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ID PMID Title PublicationDate abstract
20436075 Golimumab for rheumatoid arthritis: a systematic review. 2010 Jun OBJECTIVE: To perform a Cochrane systematic review of benefit (American College of Rheumatology 50% improvement criteria; ACR50) and safety (adverse events and withdrawals) of golimumab in patients with rheumatoid arthritis (RA). METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), OVID Medline, CINAHL, Embase, Science Citation Index (Web of Science), and Current Controlled Trials databases for randomized or controlled clinical trials of golimumab compared to placebo or disease-modifying antirheumatic drug in adults with RA. Two authors independently selected appropriate studies and abstracted study characteristics and safety and efficacy data and performed risk-of-bias assessment. We calculated mean differences for continuous measures, and relative risks for categorical measures. RESULTS: Four randomized controlled trials with 1231 golimumab-treated and 483 placebo-treated patients were included. Of these, 436 were treated with golimumab at 50 mg every 4 weeks [a dosage approved by the US Food and Drug Administration (FDA)]. At an average of 4-6 months, compared to patients treated with placebo and methotrexate (MTX), patients treated with the FDA-approved dosage of golimumab and MTX were 2.6 times more likely to reach ACR50 (p = 0.005, 95% CI 1.3, 4.9; absolute percentage, 38% vs 15%) and 0.5 times as likely to have overall withdrawals (p = 0.005, 95% CI 0.3, 0.8; absolute percentage, 5% vs 10%). Golimumab-treated patients were significantly more likely than those taking placebo to achieve remission (22% vs 4%; p < 0.00001), and to have improvement in functional ability on the Health Assessment questionnaire [0.2 points lower (p < 0.00001, 95% CI 0.25, 0.15); absolute risk difference, -20% (95% CI -25% to -15%); relative percentage difference, -11% (95% CI -14% to -8.3%)]. The studies were too small and short to be powered sufficiently for safety outcomes, but no substantive statistically significant differences were noted between golimumab and placebo regarding adverse events, serious adverse events, infections, serious infections, lung infections, tuberculosis, cancer, withdrawals due to adverse events, and withdrawals due to inefficacy and deaths. CONCLUSION: At the approved dosage, in patients with active RA taking background MTX, golimumab is significantly more beneficial than placebo. The short-term safety profile is reasonable. Longterm surveillance studies are needed for safety assessment.
20098037 Evaluation of atrial electromechanical delay and left atrial mechanical functions in patie 2009 Oct OBJECTIVES: The aim of this study was to evaluate atrial electromechanical delay measured by tissue Doppler imaging (TDI) and left atrial (LA) mechanical functions in patients with rheumatoid arthritis (RA). STUDY DESIGN: The study included 68 patients (53 females, 15 males; mean age 43.7 years) with RA. Using TDI, atrial electromechanical coupling (PA) was measured from the lateral mitral annulus (PA lateral), septal mitral annulus (PA septum), and right ventricular tricuspid annulus (PA tricuspid). Left atrial volumes (maximal, minimal, and pre-systolic) were measured by the method of discs in the apical four-chamber view and were indexed to body surface area. Mechanical function parameters of the LA were calculated. The results were compared with those of 41 age- and gender-matched healthy volunteers (32 females, 9 males; mean age 41.9 years). RESULTS: Patients with RA had significantly prolonged PA lateral, PA septum, and intra- (PA septum-PA tricuspid) and interatrial (PA lateral-PA tricuspid) electromechanical delays compared to controls (p<0.0001, p=0.05, p<0.0001, and p<0.0001, respectively). Left atrial volumes were similar in the two groups (p>0.05). Left atrial passive emptying fraction was significantly decreased, LA active emptying volume and active emptying fraction were increased in RA patients (p=0.05, p=0.01, and p<0.0001; respectively). Interatrial electromechanical delay was correlated with systolic blood pressure (r=0.20, p=0.04), left ventricular mass index (r=0.22, p=0.02), C-reactive protein (CRP) (r=0.27, p=0.005), and LA active emptying fraction (r=0.29, p=0.002). In linear regression analysis, LA active emptying fraction and CRP were independent variables of interatrial electromechanical delay (beta=0.28, p=0.002 and beta=0.25, p=0.006, respectively). CONCLUSION: Prolonged electromechanical delays and impaired LA mechanical functions may be an early manifestation of subclinical cardiac involvement in RA patients.
