). Mean grey-scale scores improved upon RTX from a 0.90 median (range 0.13-1.87) to 0.75 (range 0.19-1.50, P = 0.023). Frequency of PD positive joints was low (6.1%) at baseline and did not significantly change following RTX treatment. CONCLUSIONS: High-resolution grey-scale ultrasonography (US) examination confirmed reduced synovial hyperplasia, but the applied PD method displayed no significant changes. Therefore, only grey-scale US is recommended in follow-up examinations after RTX treatment.
21116895 Long-term results of the thrust plate prosthesis in patients with rheumatoid arthritis: a 2010 Nov BACKGROUND: The thrust plate prosthesis (TPP) is a hip prosthesis with metaphyseal fixation to the femur. Because the bone quality is reduced in patients with rheumatoid arthritis, this kind of fixation may have a higher failure rate than conventional stemmed endoprostheses in these patients. The aim of this investigation was to analyze the long-term results obtained with the TPP in patients with rheumatoid arthritis. METHODS: The survival of 51 implants in 46 patients with rheumatoid arthritis was analyzed. Clinical (Harris hip score) and radiological examinations were carried out on 47 of the 51 TPPs, with a post implantation follow-up period of at least 10 years. The Kaplan-Meier method was used to estimate the survival rates of the TPPs, with surgical revision due to the femoral implant as the endpoint of the investigation. RESULTS: The Harris hip score increased from 42.4 ± 6.5 points preoperatively to 86.6 ± 10.1 points at follow-up. The failure rate was 23% (6 aseptic and 5 septic loosening). The total rate of revision amounted to 36.2% (17/47 TPPs): six aseptic loosening of TPPs, five septic loosening of TPPs, four aseptic loosening of the acetabular component, one removal of the fishplate of a TPP, and one femoral fracture. Additionally one TPP showed radiolucent lines indicating prosthetic loosening. Revision surgeries to stemmed endoprostheses of the hip were without severe problems in any patients. CONCLUSIONS: The failure rate of the TPP was distinctly higher than that for conventional stemmed endoprostheses regarding aseptic and septic revisions. In cases with loosening of the TPP the preservation of the diaphyseal bone of the femur is poor and the TPP mostly needs a revision to a cemented stem. Thus, the estimated advantage of the TPP versus cementless stemmed prostheses for patients with rheumatoid arthritis is not evident. In conclusion, there is no evidence form this study to support the use of the TPP in this group of patients.
20155827 Do rheumatoid arthritis and lymphoma share risk factors?: a comparison of lymphoma and can 2010 May OBJECTIVE: Patients with rheumatoid arthritis (RA), in particular those with the most severe disease, are at increased risk of developing malignant lymphoma. Whether this increase is entirely a consequence of the RA disease and/or its treatment or is reflective of shared susceptibility to the two diseases remains unclear. We undertook this study to assess whether patients with RA are already at increased risk of lymphoma or of other cancers before the diagnosis of RA, and if the relative risk increases with time since RA diagnosis. METHODS: Patients with incident RA (symptom duration <1 year) (n = 6,745) registered in the Swedish Early Arthritis Registry from 1997 through 2006 were identified. For each patient, 5 general population controls were randomly matched by sex, age, marital status, and residence (n = 33,657). For all study subjects, inclusion in the nationwide Swedish Cancer Register in 1958-2006 was determined. Relative risks (RRs) (with 95% confidence intervals [95% CIs]) of lymphoma and of cancer overall, before and after diagnosis of RA, were estimated using conditional logistic regression and Cox regression, respectively. RESULTS: Before diagnosis of RA, there was no observed increase in the risk of lymphoma (RR [odds ratio] 0.67 [95% CI 0.37-1.23]) or other cancers (RR 0.78 [95% CI 0.70-0.88]). During the first 10 years following diagnosis of RA, the overall RR (hazard ratio) of lymphoma development was 1.75 (95 % CI 1.04-2.96). CONCLUSION: These findings indicate that overall, a history of cancer, including lymphoma, does not increase the risk of subsequent RA development. Shared susceptibility to RA and lymphoma may thus be of limited importance. In contrast, increased lymphoma risks were observed within the first decade following RA diagnosis.
