Etanercept Treatment In Patients Research Articles

Etanercept in Axial Spondyloarthritis, Psoriatic Arthritis, and Plaque Psoriasis: Real-World Outcome Data from German Non-interventional Study ADEQUATE.

For chronic diseases such as axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and plaque psoriasis (PsO), treatment goals include remission or at least low disease activity (LDA) by 12weeks. Improvements in symptoms such as pain and fatigue should also be treatment goals. ADEQUATE was a German, prospective, non-interventional study to evaluate the proportion of patients with rheumatoid arthritis, PsA, axSpA, or PsO who, in routine clinical practice, benefit from the continuation of treatment with etanercept (ETN) beyond 12weeks, even when their treatment goals have not yet been reached. Patient-reported outcomes (PROs) and changes in concomitant glucocorticoid use were also recorded. This article focuses on results for patients with axSpA and PsA; data for patients with PsO are described briefly. In total, 305, 254, and 70 patients with axSpA, PsA, and PsO, respectively, were included. Rates of remission at week12 and week24, respectively, were 19% and 18% for axSpA, 38% and 51% for PsA, and 7% and 19% for PsO. Rates of LDA at week12 and week24, respectively, were 39% and 45% for axSpA, 50% and 60% for PsA, and 34% and 51% for PsO. Extending treatment up to 52weeks was associated with stable rates of or further increases in remission and LDA rates. Improvements in pain, fatigue, and depression (axSpA, PsA, and PsO) and reductions in concomitant glucocorticoid use (axSpA and PsA) were observed. No new safety signals were detected. These findings confirm the effectiveness and safety of ETN in routine clinical practice for several indications and highlight potential benefits of continuing ETN treatment in patients who have not reached their treatment goals after 12weeks. Additional benefits included improvements in PROs and reduction of concomitant glucocorticoids. ClinicalTrials.gov NCT02486302.

Etanercept as a successful therapy in autoinflammatory syndrome related to TRNT1 mutations: a case-based review.

Mutations in the gene encoding tRNA nucleotidyltransferase 1 (TRNT1) are associated with heterogeneous phenotypes and multisystem involvement of variable severity and progression. Immunodeficiency and inflammation are recurrent-associated features. The use of cytokine inhibitors in suppressing the inflammatory phenotype has been recently reported, with a 3-year follow-up for patients treated with Etanercept. We report on two unrelated patients sharing the same clinical condition, who had been referred to our Pediatric Rheumatology Unit because of recurrent fever associated with cutaneous lesions and increased levels of inflammatory markers since their first months of life. Whole exome sequencing allowed to identify compound heterozygosity for functionally relevant variants in TRNT1 as the only molecular event shared by the two patients. Both patients have been treated with Etanercept during 11 years, documenting normalization of inflammatory indexes and resolution of recurrent fever and associated symptoms. This is the longest follow-up assessment of Etanercept treatment in patients with TRNT1 mutations. Our findings confirm efficacy and safety of the treatment. Key Points • Mutations in TRNT1 have been associated with phenotypic heterogeneity. • We report on two patients with early-onset autoinflammatory syndrome. • Whole exome sequencing led to reveal compound heterozygosity for two variants in TRNT1 in both patients. • The patients were successfully treated with Etanercept for more than 10 years, the longest follow-up described in literature.

BACTRIM-RESPONSIVE HIGHLY SUSPECTED PNEUMOCYSTIS PNEUMONIA IN ETANERCEPT-TREATED RHEUMATOID ARTHRITIS PATIENT WITH CHRONIC ADRENAL INSUFFICIENCY: CASE REPORT

