Assessing the Cardiovascular Risk Between Celecoxib and Nonselective Nonsteroidal Antiinflammatory Drugs in Patients With Rheumatoid Arthritis and Osteoarthritis

Objective.Hypertension (HTN), a common modifiable cardiovascular risk factor, is more common in patients with rheumatoid arthritis (RA), but the underlying mechanisms are unclear. We examined the hypothesis that mediators of inflammation and markers of cardiovascular risk are associated with HTN in RA.Methods.We compared measures of inflammation [serum C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), homocysteine, and leptin concentrations] and insulin resistance [homeostasis model assessment index (HOMA)] in RA patients with (n = 90) and without HTN (n = 79). HTN was defined as blood pressure ≥ 140/90 mm Hg or treatment with antihypertensive therapy. The independent association of markers of interest with HTN was examined using multivariable logistic regression.Results.Patients with HTN were significantly older and had longer disease duration than those without HTN (both p < 0.001). Concentrations of homocysteine [11.1 (8.5–13.5) μmol/l vs 9.3 (7.8–11.0) μmol/l] were significantly higher in patients with HTN (p < 0.001). After adjustment for age, sex, race, smoking, body mass index, and corticosteroid and nonsteroidal antiinflammatory drugs (NSAID) use, increased concentrations of homocysteine (OR 2.9, 95% CI: 1.5–5.5, p = 0.001), and leptin (OR 2.0, 95% CI: 1.0–3.8, p = 0.046) were significantly associated with HTN, but the 28-joint Disease Activity Score, IL-6, CRP, TNF-α, and HOMA index were not (all p > 0.05).Conclusion.HTN in patients with RA is not associated with generalized systemic inflammation or insulin resistance, but is associated with increasing concentrations of homocysteine and leptin. The pathogenesis of HTN in RA may involve pathways more regularly associated with fat and vascular homeostasis.

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Treatment Options for Rheumatoid Arthritis: Celecoxib, Leflunomide, Etanercept, and Infliximab

Annals of Pharmacotherapy ◽

10.1345/aph.19344 ◽

2000 ◽

Vol 34 (6) ◽

pp. 743-760 ◽

Cited By ~ 19

Author(s):

Brigitte T Luong ◽

Barbara S Chong ◽

Dionne M Lowder

Keyword(s):

Rheumatoid Arthritis ◽

English Language ◽

Data Extraction ◽

Treatment Options ◽

Nonsteroidal Antiinflammatory Drugs ◽

Antiinflammatory Drugs ◽

Safety And Efficacy ◽

Medline Search ◽

Pertinent Data

OBJECTIVE: To review new pharmacologic agents approved for use in the management of rheumatoid arthritis (RA). DATA SOURCES: A MEDLINE search (1966–January 2000) was conducted to identify English-language literature available on the pharmacotherapy of RA, focusing on celecoxib, leflunomide, etanercept, and infliximab. These articles, relevant abstracts, and data provided by the manufacturers were used to collect pertinent data. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. DATA EXTRACTION: Agents were reviewed with regard to mechanism of action, efficacy, drug interactions, pharmacokinetics, dosing, precautions/contraindications, adverse effects, and cost. DATA SYNTHESIS: Traditional pharmacologic treatments for RA have been limited by toxicity, loss of efficacy, or both. Increasing discoveries into the mechanisms of inflammation in RA have led to the development of new agents in hopes of addressing these limitations. With the development of celecoxib, a selective cyclooxygenase-2 inhibitor, the potential exists to minimize the gastrotoxicity associated with nonsteroidal antiinflammatory drugs. Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD). The biologic response modifiers, etanercept and infliximab, are alternatives that have shown benefit alone or in combination with methotrexate. However, they should be reserved for patients who fail to respond to DMARD therapy. Further studies should be conducted to evaluate the long-term safety and efficacy of these agents as well as their role in combination therapy. CONCLUSIONS: Celecoxib, leflunomide, etanercept, and infliximab are the newest agents approved for RA. Clinical trials have shown that these agents are beneficial in the treatment of RA; however, long-term safety and efficacy data are lacking.

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The Editor's Roundtable: Nonsteroidal Antiinflammatory Drugs and Cardiovascular Risk

The American Journal of Cardiology ◽

10.1016/j.amjcard.2008.08.004 ◽

2008 ◽

Vol 102 (8) ◽

pp. 1046-1055 ◽

Cited By ~ 3

Author(s):

Vincent E. Friedewald ◽

Joel S. Bennett ◽

Milton Packer ◽

William C. Roberts ◽

Gary W. Williams

Keyword(s):

Cardiovascular Risk ◽

Nonsteroidal Antiinflammatory Drugs ◽

Antiinflammatory Drugs

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Subgroup analyses to determine cardiovascular risk associated with nonsteroidal antiinflammatory drugs and coxibs in specific patient groups

Arthritis & Rheumatism ◽

10.1002/art.23911 ◽

2008 ◽

Vol 59 (8) ◽

pp. 1097-1104 ◽

Cited By ~ 60

Author(s):

Daniel H. Solomon ◽

Robert J. Glynn ◽

Kenneth J. Rothman ◽

Sebastian Schneeweiss ◽

Soko Setoguchi ◽

...

