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Tumor Necrosis Factor-? Inhibitor Use and the Risk of Incident Hypertension in Patients with Rheumatoid Arthritis.

ABSTRACT: To compare the risk of incident hypertension between initiators of tumor necrosis factor (TNF)-? inhibitors and initiators of nonbiologic disease modifying antirheumatic drugs (hereafter referred to as nonbiologics) in rheumatoid arthritis patients taking methotrexate monotherapy.We conducted a cohort study using insurance claims data (2001-2012) from the US. We identified initiators of use of either TNF-? inhibitors or nonbiologics. Subsequent exposure to these agents was measured monthly in a time-varying manner. The outcome of interest was incident hypertension, defined by a diagnosis and a prescription for an antihypertensive drug. Marginal structural models estimated hazard ratios (HRs) adjusted for both baseline and time-varying confounders. To validate the primary analysis, we designed a verification analysis to evaluate a known association between leflunomide (a nonbiologic disease modifying agent) and hypertension.We identified 4,822 initiations of TNF-? inhibitor use and 2,400 of nonbiologic use. Crude incidence rates of hypertension per 1,000 person-years of follow-up were 36 (95% CI [confidence interval]: 32, 41) for the TNF-? inhibitor group and 42 (95% CI: 34, 51) for the nonbiologics group. The crude HR of TNF-? inhibitors versus nonbiologics for the risk of incident hypertension was 0.85 (95% CI: 0.67, 1.1). After adjusting for both baseline and time-varying covariates using marginal structural models, the HR was 0.95 (95% CI: 0.74, 1.2). In the verification analysis, the adjusted HR of incident hypertension was 2.3 (95% CI: 1.7, 3.0) in leflunomide initiators compared with methotrexate initiators.Treatment with TNF-? inhibitors was not associated with a reduced risk of incident hypertension compared with nonbiologics in rheumatoid arthritis patients.See Video Abstract at http://links.lww.com/EDE/B36.

SUBMITTER: Desai RJ

PROVIDER: S-EPMC5497216 | biostudies-other | 2016 May

REPOSITORIES: biostudies-other

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Tumor Necrosis Factor-α Inhibitor Use and the Risk of Incident Hypertension in Patients with Rheumatoid Arthritis.

Desai Rishi J RJ Solomon Daniel H DH Schneeweiss Sebastian S Danaei Goodarz G Liao Katherine P KP Kim Seoyoung C SC

Epidemiology (Cambridge, Mass.) 20160501 3

<h4>Objective</h4>To compare the risk of incident hypertension between initiators of tumor necrosis factor (TNF)-α inhibitors and initiators of nonbiologic disease modifying antirheumatic drugs (hereafter referred to as nonbiologics) in rheumatoid arthritis patients taking methotrexate monotherapy.<h4>Methods</h4>We conducted a cohort study using insurance claims data (2001-2012) from the US. We identified initiators of use of either TNF-α inhibitors or nonbiologics. Subsequent exposure to these ...[more]

PMID: 26808597

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Project description:BackgroundIndividuals with rheumatoid arthritis (RA) are at high risk for depression because of the overall burden of systemic inflammation. Although some evidence suggests that treatment with powerful anti-inflammatory drugs, such as tumor necrosis factor (TNF) inhibitors, may be effective in reducing the risk for depression in patients with RA, it is unclear whether such reduction in risk is dependent on the response to TNF inhibitor therapy.ObjectiveTo evaluate the association between the response to TNF inhibitor therapy and the risk for depression among working-age adults with RA.MethodThis retrospective, observational cohort study design was based on data derived from commercial claims data in the QuintilesIMS Real World Data Adjudicated Claims database between October 1, 2009, and September 30, 2015. A total of 4222 working-age adults (18-62 years) with RA who started treatment with TNF inhibitor therapy and were continuously enrolled during the 3 observation periods (ie, 1-year baseline, 1-year treatment, and 1-year follow-up periods) were included in the study. Treatment response to a TNF inhibitor was measured using prescription drug claims based on a published validated algorithm. Multivariable logistic regression was used to examine the association between treatment response to TNF inhibitor therapy and the risk for depression, after controlling for baseline demographic characteristics, clinical characteristics, and RA-related medication use. An inverse probability of treatment weighting technique was used to control for observable differences in TNF inhibitor responders' characteristics versus TNF inhibitor nonresponders.ResultsOverall, 359 (8.5%) patients with RA had depression during the follow-up period and 1679 (39.8%) patients responded to TNF inhibitor treatment during the 1-year treatment period. A significantly lower percentage of TNF inhibitor responders (7.1%, N = 119) had depression than TNF inhibitor nonresponders (9.4%, N = 239). After controlling for other risk factors, responders to TNF inhibitors were 20% less likely to have depression during the follow-up period (adjusted odds ratio, 0.80; 95% confidence interval, 0.64-0.98) than nonresponders to TNF inhibitor therapy.ConclusionThe risk for depression was significantly reduced among patients with RA who responded to TNF inhibitor therapy compared with those who did not respond to such therapy. To determine whether the lower rate of depression observed with TNF inhibition is a direct effect of treatment with a TNF inhibitor, or whether it could be attributed to improvement in RA disease secondary to treatment, future studies need to also incorporate a control population of patients with RA who receive other antirheumatic regimens, such as disease-modifying antirheumatic drugs.