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Pneumocystis pneumonia (PCP) is a life-threatening infection that mainly occurs in immunocompromised patients. Etanercept inhibits tumor necrosis factor-alpha (TNFα) and has FDA approval to treat inflammatory arthritis including rheumatoid arthritis (RA). There are only a few cases of PCP have been reported in association to etanercept-treated RA. We report a patient with etanercept-treated RA who likley developed PCP that responded to Bactrim. CASE PRESENTATION: A 50 year old Caucasian woman with polysubstance abuse history, chronic adrenal insufficiency on hydrocortisone, and rheumatoid arthritis (RA) treated with etanercept presented from a rehabilitation facility with lethargy and sepsis. HIV was negative. Urinalysis showed 15 WBC, 4+ bacteria and + nitrite and chest X-ray (CXR) showed right lower lobe (RLL) opacities compatible with aspiration pneumonia. She was treated with IV fluids, stress dose hydrocortisone, metronidazole, and ceftriaxone and etanercept was put on hold. Blood cultures showed no bacterial growth and the urine culture grew pan-sensitive E.coli. Her lethargy improved, and sepsis resolved by day-4 of admission. On day-5, she started to have episodes of shortness of breath and became hypoxic. Arterial blood gas (ABG) on room air showed PaO2 of 46 mmHg. CXR showed worsening infiltrates. Chest computed tomography angiography showed three small peripheral pulmonary emboli, extensive bilateral interstitial infiltrates and RLL airspace disease. She was started on IV heparin. 2D echocardiogram was unremarkable. Azithromycin was added without improvement. On day-8, LDH was 277 U/L; Bactrim and prednisone were initiated and the other antibiotics were discontinued. On day-11, CXR revealed partial resolution of the bilateral infiltrates and the patient underwent bronchoscopy with bronchial washings, which were inconclusive. The patient refused a repeat diagnostic bronchoscopy. She continued to clinically improve and was discharged on day-20 on Bactrim. DISCUSSION: Patients with RA receiving biological antirheumatic drugs are at risk for developing life-threatening pulmonary fungal infections. In our case, the clinical and radiographic findings were highly suggestive of PCP despite having an inconclusive BAL, which could be explained by a low burden of organisms, inadequate specimen, and/or prior treatment. Although the patient had multiple small peripheral pulmonary embolisms, it did not explain the degree of her hypoxia and the fact that she improved with Bactrim making the diagnosis of PCP more likely. CONCLUSIONS: PCP should be suspected in hypoxic patients on etanercept therapy. In such cases coverage with Bactrim (sulfamethoxazole/trimethoprim) should be initiated on suspicion and etanercept should be discontinued. Reference #1: Tanaka M, Sakai R, Koike R, et al. Pneumocystis jirovecii pneumonia associated with etanercept treatment in patients with rheumatoid arthritis: a retrospective review of 15 cases and analysis of risk factors. Mod Rheumatol. 2012;22(6):849-858. Reference #2: Galli M, Antinori S, Atzeni F, et al. Recommendations for the management of pulmonary fungal infections in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2017;35(6):1018-1028. DISCLOSURES: No relevant relationships by Muhammad Hammami, source=Web Response No relevant relationships by ahmad irshad, source=Web Response No relevant relationships by Navneet Kaur, source=Web Response No relevant relationships by Levonti Ohanisian, source=Web Response

Serum interleukin-6 and survivin levels predict clinical response to etanercept treatment in patients with established rheumatoid arthritis

Objectives: To investigate the correlation of nine potential biomarkers with clinical response to etanercept (ETN) therapy in establish rheumatoid arthritis (RA) patients.Methods: Seventy-three patients with established RA were enrolled in the prospective cohort study. Sixty-nine of 73 cases were included into final analysis for response after 24-week ETN therapy. Serum expression of nine studied proteins was measured by enzyme-linked immunosorbent assay (ELISA). Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-17A, IL-21, IL-34, RANKL, survivin, and COMP were selected as candidate biomarkers.Results: Serum IL-6 level was increased in responders than in nonresponders at baseline, p = .034; to the contrary, serum survivin level was decreased in responders, p = .009. Receiver operating characteristic (ROC) curve illuminated the combination of IL-6 and survivin expressions could predict clinical response with a high AUC 0.875, 95% CI: 0.771–0.976. Furthermore, we found the combination of IL-6 high expression and survivin low expression increased the responding possibility to nearly 20-fold (OR 19.687, 95% CI: 4.087–94.839, p < .001) compared to IL-6 low or survivin high expression by univariate analysis. However, only survivin low expression (p = .002) and CRP (p = .014) high expression were independent predictive factors for achieving clinical response, while IL-6 lack independent predictive value (p = .267).Conclusions: Comprehensive measurement of IL-6 and survivin in serum could be served as a convincing biomarker for clinical response in ETN-treated patients with established RA.

