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1.
Artigo em Inglês | MEDLINE | ID: mdl-31628482

RESUMO

OBJECTIVES: 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (statins) are standard treatment for hyperlipidaemia. In addition to lipid-lowering abilities, statins exhibit multiple anti-inflammatory effects. The objectives of this study were to determine whether treatment of patients with RA with lovastatin decreased CRP or reduced disease activity. METHODS: We conducted a randomized double-blind placebo-controlled 12 week trial of lovastatin vs placebo in 64 RA patients with mild clinical disease activity but an elevated CRP. The primary efficacy end point was the reduction in mean log CRP. Secondary end points included disease activity, RF and anti-CCP antibody titres. Mechanistic end points included levels of serum cytokines. Safety was assessed; hepatic and muscle toxicities were of particular interest. RESULTS: Baseline features were similar between groups. No significant difference in mean log CRP reduction between the two groups was observed, and disease activity did not change from baseline in either treatment group. Mechanistic analyses did not reveal significant changes in any biomarkers. A post hoc analysis of subjects not using biologic therapy demonstrated a significantly greater proportion achieving ⩾20% reduction in CRP from baseline in the lovastatin group compared with placebo (P-value = 0.007). No difference was observed in subjects receiving biologics. Lovastatin was well tolerated with no serious safety concerns. CONCLUSION: This study showed no anti-inflammatory or clinical effects on RA disease activity after 12 weeks of treatment with lovastatin. Lovastatin had a modest effect on CRP in subjects not using biologics, suggesting statins may be anti-inflammatory in selected patients. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT00302952.

2.
Case Rep Nephrol Dial ; 9(1): 42-48, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192227

RESUMO

Crescentic glomerulonephritis (GN) without immune reactants or deposits (referred to as pauci-immune) is typically characterized by the presence of anti-neutrophilic cytoplasmic antibodies (ANCA). While ANCA-negative patients might be expected to have a more benign course, they often have poor renal outcomes, especially without treatment with steroids and immune-modulating therapy. Pauci-immune crescentic GN can also co-exist with other autoimmune conditions, including rheumatoid arthritis (RA). Here, we describe an ANCA-negative patient with RA who developed dialysis-requiring acute kidney injury (AKI) with findings consistent with focal pauci-immune crescentic GN (i.e., no IgG or immune complex on kidney biopsy). Coexistent conditions included Klebsiella sepsis attributed to pneumonia, rhabdomyolysis, leukocytoclastic immune-mediated skin vasculitis, and positive ANA. He had spontaneous improvement in renal function without immunosuppressive therapy. This crescentic GN was not associated with poor renal outcome as AKI resolved with supportive care and treatment of his infection. The AKI was likely multifactorial with co-existing acute tubular necrosis in the setting of Kebsiella sepsis and rhabdomyolysis, and the crescentic GN was felt more likely to be related to the infection rather than having a primary role. This case highlights the importance of viewing crescentic GN in the context of the clinical picture, as it may not always lead to the need of aggressive immune suppression and is not a universally poor prognostic kidney finding. However, these cases do warrant close follow-up as our patient had recurrent RA disease manifestations over the next 2 years that eventually led to his death from severe pulmonary hypertension.

3.
Arthritis Rheumatol ; 71(9): 1426-1436, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30883031

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) patients with the lowest circulating low-density lipoprotein (LDL) concentrations are at heightened risk of cardiovascular events. However, the atherosclerosis burden within this subgroup is unknown. METHODS: RA patients pooled from 4 cohort studies of cardiovascular disease (CVD; n = 546) were compared with non-RA controls from the Multi-Ethnic Study of Atherosclerosis (n = 5,279). Those taking lipid-lowering medications were excluded. Differences in cardiac computed tomography-derived Agatston coronary artery calcium (CAC) scores between the RA and control groups were compared across strata of LDL concentration. RESULTS: Among those with low LDL concentrations (<70 mg/dl), mean adjusted CAC scores were >4-fold higher for RA patients than for controls (18.6 versus 4.6 Agatston units, respectively; P < 0.001), a difference significantly greater than that in any other LDL concentration stratum except LDL concentration ≥160 mg/dl. Similarly, 32% of the RA patients with low LDL concentration had a CAC score of ≥100 Agatston units compared with only 7% of controls in the same LDL concentration stratum (odds ratio 5.97; P < 0.001), a difference significantly greater than that in all of the other LDL concentration strata. Low LDL concentration was most strongly associated with higher CAC score among RA patients who were white, had ever smoked, or were not obese. Other than a higher frequency of current smokers, RA patients with low LDL concentrations did not have more CVD risk factors or higher measures of RA disease activity or severity than RA patients with higher LDL concentrations. CONCLUSION: RA patients with low LDL concentration may represent a group for whom heightened screening and prevention of atherosclerotic CVD is appropriate.