20463189 Treating arthritis by immunomodulation: is there a role for regulatory T cells? 2010 Sep The discovery of regulatory T cells almost 15 years ago initiated a new and exciting research area. The growing evidence for a critical role of these cells in controlling autoimmune responses has raised expectations for therapeutic application of regulatory T cells in patients with autoimmune arthritis. Here, we review recent studies investigating the presence, phenotype and function of these cells in patients with RA and juvenile idiopathic arthritis (JIA) and consider their therapeutic potential. Both direct and indirect methods to target these cells will be discussed. Arguably, a therapeutic approach that combines multiple regulatory T-cell-enhancing strategies could be most successful for clinical application.
20374310 Histological analysis of synovium by treatment of etanercept for rheumatoid arthritis. 2009 Apr AIMS: In order to investigate the histological change in effect attenuation cases of etanercept compared with methotrexate (MTX), we performed immunohistochemical examination by seven different molecules. METHODS: We histologically assessed synovial tissue from five MTX-treated rheumatoid arthritis (RA) patients as control and six etanercept and MTX-treated RA patients after synovectomy by arthroscopy. The synovium of both groups were assessed by hematoxylin and eosin (HE) and we also analysed the expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), B-cell precursors and mature B-cell transmembrane protein, CD20, macrophage marker, CD68, bromodeoxyuridine (BrdU) and vascular endothelial growth factor (VEGF) by immunohistochemistry. RESULTS: HE staining showed vascular and cell proliferations of the synovium of the RA patients who received etanercept compared with the control MTX group. TNF-alpha and IL-6 were expressed in both groups.MMP-3 and CD68 expressed less significantly in the etanercept group compared with the control (P < 0.05). CD20 strongly expressed in the etanercept group significantly (P < 0.05). BrdU expressed in the synovium in the etanercept group significantly (P < 0.05). VEGF was not found overall in both group. CONCLUSION: Based on the histological change of synovium, treatment by etanercept may be involved in vascular and cell proliferations with inhibition of the expression of CD68 and MMP-3 in synovium of RA patients. These findings indicate immunohistochemical change of synovium with etanercept is one of the mechanism of efficacy of etanercept.
21046421 Management of rheumatoid arthritis: consensus recommendations from the Hong Kong Society o 2011 Mar Given the recent availability of novel biologic agents for the treatment of rheumatoid arthritis (RA), the Hong Kong Society of Rheumatology has developed consensus recommendations on the management of RA, which aim at providing guidance to local physicians on appropriate, literature-based management of this condition, specifically on the indications and monitoring of the biologic disease-modifying anti-rheumatic drugs (DMARDs). The recommendations were developed using the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis as a guide, along with local expert opinion. As significant joint damage occurs early in the course of RA, initiating therapy early is key to minimizing further damage and disability. Patients with serious disease or poor prognosis should receive early, aggressive therapy. Because of its good efficacy and safety profile, methotrexate is considered the standard first-line DMARD for most treatment-naïve RA patients. Patients with a suboptimal response to methotrexate monotherapy should receive step-up (combination) therapy with either the synthetic or biologic DMARDs. In recent years, combinations of methotrexate with tocilizumab, abatacept, or rituximab have emerged as effective therapies in patients who are unresponsive to traditional DMARDs or the anti-tumor necrosis factor (TNF)-α agents. As biologic agents can increase the risk of infections such as tuberculosis and reactivation of viral hepatitis, screening for the presence of latent tuberculosis and chronic viral hepatitis carrier state is recommended before initiating therapy.