Project description:ObjectivePatients with rheumatoid arthritis (RA) are at an increased risk of ischemic stroke. Tumor necrosis factor inhibitors (TNFi) may influence risk and mortality after ischemic stroke by reducing inflammation. This study was undertaken to examine the association of TNFi with the risk of incident ischemic stroke and with 30-day and 1-year mortality after ischemic stroke.MethodsPatients with RA starting therapy with TNFi and a biologics-naive comparator group treated with synthetic disease-modifying antirheumatic drugs (DMARDs) only were recruited to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis from 2001 to 2009. Patients were followed up via clinical and patient questionnaires as well as the national death register. Incident strokes were classified as ischemic if brain imaging reports suggested ischemia or if ischemic stroke was reported as the underlying cause of death on a death certificate. Patients with a previous stroke were excluded. Risk of ischemic stroke was compared between patients receiving synthetic DMARDs only and those ever-exposed to TNFi using a Cox proportional hazards regression model adjusted for potential confounders. Mortality after ischemic stroke was compared between synthetic DMARD-treated patients and TNFi-treated patients using logistic regression, adjusted for age and sex.ResultsTo April 2010, 127 verified incident ischemic strokes (21 in 3,271 synthetic DMARD-treated patients and 106 in 11,642 TNFi-treated patients) occurred during 11,973 and 61,226 person-years of observation, respectively (incidence rate 175 versus 173 per 100,000 person-years). After adjustment for confounders, there was no association between ever-exposure to TNFi and ischemic stroke (hazard ratio 0.99 [95% confidence interval (95% CI) 0.54-1.81]). Mortality 30 days or 1 year after ischemic stroke was not associated with concurrent TNFi exposure (odds ratio 0.18 [95% CI 0.03-1.21] and 0.60 [95% CI 0.16-2.28], respectively).ConclusionExposure to TNFi does not appear to influence the occurrence of ischemic stroke in the medium term in patients with RA. The impact on mortality after ischemic stroke remains inconclusive.

Project description:Background: This study aimed to investigate the molecular mechanism of Radix Paeoniae Alba (white peony, WP) in treating immune inflammatory diseases of rheumatoid arthritis (RA) and tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis) by using network pharmacology and molecular docking. Methods: In this study, the ingredient of WP and the potential inflammatory targets of RA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database, GeneCard, and OMIM databases, respectively. The establishment of the RA-WP-potential inflammatory target gene interaction network was accomplished using the STRING database. Network maps of the WP-RA-potential inflammatory target gene network were constructed using Cytoscape software. Gene ontology (GO) and the biological pathway (KEGG) enrichment analyses were used to further explore the RA mechanism and therapeutic effects of WP. Molecular docking technology was used to analyze the optimal effective components from WP for docking with TNF-α. Results: Thirteen active ingredients and 71 target genes were screened from WP, and 49 of the target genes intersected with RA target inflammatory genes and were considered potential therapeutic targets. Network pharmacological analysis showed that the WP active ingredients such as mairin, DPHCD, (+)-catechin, beta-sitosterol, paeoniflorin, sitosterol, and kaempferol showed better correlation with RA inflammatory target genes such as PGR, PTGS1, PTGS2, NR3C2, TNFSF15, and CHRM2, respectively. The immune-inflammatory signaling pathways of the active ingredients for the treatment of RA are the TNF-α signaling pathway, Toll-like receptor signaling pathway, cell apoptosis, interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, mitogen-associated protein kinase, etc. Molecular docking results suggested that mairin was the most appropriate natural TNFis. Conclusion: Our findings provide an essential role and basis for further immune-inflammatory studies into the molecular mechanisms of WP and TNFis development in RA.

Project description:OBJECTIVE:Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS:A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (triangle upDAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. RESULTS:Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the triangle upDAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39-0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41-1.99). CONCLUSION:Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections.

Dataset Information

Tumor Necrosis Factor-? Inhibitor Use and the Risk of Incident Hypertension in Patients with Rheumatoid Arthritis.

Publications

Tumor Necrosis Factor-α Inhibitor Use and the Risk of Incident Hypertension in Patients with Rheumatoid Arthritis.

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