4.
Arthritis Rheumatol ; 69(3): 529-541, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27696788

RESUMO

OBJECTIVE: Coronary artery disease (CAD) in the general population is characterized by an increased frequency of particular susceptibility single-nucleotide polymorphisms (SNPs). Because the frequency of CAD is increased among patients with rheumatoid arthritis (RA), we sought to determine whether the frequency of these SNPs is increased in RA patients with CAD, hypothesizing that RA could enhance CAD risk by acting through established genetic pathways predisposing to CAD. METHODS: Coronary artery calcification (CAC) as detected by computed tomography was used as a measure of CAD in 561 patients with RA. One hundred SNPs associated with CAD in the general population were genotyped or imputed, and their relationship to CAC was established through multiple regression analysis for individual SNPs and a genetic risk score representing their cumulative effect. RESULTS: Ninety-one CAD-related SNPs were genotyped successfully; of these, 81 exhibited no association with CAC (Agatston units) or different CAC categorizations, either individually or collectively, in the genetic risk score. Only rs579459 (ABO) and rs17676451 (HAL) had a consistent positive association between genotype and CAC, with a significant increase in the frequency of the effect allele in both homozygous and heterozygous genotype distributions. Five were variably negatively associated. Furthermore, a positive association between the Disease Activity Score in 28 joints and CAC was observed, and after adjustment for traditional cardiovascular risk factors, it was not modified by correcting for the CAD-related SNP genetic risk score. CONCLUSION: The increased risk of CAC in patients with RA does not appear to operate primarily through established genetically regulated atherogenic mechanisms that are preponderant in the general population.


Assuntos
Alelos , Artrite Reumatoide/complicações , Artrite Reumatoide/genética , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Polimorfismo de Nucleotídeo Único , Calcificação Vascular/complicações , Calcificação Vascular/genética , Artrite Reumatoide/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Calcificação Vascular/epidemiologia
5.
J Am Heart Assoc ; 5(1)2016 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-26727968

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA) patients. This study is the first to report the association of hydroxychloroquine (an antirheumatic medication that has been associated with decreased risk of diabetes, a less atherogenic lipid profile, and antithrombotic properties) with CVD in RA. METHODS AND RESULTS: A retrospective incident RA cohort from January 1, 2001, to October 31, 2013, excluding patients with CVD prior to RA diagnosis, was constructed. Patients were categorized as hydroxychloroquine users versus nonusers and were allowed to contribute time to either group according to hydroxychloroquine exposure. The primary outcome was adjudicated incident CVD defined as a composite of coronary artery disease, stroke, transient ischemic attack, sudden cardiac death, and peripheral artery disease with arterial revascularization procedure. The secondary outcome was a composite of incident coronary artery disease, stroke, and transient ischemic attack. Cox time-varying regression models were used to estimate the association between hydroxychloroquine exposure and development of CVD, after adjusting for propensity score and relevant confounders, including demographics, CVD-related comorbidities, RA severity, and activity indicators and medications. We included 1266 RA patients, 547 hydroxychloroquine users, and 719 nonusers. During the observation period, 102 CVD events occurred, 3 in hydroxychloroquine users and 99 in nonusers. The fully adjusted Cox model showed a hazard ratio of 0.28 (95% CI 0.12-0.63, P=0.002) for incident CVD and 0.30 (95% CI 0.13-0.68, P=0.004) for incident composite coronary artery disease, stroke, and transient ischemic attack for hydroxychloroquine users versus nonusers, respectively. CONCLUSION: In this hypothesis-generating study, hydroxychloroquine use was associated with a 72% decrease in the risk of incident CVD in RA patients. If these preliminary results are confirmed in larger studies, our findings may be used as a rationale for a randomized study of hydroxychloroquine use for primary prevention of CVD in RA or nonrheumatic high-risk patients.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Hidroxicloroquina/uso terapêutico , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Comorbidade , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Pontuação de Propensão , Modelos de Riscos Proporcionais , Fatores de Proteção , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
6.
Case Rep Med ; 2016: 7649510, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28042297

