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ABSTRACT: OBJECTIVE: We investigated changes in high-density lipoprotein (HDL) profiling in patients with rheumatoid arthritis who started treatment by taking tumor necrosis factor (TNF) inhibitors. The patients were stratified for European League Against Rheumatism (EULAR) response. METHODS: A group of 100 patients naive for TNF inhibitors at baseline were randomly selected from 204 adalimumab-treated and 203 etanercept-treated patients on the basis of their EULAR response. HDL profiling was measured using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. RESULTS: In EULAR good responders, mass charged markers representing serum amyloid A (SAA-1 and -2) decreased significantly after 4 months' therapy. There were no significant differences in HDL profiling in EULAR nonresponders. CONCLUSION: Effective suppression of inflammation with TNF inhibitors results in favorable changes in HDL composition.
The Journal of Rheumatology 05/2013; · 3.69 Impact Factor
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ABSTRACT: Rituximab is a anti-CD20 monoclonal antibody often used in the treatment of rheumatoid arthritis (RA). Infusion reactions sometimes develop following rituximab administration. Delayed complications are rare. Acute coronary syndromes are listed as side-effects of rituximab therapy. We report two cases of acute myocardial infarction following rituximab therapy for RA and review the literature regarding cardiac events in patients treated with rituximab. We would like to raise awareness of this possible complication in patients treated with rituximab.
Current pharmaceutical design 04/2013; · 4.41 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) is associated with a similar cardiovascular risk to that in diabetes, and therefore cardiovascular risk management (CV-RM) - that is, identification and treatment of cardiovascular risk factors (CRFs) - is mandatory. However, whether and to what extent this is done in daily clinical practice is unknown. In a retrospective cohort investigation, CV-RM was therefore compared between rheumatologists and primary care physicians (PCPs). Remarkably, CRFs in RA were less frequently identified and managed by rheumatologists in comparison with PCPs. In addition, PCPs assessed CRFs less frequently in RA than in diabetes. Obviously, there is a clear need for improvement of CV-RM in RA and this should be a joint effort from the rheumatologist and the PCP.
Arthritis research & therapy 03/2013; 15(2):111. · 4.27 Impact Factor
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ABSTRACT: Objective. To investigate the effect of long-term adalimumab treatment on BMD of the lumbar spine, total hip and hands in patients with RA.Methods. In 184 established RA patients treated with adalimumab for at least 1 year, BMD measurements of the total hip and lumbar spine were performed using dual-energy X-ray absorptiometry. Metacarpal cortex BMD was measured using digital X-ray radiogrammetry.Results. After 1 year of treatment, BMD of the hip and lumbar spine remained stable, while BMD of the hands decreased significantly by -1.41% (P < 0.0001). After a mean follow-up of 4.0 (s.d. 1.0) years, mean BMD change per year was -0.58% and 0.07% for the hip and lumbar spine, respectively (overall P-value of hip was <0.0001 and spine was 0.67). Predictors for BMD loss of the hip were anti-CCP positivity, non-use of bisphosphonates at baseline and BMI. In European League Against Rheumatism (EULAR) non-responders at 52 weeks, BMD change of the hip and spine was -1.25% and 1.08%, respectively, for moderate responders -0.61% and -1.87%, respectively, and in EULAR good responders, BMD remained stable: -0.02% and 0.06%, respectively. BMD of the hands decreased in non-, moderate and good responders (-2.85%, -1.47% and -1.26%, respectively).Conclusion. In patients with severe, established RA, loss of BMD in the spine was arrested over 4 years of adalimumab treatment, whereas BMD of the hands and hip continued to decrease after 1 and 4 years, respectively. The changes in BMD are related to disease activity, underlining the importance of monitoring disease activity.