Single nucleotide polymorphisms of ABCB1 gene and response to etanercept treatment in patients with ankylosing spondylitis in a Chinese Han population.

Background:Etanercept was highly recommended for patients with ankylosing spondylitis (AS), as its efficacy has been confirmed in AS, while genetic polymorphisms, by affecting drug metabolism or drug receptor, lead to interindividual variability in drug disposition and efficacy. Therefore, this study aims to investigate whether ABCB1 gene polymorphisms can predict therapeutic response to etanercept in patients with AS.Methods:A total of 185 patients with AS in our hospital were recruited into our study from December 2012 to May 2015. The frequency distributions of genotype and allele of rs2032582, rs1128503, and rs1045642 were detected by polymerase chain reaction (PCR) and electrophoresis verification enzyme products method. AS patients received etanercept treatment for 12 weeks, followed by this would be evaluated by the bath AS disease activity index (BASDAI) score improvement and the assessment of spondyloArthritis international society 20/50/70 (ASAS20/50/70) score improvements to explore the relationship between genotype of ABCB1 gene polymorphisms and therapeutic response to etanercept in patients with AS.Results:After 12 weeks, the BASDAI score mean improvement value of rs2032582 A/A genotype was 2.87 ± 0.52. The ratios of patients with rs2032582 A/A genotype reaching the BASDAI50 and ASAS20 evaluation criteria were 64.29% and 92.86%, respectively. The results indicated that efficacy of etanercept was promoted in rs2032582 A/A genotype. The BASDAI score mean improvement value of rs1128503 C/C genotype was 2.79 ± 0.54 after 12 weeks. The ratios of patients with rs1128503 C/C genotype reaching the BASDAI50 and ASAS20 evaluation criteria were 66.67% and 93.94%, respectively. The results indicated that efficacy of etanercept was promoted in rs1128503 C/C genotype. However, no significant associations were observed between rs1045642 and therapeutic response to etanercept in AS patients.Conclusion:ABCB1 gene rs2032582 and rs1128503 polymorphisms may be associated with the efficacy of etanercept in AS patients. ABCB1 gene polymorphisms can act as biological indicators of etanercept efficacy.

Combination therapy with etanercept in psoriasis: Retrospective analysis of efficacy and safety outcomes from real-life practice.

ObjectiveTo investigate the efficacy and safety outcomes of combination therapy used to optimize etanercept treatment in patients with psoriasis treated in real-life clinical practice.MethodsData from patients presenting with psoriasis, treated initially with etanercept monotherapy, were analysed retrospectively. Patients subsequently treated with combination therapy were further analysed. The Psoriasis Area and Severity Index (PASI) score was recorded for all patients receiving comedication; a subjective pain score was recorded in those with psoriatic arthritis receiving comedication after 12, 24 and 48 weeks’ treatment and thereafter at 6-month intervals.ResultsFrom the database of 400 patients treated with etanercept, 37 patients (18 male; 19 female; mean age 59.43 years) underwent combination therapy due to lack of efficacy. Patients received mostly short-term (range 4–34 weeks) comedication with corticosteroids, cyclosporine, methotrexate, nonsteroidal anti-inflammatory drugs, acitretin or sulphasalazine. There were significant reductions in the mean PASI score from baseline at all timepoints. There were also significant reductions in the mean pain VAS score from baseline at all timepoints in patients with psoriatic arthritis. The drug survival rate was 59.6% over a mean duration of 323 weeks of etanercept treatment. The safety profile of combination therapy was satisfactory.ConclusionsShort-term comedication in combination with etanercept may optimize treatment options and improve long-term drug survival in patients with psoriasis.