Keyword(s):

Cardiovascular Risk ◽

Nonsteroidal Antiinflammatory Drugs ◽

Antiinflammatory Drugs ◽

Specific Patient ◽

Subgroup Analyses ◽

Patient Groups

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A Population-level Analysis of the Differing Effects of Rheumatoid Arthritis and Spondyloarthritis on Peripartum Outcomes

The Journal of Rheumatology ◽

10.3899/jrheum.181320 ◽

2019 ◽

Vol 47 (2) ◽

pp. 197-203 ◽

Cited By ~ 3

Author(s):

Stephanie O. Keeling ◽

Samantha L. Bowker ◽

Anamaria Savu ◽

Padma Kaul

Keyword(s):

Rheumatoid Arthritis ◽

Pregnant Women ◽

Population Level ◽

Nonsteroidal Antiinflammatory Drugs ◽

Neonatal Outcomes ◽

Hypertensive Disorder ◽

Antiinflammatory Drugs ◽

Hypertensive Disorders ◽

Maternal And Neonatal Outcomes ◽

In Pregnancy

Objective.The effects of rheumatoid arthritis (RA) and spondyloarthritis (SpA) on maternal and neonatal outcomes at a population level have not previously been well compared.Methods.A contemporary pregnancy cohort of 312,081 women and corresponding birth events was assembled for the province of Alberta from the random selection of 1 live birth event per woman. We identified 3 groups: (1) no inflammatory arthritis (no IA, n = 308,989), (2) RA (n = 631), and (3) SpA (n = 2461). We compared maternal and neonatal outcomes, comorbid conditions, and medication use among the 3 groups. Multivariable logistic regression models evaluated the independent association between RA and SpA, relative to no IA, and the outcomes of small for gestation age (SGA) and hypertensive disorders during pregnancy.Results.Pregnant women with RA were significantly more likely to have preterm delivery (13.5%), cesarean delivery (33.9%), hypertensive disorders in pregnancy (10.5%), and SGA babies (15.6%), compared to pregnant women with either SpA or no IA. Nonsteroidal antiinflammatory drugs and corticosteroid use were significantly higher in pregnant women with RA compared to the other groups. Women with RA were significantly more likely to have an SGA baby (OR 1.51, 95% CI 1.21–1.88; p < 0.01), and hypertensive disorder in pregnancy (OR 1.51, 95% CI 1.16–1.97; p < 0.01), compared to women with no IA, while no difference was found between women with SpA and those with no IA.Conclusion.Women with RA have a higher risk of worse maternal and neonatal outcomes, whereas the risk of these events is similar between women with and without SpA.

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Relationship between clinical efficacy and laboratory correlates of inflammatory and immunologic activity in rheumatoid arthritis patients treated with nonsteroidal antiinflammatory drugs

Arthritis & Rheumatism ◽

10.1002/art.1780330504 ◽

1990 ◽

Vol 33 (5) ◽

pp. 623-633 ◽

Cited By ~ 18

Author(s):

John J. Cush ◽

Hugo E. Jasin ◽

Regina Johnson ◽

Peter E. Lipsky

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Efficacy ◽

Nonsteroidal Antiinflammatory Drugs ◽

Antiinflammatory Drugs ◽

Immunologic Activity

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Nonsteroidal antiinflammatory drugs in rheumatoid arthritis and osteoarthritis. Support for the concept of “responders” and “nonresponders”

Arthritis & Rheumatism ◽

10.1002/art.1780401105 ◽

1997 ◽

Vol 40 (11) ◽

pp. 1944-1954 ◽

Cited By ~ 48

Author(s):

Judith S. Walker ◽

Rachel B. Sheather-Reid ◽

John J. Carmody ◽

Richard O. Day ◽

Janet H. Vial

Keyword(s):

Rheumatoid Arthritis ◽

Nonsteroidal Antiinflammatory Drugs ◽

Antiinflammatory Drugs

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Orthopedic Surgery in Rheumatoid Arthritis in the Era of Biologic Therapy

The Journal of Rheumatology ◽

10.3899/jrheum.130118 ◽

2013 ◽

Vol 40 (11) ◽

pp. 1850-1855 ◽

Cited By ~ 18

Author(s):

Leticia Leon ◽

Lydia Abasolo ◽

Loreto Carmona ◽

Luis Rodriguez-Rodriguez ◽

Jose Ramon Lamas ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Orthopedic Surgery ◽

Total Joint Replacement ◽

Sociodemographic Factors ◽

Nonsteroidal Antiinflammatory Drugs ◽

Biologic Therapies ◽

Antiinflammatory Drugs ◽

Related Factors ◽

Orthopedic Procedure ◽

Record Review

Objective.To analyze sociodemographic and clinic-related factors associated with the use of orthopedic surgical procedures in rheumatoid arthritis (RA), focusing on the potential role of new biologic therapies.Methods.A retrospective medical record review was performed in a probability sample of 1272 patients with RA from 47 units distributed in 19 Spanish regions. Sociodemographic and clinical features, use of drugs, and arthritis-related joint surgeries were recorded following a standardized protocol.Results.A total of 94 patients (7.4%) underwent any orthopedic surgery during their disease course, with a total of 114 surgeries; 47 (41.2%) of these surgeries were total joint replacement (TJR). The median time to first orthopedic procedure was 7.9 years from the onset of RA symptoms, and the rate of orthopedic surgery (excluding TJR) was 4.5 procedures per 100 person-years from the beginning of RA, while the rate of TJR was 2.25 interventions per 100 person-years. A higher risk of undergoing an orthopedic surgical procedure was associated with taking nonsteroidal antiinflammatory drugs (NSAID) in the previous 2 years, female sex, longterm disease, and the presence of extraarticular complications. The risk factors for undergoing a TJR were being old, having a longterm disease, and taking biologic therapies.Conclusion.In the era of biologics, our national audit found a low percentage of patients who underwent orthopedic surgery, probably reflecting a thorough management of the RA. Sociodemographic factors, longterm RA, extraarticular complications, and NSAID were associated with orthopedic surgery.

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