Severe Extraarticular Manifestations in a Community-based Cohort of Patients with Rheumatoid Arthritis: Risk Factors and Incidence in Relation to Treatment with Tumor Necrosis Factor Inhibitors

2017 ◽  
Vol 44 (7) ◽  
pp. 981-987 ◽  
Author(s):  
Lisa Theander ◽  
Britt-Marie Nyhäll-Wåhlin ◽  
Jan-Åke Nilsson ◽  
Minna Willim ◽  
Lennart T.H. Jacobsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tnf Inhibitors ◽  
Time Dependent ◽  
Community Based ◽  
Rheumatoid Arthritis Risk ◽  
Increased Risk ◽  
Clinical Records ◽  
Necrosis Factor

Objective.The aims of this study were to evaluate whether treatment with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) affects the risk of developing severe extraarticular rheumatoid arthritis (ExRA) manifestations and to investigate potential predictors for developing ExRA.Methods.A dynamic community-based cohort of patients with RA was studied (n = 1977). Clinical records were reviewed and cases of severe ExRA were identified. Information on exposure to TNF inhibitors was obtained from a regional register. Exposure to TNF inhibitors was analyzed in a time-dependent fashion and the incidence of severe ExRA in exposed patients was compared with the incidence in unexposed patients. Cox regression models were used to assess potential predictors of severe ExRA.Results.During treatment with TNF inhibitors, there were 17 patients with new onset of severe ExRA in 2400 person-years at risk (PY; 0.71/100 PY, 95% CI 0.41–1.13) compared with 104 in 15,599 PY (0.67/100 PY, 95% CI 0.54–0.81) in patients without TNF inhibitors. This corresponded to an incidence rate ratio of 1.06 (95% CI 0.60–1.78). The age- and sex-adjusted HR for ExRA in anti-TNF–treated patients was 1.21 (95% CI 1.02–1.43), with similar findings in models adjusted for time-dependent Health Assessment Questionnaire and propensity for anti-TNF treatment. Male sex, positive rheumatoid factor (RF), long disease duration, and greater disability were predictors for ExRA.Conclusion.This study suggests that patients treated with TNF inhibitors are at a slightly increased risk of developing severe ExRA. RF-positive patients with disabling disease of long duration were more likely to develop severe ExRA.

scholarly journals Changing Patterns of Tumor Necrosis Factor Inhibitor Use in 9074 Patients with Rheumatoid Arthritis

2009 ◽  
Vol 36 (5) ◽  
pp. 907-913 ◽  
Author(s):  
YUSUF YAZICI ◽  
SVETLANA KRASNOKUTSKY ◽  
JAIME P. BARNES ◽  
PATRICIA L. HINES ◽  
JASON WANG ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Dose Escalation ◽  
Tumor Necrosis ◽  
Randomized Clinical Trials ◽  
Tnf Inhibitors ◽  
Tnf Inhibitor ◽  
Insurance Claims ◽  
Claims Database ◽  
Necrosis Factor

Objective.Patients with rheumatoid arthritis (RA) commonly switch between tumor necrosis factor (TNF) inhibitors after failing to control disease activity. Much of the clinical data that support switching to a second TNF agent when one agent fails to work has come from small, short-term studies. We utilized a US insurance claims database to determine patterns of use such as dose escalation, time to discontinuation, and switching between TNF inhibitors in patients with RA.Methods.A retrospective analysis was performed using an insurance claims database in the US from 2000 to 2005. TNF inhibitor use, time to switch, dose escalation, and continuation times were analyzed in patients with RA.Results.Nine thousand seventy-four patients with RA started TNF inhibitors during the period 2000 to 2005. Etanercept was the most commonly used TNF inhibitor; infliximab had the highest duration of continuation, about 50% at 2 years. In addition, infliximab showed higher rates of dose escalation compared to etanercept and adalimumab. For all TNF inhibitors, time to switching decreased from 2000 to 2005.Conclusion.TNF inhibitor use patterns changed from 2000 to 2005, with more frequent changes among the different TNF inhibitors and a shorter duration of treatment before the change. Only about 50% of TNF inhibitors are still continued at 2 years, reflecting the difference between randomized clinical trials and real-world experience.