Rheumatology (Oxford, England) 12/2012; · 4.24 Impact Factor
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ABSTRACT: Spondyloarthritis (SpA) is a chronic inflammatory disease with either predominantly axial symptoms of the spine and sacroiliac joints (axial SpA, including ankylosing spondylitis) or predominantly arthritis (peripheral SpA). Next to these spinal and articular symptoms, many patients with SpA also have extra-articular manifestations (EAMs). EAMs associated with SpA include anterior uveitis (25-30%), psoriasis (10-25%) or inflammatory bowel disease (IBD) (5-10%) and cardiovascular manifestations. Peripheral arthritis occurs in approximately 30% of patients, especially in large joints, and shows an asymmetrical, oligoarticular pattern. Other common joint complaints are due to enthesitis, which manifest as extra-articular bony tenderness in areas such as the Achilles tendon. Acute anterior uveitis presents with acute pain, loss of vision and redness in one eye that usually subsides spontaneously after several weeks. Rapid treatment by an ophthalmologist is required to prevent synechiae formation which could ultimately result in glaucoma and blindness. Although less common, organ involvement in SpA can also be located in the heart, lungs or kidneys. The risk of cardiovascular events is increased in SpA. Cardiac manifestations can involve the aortic valve (1-10%) or the atrioventricular node and the risk of atherosclerotic events is increased in this group. Treatment of SpA includes physical exercise and nonsteroidal anti-inflammatory drugs (NSAIDs), and in case of peripheral arthritis, sulphasalazine can be added. When there is insufficient response to NSAIDs, tumor necrosis factor blockers, especially infliximab, etanercept, adalimumab and golimumab, are very effective in treating axial manifestations, arthritis, enthesitis and psoriasis. Anterior uveitis in SpA can be treated adequately by the ophthalmologist and in the case of refractory uveitis, treatment with adalimumab and infliximab seems to be more effective compared with etanercept. When IBD occurs with SpA, the use of NSAIDs should be minimized, except for celecoxib, and infliximab or adalimumab are preferred to etanercept. The incidence of atherosclerotic events or SpA-specific cardiac manifestations may be decreased by cardiovascular risk management or effective antirheumatic treatment. Overall it is important to realize that extra-articular manifestations frequently occur in patients with SpA and should be taken into account in the choice of treatment.
Therapeutic advances in musculoskeletal disease 12/2012; 4(6):413-22.
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ABSTRACT: OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) risk, but mechanisms behind this increased risk have not been fully elucidated. Carotid arterial remodeling is the change of structural properties in response to hemodynamic or metabolic factors aimed at keeping wall stress within certain limits. This process might become maladaptive when stress on the arterial wall increases beyond these limits. We investigated whether maladaptive carotid arterial remodeling is present in RA compared with control subjects. METHODS: The 2 cohorts were 96 patients with RA and 274 healthy subjects, who were investigated cross-sectionally. Carotid intima-media thickness (cIMT) and interadventitial diameter (IAD) were assessed by B-mode carotid ultrasonography. Lumen diameter (LD), circumferential wall stress (CWS), and circumferential wall tension (CWT) were calculated. Linear regression analyses were used to investigate the association between presence of RA and carotid arterial remodeling. RESULTS: Compared with healthy subjects, RA was associated with a 0.40 mm (9.3%) greater LD, 0.41 mm (7.8%) greater IAD, 10% higher CWS, and 8% higher CWT. The groups had comparable cIMT. Associations remained similar after exclusion of patients with prior CV disease and after adjustment for demographic factors and CV risk factors. CONCLUSION: RA is associated with maladaptive outward carotid arterial remodeling. These results are relevant because maladaptive outward remodeling is associated with plaque instability and rupture. These results indicate an alternative pathway, beyond the traditional CV risk factors, in RA that amplifies the CV risk.
The Journal of Rheumatology 10/2012; · 3.69 Impact Factor
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The American journal of cardiology 09/2012; 110(5):763. · 3.58 Impact Factor
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ABSTRACT: Objective.To compare rates of sustained low and minimal disease activity and ACR/EULAR remission during 3-year follow-up in rheumatoid arthritis (RA) patients treated with etanercept and adalimumab in routine care. Methods. Four-hundred and seven RA patients previously unexposed to tumor necrosis factor antagonists were treated with etanercept (n=203) or adalimumab (n=204) and assessed at 3- and later 6 month intervals. Treatment allocation was at the discretion of the treating rheumatologist. Clinical parameters and anti-adalimumab antibodies (AAA) were measured at each time point. Achievement of clinical outcome was defined as the occurrence of sustained (at least 12 consecutive months) low disease activity (sLDA; DAS28 <3.2), minimal disease activity (sMDA; DAS28 <2.6) or ACR/EULAR remission (sSDAI). Non-overlapping response rates were calculated. Results. In the adalimumab group, 13% reached sLDA but not sMDA, 15% reached sMDA but not sSDAI and 16% reached sSDAI remission. In the etanercept group corresponding rates were 16%, 11% and 12%, respectively (overall test for linear trend: p=0.42). Adalimumab-treated patients without antibodies (AAA(-); n=150, 74%) had best outcomes and AAA(+) patients the worst, with etanercept-treated patients in between (p<0.0001). Differences were most apparent in the sSDAI and sMDA categories. For example, 40% of AAA (-) , 23% of etanercept and 4% of AAA (+) patients achieved at least sMDA. Conclusion. Overall, etanercept and adalimumab treatment appear similar in inducing a good long-term clinical outcome. However, in the case of adalimumab this is strongly dependent on the presence or absence of AAA. © 2012 American College of Rheumatology.