19773406 Fatigue is a reliable, sensitive and unique outcome measure in rheumatoid arthritis. 2009 Dec OBJECTIVE: Fatigue is an important symptom in patients with RA. Measurement of fatigue in clinical trials and in clinical practice requires scales that are reproducible, sensitive to change and practical. This study examined the reliability and sensitivity to change of fatigue and its relative independence as an outcome measure in RA. METHODS: Successive patients referred to the rheumatology clinic at St Vincent's University Hospital and Our Lady's Hospice were evaluated. Clinical assessments were undertaken at baseline and 3 months after commencing TNF-alpha blockade. Fatigue was measured using an 11-point numeric rating scale (NRS). Sensitivity to change when compared with current core set outcome measures was determined by calculation of the standardized response mean (SRM). Multiple regression analysis was employed to determine the independent variance of fatigue scores relative to the core set. RESULTS: Forty-nine patients were evaluated. At baseline, mean (s.d.) fatigue scores were 6.7 +/- 2.1. At 3 months, fatigue scores had fallen to 4.3 +/- 2.6 (P < 0.001). Test-retest intraclass correlation coefficient for the NRS was 0.79 (P < 0.008). Fatigue was ranked third for relative sensitivity to change as shown by SRM: pain, 1.37; tender joint count (TJC), 1.09; fatigue, 0.92; swollen joint count (SJC), 0.86; HAQ, 0.82; CRP, 0.69; and patient global health (GH), 0.25. The relative independent variance in fatigue of 22% was higher than that of the core set: TJC, 20%; pain, 19%; SJC, 16%; GH, 8%; HAQ, 7%; and CRP, 8%. CONCLUSIONS: This study demonstrates that measures of fatigue are reliable and sensitive to change, and should be considered for inclusion as a core outcome measure in RA.
18972320 Serum prohepcidin concentrations in rheumatoid arthritis. 2009 Feb AIM: Hepcidin, a recently identified peptide, acts as a central regulator of iron metabolism. It is regarded as a factor regulating the uptake of dietary iron and its mobilisation from macrophages and hepatic stores. It is considered as a mediator of anaemia of inflammation. The aim of this study was to assess whether serum prohepcidin concentration is able to distinguish iron deficiency from anaemia of inflammation in patients with rheumatoid arthritis (RA). METHOD: Blood samples were obtained from 20 healthy blood donors, 30 RA patients who presented with anaemia and 30 patients who had pure iron deficiency anaemia (IDA). The samples were analysed for full blood count, iron, ferritin, transferrin, soluble transferrin receptor and prohepcidin. RESULTS: The mean prohepcidin level in the control subjects was 256 microg/L. The prohepcidin level was significantly lower in IDA patients (100 microg/L; p < 0.0001) but not significantly different from that of control in RA patients (250 microg/L; p > 0.05). Higher serum soluble transferrin receptor (sTfR) levels were observed in IDA (p < 0.0001) but not in RA compared with that of control (p > 0.05). RA patients were divided into iron depleted and iron repleted subgroups based on the ferritin level. Prohepcidin in the iron depleted group was significantly lower than the iron repleted group and the control (p < 0.0001) and higher levels were observed in the iron repleted group (p < 0.01). sTfR levels in the iron depleted group were significantly higher than the control and the iron repleted patients (p < 0.001). In the iron repleted group, sTfR level was not statistically different from that of control (p > 0.05). CONCLUSION: Serum prohepcidin is clearly reduced in uncomplicated iron deficiency anaemia. The reduced prohepcidin levels in the iron depleted RA patients suggests that there may be conflicting signals regulating hepcidin production in RA patients. In RA patients who have reduced hepcidin in the iron depleted group (ferritin <60 microg/L) where sTfR levels are increased suggests that these patients are iron deficient. Further studies with a larger cohort of patients are required to substantiate this point.