20225006 Differences between the Health Assessment Questionnaire Disability Index (HAQ-DI) and the 2010 Aug We conducted a 1-year prospective study to clarify differences between the Health Assessment Questionnaire disability index (HAQ-DI) and the modified HAQ (mHAQ) score among rheumatoid arthritis (RA) patients treated with infliximab. A total of 87 patients were scheduled to receive infliximab infusion at a dose of 3 mg/kg at weeks 0, 2, and 6, and every 8 weeks thereafter for 54 weeks; all patients received a full examination at each infusion appointment. The 28-joint disease activity score (DAS28) and functional capability of each patient was assessed at each visit, using the HAQ-DI and the mHAQ score. A strong correlation was observed between the HAQ-DI and the mHAQ score at baseline (r = 0.892). Over the course of the treatment, the mean mHAQ score changed similarly to the HAQ-DI, but the mean HAQ-DI was significantly higher than the mean mHAQ score at each time-point (for the HAQ-DI vs. mHAQ score, baseline: 1.5 +/- 0.7 vs. 0.9 +/- 0.6, p < 0.0001; 6 weeks: 1.1 +/- 0.7 vs. 0.6 +/- 0.5, p < 0.0001; 30 weeks: 1.0 +/- 0.7 vs. 0.6 +/- 0.5, p < 0.0001; 54 weeks: 0.9 +/- 0.7 vs. 0.6 +/- 0.6, p = 0.0006). In the categories of "eating", "reaching", and "other activities", the scores for several items excluded from the mHAQ score were significantly higher than those included in the mHAQ score over the year-long study period. We identified items contributing to significant differences between the HAQ-DI and the mHAQ score among RA patients treated with infliximab.
19184029 Characterization of synovial tissue from arthritis patients: a proton magnetic resonance s 2009 Aug Hypoxia may contribute to the pathogenesis of synovitis in rheumatoid arthritis (RA). Magnetic resonance spectroscopy (MRS) is a technique that uses radiofrequency waves to generate a signal which allows a qualitative and quantitative assessment of the biochemical composition of tissue. MRS was used to evaluate RA synovial tissue for evidence of hypoxia and anaerobic metabolism. Synovial tissue samples obtained from eighteen RA patients and four osteoarthritis control patients undergoing total knee replacement were analyzed using proton MRS, processed for histopathology and scored for inflammation and vascularity. Spectra from severely and mildly inflamed tissue differed in peak intensity at regions 1.3 ppm (representing lactic acid and lipid), 3.0 ppm (representing creatine), 3.2 ppm (representing choline containing metabolites), and 3.8 ppm (representing carbohydrates, possibly glucose). With increasing inflammation, the intensities of the peak resonance at 1.3 ppm increased and that at 3.8 ppm decreased. The intensities of the 3.8 and 3.0 ppm peaks were reduced in highly vascular tissue. Specific MR spectral features reflect the anaerobic metabolism that is evident with progressively increasing degrees of RA synovial inflammation and vascularity. These features correlate partially with synovial histopathology.
20848564 The transcriptional response of normal and rheumatoid arthritis synovial fibroblasts to hy 2010 Dec OBJECTIVE: Hypoxia is a prominent feature in rheumatoid arthritis (RA) synovium. However, its contribution to the pathogenesis of RA remains unclear. We undertook this study to systematically characterize the changes in gene expression induced by hypoxia in synovial fibroblasts. METHODS: We used microarray expression profiling in paired normoxic and hypoxic cultures of healthy synovial fibroblasts (HSFs) and RA synovial fibroblasts (RASFs). We used Student's paired t-test with Benjamini and Hochberg multiple testing correction to determine statistical significance. Validation of microarray data was performed by quantitative real-time reverse transcription-polymerase chain reaction analysis of selected genes. Biologic pathways differentially modulated by hypoxia in RASFs or HSFs were identified using unsupervised Ingenuity Pathways Analysis. RESULTS: Hypoxia induced significant changes in the expression of a large group of genes in both HSFs and RASFs. In RASFs, we observed a lower number of hypoxia-regulated genes and partial differences in their functional categories. The number of differentially expressed genes in RASFs compared with HSFs was significantly increased by hypoxia. Multiple gene sets involved in energy metabolism, intracellular signal transduction, angiogenesis, and immune and inflammatory pathways were significantly modified, the last in both proinflammatory and antiinflammatory directions. CONCLUSION: These data demonstrate that hypoxia induces significant changes in gene expression in HSFs and RASFs and identify differences between RASF and HSF profiles. The hypoxia-induced gene expression program in synovial fibroblasts identifies new factors and pathways relevant to understanding their contribution to the pathogenesis of chronic arthritis.