EFFICACY AND SAFETY OF ETANERCEPT TREATMENT IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS WITHOUT SYSTEMIC MANIFESTATIONS. THE RESULTS OF AN OPEN PROSPECTIVE STUDY ON THE BASIS OF THE SCIENTIFIC CENTER OF CHILDREN'S HEALTH (MOSCOW)

Background : Addition of genetically engineered biological agents in the paradigm of juvenile idiopathic arthritis (JIA) treatment significantly increased the efficacy of the antirheumatic therapy in patients with this severe chronic disease. Objective . Our aim was to assess the efficacy and safety of etanercept treatment in patients with JIA without systemic manifestations. Methods . The open prospective study included patients with JIA without systemic manifestations treated with etanercept. The treatment was carried out on the basis of the rheumatological department of the Scientific Center of Children's Health (Moscow) in the period from December 2009 to August 2014. To assess the therapy efficacy in a year, we used the improvement definition for pediatric patients of the American College of Rheumatology (ACR pedi ) 30, 50, 70, and 90. Reaching the stage of inactive disease/remission were recorded under С . Wallace criteria and threshold value of the JIA activity index (JADAS71). Results . Totally, the study included 197 patients. After 1 year from the treatment beginning, the ACR pedi 30 improvement was reported in 179 (90.9%) patients, ACR pedi 50 — in 177 (89.8%), ACR pedi 70 — in 168 (85.3%), and ACR pedi 90 — in 135 (68.5%). The stage of inactive disease/remission under C. Wallace criteria was ascertained in 132 (67.0%), under JADAS71 index — in 92 (46.7%) patients. Conclusion. After 1 year of etanercept treatment, the stage of inactive disease/remission and the improvement under ACR pedi 90 criterion have been reported in almost half (45.7%) of patients with juvenile idiopathic arthritis without systemic manifestations. The predictors of a high response to etanercept were a short disease duration, less number of used disease-modifying antirheumatic drugs, and a low level of C-reactive protein in the blood serum before etanercept prescription.

Employment is maintained and sick days decreased in psoriasis/psoriatic arthritis patients with etanercept treatment.

BackgroundPsoriasis and psoriatic arthritis (PsA) impair quality of life, including reduction in employment or job duties. The PRESTA (Psoriasis Randomized Etanercept STudy in Patients with Psoriatic Arthritis) study, a randomized, double-blind, two-dose trial, examined the efficacy of etanercept treatment in patients with moderate-to-severe plaque psoriasis and PsA and the main results have been presented previously. This analysis examined employment status, job duties and sick days, pre-defined endpoints in PRESTA, among this patient population.MethodsParticipants (N = 752) were randomized to receive etanercept 50 mg twice weekly (BIW; n = 379) or 50 mg once weekly (QW; n = 373) for 12 weeks by subcutaneous injection. All participants then received open-label etanercept 50 mg QW for 12 additional weeks, while remaining blinded to the randomization. A pharmacoeconomic questionnaire was administered at baseline, week 12 and week 24 of treatment. The questionnaire included employment status and changing job responsibilities and sick time taken due to psoriasis or PsA. The statistical methods included analysis of covariance, t-test, Fisher’s exact test and McNemar’s test. Last-observation-carried-forward imputation was used for missing data.ResultsEmployment was at least maintained from baseline to week 24 in both dose groups (56% [BIW/QW] and 60% [QW/QW] at baseline, 61% and 60%, respectively, at week 24). Among employed participants, the proportion of patients whose job responsibilities changed due to PsA decreased significantly from baseline to week 24 (17–23% to 5–8%; p < 0.01). Similar results were seen with job responsibility changes due to psoriasis (11–14% to 4%; p < 0.01). The number of monthly sick days also decreased from baseline to week 24 (2.4 days for both treatment groups to 0.7 (BIW/QW) and 1.1 (QW/QW); p ≤ 0.03 for each). No significant differences between the treatment groups were observed for any economic endpoint at any time point.ConclusionsFor patients with moderate-to-severe plaque psoriasis and PsA, etanercept treatment resulted in reducing job responsibility changes due to disease and in reducing sick time. Effective treatment of psoriasis and PsA may reduce missed work days.