Arthritis & Rheumatism 08/2012; · 7.87 Impact Factor
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ABSTRACT: BACKGROUND: There is accumulating evidence for an increased cardiovascular burden in inflammatory arthritis, but the true magnitude of this cardiovascular burden is still debated. We sought to determine the prevalence rate of non-fatal cardiovascular disease (CVD) in inflammatory arthritis, diabetes mellitus and osteoarthritis (non-systemic inflammatory comparator) compared to controls, in primary care. METHODS: Data on CVD morbidity (ICPC codes K75 (myocardial infarction), K89 (transient ischemic attack), and/or K90 (stroke/cerebrovascular accident)) from patients with inflammatory arthritis (n = 1,518), diabetes mellitus (n = 11,959), osteoarthritis (n = 4,040) and controls (n = 158,439) were used from the Netherlands Information Network of General Practice (LINH), a large nationally representative primary care based cohort. Data were analyzed using multi-level logistic regression analyses and corrected for age, gender, hypercholesterolemia and hypertension. RESULTS: CVD prevalence rates were significantly higher in inflammatory arthritis, diabetes mellitus and osteoarthritis compared with controls. These results attenuated - especially in diabetes mellitus - but remained statistically significant after adjustment for age, gender, hypertension and hypercholesterolemia for inflammatory arthritis (OR = 1.5 (1.2-1.9)) and diabetes mellitus (OR = 1.3 (1.2-1.4)). The association between osteoarthritis and CVD reversed after adjustment (OR = 0.8 (0.7-1.0)). CONCLUSIONS: These results confirm an increased prevalence rate of CVD in inflammatory arthritis to levels resembling diabetes mellitus. By contrast, lack of excess CVD in osteoarthritis further suggests that the systemic inflammatory load is critical to the CVD burden in inflammatory arthritis.
BMC Musculoskeletal Disorders 08/2012; 13(1):150. · 1.58 Impact Factor
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ABSTRACT: Chronic inflammatory spondyloarthritis involves axial symptoms of the spine and sacroiliac joints, or peripheral arthritis. Many patients suffer from extra-articular manifestations. With acute anterior uveitis, rapid treatment prevents synechiae. Other organs can be involved. Treatment includes exercise, nonsteroidal antiinflammatory drugs (if insufficient response, tumor necrosis factor blockers), and (with peripheral arthritis) sulfasalazine. Patients with ankylosing spondylitis have comorbidities and increased cardiovascular risk. For uveitis or inflammatory bowel disease, patients should be referred to an ophthalmologist or gastroenterologist. Cardiovascular risk may originate from atherosclerotic disease and cardiac manifestations. Epidemiological studies should be conducted before echocardiogram screening and cardiovascular risk management.
Rheumatic diseases clinics of North America 08/2012; 38(3):523-38. · 2.59 Impact Factor
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ABSTRACT: OBJECTIVE: An atherogenic lipid profile is an established risk factor for cardiovascular (CV) diseases. Interestingly, high inflammatory states as present in rheumatoid arthritis (RA) are associated with unfavourable lipid profile. Data about effects of novel immunomodulating agents as rituximab (RTX) on lipid profile are limited. Therefore, changes in lipids in RTX treated RA patients were evaluated. METHODS: In 49 consecutive RTX treated RA patients, serum and EDTA plasma samples were collected at baseline, 1, 3 and 6 months. In these samples, lipid and levels were assessed to determine changes in time. Surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) MS analysis was performed in six good and six non-responding RA patients to study functional high density lipoprotein (HDL) protein composition changes in time. RESULTS: In the total group (n=49), the atherogenic index decreased from 4.3 to 3.9 (∼9%) after 6 months. Testing for effect modification revealed a difference in the effect on lipid levels between responders and non-responders upon RTX (p<0.001). ApoB to ApoA-I ratios decreased significantly (∼9%) in good responding (n=32) patients. SELDI-TOF MS analysis revealed a significant decrease in density of mass charge (m/z) marker 11743, representing a decrease in serum amyloid A, in good responding patients. CONCLUSION: This study indicates beneficial effects on cholesterol profile upon RTX treatment along with improvement of disease activity. Proteomic analysis of the HDL particle reveals composition changes from proatherogenic to a less proatherogenic composition during 6 months RTX treatment. Whether these HDL particle alterations during immunotherapies result in a lower CV event rate remains to be established.
