Etanercept Treatment Research Articles

OP0176 Comorbidity profiles among adult patients with JIA who were treated with etanercept – results of the biologic register jumbo

BackgroundJuvenile idiopathic arthritis (JIA) is a heterogeneous inflammatory disease that persists in about half the cases into adulthood. Little is known about the morbidity spectrum of adult patients with JIA.ObjectivesTo...

AB1136 Etanercept in a real clinical practice in patients with active juvenile idiopathic arthritis (JIA)

BackgroundThe appearance of biologics in the last decade of the 20th century has significantly changed life perspectives for patients with rheumatic diseases. Etanercept, a soluble anti-tumor necrosis factor alpha (TNF-α)...

AB0068 Distribution of blood dendritic cell subsets in patients with rheumatoid arthritis, spondyloarthritis and psoriatic arthritis treated with etanercept

ObjectivesDendritic cells play a pivotal role in the initiation of innate and adaptive immune responses in host reaction to microbial infection as well as in autoimmune pathology. DC subsets in...

FRI0423 Effective prevention of new inflammatory bony lesions on magnetic resonance imaging in patients with early axial spondyloarthritis during treatment with etanercept over 2 years - data of the esther trial

ObjectivesIn patients with early axial spondyloarthritis (SpA) with a disease duration of less than 5 years and evidence of active inflammation on whole-body magnetic reonance imaging (MRI) in the spine...

THU0464-HPR Nursing evaluation in the etanercept switching from a prefilled syringe into a pen myclic in patients with chronic arthritis

BackgroundEtanercept is an anti-TNF biological therapy, which is available in either a prefilled syringe or a pen myclic. Nursing staff play an important role in the administration and monitoring of...

AB1134 Efficacy and safety of therapy by etanercept in combination with methotrexate for patients with juvenile idiopathic arthritis

BackgroundJuvenile idiopathic arthritis (JIA) - a chronic disease that leads to early disability of patients. Treatment of JIA is one of the most complex and urgent problems of rheumatology. The...

THU0358 Constant Clinical Response in Patients with Early Axial Spondyloarthritis after Continuous Treatment with Etanercept - 4 Year Data of the Esther Trial

ObjectivesIn patients with early axial spondyloarthritis (SpA) with a disease duration of < 5 years and evidence of active inflammation on whole-body magnetic resonance imaging in the spine and/or sacroiliac-joints...

FRI0185 In rheumatoid arthritis patients with stable low disease activity on methotrexate plus etanercept, continuation of etanercept at 50 mg or 25 mg weekly are both clinically superior to discontinuation: results from a randomized, 3-arm, double-blind study

BackgroundThe efficacy of etanercept (ETN) plus methotrexate (MTX) in rheumatoid arthritis (RA) is well-established; long-term trials have shown that continued treatment maintains clinical response and prevents radiographic damage.ObjectivesTo study whether...

FRI0199 Usefulness of matrix metalloproteinase-3 as a predictor of total knee arthroplasty in patients with rheumatoid arthritis

BackgroundThe main goal of rheumatoid arthritis (RA) treatment is to maximize the patient’s long-term QOL. In addition to achievement/maintenance of clinical remission, prevention of structural change such as joint destruction...

Etanercept for the treatment of rheumatoid arthritis.