Cardiometabolic profile, clinical features, quality of life and treatment outcomes in patients with moderate-to-severe psoriasis and psoriatic arthritis

Cardiometabolic, clinical and quality-of-life (QoL) measures were assessed before and after etanercept treatment in patients who had moderate-to-severe plaque psoriasis with and without psoriatic arthritis (PsA) in the PRISTINE trial. Adult patients were randomized to receive etanercept 50 mg once weekly or twice weekly double-blind for 12 weeks; all patients subsequently received etanercept 50 mg once weekly open-label through week 24. Metabolic syndrome was identified in 44 and 41% of patients with and without PsA, elevated blood pressure in 73 and 56% (p < 0.05) and diabetes in 21 and 9% (p < 0.01), respectively. Significant improvements from baseline in Psoriasis Area Severity Index were observed with etanercept therapy at all time points over 24 weeks (p < 0.001) independent of PsA history. At baseline, patients with PsA had worse QoL than patients without PsA. After 24 weeks of etanercept, both groups had significant improvement from baseline in QoL, but the PsA group had greater improvement than that without PsA. Cardiovascular comorbidities were common in psoriasis patients with and without PsA, suggesting that clinicians need to be attentive to cardiometabolic parameters in this population. Worse QoL was demonstrated in PsA versus psoriasis alone. Regardless of patients’ PsA status, treatment with etanercept significantly improved skin symptoms and QoL measures.

FRI0175 The influence of smoking on clinical response to etanercept therapy in patients with rheumatoid arthritis

BackgroundMany recent studies have suggested that smoking is an important risk factor for rheumatoid arthritis (RA), particulary IgM rheumatoid factor (IgM-RF) and antibodies to citrullinated peptide (ACPA) positive RA, as...

Discontinuation and Adverse Events or Events of Etanercept Treatment in Patients with Rheumatoid Arthritis

Background: This study examined the long-term safety of Etanercept treatment and predictors of the discontinuation and adverse events or events of therapy in patients with rheumatoid arthritis (RA). Material and Method: Adverse events or events were recorded and analyzed for 181 consecutive RA patients followed in our department from 2003 to 2010. All enrolled patients were treated with Etanercept reimbursed by National Health Insurance. Results: A total of 181 RA patients being treated with Etanercept were enrolled, of whom 153 (84.5%) were women. The mean age at diagnosis was 44.8 ± 13.9 years, and the mean age for starting Etanercept treatment was 51.4 ± 13.6 years. The mean duration of Etanercept treatment was 39.4 ± 27.5 months (median 32.6 months; range 1.4 to 87.0 months). At baseline, the mean DAS-28 score was 6.90 ± 1.06. Of the 181 patients, 34 cases (18.8%) developed adverse events or events during the treatment period (mycobacteria in 4, bacterial infections in 17, virus infection in 7, neuropathy in 3, malignancy in 2, and other drug related event in 1). One of the tuberculosis cases with left upper lobe lung lesion was possible due to reactivation. One case had left lower lobe nontuberculous mycobacterium (NTM) pneumonia. One mortality case with hepatitis B virus carrier had hepatitis B flare up with acute liver failure. Of these 34 cases, 16 (34%) discontinued Etanercept treatment. Concomitant treatment with corticosteroid increased the risk of adverse events or events (OR 4.83, 95% CI 1.05-22.19, p=0.043). Patients with an initial DAS-28 score greater than 8.0 (OR 3.20, 95% CI 1.59-6.46, p=0.001) and patients who experienced adverse events or events (OR 2.50, 95% CI 1.30-4.79, p=0.006) were more likely to discontinue Etanercept treatment. Conclusion: Despite the good clinical efficacy of Etanercept treatment, physicians must remain alert for adverse events or events in patients treated with this medication. Extra vigilance is required when treating patients with a combination of Etanercept and corticosteroid. Patients who had initial DAS-28 scores more than 8.0 were more likely to discontinue Etanercept treatment.