Annals of the rheumatic diseases 05/2012; · 8.11 Impact Factor
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Annals of the rheumatic diseases 05/2012; 71(11):1914-5. · 8.11 Impact Factor
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The Journal of Rheumatology 05/2012; 39(5):885-6. · 3.69 Impact Factor
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ABSTRACT: B cell depletion therapy is efficacious in rheumatoid arthritis (RA) patients failing on tumor necrosis factor (TNF) blocking agents. However, approximately 40% to 50% of rituximab (RTX) treated RA patients have a poor response. We investigated whether baseline gene expression levels can discriminate between clinical non-responders and responders to RTX.
In 14 consecutive RA patients starting on RTX (test cohort), gene expression profiling on whole peripheral blood RNA was performed by Illumina® HumanHT beadchip microarrays. Supervised cluster analysis was used to identify genes expressed differentially at baseline between responders and non-responders based on both a difference in 28 joints disease activity score (ΔDAS28 < 1.2) and European League against Rheumatism (EULAR) response criteria after six months RTX. Genes of interest were measured by quantitative real-time PCR and tested for their predictive value using receiver operating characteristics (ROC) curves in an independent validation cohort (n = 26).
Genome-wide microarray analysis revealed a marked variation in the peripheral blood cells between RA patients before the start of RTX treatment. Here, we demonstrated that only a cluster consisting of interferon (IFN) type I network genes, represented by a set of IFN type I response genes (IRGs), that is, LY6E, HERC5, IFI44L, ISG15, MxA, MxB, EPSTI1 and RSAD2, was associated with ΔDAS28 and EULAR response outcome (P = 0.0074 and P = 0.0599, respectively). Based on the eight IRGs an IFN-score was calculated that reached an area under the curve (AUC) of 0.82 to separate non-responders from responders in an independent validation cohort of 26 patients using Receiver Operator Characteristics (ROC) curves analysis according to ΔDAS28 < 1.2 criteria. Advanced classifier analysis yielded a three IRG-set that reached an AUC of 87%. Comparable findings applied to EULAR non-response criteria.
This study demonstrates clinical utility for the use of baseline IRG expression levels as a predictive biomarker for non-response to RTX in RA.
Arthritis research & therapy 04/2012; 14(2):R95. · 4.27 Impact Factor
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ABSTRACT: OBJECTIVE: Data regarding cardiovascular comorbidity and cardiovascular risk factors in patients with psoriatic arthritis (PsA) are limited. To evaluate the cardiovascular risk profile, a systematic literature search was performed to provide an extensive summary of all studies available on cardiovascular risk in PsA.METHODS: Medline, EMBASE and the Cochrane library were searched from January 1966 to April 2011 for English language articles on data concerning cardiovascular diseases and cardiovascular risk factors in PsA. Review articles, case reports and studies on psoriasis alone were excluded.RESULTS: Twenty-eight articles were included in this review. Studies on all-cause mortality revealed mixed results. Available data on cardiovascular disease appeared more consistent, indicating an increased cardiovascular mortality and morbidity in PsA. Commensurate with this, surrogate markers of subclinical atherosclerosis, arterial stiffness and cardiovascular risk factors, for example hypertension, dyslipidaemia, obesity and metabolic-related factors, were more prominent in PsA compared with controls. Suppression of inflammation was linked with a favourable effect on cardiovascular surrogate markers, for example carotid intima media thickness and endothelial dysfunction, in several (un)controlled studies.CONCLUSION: Most studies point towards an increased cardiovascular risk in PsA, broadly on a par with the risk level in rheumatoid arthritis, emphasising the need for similar cardiovascular risk management in both conditions. Further studies are needed to indicate whether inflammatory suppression or modification of traditional cardiovascular risk factors, or both, will reduce cardiovascular risk.
