Tumor necrosis factor-α blockade, cardiovascular outcomes, and survival in rheumatoid arthritis

doi:10.1016/j.trsl.2010.09.005

Translational Research

Volume 157, Issue 1, January 2011, Pages 10-18

https://doi.org/10.1016/j.trsl.2010.09.005 Get rights and content

The effect of TNF-α blockade on the risk of cardiovascular outcomes and long-term survival in patients with rheumatoid arthritis (RA) is not known. We assembled a cohort of 20,811 (75,329 person-years) U.S. veterans who were diagnosed with RA between October 1998 and September 2005, and who were treated with a disease-modifying anti-rheumatic drug (DMARD). Cox survival models were built to examine the effect of TNF-α antagonists on the risk of a composite endpoint of cardiovascular outcomes defined as the occurrence of atherosclerotic heart disease, congestive heart failure, peripheral artery disease, or cerebrovascular disease, and on the risk of death. Treatment with TNF-α antagonists was not associated with a significant effect on the composite endpoint of cardiovascular outcomes. When each outcome was examined separately, the use TNF-α antagonists was not associated with an increased risk of atherosclerotic heart disease, congestive heart failure, or peripheral artery disease, but it was associated with decreased risk of cerebrovascular disease (hazard ratio [HR] = 0.83; confidence interval [CI] = 0.70–0.98). The use of TNF-α antagonists did not affect the risk of death (HR = 0.99; CI = 0.87–1.14). In subgroup analyses, the use TNF-α antagonists was associated with a reduced risk of cardiovascular outcomes (HR = 0.90, CI = 0.83–0.98) in patients younger than the median age of our cohort (63 years). The use TNF-α antagonists was not associated with a change in the risk of death in any other subgroup. These results show that the risk of cardiovascular events and survival in patients who receive TNF-α antagonists is not different than those who receive other DMARDs.

Section snippets

Study population

We built a cohort of 20,811 U.S. veterans who were diagnosed with RA between October 1998 and September 2005. Patients were included in the cohort if they had an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for RA during the study period and who, after ≥4-month history of receiving medications from the Veterans Administration (VA) during the study period, subsequently received a first prescription of DMARD. Prior experience demonstrates that

Results

The total number of patients who met our diagnostic criteria for RA between October 1998 and September 2005 was 20,811 (75,329 person years). Among those, 19,899 (65,766 person years) individuals received nonbiologic DMARDs and 3796 (9563 person years) individuals received TNF-α antagonists at some time during the study period. The demographic and clinical characteristics of these groups are presented in Table I.

In univariate analyses, the patients treated with TNF-α antagonists were younger

Discussion

In this study, we show that long-term exposure to TNF-α antagonists has no significant effect on combined cardiovascular outcomes or all-cause mortality. Interestingly, we found a decreased risk of cardiovascular events associated with the use of TNF-α antagonists in patients who were younger than 63 years old, and patients treated with TNF-α antagonists had decreased risk of cerebrovascular disease.

The effect of TNF-α blockade on the risk atherosclerotic heart disease, peripheral artery