20080912 Interleukin 10 and tumor necrosis factor-alpha genotypes in rheumatoid arthritis--associat 2010 Mar OBJECTIVE: There are dysregulated levels of interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) in rheumatoid arthritis (RA), and their role in the disease is controversial. We analyzed the association of functional polymorphisms of IL-10 and TNF-alpha with susceptibility and disease characteristics at the time of diagnosis, and we also evaluated their possible use as predictors of clinical response to treatments. METHODS: Patients with recent-onset RA (n = 162) and healthy controls (n = 373) were genotyped for -1082 IL-10 and -308 TNF-alpha polymorphisms and data were related to clinical and immunological measurements of patients at the time of diagnosis. Response to treatment after 6 months was determined in 125 patients by the absolute change in Disease Activity Score (DAS28) and the American College of Rheumatology criteria for improvement. RESULTS: We found a reduced frequency of the low IL-10 producer genotype (-1082AA) in patients with RA compared to controls (26.5% vs 38.9%; p = 0.006), while it is a risk factor for anticyclic citrullinated peptide antibodies (anti-CCP) positivity (p = 0.028). Evaluation of clinical response to treatments indicated that carriage of the high IL-10 genotype was associated with a favorable outcome (p = 0.009), specifically to prednisone therapy (p = 0.0003). No significant effects were observed with TNF-alpha polymorphism alone; however, in combination with the IL-10 genotype, it increased the strength of these associations. CONCLUSION: Results show an association between the low IL-10 producer genotype and protection from RA; nevertheless, when other specific genetic and/or environmental factors trigger onset of RA, this genotype may predispose to development of anti-CCP+ RA disease with reduced response to prednisone treatment.
20300755 The relationship between vitamin D and disease activity and functional health status in rh 2011 Jul We aimed to establish the relationship between serum vitamin D levels and disease activity and health status in rheumatoid arthritis. Sixty-five patients with RA fulfilling ACR criteria for the classification of rheumatoid arthritis and forty healthy controls were included in this study. Disease activity was assessed according to the Disease Activity Score including 28 joint counts. C-reactive protein (CRP, mg/dl) was determined by the nephelometric method. Erythrocyte sedimentation rate (ESR, mm/h) was determined by the Westergren method. Rheumatoid factor (RF, IU/ml) was also determined by the nephelometric method, and RF > 20 IU/ml was defined as positive. 25-OH Vitamin D EIA Kit was used to measure serum 25-OH Vitamin D levels. We found that the mean of the 25-OH D vitamin levels of the patients with RA was not different than that of controls (P = 0.936). We divided patients with RA into three groups according to DAS28 as low activity group (group 1, n = 25), moderate activity group (group 2, n = 25), and high activity group (group 3, n = 15). 25-OH vitamin D levels of the patients in the high activity group (group 3) were found to be the lowest (P < 0.001), and the patients with moderate disease activity had lower levels than those in the mild group (P = 0.033). Serum 25-OH vitamin D levels were significantly negatively correlated with DAS28, CRP, and HAQ (respectively, r = -0.431, P = 0.000, r = -0.276, P = 0.026, and r = -0.267, P = 0.031). Serum vitamin D levels in patients with RA were similar those in the healthy controls, while it significantly decreases in accordance with the disease activity and decreasing functional capacity.
19262425 Investigation of genetic variants within candidate genes of the TNFRSF1B signalling pathwa 2009 Apr The introduction of anti-tumour necrosis factor (TNF) agents has greatly improved the treatment of rheumatoid arthritis; however, a significant proportion of patients fail to respond to therapy. We hypothesized that genes within the TNF receptor superfamily member 1B signalling pathway contribute towards the observed variation in patient response. This was tested by genotyping 73 single-nucleotide polymorphisms (SNPs) from six candidate genes (DUSP1, HRB, IKBKAP, MAP3K1, MAP3K14 and TANK) in a large UK cohort of rheumatoid arthritis patients (n=642). Two SNPs [rs96844 (MAP3K1) and rs4792847 (MAP3K14)] showed evidence of association (P<0.05) to treatment response and were subsequently examined in an independent cohort of patients (n=428). Replication of association to either SNP was not achieved, but combined analysis of the complete cohort (n=1070) provided nominal evidence of association to both SNPs. We conclude that analysis of the common variation in the selected candidate genes did not provide strong evidence to implicate their involvement in varying patient response to anti-TNF treatment.