20476859 Mortality and cause of death in Japanese patients with rheumatoid arthritis based on a lar 2010 OBJECTIVES: To investigate mortality, cause of death, and risk factors related to mortality in Japanese patients with rheumatoid arthritis (RA). METHODS: The IORRA cohort is a large observational cohort established in 2000 at the Institute of Rheumatology, Tokyo Women's Medical University. Essentially, all RA patients were registered and clinical parameters were assessed biannually. For patients who failed to participate in subsequent surveys, simple queries were mailed to confirm survival. Standardized mortality ratios (SMRs) were calculated and mortality risk factors were analysed using a Cox proportional hazard model. RESULTS: We analysed 7926 patients (81.9% females; mean age 56.3 ± 13.1 years; mean disease duration 8.5 ± 8.3 years) with RA who enrolled in IORRA from October 2000 to April 2007. During the observational period (35 443.0 person-years), 289 deaths were reported. Major causes of death included malignancies (24.2%), respiratory involvement (24.2%) including pneumonia (12.1%) and interstitial lung disease (ILD) (11.1%), cerebrovascular disease (8.0%), and myocardial infarction (7.6%). As death was not confirmed in all patients, the SMR was deduced to be between 1.46 [95% confidence interval (CI) 1.32-1.60] and 1.90 (95% CI 1.75-2.07) for all patients, between 1.45 (95% CI 1.22-1.70) and 1.70 (95% CI 1.45-1.97) for men, and between 1.46 (95% CI, 1.29-1.65) and 2.02 (95% CI 1.82- 2.24) for women. Factors associated with increased mortality included male gender, older age, worse physical disability, positive rheumatoid factor (RF), corticosteroid use, and presence of ILD. CONCLUSION: The mortality of Japanese RA patients is comparable to that in previous reports from western countries, even though the causes of death were significantly different.
19785864 ['Rheumatoid arthritis' in a Surinamese man: leprosy]. 2009 Rheumatoid arthritis was diagnosed in a 65-year-old man from Suriname, on the basis of clinical and radiological findings. However, he was eventually diagnosed with leprosy. This emerged when the patient developed skin lesions and complained of increasing sensibility disorders during treatment for the alleged rheumatoid arthritis. He was treated with a combination therapy consisting of rifampicin, clofazimine, dapsone, and prednisone. The skin lesions and joint symptoms were resolved as a result of this, but the sensibility disorders persisted. As physicians are not sufficiently familiar with leprosy and the condition has many manifestations that can mimic more frequently occurring diseases, leprosy is often diagnosed at a later stage. This may result in irreversible damage, especially to the peripheral nerves, which may lead to disability. Therefore, for patients who originate from areas where leprosy is endemic and who suffer from joint complaints in combination with skin or sensibility disorders, the diagnosis of leprosy should be considered.
19213849 High disease activity disability burden and smoking predict severe extra-articular manifes 2009 Apr OBJECTIVES: To identify patients with severe extra-articular RA (ExRA) in an early RA cohort and to investigate potential risk factors. METHODS: From a cohort (n = 2900) in a structured programme for newly diagnosed RA, 40 patients with severe ExRA after RA diagnosis were identified. Disease activity score (DAS28), functional disability (HAQ) and treatment with glucocorticosteroids (GCs) and DMARDs were assessed regularly. Cases with ExRA were compared with RA controls from the same cohort matched for age, sex and duration of symptoms at inclusion. RESULTS: Patients who developed severe ExRA were more often current smokers and had higher mean DAS28, HAQ and CRP at baseline. Among the ExRA cases, 93% had a positive RF vs 59% of the controls. The area under the curve (AUC) of DAS28 odds ratio (OR) 7.79/S.D.; 95% CI 3.04, 19.95, HAQ (OR 2.30/S.D.; 95% CI 1.37, 3.88) and CRP (OR 3.05/S.D.; 95% CI 1.77, 5.26) during the first 2 years of follow-up were strong predictors of subsequent development of ExRA. The most frequently used DMARDs were MTX and SSZ, with similar frequency and duration of treatment among cases and controls. The cases were treated with GC before onset of ExRA more frequently (73 vs 47%; P = 0.005) and with higher mean cumulative dose (3667 vs 2037 mg, P = 0.015). CONCLUSIONS: High levels of disease activity and disability during the first 2 years after RA diagnosis, smoking and RF predict the development of severe extra-articular RA.