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The role of registries in the treatment of rheumatoid arthritis with biologic disease-modifying anti-rheumatic drugs
2019, Pharmacological Research
Citation Excerpt :
Serious infections and insufficient treatment of cardiovascular diseases were identified as independent drivers of stroke risk in RABBIT [115]. In a cohort of 20811 U.S.A. veterans, treatment with TNFi was not associated with an increased risk of atherosclerotic heart disease, congestive heart failure, or peripheral artery disease, but it was associated with decreased risk of cerebrovascular disease [116]. This is in keeping with data from the BSRBR [117].
Registries characterize the effectiveness and safety of therapeutic interventions in daily clinical practice. Data from registries enable mining the records of tens of thousands of patients towards determining the effectiveness, safety, and cost-benefit of any given therapeutic. The strengths of registries include real-life settings, greater power than clinical trials to detect rare events, and the study of multiple outcomes and several research questions. Registries also have their weaknesses. They are expensive, less accurate than clinical trials, affected by channelling bias, often require links to external sources or use historic and selected control cohorts or combine datasets to increase power, and have the risk of multiple confounders. Since the beginning of biological era, registries were developed to profile emerging treatments. This article reviews the role of registries in the treatment of rheumatoid arthritis with biologic disease-modifying anti-rheumatic drugs.
Treatment of rheumatoid arthritis with biologic agents lowers the risk of incident chronic kidney disease
2018, Kidney International
Citation Excerpt :
Information about RA disease activity measures such as the Clinical Disease Activity Index and Disease Activity Score, as well as the erythrocyte sedimentation rate and C-reactive protein values, were not available in this cohort. Instead, we included the number of various RA-related articular procedures as a measure of RA severity, as reported previously.33–36 Finally, as with all observational studies, we cannot eliminate the possibility of unmeasured confounders.
Rheumatoid arthritis is associated with reduced kidney function, possibly due to chronic inflammation or the use of nephrotoxic therapies. However, little is known about the effects of using the newer novel non-nephrotoxic biologic agents on the risk of incident chronic kidney disease (CKD). To study this we used a cohort of 20,757 United States veterans diagnosed with rheumatoid arthritis with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m² or more, recruited between October 2004 and September 2006, and followed through 2013. The associations of biologic use with incident CKD (eGFR under 60 with a decrease of at least 25% from baseline, and eGFR under 45 mL/min/1.73m²) and change in eGFR (<-3, -3 to <0 [reference], and ≥0 mL/min/1.73m²/year) were examined in propensity-matched patients based on their likelihood to initiate biologic treatment, using Cox models and multinomial logistic regression models, respectively. Among 20,757 patients, 4,617 started biologic therapy. In the propensity-matched cohort, patients treated (versus not treated) with biologic agents had a lower risk of incident CKD (hazard ratios 0.95, 95% confidence interval [0.82-1.10] and 0.71 [0.53-0.94] for decrease in eGFR under 60 and under 45 mL/min/1.73m², respectively) and progressive eGFR decline (multinomial odds ratios [95% CI] for eGFR slopes <-3 and ≥0 [versus -3 to <0] mL/min/1.73m²/year, 0.67 [0.58-0.79] and 0.76 [0.69-0.83], respectively). A significant deceleration of eGFR decline was also observed after biologic administration in patients treated with biologics (-1.0 versus -0.4 [mL/min/1.73m²/year] before and after biologic use). Thus, biologic agent administration was independently associated with lower risk of incident CKD and progressive eGFR decline.
What role does rheumatoid arthritis disease activity have in cardiovascular risk?
2018, Reumatologia Clinica
La artritis reumatoide (AR) presenta una mortalidad de 1,3 a 3 veces superior a la población general; la principal causa de muerte son las complicaciones cardiovasculares (40-50%). En el abordaje inicial se debe incluir la valoración del riesgo cardiovascular (RCV) mediante algoritmos adaptados para esta población. Si bien el SCOREm constituye un avance importante, hay datos que indican que podría infradiagnosticar la ateroesclerosis subclínica.
Estimar la fuerza de asociación entre la ecografia carotídea y el SCOREm en esta población, así como la implicancia de la actividad de la enfermedad.
Estudio observacional, transversal y analítico, realizado en el Hospital General de Ciudad Real durante el periodo junio de 2013-mayo de 2014. Se realizó la valoración del RCV y según el SCOREm se dividió a la población en riesgo bajo y alto (medio, alto y muy alto). Se estudió la presencia de ateroesclerosis subclínica en los pacientes de riesgo bajo.
Del total de 119 pacientes con AR, el 73,1% presentaba factores de riesgo tradicionales. Se excluyeron 38 pacientes por evento cardiovascular previo, diabetes mellitus y nefropatía. Se objetivó placa ateromatosa en el 14,63% de la población de riesgo bajo. El factor con mayor asociación con la presencia de aterosclerosis subclínica fue el grado de actividad moderada/alta de la AR medida mediante el SDAI, con un OR de 4,95 (IC 95%: 1,53-16,01).
Aunque existe una aceptable asociación entre la presencia de aterosclerosis subclínica y el SCOREm, hay una proporción no despreciable de pacientes clasificados de riesgo bajo con placas ateromatosas. La actividad de la enfermedad fue el factor de riesgo más asociado al incremento del RCV.
Rheumatoid arthritis (RA) is associated with a 1.3 to 3-fold increase in mortality, being the major cause of death from cardiovascular complications (40%-50%). Therefore, the initial approach should include cardiovascular risk (CVR) assessment using algorithms adapted for this population. Although, SCOREM is an important advance, there are data indicating that subclinical atherosclerosis may be underdiagnosed.
To estimate the strength of association between carotid ultrasound and SCOREM in this population, as well as the implication of disease activity.
Cross-sectional, observational, analytical study performed at the General Hospital of Ciudad Real, Spain, between June 2013 and May 2014. The evaluation of CVR was performed and, according to SCOREM, the population was divided into low and high (medium, high and very high) risk. We studied the presence of subclinical atherosclerosis in low-risk patients.
Of the total of 119 RA patients, 73.1% had traditional risk factors. Thirty-eight patients were excluded because of a previous cardiovascular event, diabetes mellitus and/or nephropathy. Atheromatous plaque was observed in 14.63% of the low-risk population. The factor with the strongest association to the presence of subclinical atherosclerosis was a moderate or high activity of RA measured by the simplified disease activity index with an odds ratio of 4.95 (95% CI: 1.53-16.01).
Although there was an acceptable correlation between the presence of subclinical atherosclerosis and SCOREM, there was a considerable proportion of atheromatous plaques in low-risk patients. Disease activity was the risk factor most closely associated with increased CVR.
Rheumatoid arthritis; a systemic disease with an under-estimated cardiovascular risk
2018, Revista Colombiana de Reumatologia
Determinar el riesgo cardiovascular y la prevalencia de factores de riesgo cardiovascular (RCV) en los pacientes con artritis reumatoide.
Estudio observacional, descriptivo y transversal, realizado en el Hospital General de Ciudad Real, entre junio de 2013 y mayo de 2014. Se realizó una analítica completa, se elaboró un perfil clínico, se calculó el SCOREm y se estratificó el RCV. Finalmente, se determinó la presencia de aterosclerosis subclínica mediante la realización de una ecografía carotídea.
119 pacientes aceptaron participar en el estudio. Hubo una prevalencia del 73,1% de los factores de riesgo tradicionales, 6,72% había presentado un evento cardiovascular al momento del estudio, 22,68% poseía un infradiagnóstico de diabetes mellitus o nefropatía. La distribución final del RCV fue: riesgo bajo 46 (38,7%), riesgo intermedio 33 (27,7%), riesgo alto 2 (1,7%), riesgo muy alto 38 (31,9%).
Existe una alta prevalencia de factores de RCV y riesgo elevado infradiagnosticado en esta población. Por lo que si bien la artritis reumatoide se manifiesta de forma más aparente a nivel articular, ha de considerarse una enfermedad sistémica asociada a una mayor incidencia de eventos cardiovasculares.
To determine the cardiovascular risk and the prevalence of cardiovascular risk (CVR) factors in patients with rheumatoid arthritis.
Observational, descriptive and cross-sectional study performed in the General Hospital of Ciudad Real from June 2013 to May 2014. A complete laboratory analysis was performed, a clinical profile was prepared, the Systematic COronary Risk Evaluation (SCOREm) was calculated, and the CVR was stratified. Finally, the presence of sub-clinical atherosclerosis was determined by performing a carotid ultrasound.
119 patients accepted to participate in the study. There was a prevalence of 73.1% of traditional risk factors; 6.72% having had a cardiovascular event at the time of the study, and 22.68% had an underdiagnosis of diabetes mellitus and/or nephropathy. The final distribution of the CVR was: Low risk 46 (38.7%), intermediate risk 33 (27.7%), high risk 2 (1.7%), very high risk 38 (31.9%).
There is a high prevalence of CVR factors and an elevated risk of underdiagnosis in the rheumatoid arthritis population. Therefore, although rheumatoid arthritis manifests itself more in the joints, it should be considered a systemic disease associated with a higher incidence of cardiovascular events.
Reducing cardiovascular risk in immune-mediated inflammatory diseases: Tumour necrosis factor inhibitors compared to conventional therapies—A systematic review and meta-analysis
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Differential Impact of Biologic Therapy on Heart Function Biomarkers in Rheumatoid Arthritis Patients: Observational Study on Etanercept, Adalimumab, and Tocilizumab
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View all citing articles on Scopus