Etanercept is a soluble tumour necrosis factor alpha-receptor disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). The purpose of this review was to update the previous Cochrane systematic review published in 2003 assessing the benefits and harms of etanercept for the treatment of RA. In addition, we also evaluated the benefits and harms of etanercept plus DMARD compared with DMARD monotherapy in those people with RA who are partial responders to methotrexate (MTX) or any other traditional DMARD. Five electronic databases were searched from 1966 to February 2003 with no language restriction. The search was updated to January 2012. Attempts were made to identify other studies by contact with experts, searching reference lists and searching trial registers. All controlled trials (minimum 24 weeks' duration) comparing four possible combinations: 1) etanercept (10 mg or 25 mg twice weekly) plus a traditional DMARD (either MTX or sulphasalazine) versus a DMARD, 2) etanercept plus DMARD versus etanercept alone, 3) etanercept alone versus a DMARD or 4) etanercept versus placebo. Two review authors independently extracted data and assessed the risk of bias of the trials. Three trials were included in the original version of the review. An additional six trials, giving a total of 2842 participants, were added to the 2012 update of the review. The trials were generally of moderate to low risk of bias, the majority funded by pharmaceutical companies. Follow-up ranged from six months to 36 months.BenefitAt six to 36 months the American College of Rheumatology (ACR) 50 response rate was statistically significantly improved with etanercept plus DMARD treatment when compared with a DMARD in those people who had an inadequate response to any traditional DMARD (risk ratio (RR) 2.0; 95% confidence interval (CI) 1.3 to 2.9, absolute treatment benefit (ATB) 38%; 95% CI 13% to 59%) and in those people who were partial responders to MTX (RR 11.7; 95% CI 1.7 to 82.5, ATB 36%). Similar results were observed when pooling data from all participants (responders or not) (ACR 50 response rates at 24 months: RR 1.9; 95% CI 1.3 to 2.8, ATB 29%; 36 months: RR 1.6; 95% CI 1.3 to 1.9, ATB 24%). Statistically significant improvement in physical function and a higher proportion of disease remission were observed in combination-treated participants compared with DMARDs alone ((mean difference (MD) -0.36; 95% CI -0.43 to -0.28 in a 0-3 scale) and (RR 1.92; 95% CI 1.60 to 2.31), respectively) in those people who had an inadequate response to any traditional DMARD. All changes in radiographic scores were statistically significantly less with combination treatment (etanercept plus DMARD) compared with MTX alone for all participants (responders or not) (Total Sharp Score (TSS) (scale = 0 to 448): MD -2.2, 95% CI -3.0 to -1.4; Erosion Score (ES) (scale = 0 to 280): MD -1.6; 95% CI -2.4 to -0.9; Joint Space Narrowing Score (JSNS) (scale = 0 to 168): MD -0.7; 95% CI -1.1 to -0.2), and with combination treatment compared with etanercept alone (TSS: MD -1.1; 95% CI -1.8 to -0.5; ES: MD -0.7; 95% CI -1.1 to -0.2; JSNS: MD -0.5, 95% CI -0.7 to -0.2). The estimate of irreversible physical disability over 10 years given the radiographic findings was 0.45 out of 3.0.When etanercept monotherapy was compared with DMARD monotherapy, there was generally no evidence of a difference in ACR50 response rates when etanercept 10 mg or 25 mg was used; at six months etanercept 25 mg was significantly more likely to achieve ACR50 than DMARD monotherapy but this difference was not found at 12, 24 or 36 months. TSS and ES radiographic scores were statistically significantly improved with etanercept 25 mg monotherapy compared with DMARD (TSS: MD -0.7; 95% CI -1.4 to 0.1; ES: MD -0.7; 95% CI -1.0 to -0.3) but there was no evidence of a statistically significant difference between etanercept 10 mg monotherapy and MTX.HarmsThere was no evidence of statistically significant differences in infections or serious infections between etanercept plus DMARD and DMARD alone at any point in time. Infection rates were higher in people receiving etanercept monotherapy compared with DMARD; however, there were no differences regarding serious infections. For those participants who had an inadequate response to DMARDs, the rate of total withdrawals was lower for the etanercept plus DMARD group compared with DMARD alone (RR 0.53; 95% CI 0.36 to 0.77, ATB 18%). No other statistically significant differences were observed in any of the assessed comparisons. Etanercept 25 mg administered subcutaneously twice weekly together with MTX was more efficacious than either etanercept or MTX monotherapy for ACR50 and it slowed joint radiographic progression after up to three years of treatment for all participants (responders or not). There was no evidence of a difference in the rates of infections between groups.