RESUMO

Secondary amyloidosis can complicate chronic inflammatory autoimmune diseases. However, the clinical findings of primary amyloidosis may mimic those of primary rheumatologic disorders. We present the case of a 53-year-old woman who presented with dystrophic nail changes, dry eyes, bilateral carpal tunnel syndrome, Raynaud's phenomenon, and high titer positive nucleolar pattern antinuclear antibody. She was initially misdiagnosed as having Undifferentiated Connective Tissue Disease (UCTD). On further workup, she was eventually diagnosed with lambda light chain systemic amyloidosis by abdominal fat pad biopsy. Her symptoms completely resolved after autologous stem cell transplantation. With this case, we would like to highlight the similarities in the clinical features between light chain amyloidosis and rheumatological disorders. We would also like to emphasize the importance of the prompt recognition of the clinical features of amyloidosis which are crucial to triggering appropriate diagnostic procedures, since early diagnosis is a key to improving outcomes in this disease with an otherwise poor prognosis.

7.
Diabetologia ; 58(10): 2336-43, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26197707

RESUMO

AIMS/HYPOTHESIS: Hydroxychloroquine (HCQ), an antimalarial drug with anti-inflammatory properties, is employed in rheumatic diseases. In observational studies, patients with rheumatic diseases treated with HCQ have a lower risk of developing diabetes. However, the physiological mechanisms remain unexplained. We hypothesised that HCQ may have favourable effects on insulin sensitivity and/or beta cell function. METHODS: This was a randomised, double-blind, parallel-arm (placebo vs HCQ 400 mg/day) trial at the University of Pittsburgh. Randomisation was conducted by a computer system with concealment by sealed envelopes. Treatment duration was 13 ± 1 weeks. Randomised participants (HCQ n = 17; placebo n = 15) were non-diabetic volunteers, age >18, overweight or obese, with one or more markers of insulin resistance. All participants were included in intention-to-treat analysis. Outcomes were changes in insulin sensitivity and beta cell function measured by intravenous glucose tolerance tests and minimal model analysis. RESULTS: There was a positive change in insulin sensitivity with HCQ but not placebo (mean ± SEM: +20.0% ± 7.1% vs -18.4% ± 7.9%, respectively; p < 0.01; difference: 38.3% ± 10.6%; 95% CI: 17%, 60%). Improvement in beta cell function was also observed with HCQ but not placebo (+45.4% ± 12.3% vs -19.7% ± 13.6%; p < 0.01; difference: 65% ± 19%; 95% CI: 27%, 103%). There were modest treatment effects on fasting plasma glucose and HbA(1c) (p < 0.05) but circulating markers of inflammation (IL-6, IL-1, TNF-α, soluble intercellular adhesion molecule) were not affected in either group. In contrast, adiponectin levels increased after HCQ treatment but not after placebo (+18.7% vs +0.7%, respectively; p < 0.001). Both low- and high-molecular-weight adiponectin forms accounted for the increase. There were no serious or unexpected adverse effects. CONCLUSIONS/INTERPRETATION: HCQ improves both beta cell function and insulin sensitivity in non-diabetic individuals. These metabolic effects may explain why HCQ treatment is associated with a lower risk of type 2 diabetes. An additional novel observation is that HCQ improves adiponectin levels, possibly being a mediator of the favourable effects on glucose metabolism. Our findings suggest that HCQ is a drug with considerable metabolic effects that warrant further exploration in disorders of glucose metabolism. TRIAL REGISTRATION: Clinicaltrials.gov NCT01326533 FUNDING: This study was funded by National Institutes of Health no. 5R21DK082878, UL1-RR024153 and UL-1TR000005.