Rates of Serious Infections and Malignancies Among Patients with Rheumatoid Arthritis Receiving Either Tumor Necrosis Factor Inhibitor or Rituximab Therapy

2015 ◽  
Vol 42 (3) ◽  
pp. 372-378 ◽  
Author(s):  
Kalle Jyri Aaltonen ◽  
Jaana Tuulikki Joensuu ◽  
Liisa Virkki ◽  
Tuulikki Sokka ◽  
Pasi Aronen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Inhibitor ◽  
Poisson Model ◽  
Tnf Inhibitor ◽  
Biologic Treatment ◽  
Increased Risk ◽  
Serious Infections ◽  
Necrosis Factor

Objective.Because of the role of tumor necrosis factor (TNF) in host defense, it was hypothesized that its inhibition might lead to an increased risk of malignancies and infections. The objective of our study was to assess the incidence of serious infections leading to hospitalization and malignancies among patients with rheumatoid arthritis (RA) receiving either TNF inhibitor or rituximab (RTX) therapy.Methods.The study population was identified from the National Register for Biologic Treatment in Finland and the hospital records of Central Finland Central Hospital for conventional disease-modifying antirheumatic drug (cDMARD) users. Data on infections and malignancies were acquired from national healthcare registers. A Poisson model was used to calculate the adjusted incidence rate ratios (aIRR) and was composed of age, sex, time from diagnosis, year of the beginning of the followup, rheumatoid factor status, Disease Activity Score at 28 joints, Health Assessment Questionnaire, prior malignancy, prior serious infection, prior biologic use, and time-updated use of methotrexate, sulfasalazine, hydroxychloroquine, and oral corticosteroids as confounders.Results.In total, during the followup of 10,994 patient-years, 92 malignancies and 341 serious infections were included in the analyses. The aIRR of infections compared to cDMARD users were 1.2 (95% CI 0.63–2.3), 0.84 (95% CI 0.53–1.3), 0.98 (95% CI 0.60–1.6), and 1.1 (95% CI 0.59–1.9) for the patients treated with infliximab (IFX), etanercept, adalimumab, and RTX, respectively. The crude rates of malignancies were highest among the users of cDMARD and RTX, and lowest among patients treated with IFX with no differences in aIRR.Conclusion.Our results provide some reassurance of the safety of biologic treatments in the treatment of RA.

scholarly journals Clinical Pharmacology Aspects in Patients Treated with TNF Inhibitors During SARS-Cov-2 Pandemic

2020 ◽  
Vol 11 (3) ◽  
pp. 393-394
Author(s):  
Francesco Ferrara ◽  
Priscilla Santilli ◽  
Vilma D'Aiuto ◽  
Antonio Vitiello
Keyword(s):  
Risk Factors ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Current Knowledge ◽  
Tnf Inhibitors ◽  
Global Pandemic ◽  
Increased Risk ◽  
Key Factor ◽  
Drug Treatments ◽  
Necrosis Factor

In this period of global pandemic caused by SARS-Cov-2, it is of paramount importance to recognize all risk factors that may increase the likelihood of infection. In addition to the risk factors known as pre-existing diseases and old age, risk factors could be drug treatments for chronic diseases, such as immunomodulating drugs that can alter immune defences and response to infectious agents. Antibodies that inhibit tumor necrosis factor (TNF) such as adalimumab infliximab etanercept and golimumab have been used for over 20 years in severe cases of autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease or ankylosing spondylitis. Due to their mechanism of action they reduce inflammation and can stop the progression of the disease by inhibiting a key factor of inflammation such as Tumor Necrosis Factor (TNF). In this article we want to examine the possible correlation between therapy with TNF inhibitors and the increased risk of SARS-CoV-2 infection, and the possible paradoxical therapeutic efficacy in patients with ongoing infection, especially in phase two and three. We express our opinion on this very complex and sensitive topic which is the subject of discussion among physicians and experts, based on current knowledge of the literature.