19010354 A possible role of Fas-ligand-mediated "reverse signaling" in pathogenesis of rheumatoid a 2009 Jan 29 Fas/FasL system is involved in pathogenesis of a variety of autoimmune diseases. In overwhelming majority of situations alterations in Fas and FasL expression are viewed in frames of Fas-mediated apoptosis. In the present work we tested a possible involvement of Fas-ligand-mediated "reverse signaling" in pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We show that high level of sFas in RA patient blood correlates with a high activity of disease; in SLE patients with elevated sFas level there was a correlation between sFas concentration and leucopenia, and tissue and organ damage. We showed for the first time that at high concentrations in serum sFas is present in oligomeric form. Oligomeric sFas demonstrated cytotoxicity in lymphocyte primary culture and in transformed cells, while non-toxic recombinant Fas-ligand partially blocked this effect. Besides, immunohistochemical analysis of PBLs and injured synovia of RA patients revealed the high expression of Fas-ligand. All this together allow assuming the involvement of cytotoxic "reversed signaling" in the pathogenesis of autoimmune diseases.
18276742 Detection, identification and in vivo treatment responsiveness of bone morphogenetic prote 2009 Jan OBJECTIVE: To characterise the bone morphogenetic protein (BMP) target cells positive for phosphorylated (P)-SMAD1/5, in rheumatoid arthritis (RA) synovium. METHODS: Synovial biopsies were obtained by needle arthroscopy. Anti-P-SMAD1/5 antibodies were used for Western blot (WB) on protein extracts from RA and normal synovium and for immunostaining of synovial biopsy sections. Positive cells were further identified by double staining for CD3, CD20, CD68, CD138, CD90, alpha smooth muscle actin (SMA), endoglin (CD105) and von Willebrand factor (VWF). In sections from early patients with RA taken before and under antirheumatic treatment, the degree of inflammation and activation of the BMP pathway were quantified. RESULTS: P-SMAD1/5 protein was detected by WB in RA and to a lesser extent in normal synovium. Different P-SMAD1/5 positive cell populations were identified in RA synovium, mainly in perivascular and sublining cells. P-SMAD1/5 positive perivascular cells were alphaSMA positive and located around VWF positive endothelial cells. Some CD90 positive synovial fibroblasts were P-SMAD1/5 positive, as was part of the CD68 positive synovial cells but other cells of the haematopoietic lineage showed no SMAD1/5 phosphorylation. Treatment resulted in an absolute but not relative decrease in BMP activation in the synovium. CONCLUSION: BMP-activated cells belong to distinct stromal compartments in RA synovium and some of them express markers associated with the mesenchymal progenitor cell lineage. Antirheumatic treatment effectively downregulates synovial inflammation, but BMP activation in the synovium does persist albeit reduced.
21128990 Eternacept for the treatment of patients with rheumatoid arthritis and concurrent intersti 2012 Feb WHAT IS KNOWN AND OBJECTIVE: Tumour necrosis factor-α (TNF-α)-blocking agents are increasingly used in the management of refractory rheumatoid arthritis (RA). Although effective, they are associated with rare but potentially fatal adverse effects, including interstitial lung disease (ILD). In patients with pre-existing ILD, eternacept (ETN) monotherapy is often regarded as a suitable choice. Other anti-TNF-α blockers such as infliximab and adalimumab, are used in combination therapy with methotrexate (MTX) in most of the cases. We report on a case of fatal exacerbation of ILD in a patient given ETN monotherapy and review the literature on ETN-associated ILD. METHODS: We report on a case of a 75-year-old male with RA who developed severe ILD after the introduction of ETN, and we undertook a literature search to identify other reports of similar cases. We then critically assessed those reports. RESULTS AND DISCUSSION: In addition to our case, 11 other patients have been reported to have developed ILD in association with the use of ETN. Six patients had pre-existing ILD. Although four patients received MTX, eight patients developed severe ILD without MTX. Ten patients recovered after termination of ETN, although two patients died. WHAT IS NEW AND CONCLUSION: Although ETN is often regarded as safe for patients with ILD, our case and the literature reports suggest that caution is still required.