19758137 Optimization of high-throughput autoantibody profiling for the discovery of novel antigeni 2009 Sep A major focus in rheumatoid arthritis (RA) research is the identification of the antigens that are targeted by the joint-directed autoimmune response. B cells and associated autoantibodies have been studied in RA to identify the antigenic targets and to discover RA-associated autoantibodies which can be used as disease markers. This research indicated the heterogeneity of the autoantibody profile in RA and the large overlap in antibody specificities with other rheumatic diseases pointing toward the need for multiplexing to identify an RA-associated autoantibody profile. The discovery of antibodies directed against cyclic citrullinated peptides (ACPA) has led to great advances in RA research. This finding generated novel autoantigen suspects in ACPA-positive RA patients, which comprise approximately two-thirds of the entire RA population, namely citrullinated peptides and/or proteins. One-third of the RA patients, however, do not show ACPA, and it is now postulated that ACPA-positive and ACPA-negative RA are two different disease entities with different genetic associations, pathogenesis, and etiology. The analysis of autoantibodies in ACPA-negative RA could provide insight into the identity of antigenic targets and markers for this disease subtype. We report here the optimization of an unbiased, high-throughput autoantibody profiling procedure based on cDNA phage display for the detection of novel autoantibody targets in ACPA-negative RA. The discovery of specific autoantibodies in this RA subtype could lead to great advances in the diagnosis of these patients and could provide clues regarding disease etiology and pathogenesis of ACPA-negative RA.
20080919 Clinical improvement in rheumatoid arthritis is associated with healthier microvascular fu 2010 Mar OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) mortality. Microvascular endothelial dysfunction occurs early in the development of CV disease and is worsened by inflammation. The effect of drug treatment for RA on microvascular function has been poorly studied. We assessed the effect of antirheumatic treatment on microvascular endothelial function in patients with RA, particularly to examine responders versus nonresponders to therapy. METHODS: Fifty-one patients with active RA and no previous history of CV disease were assessed at baseline and after 2 and 4 months' therapy with either anti-tumor necrosis factor-alpha drugs (etanercept, n = 27, adalimumab, n = 3) or methotrexate, n = 21. RA disease activity, inflammatory measures, and skin microvascular responses, measured using laser Doppler imaging after iontophoretic delivery of acetylcholine (ACh) and sodium nitroprusside (SNP), were assessed at each study visit. RESULTS: Disease Activity Score (DAS28) decreased significantly from baseline to visit 2 and 3 (6.04 +/- 1.2, 4.34 +/- 1.3, 4 +/- 1.3, respectively; p < 0.0001). Endothelium-dependent (ACh) and independent (SNP) responses for the whole cohort did not improve significantly after drug treatment (p = 0.250, p = 0.062, respectively). When patients who responded to antirheumatic therapy (n = 31) were analyzed, there were significant improvements in both ACh (p = 0.028) and SNP responses (p = 0.019). CONCLUSION: Microvascular endothelial function improves in patients who respond to antirheumatic therapy. These results support the importance of effective therapy for RA patients in terms of CV effects, which might extrapolate to reduced CV events in the future. Clinical trial registration no. ISRCTN57761809.
20837497 Haematopoietic stem and progenitor cells in rheumatoid arthritis. 2011 Feb RA is the prototypic chronic inflammatory disease, characterized by progressive articular cartilage and bone destruction. The systemic nature of RA is evidenced by the increased risk of atherosclerosis and lymphoproliferative disorders. Components of both the innate and adaptive immune system are implicated in the pathophysiology of the articular and extra-articular manifestations of the disease. A fundamental process in the onset of RA is the breakdown in self-tolerance. Accelerated ageing of immune cells (immunosenescence) appears to be a major mechanism favouring the disruption of tolerance. Telomere erosion, a hallmark of immunosenescence, is present in lymphoid (naïve and memory T cells) and myeloid (granulocytes) cells in RA. The premature ageing process also involves the haematopoietic stem and progenitor cells (CD34(+) HSPC), thus extending the RA immunopathogenesis to include early events in the shaping of the immune system. This review summarizes current concepts of HSPC ageing and its impact on immune regeneration, highlighting the phenotypic and functional similarities between elderly and RA HSPC.