Annals of the rheumatic diseases 04/2012; · 8.11 Impact Factor
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ABSTRACT: Hypothyroidism and inflammatory arthritis tend to coexist, but data on this association are sparse. In terms of cardiovascular risk, this association may have clinical relevance as this coexistence may carry an additional cardiovascular risk. This study calculates, first, the prevalence of hypothyroidism in patients with inflammatory arthritis and, second, the cardiovascular disease (CVD) prevalence rate in patients with either hypothyroidism or inflammatory arthritis, or both.
Data from the Netherlands Information Network of General Practice, a representative Dutch sample of 360,000 registered patients, were used. Prevalence rates of hypothyroidism were calculated, and multilevel logistic regression analyses were used to calculate CVD prevalence rates.
Hypothyroidism prevalence was 6.5% in female patients with arthritis compared to 3.9% in controls (p<0.001). CVD prevalence was 4.3% in patients with hypothyroidism, 5.9% in patients with inflammatory arthritis, 14.3% in patients with hypothyroid inflammatory arthritis and 2.1% in controls. Adjusted CVD prevalence rates were 1.2 (95% CI 0.99 to 1.4) for hypothyroidism, 1.5 (95% CI 1.1 to 2.0) for inflammatory arthritis and 3.7 (95% CI 1.7 to 8.0) for hypothyroid inflammatory arthritis as compared with controls.
These data raise awareness on the coexistence of hypothyroidism and inflammatory arthritis and emphasise the importance of cardiovascular risk management in these patients, particularly when hypothyroidism and inflammatory arthritis coexist.
Annals of the rheumatic diseases 03/2012; 71(7):1216-8. · 8.11 Impact Factor
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ABSTRACT: Ankylosing Spondylitis (AS) is characterised by limitations in physical function. The Bath Ankylosing Spondylitis Functional Index (BASFI) is considered to be the gold-standard to assess physical function in AS patients. However, the BASFI questionnaire is a self-reported outcome measure and susceptible to subjective interpretation (under- or over-estimation). More objective outcome measures, like performance-based tests, could provide an objective outcome measurement for the evaluation of limitations in physical function. Therefore, the primary aim of this study was to determine the association between performance-based measures and the BASFI questionnaire.
In this cross-sectional study 126 AS patients completed the BASFI questionnaire and eight performance-based tests based on BASFI-items. Each test received three scores: one for performance (time or points) and a score for exertion and pain experienced during performance (using modified Borg-scale and VAS 0-100 mm, respectively). Linear regression analyses were used to assess the associations between the BASFI questionnaire and performance-based tests.
The univariable association between performance and BASFI-score was moderate with a R-square of 0.31 and Beta of 0.56 (p's < 0.05). In a multivariable analysis, the association between performance, exertion and pain on the one hand and BASFI-score on the other was assessed; R-square increased to 0.54: the Beta's for exertion and pain during performance were 0.38 and 0.26, respectively; the Beta for performance decreased to 0.19 (p's < 0.05).
This study demonstrates that alongside actual performance, patients seem to incorporate exertion and pain in their assessment of perceived physical function on the BASFI questionnaire. Performance-based tests could provide an objective outcome measurement for the evaluation of physical function and give relevant new information in addition to the BASFI questionnaire.
Arthritis research & therapy 03/2012; 14(2):R52. · 4.27 Impact Factor
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ABSTRACT: There is abundant evidence that rheumatoid arthritis (RA), a chronic inflammatory disorder, is associated with an increased risk for cardiovascular (CV) disease. While there may be several mechanisms contributing to a higher CV risk in RA patients, inflammation is considered to be the main cause explaining the excess CV burden. Inflammatory processes appear pivotal to the atherothrombotic process and are linked to endothelial dysfunction, fatty streak initiation and progression, deterioration of fatty streaks into (unstable) plaques, and plaque rupture. Moreover, systemic inflammation, through tumor necrosis factor (TNF) or related cytokines, appears to accelerate atherothrombosis either directly or via effects on conventional and novel CV risk factors, such as lipids and lipoproteins, blood pressure, haemostatic factors, and insulin resistance. New and highly specific therapeutic agents (TNF inhibitors) may significantly lower CV risk in RA. This review summarizes the evidence base supporting the notion that TNF inhibitors confer benefit CV disease risk in RA.
Current pharmaceutical design 02/2012; 18(11):1502-11. · 4.41 Impact Factor
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Seminars in arthritis and rheumatism 12/2011; 41(4):e6. · 4.72 Impact Factor
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Michael T Nurmohamed
Nature Reviews Rheumatology 08/2011; 7(10):561-2. · 8.39 Impact Factor