Pneumocystis jirovecii pneumonia associated with etanercept treatment in patients with rheumatoid arthritis: a retrospective review of 15 cases and analysis of risk factors

Objectives The association of anti-tumor necrosis factor therapy with opportunistic infections in rheumatoid arthritis (RA) patients has been reported. The goal of this study was to clarify the clinical characteristics and the risk factors of RA patients who developed Pneumocystis jirovecii pneumonia (PCP) during etanercept therapy.Methods We conducted a multicenter, case–control study in which 15 RA patients who developed PCP were compared with 74 RA patients who did not develop PCP during etanercept therapy.Results PCP developed within 26 weeks following the first injection of etanercept in 86.7% of the patients. All PCP patients presented with a rapid and severe clinical course and the overall mortality was 6.7%. Independent risk factors were identified using multivariate analysis and included age ≥ 65 years [hazard ratio (HR) 3.35, p = 0.037], coexisting lung disease (HR 4.48, p = 0.009), and concomitant methotrexate treatment (HR 4.68, p = 0.005). In patients having a larger number of risk factors, the cumulative probability of developing PCP was significantly higher (p < 0.001 for patients with two or more risk factors vs. those with no risk factor, and p = 0.001 for patients with one risk factor vs. those with no risk factor).Conclusion Physicians must consider the possibility of PCP developing during etanercept therapy in RA patients, particularly if one or more risk factors are present.

Effects of TNF inhibitor on innate inflammatory and Th17 cytokines in stimulated whole blood from rheumatoid arthritis patients

Recent studies point to important roles for IL-17 and Th17 cells in sustaining chronic inflammation and articular destruction in rheumatoid arthritis (RA). We investigated the effects of TNF inhibitor on innate inflammatory and Th17 cytokines production by ex vivo lipopolysaccharide (LPS)-stimulated whole blood in patients with RA and the associations of cytokine levels in whole blood cultures with autoantibodies and markers of disease activity. Whole blood cultures from 18 healthy volunteers and 19 RA patients on etanercept therapy were stimulated with LPS and the production of IL-6, TNF-α, IL-23, IL-17A and IL-21 was measured by ELISA. After stimulation with LPS, the interleukin (IL)-17A (p=0.020) and IL-21 (p=0.0001) secretions were significantly higher in patients with RA than in controls, while the TNF-α (p=0.002) was significantly lower at baseline. Etanercept significantly decreased IL-21 production (p=0.007), while IL-6 production (p=0.005) significantly increased after 6months of therapy. IL-21 significantly correlated with RF (r=0.917, p<0.01) and antimutated citrullinated vimentin antibodies (r=0.770, p<0.01) at baseline. Logistic regression analysis revealed that baseline IL-21 levels (p=0.004) were significant predictors of DAS28-ESR at 6months follow-up. Stimulation with LPS increased production of Th17 cytokines in whole blood cultures in patients with RA. Etanercept therapy decreased IL-21 secretion, while the capacity of whole blood cells to produce IL-6 increased. IL-21 production is strongly associated with the levels of autoantibodies. Our findings suggest that IL-21 production in LPS-stimulated whole blood cultures may be predictive of clinical response to etanercept treatment in patients with RA.

Frequency and duration of drug-free remission after 1 year of treatment with etanercept versus sulfasalazine in early axial spondyloarthritis: 2 year data of the ESTHER trial

PurposeThe aims of this study were (1) to assess the frequency and duration of drug-free remission and efficacy of etanercept (ETA) treatment after flare in patients with early active axial...

Pneumocystis jirovecii pneumonia associated with etanercept treatment in patients with rheumatoid arthritis: a retrospective review of 15 cases and analysis of risk factors

The association of anti-tumor necrosis factor therapy with opportunistic infections in rheumatoid arthritis (RA) patients has been reported. The goal of this study was to clarify the clinical characteristics and the risk factors of RA patients who developed Pneumocystis jirovecii pneumonia (PCP) during etanercept therapy. We conducted a multicenter, case-control study in which 15 RA patients who developed PCP were compared with 74 RA patients who did not develop PCP during etanercept therapy. PCP developed within 26weeks following the first injection of etanercept in 86.7% of the patients. All PCP patients presented with a rapid and severe clinical course and the overall mortality was 6.7%. Independent risk factors were identified using multivariate analysis and included age ≥65years [hazard ratio (HR) 3.35, p=0.037], coexisting lung disease (HR 4.48, p=0.009), and concomitant methotrexate treatment (HR 4.68, p=0.005). In patients having a larger number of risk factors, the cumulative probability of developing PCP was significantly higher (p<0.001 for patients with two or more risk factors vs. those with no risk factor, and p=0.001 for patients with one risk factor vs. those with no risk factor). Physicians must consider the possibility of PCP developing during etanercept therapy in RA patients, particularly if one or more risk factors are present.