High-density Lipoprotein Profiling Changes in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor Inhibitors: A Cohort Study

2013 ◽  
Vol 40 (6) ◽  
pp. 825-830 ◽  
Author(s):  
Anna Jamnitski ◽  
Johannes H. Levels ◽  
Inge A. van den Oever ◽  
Michael T. Nurmohamed
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
High Density Lipoprotein ◽  
Tumor Necrosis ◽  
Density Lipoprotein ◽  
High Density ◽  
Tnf Inhibitors ◽  
Eular Response ◽  
Amyloid A ◽  
Necrosis Factor

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.

Observational Studies of Infections in Rheumatoid Arthritis: A Metaanalysis of Tumor Necrosis Factor Antagonists

2010 ◽  
Vol 37 (5) ◽  
pp. 928-931 ◽  
Author(s):  
SASHA BERNATSKY ◽  
YOUSSEF HABEL ◽  
ELHAM RAHME
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Observational Studies ◽  
Tumor Necrosis ◽  
Case Control Studies ◽  
Tnf Antagonists ◽  
Serious Infection ◽  
Increased Risk ◽  
Increase Risk ◽  
Necrosis Factor

Objective.Published metaanalyses of tumor necrosis factor (TNF) antagonists and infection have focused on randomized controlled trials, which tend to have short duration, relatively small size, and stringent inclusion/exclusion criteria that may limit enrollment to patients at low risk of infection. We performed a systematic review and synthesis of observational studies of TNF antagonists and infection risk.Methods.We conducted a systematic literature search of studies estimating overall risk of serious infection after anti-TNF exposure in rheumatoid arthritis (RA). We estimated a pooled relative risk (RR) for the relevant observational studies, using a random-effects model.Results.Five cohort studies and 2 nested case-control studies were included in the metaanalysis. Anti-TNF therapy appeared to significantly increase risk of serious infection (pooled adjusted RR 1.37, 95% CI 1.18, 1.60).Conclusion.Our metaanalysis of observational data demonstrated an increased risk of serious infection in subjects with RA receiving anti-TNF therapy, versus those not receiving these agents.

Anti-Ro/SSA Antibodies Are an Independent Factor Associated with an Insufficient Response to Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis

2011 ◽  
Vol 38 (11) ◽  
pp. 2346-2354 ◽  
Author(s):  
RAN MATSUDAIRA ◽  
NAOTO TAMURA ◽  
FUMIO SEKIYA ◽  
MICHIHIRO OGASAWARA ◽  
KENJIRO YAMANAKA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Clinical Response ◽  
Tumor Necrosis ◽  
Tnf Inhibitors ◽  
Multivariable Logistic Regression Analysis ◽  
Discontinuation Rate ◽  
Eular Response ◽  
Insufficient Response ◽  
Necrosis Factor

Objective.To study the significance of anti-Ro/SSA antibodies (anti-Ro) in the clinical response to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA).Methods.The clinical responses of a cohort of 190 patients with RA who were treated with infliximab, etanercept, or adalimumab (n = 112, 64, and 14, respectively) as the first biologics were examined using the Disease Activity Score in 28 joints (DAS28) at 24 weeks and the discontinuation rate at 56 weeks. The baseline characteristics of responders and the nonresponders were compared. The clinical response was compared between anti-Ro-negative and -positive patients. The factors associated with the inefficiency of TNF inhibitors were estimated with a multivariable logistic regression analysis.Results.The positive rate of anti-Ro was significantly higher in patients with no European League Against Rheumatism (EULAR) response at 24 weeks (OR 3.64, 95% CI 1.45–9.01, p = 0.003). In anti-Ro-positive patients, a moderate or good EULAR response rate was significantly lower with a sustaining higher median DAS28 (p = 0.006), and this difference was greater among infliximab-treated patients. The discontinuation rate for TNF inhibitors due to inefficacy at 56 weeks was also higher in anti-Ro-positive patients (OR 4.68, 95% CI 1.82–11.99, p = 0.0005), and 75% of these patients received infliximab. The presence of anti-Ro was strongly associated with no EULAR response at 24 weeks and a higher discontinuation rate of TNF inhibitors by 56 weeks (OR 5.22, 95% CI 1.75–15.57, p = 0.003 and OR 10.18, 95% CI 2.18–49.56, p = 0.003).Conclusion.The presence of anti-Ro might be related to the lesser clinical response to infliximab compared to other TNF inhibitors, suggesting that the presence of anti-Ro should be considered when choosing the appropriate biologics for patients with RA.