19721046 Total shoulder replacement in rheumatoid disease: a 16- to 23-year follow-up. 2009 Sep We describe the longer term clinical and radiological findings in a prospectively followed series of 49 rheumatoid patients (58 shoulders) who had undergone Neer II total shoulder replacement. The early and intermediate results have been published previously. At a mean follow-up of 19.8 years (16.5 to 23.8) 14 shoulders survived. Proximal migration of the humeral component was associated with progressive loosening of the glenoid and humeral components, but was independent of the state of the rotator cuff at the time of operation. Despite these changes the range of movement was preserved. Most patients had little or no pain in the shoulder, could sleep undisturbed and could attend to personal hygiene and grooming.
20847201 Using genetic and clinical data to understand response to disease-modifying anti-rheumatic 2011 Jan The objective of this review is to report on the progress of the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) Registry data collection and summarize previous research in understanding therapeutic response to DMARDs using clinical and genetic data. The BRASS Registry, established in 2003, is a large, single-centre, prospective and observational cohort of 1100 RA patients. Patients with either new-onset or established RA disease are recruited from the practices of rheumatologists. Annual visits collect information on demographics, 28-joint DAS-CRP3 (DAS-28-CRP3), medication use, comorbidities and functional status (Modified Health Assessment Questionnaire, Short Form Health Survey 12). Two published studies have utilized BRASS to examine genetic predictors of treatment response. In a cross-sectional study, examining the association between candidate single nucleotide polymorphisms (SNPs) and disease activity in a subset of 120 RA patients on MTX monotherapy, the minor allele of ATIC rs4673993 was associated with low disease activity (P=0.01, DAS-28-CRP3≤3.2). In an international collaboration, 55 BRASS patients receiving anti-TNF therapy were genotyped for 31 SNPs associated with the risk of RA. With our collaborators, we discovered an SNP at the protein tyrosine phosphatase, receptor type, C (PTPRC) gene locus that was associated with EULAR 'good response'. With accurate data collection and the capacity to run genome-wide association studies and SNP analyses, the BRASS Registry has the ability to determine the contribution of genetic variants to disease onset and to assess their usefulness as biomarkers for treatment response and drug toxicity.
19603251 Long-term efficacy of leflunomide on disease activity and inhibition of joint damage: retr 2009 We retrospectively compared treatment impact with leflunomide (LEF) or methotrexate (MTX) on retarding joint damage and clinical symptom including a 28-joint-count Disease Activity Score/erythrocyte sedimentation rate (DAS28-ESR) between two similar groups in patients with rheumatoid arthritis (RA) over an approximately 3-year treatment. One group included 29 patients treated with LEF alone (average dose 16.1 mg/day); the other group included 26 patients treated with MTX (average dose 7.4 mg/week) alone or combined with other disease-modifying antirheumatic drugs. At baseline, mean disease duration was 7.1 and 6.9 years, and mean DAS28-ESR was 5.79 and 5.69, respectively. The average DAS28-ESR improvement of 1.750 (from 5.79 to 4.04) in the LEF-treated group was significantly greater than the effect of 1.007 (from 5.69 to 4.68) seen in the MTX group (P = 0.0455), with the same results being observed on European League Against Rheumatism (EULAR) response criteria. Annual changes observed in Larsen score in total joints were 0.030 in the LEF group and 0.085 in the MTX group: LEF retards joint damage significantly better than MTX (P = 0.003). This inhibitory effect was better in small joints (P = 0.004) than in middle and large joints (P = 0.075). A negative correlation was noticed between improved DAS28-ESR and the progression of joint damage in the LEF group (r = -0.7068, P < 0.0001), whereas there was no correlation in the MTX group (r = -0.0311, P = 0.882). In daily clinical practice, LEF showed significant clinical and radiological improvement compared with the standard MTX regimen in Japan.