Significant Decrease in Serum IL-6 and MMP-3 after Etanercept Treatment in Ankylosing Spondylitis Patients

Objective: To evaluate the changes in the level of serum cytokines and inflammation-related mediators before and after etanercept treatment in patients with ankylosing spondylitis (AS).Methods: In an open-label 12-week trial of etanercept (25 mg twice per week) in ethnic Chinese patients with AS, 14 subjects received laboratory tests before and after etanercept. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), transforming growth factor-β (TGF-β), TNF-related apoptosis-inducing ligand (TRAIL) and matrix metalloproteinase (MMP) were measured by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells (PBMC) were stained for toll-like receptor (TLR) 2 and 4, using flow cytometry.Results: Before and 3 months after etanercept treatment, the results showed TNF-α was not detectable at baseline, but significantly increased after etanercept treatment for 2 weeks; however, there was no significant change from month to month. IL-6 in the serum was not very high at baseline, but it was significantly reduced after etanercept treatment (baseline, 14.2 ± 14.5 pg/mL vs. 3 months 4.0 ± 2.8 pg/mL, p=0.001). Like IL-6, MMP-3 also decreased signifi cantly after etanercept treatment (baseline 42.2 ±29.7 ng/mL vs. 3 months 28.6 ± 26.5 ng/mL, p=0.005). IL-1 and IL-8 were not detected. IL-10, TGF-β, and TRAIL levels showed no change. The expression of TLR-2 and TLR-4 on PBMC decreased after 12 weeks, but this was not significant.Conclusion: Serum levels of IL-6 and MMP-3 were significantly decreased after short-term etanercept therapy.

Ultrasonographic assessment of the response to Etanercept treatment in patients with rheumatoid arthritis

To evaluate, using musculoskeletal ultrasound (MSUS), the effects of Etanercept therapy in patients with rheumatoid arthritis (RA) over 3 months of treatment. Eighteen consecutive patients, 3 male and 15 female, affected by RA (ACR criteria) who were non-responders or partial responders to DMARDs therapy were commenced on Etanercept treatment. MSUS was performed bilaterally in the 2nd and 5th metacarpophalangeal, 3rd interphalangeal, wrist and knee joints, using a Philips/HP Image Point HX machine with a 7,5 MHz linear probe for knee joints and a 14 MHz probe for the hands and wrists. In addition, power Doppler was used with the following settings: PRF 700-1000Hz, gain 60-65 dB, low filter. For all the changes a semi-quantitative score (0-3) was used to indicate the presence of a localised inflammatory process (synovitis, tenosynovitis). An overall score was then calculated based on the sum of the single scores in order to obtain a comprehensive score indicative of the global pathological change. The overall score significantly (p<10-5) reduced between T0 (8,5) and T3 (5). Even the most part of the local joint scores significantly reduced. A positive response to treatment with Etanercept was demonstrated by MSUS examination of several joints. The results of our study are supportive of those presented in other reports where MSUS was used to monitor disease activity. We were able however to demonstrate this in a wider range of anatomical targets than in previous studies. MSUS is a useful tool in the monitoring of biologic therapy in RA.