20557816 Comparison of bioreplaceable interposition arthroplasty with metatarsal head resection of 2010 Jun BACKGROUND: Interposition arthroplasty with bioreplaceable poly-L/D-lactic acid (PLDLA) implants has been studied in Finland with promising results in reconstruction of the rheumatoid hand. We evaluated this material in a series of patients with rheumatoid forefoot deformities. MATERIALS AND METHODS: Thirty-five patients were randomized to either PLDLA metatarsophalangeal joint interposition arthroplasty group (16 patients) or to conventional metatarsal head resection group (19 patients). RESULTS: At 3 months after surgery, the function VAS was significantly better in the control group (p = 0.003). The difference disappeared by 12 months. Otherwise, comparison between the two groups did not reveal any statistically significant differences in the AOFAS scores or the pain VAS at 3 or 12 months. CONCLUSION: Early results after PLDLA interposition arthroplasty of metatarsophalangeal joints were not as promising as previously reported with rheumatoid metacarpophalangeal reconstruction.
20851020 Traditional cardiovascular risk factors in rheumatoid arthritis: a meta-analysis. 2011 Mar OBJECTIVE: Rheumatoid arthritis is associated with increased cardiovascular morbidity and mortality. We performed a systematic review of the literature and a meta-analysis to look for differences in the prevalence of traditional cardiovascular risk factor between RA patients and controls. METHODS: Medline database was searched to identify studies evaluating the prevalence of traditional cardiovascular risk factors in rheumatoid arthritis patients and controls. Studies were selected and reviewed by two investigators. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated through the use of Chi2 and I2 statistics. RESULTS: Fifteen case-control studies with a total of 2956 patients and 3713 controls met the inclusion criteria. The prevalence of smoking was increased in RA patients in comparison with controls: OR (95%CI) 1.56 (1.35-1.80) (P < 0.00001). The prevalence of hypertension did not differ: OR (95% CI) 1.09 (0.91-1.31) (P = 0.35). The prevalence of diabetes mellitus was increased in RA: OR (95%CI) 1.74 (1.22-2.50) (P = 0.003). The prevalence of hypercholesterolemia did not differ: OR (95%CI) 0.84 (0.67-1.04) (P = 0.11). HDL cholesterol levels were lower in RA patients: weighted mean difference -17.72 mg/dl (-18.35 - -17.08) (P < 0.00001). Significant heterogeneity among studies was found for diabetes mellitus and HDL cholesterol levels. CONCLUSIONS: Some traditional cardiovascular risk factors, such as smoking, diabetes mellitus or lower HDL cholesterol levels, appear more prevalent in rheumatoid arthritis patients and could contribute to the increased cardiovascular morbidity and mortality observed in rheumatoid arthritis.
20480169 [Does TNF play a role in the pathogenesis of solid tumors?]. 2010 Aug Tumor necrosis factor (TNF)-alpha blocking agents play an important role in rheumatology. For this reason, questions about the pathogenic characteristics of TNF in carcinogenesis are of the utmost importance. The observation that TNF leads to necrosis in tumor tissue gave rise to the hope that an agent had been identified for the treatment of malignant tumors. However, this expectation remained unfulfilled, not the least due to the toxicity of systemically applied TNF. In addition, TNF is produced by many tumor cells. There is evidence that for some tumors TNF promotes tumor growth, invasiveness and metastasis. It is quite possible, therefore, that the inhibition of TNF-alpha has an inhibitive effect on carcinogenesis and/or tumor progression. In 2009 the US Food and Drug Administration (FDA) issued a cancer warning for the use of TNF inhibitors in children and adolescents. There is still some controversy as to whether TNF blocking therapy, co-medication or the rheumatic disease itself leads to an increased cancer risk in these young patients. In adults, safety information so far available suggests a favorable risk-benefit profile for the long-term use of TNF inhibitors. However, many questions remain unanswered as to the role TNF itself plays in the pathogenesis of solid tumors.