Metabolic Profiling Predicts Response to Anti–Tumor Necrosis Factor α Therapy in Patients With Rheumatoid Arthritis

ObjectiveAnti–tumor necrosis factor (anti-TNF) therapies are highly effective in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), but a significant number of patients exhibit only a partial or no therapeutic response. Inflammation alters local and systemic metabolism, and TNF plays a role in this. We undertook this study to determine if the patient's metabolic fingerprint prior to therapy could predict responses to anti-TNF agents.MethodsUrine was collected from 16 RA patients and 20 PsA patients before and during therapy with infliximab or etanercept. Urine metabolic profiles were assessed using nuclear magnetic resonance spectroscopy. Discriminating metabolites were identified, and the relationship between metabolic profiles and clinical outcomes was assessed.ResultsBaseline urine metabolic profiles discriminated between RA patients who did or did not have a good response to anti-TNF therapy according to European League Against Rheumatism criteria, with a sensitivity of 88.9% and a specificity of 85.7%, with several metabolites contributing (in particular histamine, glutamine, xanthurenic acid, and ethanolamine). There was a correlation between baseline metabolic profiles and the magnitude of change in the Disease Activity Score in 28 joints from baseline to 12 months in RA patients (P = 0.04). In both RA and PsA, urinary metabolic profiles changed between baseline and 12 weeks of anti-TNF therapy. Within the responders, urinary metabolite changes distinguished between etanercept and infliximab treatment.ConclusionThe clear relationship between urine metabolic profiles of RA patients at baseline and their response to anti-TNF therapy may allow development of novel approaches to the optimization of therapy. Differences in metabolic profiles during treatment with infliximab and etanercept in RA and PsA may reflect distinct mechanisms of action.

Treatment patterns with etanercept and adalimumab for psoriatic diseases in a real-world setting

Background: This study examined real-world etanercept and adalimumab treatment patterns in patients with psoriasis, psoriatic arthritis, or both. Methods: This retrospective analysis utilized data from patients with psoriasis, psoriatic arthritis, or both from a large, US claims database. Outcome measures included persistence on index therapy; pauses (7–59 days) and gaps (≥60 days) in therapy; and rates of discontinuing, switching and restarting index therapy in nonpersistent patients. Results: Of 4,453 patients, 2,534 initiated etanercept and 1,919 initiated adalimumab. In psoriasis patients (n = 2,775), 46.4% and 56.8% on etanercept and adalimumab, respectively, were persistent for ≥12 months, 49.0% and 56.3% discontinued, 23.8% and 22.4% restarted and 14.9% and 11.3% switched index therapy within 12 months. In psoriatic arthritis patients (n = 1,197), 60.7% and 63.3% on etanercept and adalimumab, respectively, were persistent for ≥12 months, 48.3% and 51.6% discontinued, 25.8% and 20.0% restarted and 16.5% and 17.9% switched index therapy. In patients with both (n = 481), 58.1% and 59.6% on etanercept and adalimumab, respectively, were persistent for ≥12 months, 42.7% and 63.2% discontinued, 24.3% and 12.6% restarted and 21.4% and 15.8% switched index therapy. Conclusions: Treatment modifications were common in patients with psoriasis, psoriatic arthritis, or both within 12 months of initiating etanercept or adalimumab.

Inhibition of TNF in the Brain Reverses Alterations in RAS Components and Attenuates Angiotensin II-Induced Hypertension

Dysfunction of brain renin-angiotensin system (RAS) components is implicated in the development of hypertension. We previously showed that angiotensin (Ang) II-induced hypertension is mediated by increased production of proinflammatory cytokines (PIC), including tumor necrosis factor (TNF), in brain cardiovascular regulatory centers such as the paraventricular nucleus (PVN). Presently, we tested the hypothesis that central TNF blockade prevents dysregulation of brain RAS components and attenuates Ang II-induced hypertension. Male Sprague-Dawley rats were implanted with radio-telemetry transmitters to measure mean arterial pressure (MAP) and subjected to intracerebroventricular (ICV) infusion of etanercept (10 µg/kg/day) with/without concurrent subcutaneous 4-week Ang II (200 ng/kg/min) infusion. Chronic Ang II infusion resulted in a significant increase in MAP and cardiac hypertrophy, which was attenuated by inhibition of brain TNF with etanercept. Etanercept treatment also attenuated Ang II-induced increases in PIC and decreases in IL-10 expression in the PVN. Additionally, Ang II infusion increased expression of pro-hypertensive RAS components (ACE and AT1R), while decreasing anti-hypertensive RAS components (ACE2, Mas, and AT2 receptors), within the PVN. ICV etanercept treatment reversed these changes. Ang II-infusion was associated with increased oxidative stress as indicated by increased NAD(P)H oxidase activity and super oxide production in the PVN, which was prevented by inhibition of TNF. Moreover, brain targeted TNF blockade significantly reduced Ang II-induced NOX-2 and NOX-4 mRNA and protein expression in the PVN. These findings suggest that chronic TNF blockade in the brain protects rats against Ang II-dependent hypertension and cardiac hypertrophy by restoring the balance between pro- and anti-hypertensive RAS axes and inhibiting PIC and oxidative stress genes and proteins in the PVN.