Assuntos
Hidroxicloroquina/farmacologia , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/efeitos dos fármacos , Sobrepeso/metabolismo , Adulto , Glicemia/metabolismo , Citocinas/sangue , Método Duplo-Cego , Feminino , Humanos , Insulina/sangue , Células Secretoras de Insulina/metabolismo , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/metabolismo , Sobrepeso/sangue , Resultado do Tratamento
8.
Rheumatol Int ; 35(6): 1059-67, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25540049

RESUMO

The aim of this article was to examine the association of glucocorticoid use and dose and changes in the lipid profile in rheumatoid arthritis (RA) patients. RA patients between January 1, 2001, and November 30, 2011, who received oral or intravenous glucocorticoids and who had lipid levels within 1 year before and 1 year after ongoing (at least 3 months) glucocorticoids use along with RA patients who did not take glucocorticoids (controls) were included. Glucocorticoid exposure was calculated as a weighted daily dose in prednisone equivalents and analyzed using as cutoff dose prednisone equivalent of 7.5 mg/day. Outcomes were changes in high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), triglycerides, and TC/HDL ratio and were calculated in linear regression models adjusting for relevant confounders. In total, 202 subjects on glucocorticoids and 436 controls were included. The glucocorticoid group of ≥7.5 mg/day had the greatest increase in HDL of 6.0 mg/dL (p = 0.003 compared to controls) with lower increases of 3.1 and 2.4 mg/dL in the glucocorticoid group of <7.5 mg/day and controls, respectively. There were no significant differences in other parameters of the lipid profile between the two glucocorticoid groups and controls. In this RA cohort, glucocorticoid dose equivalent of prednisone ≥7.5 mg/day was associated with increased HDL and no change in LDL or TC/HDL ratio compared to no glucocorticoid use These results suggest that this glucocorticoid dose is not associated with an atherogenic lipid profile in RA, a finding that is important in this patient population at high risk for cardiovascular disease.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/administração & dosagem , Lipoproteínas HDL/sangue , Prednisona/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Esquema de Medicação , Registros Eletrônicos de Saúde , Glucocorticoides/efeitos adversos , Humanos , Prednisona/efeitos adversos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
9.
Cleve Clin J Med ; 81(2): 115-27, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24493494

RESUMO

Tumor necrosis factor (TNF) inhibitors have many beneficial effects, but they also pose infrequent but significant risks, including serious infection and malignancy. These risks can be minimized by judicious patient selection, appropriate screening, careful monitoring during treatment, and close communication between primary care physicians and subspecialists.


Assuntos
Antirreumáticos/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Fármacos Gastrointestinais/efeitos adversos , Neoplasias/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Doenças Autoimunes/induzido quimicamente , Doenças Cardiovasculares/induzido quimicamente , Doenças Desmielinizantes/induzido quimicamente , Humanos
10.
Ann Rheum Dis ; 73(1): 161-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23300117

RESUMO

OBJECTIVES: To assess the effect of golimumab, with or without methotrexate (MTX), on serum lipids and inflammatory markers of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) in two phase 3, randomised, placebo-controlled trials (GO-BEFORE and GO-FORWARD). METHODS: Patients in GO-BEFORE (n=637, MTX-naïve) and GO-FORWARD (n=444, MTX-inadequate response) were randomised to placebo+MTX, golimumab 100 mg+placebo, golimumab 50 mg+MTX, or golimumab 100 mg+MTX. Subcutaneous injections (placebo and golimumab) were given every 4 weeks. Patients with an insufficient response entered early escape at week 16 (GO-FORWARD) or 28 (GO-BEFORE). All placebo+MTX patients in GO-FORWARD crossed over to golimumab 50 mg+MTX at week 24. Changes from baseline to weeks 14 (GO-FORWARD) or 24 (GO-BEFORE), and 52 in serum lipid levels and inflammatory markers were assessed. RESULTS: At week 14 in the GO-FORWARD trial, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) increased in golimumab+MTX patients versus MTX-only patients (16.00 vs 2.00 (p<0.001); 3.00 vs 0.00 (p<0.05); 8.00 vs 4.00 (p<0.001); respectively); favourable changes in LDL subfractions were only observed in golimumab-treated patients. At week 24 in GO-BEFORE, TC and LDL increased, and LDL subfractions improved in the MTX-only and golimumab+MTX groups. Inflammatory markers of CVD risk improved significantly with golimumab+MTX versus placebo+MTX in both studies and were generally maintained through week 52. Atherogenic indices were generally stable. CONCLUSIONS: While TC and LDL levels increased mildly in RA patients receiving golimumab+MTX, atherogenic indices generally remained stable, favourable changes in LDL subfractions were observed, and inflammatory markers improved.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Metotrexato/administração & dosagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Biomarcadores/sangue , Quimioterapia Combinada , Feminino , Humanos , Lipídeos/sangue , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Placebos , Resultado do Tratamento
11.
J Clin Rheumatol ; 20(1): 1-10, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24356481