19995751 "Go upstream, young man": lessons learned from the p38 saga. 2010 Jan Despite the success of biological therapies in rheumatoid arthritis (RA), orally active small-molecule drugs are desirable. Signal transduction inhibitors have been the focus of intense efforts, with some recent notable successes and failures. p38alpha is a signalling molecule that regulates proinflammatory cytokines, which makes it a logical target for RA. Unfortunately, selective p38alpha inhibitors have limited efficacy. An attempt is made here to put these studies into perspective and offer possible explanations for the failure of p38alpha blockers. Alternative strategies, such as targeting kinases higher in the signalling cascade or using less selective compounds, might be more successful as suggested by the efficacy seen with Syk and JAK inhibitors.
21053358 Nonmelanoma skin cancer in inflammatory bowel disease: a review. 2011 Jun At least 1 million new cases of nonmelanoma skin cancer (NMSC) are diagnosed in the United States each year and the incidence is increasing. A higher incidence of NMSC in organ transplant recipients on immunosuppression has been documented for some time, and recent studies indicate that patients with inflammatory bowel disease (IBD), particularly those treated with immunosuppressive medications, might also be at higher risk for this condition. In this review we summarize recent data evaluating the associations between immunomodulators, antitumor necrosis factor-α biologic agents and NMSC in patients with IBD and other autoimmune conditions such as rheumatoid arthritis. We also offer recommendations for prevention of NMSC in these populations.
21043003 Anti-cytokine vaccination in autoimmune diseases. 2010 The concept of therapeutic vaccination represents a novel strategy of active immunotherapy that can be applied to autoimmune disease. The principle is to design molecules which can trigger an immune response, targeting a cytokine that is pathogenic and over-expressed in a given disease. The mostly available vaccines are an application of vaccination using either the self-protein coupled to a carrier (type I A), or a modified form of the protein engineered to include neo-epitopes (type I B). These approaches have been developed in models of several autoimmune diseases, mainly in TNFα-dependent diseases such as rheumatoid arthritis and Crohn's disease, but also in systemic lupus erythematosus, multiple sclerosis and myasthenia gravis. Clinical trials are in progress in rheumatoid arthritis, Crohn's disease and diabetes. The benefit/risk ratio of anti-cytokine vaccination is currently under study to further develop the vaccination strategies.
19276959 Hypervascular synovitis and American College of Rheumatology Classification Criteria as pr 2009 Mar To investigate if serial clinical and ultrasound evaluations differ between early rheumatoid arthritis patients who do or do not develop erosive disease and to identify predictors of erosions. METHODS: Patients with at least 7 consecutive 2-monthly clinical and 3 consecutive 6-monthly ultrasound evaluations were included. Ultrasound (gray scale and power Doppler) assessed synovitis, power Doppler-positive synovitis (PD+) and power Doppler-negative synovitis (PD-) in each of 14 joints of the dominant hand. After 1 and 2 years, erosive disease was defined according to digitized radiography. Areas under the curve (AUCs) for serial assessments were calculated. Multivariate logistic regression analysis was performed. RESULTS: Seventy-one and 38 patients completed 1- and 2-year consecutive assessments. After 2 years (21.5 +/- 6.2 months), 13 patients developed erosions. At baseline, nonerosive patients had shorter duration of symptoms to RA diagnosis, lower number of the American College of Rheumatology (ACR) classification criteria, lesser synovitis and PD+ synovitis than erosive patients. At follow-up, erosive and nonerosive patients showed similar AUC for clinical, serological, and treatment parameters; erosive patients had higher AUCs for synovitis and PD+ synovitis than nonerosive patients. In the multivariate model, the amount of PD+ synovitis (odds ratio, 1.3; 95% confidence interval, 1.11-1.51; P = 0.001) and more ACR classification criteria (odds ratio, 2.3; 95% confidence interval, 1.05-5.02; P = 0.04), both at baseline, predicted erosive disease. CONCLUSIONS: Serial Power Doppler ultrasonography-assessed synovitis was greater in patients who developed erosions than in those who did not. More power Doppler positive (hypervascular) synovitis and more ACR classification criteria, both at baseline, were the only predictors of erosions.