The effect of etanercept on aortic nitric oxide-dependent vasorelaxation in an unpredictable chronic, mild stress model of depression in rats

Stress has been recognized as a risk factor for cardiovascular disease and depression, but the correlation is not well understood. However, inflammation is known to have a crucial role in both cardiovascular disease and depression. Tumor necrosis factor alpha (TNF-α) is a major cytokine for the activation of neuroendocrine, immune and behavioral responses. Therefore, we aimed to explore the effects of etanercept, an anti-TNF-α fusion protein, on endothelium-dependent vascular reactivity, blood pressure and endothelial nitric oxide synthase (eNOS) immunoreactivity in a model of unpredictable chronic mild stress (UCMS). Male rats were exposed to UCMS for 8 weeks, and etanercept (0.8mg/kg, weekly) was administered during UCMS induction. The systolic blood pressure was recorded by the tail cuff method, and the relaxant responses of the aorta induced by carbachol, sodium nitroprusside (SNP) and papaverine were evaluated in an isolated organ bath system. UCMS rats exhibited an impaired carbachol-induced relaxant response compared to control rats, but there were no significant differences in the SNP- and papaverine-induced relaxant responses between the control and stressed rats. Etanercept treatment improved the carbachol-induced endothelium dependent relaxations observed in rats that experienced UCMS. No significant change in the systemic blood pressure was observed, but decreased expression of eNOS was detected in the UCMS group. Moreover, there were no significant changes in the etanercept treatment group compared to the control rats. Our results suggest that TNF-α could be a mediator of vascular dysfunction associated with UCMS, which leads to decreased expression of eNOS.

Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: a first in human study

ObjectiveThe inflammatory cytokine, tumour necrosis factor α (TNF-α), exerts deleterious cardiovascular effects. We wished to determine the effects of TNF-α antagonism on endothelial function and platelet activation in patients with...

TNF‐a–mediated hyperglycemia in Obese Zucker rats following orthopedic trauma

Obese patients with orthopedic trauma exhibit increased inflammation and complications correlated with high glucose levels. We hypothesize that in obesity there is increase risk of trauma‐induced hyperglycemia due to insulin resistance and inflammation. Fasted lean (LZ) and obese Zucker (OZ) rats were treated with vehicle or etanercept, a TNF‐α inhibitor (2mg/kg, ip.). One hour after the treatment, orthopedic trauma was mimicked by soft tissue injury followed by an injection of bone components into bilateral hindlimbs. Glucose levels were measured for 6 hours following trauma. Under control conditions, OZ exhibited similar basal fasting glucose levels but impaired glucose tolerance (OGTT) as compared with LZ. Etanercept treatment had no effect on the OGTT in LZ or OZ. After trauma, the glucose levels in LZ were moderately increased within 10 minutes and decreased to basal levels after 6 hours (Figure). However, OZ exhibited a severe hyperglycemia as compared with LZ during the 6 hours of recovery after trauma. Etanercept treatment markedly improved the trauma‐induced hyperglycemia in OZ with no effect in LZ. These results suggest an exacerbated trauma‐induced hyperglycemia in obesity due to TNF‐α‐dependent mechanisms. Supported by AHA‐12SDG12050525, NIH HL‐51971, and HL‐89581