RESUMO

OBJECTIVE: The objective of this study was to assess the effect of golimumab on carotid ultrasound measures and cardiovascular serious adverse events (SAEs) in patients with inflammatory arthritides. METHODS: An exploratory carotid artery ultrasound substudy was performed in the GO-BEFORE study of methotrexate (MTX)-naive rheumatoid arthritis patients, with ultrasounds performed at weeks 0, 24, and 52 to measure common carotid artery intima-media thickness, distensibility coefficient, interadventitial diameter, and plaque count. Cardiovascular SAEs reported over 2 years of follow-up were assessed in 5 golimumab phase 3 clinical trials of patients with rheumatoid arthritis (GO-BEFORE, GO-FORWARD, and GO-AFTER), psoriatic arthritis (GO-REVEAL), and ankylosing spondylitis (GO-RAISE). In GO-BEFORE and GO-FORWARD, patients received placebo + MTX, golimumab 50 mg + MTX, or golimumab 100 mg +/- MTX at baseline and every 4 weeks; in the other 3 trials, patients received placebo or golimumab 50 or 100 mg. RESULTS: The carotid ultrasound substudy showed inconsistent changes in common carotid artery intima-media thickness in the golimumab + MTX groups over time, and there was large variability in the measurements. Increases in interadventitial diameter were observed in the golimumab 100 mg + placebo group, but not in the golimumab + MTX groups. There were no significant differences in the distensibility coefficient and plaque count between the golimumab and placebo groups. Very few patients overall experienced a cardiovascular SAE, and the incidence of cardiovascular SAEs was not statistically different between the golimumab and placebo groups. CONCLUSIONS: The results of the carotid ultrasound substudy were inconclusive, and no increase or decrease in cardiovascular SAEs was observed following 2 years of treatment with golimumab with or without MTX.


Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Artrite/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Artérias Carótidas/efeitos dos fármacos , Doenças das Artérias Carótidas/epidemiologia , Espessura Intima-Media Carotídea , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/uso terapêutico , Doenças Cardiovasculares/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Incidência , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Ultrassonografia de Intervenção
12.
Arthritis Care Res (Hoboken) ; 66(3): 355-63, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24023053

RESUMO

OBJECTIVE: To determine the association of tumor necrosis factor α (TNFα) inhibitors with risk for cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients. METHODS: A retrospective cohort of 2,101 incident RA patients was established. Medication exposure was categorized into the following groups: TNFα inhibitors alone or in combination with methotrexate (MTX; aTNF group); MTX alone or in combination with other nonbiologic disease-modifying antirheumatic drugs (DMARDs; MTX group); and no MTX, nonbiologic DMARDs (reference group). Primary outcome was adjudicated incident coronary artery disease (CAD), defined as myocardial infarction, unstable angina, or coronary revascularization procedure. Secondary outcome was adjudicated incident CVD, defined as a composite of CAD, stroke, transient ischemic attack, abdominal aortic aneurysm, peripheral arterial disease, or arterial revascularization procedure. Cox regression models were used to calculate the hazard ratio for CAD and CVD for the aTNF and MTX groups compared to the reference group. RESULTS: There were 46 incident CAD and 82 incident CVD events. Adjusting for covariates associated with CAD and CVD, the hazard ratio for incident CAD was 0.45 (95% confidence interval [95% CI] 0.21-0.96) for the aTNF group and 0.54 (95% CI 0.27-1.09) for the MTX group compared to the reference group. Use of TNFα inhibitors for >16.1 months was associated with a relative risk for CAD of 0.18 (95% CI 0.06-0.50) and for CVD of 0.31 (95% CI 0.15-0.65) compared to the reference group. A similar, although not significant, trend was seen with the MTX group. CONCLUSION: Use of TNFα inhibitors is associated with a decreased risk for CAD in RA; the risk decreases further with long-term use. This should be considered when weighing the risks versus benefits of these medications.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doença da Artéria Coronariana/prevenção & controle , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Antirreumáticos/farmacologia , Artrite Reumatoide/complicações , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Rheumatology (Oxford) ; 52(10): 1845-55, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23838027