scholarly journals SAT0019 HISTOPATHOLOGICAL CHANGES OF SYNOVIAL TISSUE IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TNF INHIBITORS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 939.1-940
Author(s):  
Y. Takashima ◽  
K. Fukuda ◽  
S. Hayashi ◽  
T. Kamenaga ◽  
M. Fujita ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Synovial Tissue ◽  
Tumor Necrosis ◽  
Tnf Inhibitors ◽  
M2 Macrophage ◽  
Synovial Cells ◽  
Hydropic Degeneration ◽  
Synovial Tissues ◽  
Necrosis Factor

Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by hyperplasia of synovial tissues [1]. Tumor necrosis factor (TNF)-α is one of the pro-inflammatory cytokines that play a crucial role in the pathogenesis of RA synovitis, and TNF inhibitors (TNFi) were reported to force the RA to go into remission or low disease activity and have brought revolutionary impacts on RA treatment [2]. TNFi have been shown to act on inflammatory cells and form the discoid fibrosis in the sublining layers [3,4]. However, the changes of synovial tissue and the cause of discoid fibrosis in RA patients treated with TNFi has not been determined in detail.Objectives:The purpose of this study is to demonstrate the histological changes and the types of cells around discoid fibrosis in RA synovium treated with TNFi.Methods:Synovial tissues were obtained from 30 patients with RA during joint surgeries. 6 patients were treated with TNFi (1 patient with golimumab, 3 patients with etanercept, 2 patients with infliximab). As a control, synovial tissues were obtained from 6 patients who were treated only with csDMARDs (6 patients with MTX). The frozen sections were stained by hematoxylin and eosin (HE). To detect the apoptosis, TdT-mediated dUTP nick end labeling (TUNEL) was performed. The immunohistochemical characterization of the synovial cells was performed by using following antibodies: CD20 and CD3 for detecting B and T lymphocytes respectively, CD163 and CD86 for detecting M1 and M2 macrophage respectively.Results:In the sections stained with HE, the formation of discoid fibrosis and the other characteristic changes including hydropic degeneration, vacuolation, sclerosis of small vasculature, and the number of multilayered synovial cells was decreased in synovium from RA patients treated with TNFi. In the sections with TUNEL stain, apoptosis of lining cells around the discoid fibrosis was detected in RA synovium treated with TNFi (Figure 1a, 1b). In the sections with immunohistochemistry stain, CD86 expression increased in lining layer of RA synovium treated with TNFi. CD163 positive cells showed diffuse expression in RA synovium treated with TNFi. In contrast, CD20 and CD3 positive cells decreased around discoid fibrosis compared to control sections. These results showed indicated that the types of cells in lining and sublining layers were mainly macrophages and that the apoptosis of macrophages might form the discoid fibrosis in lining layers.Conclusion:This study showed the apoptosis of lining cells derived from macrophages resulted in the formation of the discoid fibrosis. These findings indicated TNFi might induce apoptosis of macrophage leading to the suppression of RA synovitis.References:[1] Scott Dl, et al. Progression of radiological changes in rheumatoid arthritis. Ann Rheum Dis. 1984.[2]van der Heijde D,et al. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum. 2006.[3] Hirohata S,et al. TNF inhibitors induce discoid fibrosis in the sublining layers of the synovium with degeneration of synoviocytes in rheumatoid arthritis. Rheumatol Int. 2013.[4] Yamanaka H,et al. Scoring evaluation for histopathological features of synovium in patients with rheumatoid arthritis during anti-tumor necrosis factor therapy. Rheumatol Int. 2010.Acknowledgments :This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Disclosure of Interests:None declared

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