Etanercept Improves Lipid Profile and Oxidative Stress Measures in Patients with Juvenile Idiopathic Arthritis

To investigate the effect of 1-year treatment with the anti-tumor necrosis factor-α (TNF-α) drug etanercept on lipid profile and oxidative stress in children and adolescents with juvenile idiopathic arthritis (JIA). Thirty children with JIA (22 females; mean age 12.3 ± SD 5.7 yrs), all eligible for anti-TNF-α treatment, were assessed at baseline and after 6- and 12-month treatment with etanercept. Disease activity was determined using the Juvenile Arthritis Disease Activity Score (JADAS). Blood samples were drawn to measure the acute-phase reactants C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), lipids, and the proinflammatory cytokines TNF-α, interleukin-1β (IL-1β), IL-6 and interferon-γ. To measure the oxidative stress marker 8-iso-prostaglandin F2α, 24-h urine samples were collected. Inflammatory indicators (CRP and ESR) and JADAS scores improved significantly after 1 year of etanercept treatment (all p < 0.001). Proinflammatory cytokines showed significant reduction during the study period (all p < 0.001). Similar reductions were detected in total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p = 0.04), and triglycerides (p < 0.001), whereas no significant change was found in high-density lipoprotein cholesterol. No side effects were observed during the treatment period. This study shows for the first time that anti-TNF-α therapy for JIA is associated not only with a beneficial effect on clinical disease activity and inflammatory indexes, but also with improved lipid profile and oxidative stress. These findings suggest that TNF-α blockers might reduce atherosclerotic risk in children with JIA.

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10−8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10−11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry.

Circulating endothelial cell levels in psoriatic patients and their modification after an anti‐TNF‐alpha (Etanercept) treatment

Endothelial function in psoriatic patients has been mainly evaluated through a high-resolution ultrasound measurement of flow-mediated vasodilation in the brachial artery, which is an operator-dependent and technically demanding technique: this characteristic, together with different patient selection criteria, could account for the conflicting results emerging from different studies. Recently, Circulating Endothelial Cells (CECs) level has been suggested as a novel biomarker of vascular injury. The number of CECs was determined by a semi-automated immunomagnetic system (CellSearch system) in peripheral blood of psoriatic patients (n = 48) and healthy subjects (n = 50). In 15 patients, CEC level was also evaluated after 6 months of treatment with an anti-TNF-alpha agent, Etanercept. The plasma levels of high-sensitivity C-reactive Protein (CRP), E-selectin, VEGF and PAI-1 were measured by ELISA. The psoriasis severity was assessed by PASI score. A statistically significant difference (P = 0.001) was found between CEC level in psoriatic patients (10.6 ± 9.4 cells/mL) vs. the control group (3.9 ± 0.9 cells/mL). This count inversely correlated with sE-selectin levels (r(2) = 0.16; P = 0.03). After 6 months of therapy, patients experienced a significant (P < 0.05) decrease in CEC levels (3.4 ± 1.3 cells/mL) and in PASI score (from 11.7 ± 8.1 to 2.1 ± 4.0). The elevated CECs level that we found in a sample of high selected psoriatic patients could be expression of endothelial damage. Lowering of CECs count after treatment with Etanercept support the hypothesis that an effective systemic therapy of psoriasis may also improve the endothelial function.

Resolution with rituximab of localized scleroderma occurring during etanercept treatment in a patient with rheumatoid arthritis

ejd.2013.1929 Auteur(s) : Maria Sole Chimenti1, Miriam Teoli2, Alessandro Di Stefani3, Alessandro Giunta2, Maria Esposito2 espositomaria@virgilio.it, Roberto Perricone1 1 Department of Rheumatology, 2 Department of Dermatology, 3 Institute of Anatomic Pathology, University of Rome “Tor Vergata”, Viale Oxford 81, 00133 Rome, Italy A 54-year-old man affected by active rheumatoid arthritis (RA) referred to our department for a severe disease exacerbation (disease activity score-28 erythrocyte sedimentation [...]