RESUMO

OBJECTIVE: To evaluate the effect of golimumab on haemoglobin levels in patients with RA, PsA or AS. METHODS: Secondary analysis was performed on integrated data from five randomized controlled studies: three RA, one PsA and one AS (2303 patients total). Golimumab 50 or 100 mg was injected s.c. every 4 weeks with or without MTX. Control groups received placebo injections plus MTX or background therapy. Patients with haemoglobin levels below the age- and sex-specific normal ranges were considered to have anaemia. Ferritin levels were used to distinguish anaemia of mixed aetiology (≥ 15 and <60 ng/ml) and anaemia of inflammation (≥ 60 ng/ml). Changes from baseline to weeks 14 and 24 in haemoglobin level were compared between treatment groups using an analysis of variance on the van der Waerden normal scores. RESULTS: At baseline, 21% of RA patients, 9% of PsA patients and 15% of AS patients had anaemia. Of these, 24%, 57% and 25%, respectively, had anaemia of inflammation. The median increase from baseline to week 14 in the haemoglobin level of anaemic patients was 0.3 g/dl in the control group and 0.9 g/dl in the golimumab group (P < 0.001). Haemoglobin levels improved within the subgroups of patients with anaemia of mixed aetiology (control, 0.4 g/dl vs golimumab, 0.7 g/dl) (P = 0.305) and with anaemia of inflammation (0.2 vs 1.4 g/dl, respectively) (P < 0.001). CONCLUSION: Compared with the control group, patients receiving golimumab treatment had significantly improved haemoglobin levels, particularly among patients with anaemia of inflammation.


Assuntos
Anticorpos Monoclonais/farmacologia , Antirreumáticos/farmacologia , Artrite/sangue , Hemoglobinas/efeitos dos fármacos , Adulto , Anemia/tratamento farmacológico , Anemia/etiologia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Artrite/complicações , Artrite/tratamento farmacológico , Artrite Psoriásica/sangue , Artrite Psoriásica/complicações , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Proteína C-Reativa/metabolismo , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Hemoglobinas/metabolismo , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Espondilite Anquilosante/sangue , Espondilite Anquilosante/complicações , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
15.
Arthritis Rheum ; 65(7): 1719-24, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23553485

RESUMO

OBJECTIVE: To investigate whether citrullinated proteins within the atherosclerotic plaque can be targeted by anti-citrullinated protein antibodies (ACPAs), forming stimulatory immune complexes that propagate the progression of atherosclerosis. METHODS: Protein lysates prepared from atherosclerotic segments of human aorta were assessed for the presence of citrulline-modified proteins, and specifically citrullinated fibrinogen (Cit-fibrinogen), by immunoprecipitation and/or immunoblotting followed by mass spectrometry. Immunohistochemical analysis of coronary artery plaque was performed to determine the presence of citrullinated proteins and peptidylarginine deiminase type 4 (PAD-4). Serum levels of anti-cyclic citrullinated peptide (anti-CCP), anti-citrullinated vimentin (anti-Cit-vimentin), and anti-Cit-fibrinogen antibodies were measured in 134 women with seropositive rheumatoid arthritis; these subjects had previously been characterized for the presence of subclinical atherosclerosis, by electron beam computed tomography scanning. RESULTS: Western blot analysis of atherosclerotic plaque lysates demonstrated several citrullinated proteins, and the presence of Cit-fibrinogen was confirmed by immunoprecipitation and mass spectrometry. Immunohistochemical analysis showed colocalization of citrullinated proteins and PAD-4 within the coronary artery plaque. In age-adjusted regression models, antibodies targeting Cit-fibrinogen and Cit-vimentin, but not CCP-2, were associated with an increased aortic plaque burden. CONCLUSION: Citrullinated proteins are prevalent within atherosclerotic plaques, and certain ACPAs are associated with the atherosclerotic burden. These observations suggest that targeting of citrullinated epitopes, specifically Cit-fibrinogen, within atherosclerotic plaques could provide a mechanism for the accelerated atherosclerosis observed in patients with RA.


Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Placa Aterosclerótica/imunologia , Idoso , Complexo Antígeno-Anticorpo/imunologia , Aortografia , Artrite Reumatoide/metabolismo , Western Blotting , Calcinose/diagnóstico por imagem , Calcinose/imunologia , Citrulina/imunologia , Citrulina/metabolismo , Eletroforese em Gel de Poliacrilamida , Feminino , Fibrinogênio/imunologia , Fibrinogênio/metabolismo , Humanos , Hidrolases/metabolismo , Imunoensaio , Masculino , Peptídeos Cíclicos/imunologia , Placa Aterosclerótica/metabolismo , Desiminases de Arginina em Proteínas , Análise de Regressão , Vimentina/imunologia , Vimentina/metabolismo
16.
Arthritis Care Res (Hoboken) ; 65(6): 986-91, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23213026

RESUMO

OBJECTIVE: Persons with systemic lupus erythematosus (SLE) are at an increased risk of cardiovascular disease (CVD) events, but this excess CVD burden in the perioperative setting is yet to be determined. We aimed to determine the risk of perioperative short-term all-cause mortality and CVD events among women with SLE compared to those without SLE. METHODS: We conducted a cross-sectional analysis of pooled hospital discharge data of the Nationwide Inpatient Sample from 1998-2002. We abstracted diseases and procedures using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The principal procedure was categorized into either a low, intermediate, or high risk level. Survey logistic regression adjusting for potential confounders provided estimates for stratum-specific odds of adverse events in women with SLE relative to those without SLE for each procedure risk level. RESULTS: All-cause mortality was significantly greater among women with SLE having a low- (odds ratio [OR] 1.54, 95% confidence interval [95% CI] 1.00-2.37) or a high-risk principal procedure (OR 2.52, 95% CI 1.34-4.75) relative to women without SLE, but did not differ significantly among persons with intermediate-risk procedures. Women with SLE with a low-risk procedure were also more likely to experience a composite CVD event relative to women without SLE (OR 1.40, 95% CI 1.04-1.87). CONCLUSION: Women with SLE are at an increased risk for short-term perioperative adverse events. These results highlight a need for greater scrutiny during perioperative evaluation and management of women with SLE.


Assuntos
Doenças Cardiovasculares/epidemiologia , Procedimentos Cirúrgicos Eletivos/mortalidade , Lúpus Eritematoso Sistêmico/complicações , Período Perioperatório , Idoso , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Alta do Paciente/estatística & dados numéricos , Fatores de Risco , Fatores de Tempo
17.
Arthritis Rheum ; 65(2): 334-42, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23044791

RESUMO

OBJECTIVE: While medications used to treat rheumatoid arthritis (RA) may affect survival in RA, few studies take into account the propensity for medication use, which may reflect selection bias in treatment allocation in survival models. We undertook this study to examine the relationship between methotrexate (MTX) use and mortality in RA, after controlling for individual propensity scores for MTX use. METHODS: We studied 5,626 RA patients prospectively for 25 years to determine the risk of death associated with MTX use, modeled in time-varying Cox regression models. We used the random forest method to generate individual propensity scores for MTX use at study entry and during followup in a time-varying manner; these scores were included in the multivariate model. We also investigated whether selective discontinuation of MTX immediately prior to death altered the risk of mortality, and we examined the association of duration of MTX use with survival. RESULTS: During followup, 666 patients (12%) died. MTX use was associated with reduced risk of death (adjusted hazard ratio 0.30 [95% confidence interval 0.09-1.03]). Selective MTX cessation immediately before death did not account for the protective association of MTX use with mortality. Only MTX use for >1 year was associated with lower risks of mortality, but associations were not stronger with longer durations of use. CONCLUSION: MTX use was associated with a 70% reduction in mortality in RA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/mortalidade , Metotrexato/uso terapêutico , Adulto , Idoso , Artrite Reumatoide/tratamento farmacológico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
18.
J Rheumatol ; 39(5): 946-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22467937