Serum MMP-3 Level as a Biomarker for Monitoring and Predicting Response to Etanercept Treatment in Ankylosing Spondylitis

To investigate whether level of serum matrix metalloproteinase-3 (MMP-3) can serve as a biomarker for monitoring and predicting response to etanercept treatment in patients with ankylosing spondylitis (AS) in daily clinical practice. Ninety-two consecutive AS outpatients with active disease who started etanercept treatment were included in this longitudinal observational study. Clinical data were collected prospectively at baseline and after 3 and 12 months of treatment. At the same timepoints, serum MMP-3 levels were measured retrospectively by ELISA. Since baseline serum MMP-3 levels were significantly higher in male compared to female patients with AS, data analysis was split for gender. Changes in serum MMP-3 levels after etanercept treatment correlated positively with changes in clinical assessments of disease activity and physical function in both male and female patients. Receiver operating characteristic analysis in male patients showed that baseline serum MMP-3 levels had poor accuracy (AUC < 0.7) to discriminate between Assessments in Ankylosing Spondylitis 20 (ASAS20) or ASAS40 responders and nonresponders after 3 or 12 months of treatment. The accuracy of change in serum MMP-3 levels from baseline to 3 months in predicting response after 3 or 12 months of treatment was poor for ASAS40 (AUC < 0.7) or moderate for ASAS20 (AUC = 0.752 and 0.744, respectively), and was not superior to the accuracy of change in the currently used objective biomarkers, erythrocyte sedimentation rate and C-reactive protein. Although significant changes in serum MMP-3 levels were found after etanercept treatment, data analysis indicates that serum MMP-3 levels are not very useful for monitoring and predicting response to etanercept treatment in patients with AS in daily clinical practice.

Resolved Psoriasis Lesions Retain Expression of a Subset of Disease-Related Genes

Psoriasis is a complex inflammatory disease that usually heals without visible scarring. Histological evaluation often suggests complete resolution, but reversal of genomic disease-associated alterations has not yet been defined. Gene expression profiling was used to determine the extent to which the psoriasis genes were reversed after 3 months of etanercept treatment in patients who responded to treatment. We reviewed the histology, leukocyte counts, and PCR data for inflammatory genes, to compare recovery of these parameters and the genomic studies. Many cellular markers do return close to nonlesional levels, although five inflammatory genes did not improve by >75% (IL-12p35, MX1, IL-22, IL-17, and IFNγ). Psoriasis-related genes with <75% improvement were defined as comprising a "residual disease genomic profile," composed of 248 probe sets. Genes of interest in psoriasis tissue that did not return to baseline included LYVE-1, WNT5A, RAB31, and AQP9. It appears that even when the epidermal reaction in psoriasis is fully resolved, inflammation, as defined by expression of key cytokines and chemokines, is not completely resolved in treated lesions. We also found that structural cells of the skin continued to express molecular alterations, and that some subtle features of skin structure, for example, lymphatics, were not fully normalized with treatment.

Clinical, power Doppler sonography and histological assessment of the psoriatic plaque: short-term monitoring in patients treated with etanercept

To date, the diagnosis of psoriasis is based on both clinical history and physical examination, and its severity is assessed by the Psoriasis Area and Severity Index (PASI). Continuous technological advances in the field of sonography have led to the development of equipment with high power Doppler frequency, which allows for very detailed morphological information regarding the dermal blood flow. To compare power Doppler sonography (PDS) with clinical and histological findings before and after etanercept treatment in patients with psoriasis. Twelve patients with a clinical diagnosis of psoriasis were enrolled in this study. The PASI, PDS and histological examinations were assessed in all patients on the same day at baseline, and after 12 weeks of biological treatment. PDS examination was performed by an experienced sonographer, using a sonographic system equipped with transducer ranging from 6 to 18 MHz and Doppler frequency ranging from 7 to 14 MHz. At follow up there was a significant decrease in PASI. A significant change was also detected for the PDS findings (P = 0·005). At baseline the median value for factor VIII staining was 1·5, and the median value for vascular endothelial growth factor (VEGF) staining was also 1·5. At follow up there was a significant decrease in both factor VIII and VEGF staining scores. Moreover, a positive correlation between reduction in PDS score and improvement in clinical and histological scores was found: Spearman's ρ = 0·639, P = 0·0022; Spearman's ρ = 0·619, P = 0·0013; Spearman's ρ = 0·765, P = 0·0002, respectively. Our results show a significant correlation between PDS findings and both PASI and histological degree of vascularization before and after etanercept treatment. These data provide evidence in favour of the validity of PDS in the assessment of dermal perfusional changes in patients with psoriatic plaques.