: Supported by a Department of Veterans Affairs (VISN 15) Career Development Award (to Z. A.A.).

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Published by Elsevier B.V.

Original ArticleTumor necrosis factor-α blockade, cardiovascular outcomes, and survival in rheumatoid arthritis

Section snippets

Study population

Results

Discussion

Transl Res

Adv Chronic Kidney Dis

Adv Chronic Kidney Dis

J Am Med Inform Assoc

Int J Cardiol

Am Heart J

Am J Med

Kidney Int

Kidney Int

Tumor necrosis factor inhibitors for rheumatoid arthritis

N Engl J Med

Medial vascular calcification in diabetes mellitus and chronic kidney disease: the role of inflammation

Cardiovasc Hematol Disord Drug Targets

Cardiovascular risk in rheumatoid arthritis: effects of anti-TNF drugs

Expert Opin Pharmacother

Accelerated atherosclerosis in rheumatoid arthritis

Ann N Y Acad Sci

Potential effect of anti-tumour necrosis factor-alpha treatment on reducing the cardiovascular risk related to rheumatoid arthritis

Curr Vasc Pharmacol

Aortic Msx2-Wnt calcification cascade is regulated by TNF-alpha-dependent signals in diabetic Ldlr-/- mice

Arterioscler Thromb Vasc Biol

Disease-modifying anti-rheumatic drugs: do they reduce cardiac complications of RA?

Heart

Original Article
Tumor necrosis factor-α blockade, cardiovascular outcomes, and survival in rheumatoid arthritis