RESUMO

OBJECTIVE: To determine the association of use of tumor necrosis factor-α (TNF-α) inhibitors with differences in lipid levels in patients with rheumatoid arthritis (RA). METHODS: We studied 807 patients with incident RA to compare differences in lipid levels in TNF-α inhibitor users versus nonusers, with adjustment for relevant covariables. RESULTS: TNF-α inhibitor use was not associated with differences in levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides, LDL:HDL, or TC:HDL compared to nonusers. CONCLUSION: Use of TNF-α inhibitor was not associated with differences in lipid levels in patients with RA.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Metabolismo dos Lipídeos/fisiologia , Metotrexato/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso , Antirreumáticos/uso terapêutico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Triglicerídeos/sangue
19.
Arthritis Rheum ; 64(8): 2429-37, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22354534

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) burden similar to that of diabetes mellitus (DM). This risk may warrant preoperative CV assessment as is performed for patients with DM. We aimed to determine whether the risks of perioperative death and CV events among patients with RA differed from those among unaffected controls and patients with DM. METHODS: We used 1998-2002 data from the Nationwide Inpatient Sample (NIS) database of the Healthcare Cost Utilization Project (HCUP) to identify hospitalizations of patients undergoing elective noncardiac surgery. Using established guidelines, surgical procedures were categorized as either low risk, intermediate risk, or high risk of having CV events. Logistic models provided the adjusted odds of study end points in patients with RA, DM, or both relative to patients with neither condition. RESULTS: Among 7,756,570 patients undergoing a low-risk, intermediate-risk, or high-risk noncardiac procedure, 2.34%, 0.51%, and 2.12%, respectively, had a composite CV event, and death occurred in 1.47%, 0.50%, and 2.59%, respectively. Among those undergoing an intermediate-risk procedure, death was less likely in RA patients than in DM patients (0.30% versus 0.65%; P < 0.001), but the difference in mortality rates among those undergoing low-risk versus high-risk procedures was not significant. Patients with RA were less likely to have a CV event than were patients with DM for procedures of low risk (3.38% versus 5.30%; P < 0.001) and intermediate risk (0.34% versus 1.07%; P < 0.001). In adjusted models, RA was not independently associated with an increased risk of perioperative death or a CV event. CONCLUSION: RA was not associated with adverse perioperative CV risk or mortality risk, which suggests that current perioperative clinical care does not need to be changed in this regard.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/epidemiologia , Complicações do Diabetes/complicações , Complicações do Diabetes/epidemiologia , Período Perioperatório/mortalidade , Idoso , Causas de Morte , Comorbidade , Estudos Transversais , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
20.
Arthritis Care Res (Hoboken) ; 64(2): 215-21, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21972198

RESUMO

OBJECTIVE: To examine the association of tumor necrosis factor α (TNFα) inhibitor use and the risk of developing diabetes mellitus in a rheumatoid arthritis (RA) inception cohort. METHODS: Adults diagnosed with RA between January 1, 2001, and December 31, 2009, were identified (n = 1,881). Prevalent cases of diabetes mellitus (n = 294) were excluded. Information on sociodemographic data, medical history, body mass index (BMI), laboratory measures, and medications was collected from the electronic health record. Incident diabetes mellitus was defined using the 2010 American Diabetes Association criteria or physician-established diagnosis. Time-varying Cox proportional hazards regression models were used to adjust for age, sex, race, BMI, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP), erythrocyte sedimentation rate (ESR), and use of nonsteroidal antiinflammatory drugs (NSAIDs), glucocorticoids, hydroxychloroquine, and methotrexate. RESULTS: A total of 1,587 incident RA patients without diabetes mellitus were included. The anti-TNFα users (n = 522) had a lower median age but greater baseline BMI; maximum ESR, RF, and anti-CCP positivity; and NSAID, glucocorticoid, or methotrexate use. The median followup time for the ever and never TNFα inhibitor users was 44.9 months (interquartile range [IQR] 23.7-73.0 months) and 37.1 months (IQR 16.3-65.1 months), respectively (P < 0.001). Of the 91 patients developing diabetes mellitus, 16 were ever and 75 were never TNFα inhibitor users, yielding incidence rates of 8.6 and 17.2 per 1,000 person-years (P = 0.048), respectively. Adjusting for covariates, the hazard ratio for incident diabetes mellitus in TNFα inhibitor users was 0.49 (95% confidence interval 0.24-0.99, P = 0.049) compared to the never users. CONCLUSION: In this inception RA cohort, anti-TNFα use was associated with a 51% reduction in risk of developing diabetes mellitus.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Comorbidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco
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