Etanercept Treatment Research Articles

Unexpected multiple sclerosis-like symptoms in a rheumatoid arthritis patient treated with Etanercept: A case report.

Although tumor necrosis factor (TNF) inhibitors are used to prevent autoimmune disease, but they can cause adverse effects. Multiple sclerosis syndrome is one of the rare complications following treatment with TNF inhibitor. We reported a case of rheumatoid arthritis with unfavorable outcome post Etanerecept therapy. Tumor necrosis factor (TNF) inhibitors are prescribed to treat various autoimmune diseases such as rheumatoid arthritis (RA). Etanercept, a human anti-TNF monoclonal antibody, is a therapeutic option in autoimmune and inflammatory diseases. One of the rare adverse effects of Etanercept is developing central nervous system and peripheral nervous system demyelination however, there is controversy in the cause of it. In this case, we presented a 35-year-old woman with multiple sclerosis (MS)-like symptoms due to taking Etanercept. She had a history of RA since the age of 18 years and was referred to the emergency department with signs and symptoms of para paresthesia, progressive paraparesis of both lower limbs, and urinary retention a year after Etanercept treatment. We discontinued the Etanercept and started Methylprednisolone and Rituximab. Rapid clinical improvement was noted and in the approximately 6-month follow-up, she did not exhibit any neurological worsening. So it is probable that the initiation of Etanercept triggered MS-like syndrome in these patients and healthcare practitioners should take heed of this adverse effect.

Factors Associated with the Development of Anti-drug Antibodies to TNFi and the Consequences for Axial Spondyloarthritis: A Two-year Follow-up Study.

To evaluate the development of anti-drug antibodies (ADAb) against tumor necrosis factor inhibitors (TNFi) therapy during a 2-year period and search the factors linked to patients with axial spondyloarthritis (axSpA). Biologic-naive patients with axSpA were included in this observational study. Serum drug levels and ADAb were measured at weeks 12, 24, 52, and 104 of treatment by enzyme-linked immunosorbent assay (ELISA). The development of ADAb and factors related to ADAb over time were investigated using generalized estimating equations (GEE). A total of 180 patients with axSpA (116 male, mean (±SD) 45.6 (±11.9) years) who started TNFi treatment (etanercept (32.2%), adalimumab (27.2%), golimumab (20.6%), infliximab (20%)) were included. In the etanercept treatment group, only 1 patient had ADAb at 12 weeks and 24 weeks. Anti-drug antibodies against TNFi drugs were present in the adalimumab group in 32.7% of patients and in the infliximab group in 21.2% of patients at 12 weeks, and the proportion of ADAb-positive patients were found to be stable throughout the follow-up for adalimumab- and infliximab-treated patients. In the golimumab group, one patient had ADAb against golimumab at 12 weeks and the proportion of ADAb-positive patients increased throughout follow-up. In longitudinal analysis, baseline age, TNFi type, longitudinal Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and ASDAS-CRP scores, serum C-eeactive protein (CRP) levels, presence of adverse events and treatment discontinuation were associated with the presence of ADAb. The development of ADAb against TNFi therapy is associated with younger age, high disease activity, the development of adverse events and more common treatment discontinuation in patients with axSpA during 2-year follow-up.

The Expression of Vitamin D Receptor on Peripheral Blood Mononuclear Cells in Patients with Psoriasis.

Vitamin D plays an important role in psoriasis, but its involvement in pathogenesis remains unclear. This study aimed to evaluate vitamin D receptor (VDR) expression on peripheral blood mononuclear cells (PBMCs) in patients with psoriasis and healthy controls and to study the effects of the Etanercept treatment on VDR expression on PBMCs in patients with psoriasis. Twenty patients with moderate to severe psoriasis received treatment with Etanercept for 24 weeks. The age- and sex-matched controls did not receive any intervention. VDR expression on CD3+ lymphocytes and CD14+ monocytes, and serum levels of total and free 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxy vitamin D (1,25(OH)2D) were analyzed at baseline, after 10-12 weeks, and after 24 weeks in both groups. VDR expression was analyzed using flow cytometry. We observed higher expression of the VDR on CD14+ monocytes in psoriasis patients compared to healthy controls at baseline. This difference was no longer significant after 24 weeks of the Etanercept treatment. The patients with psoriasis improved clinically. However, VDR expression was unaltered during the Etanercept treatment, and there was no correlation between VDR expression and disease severity.

Summary of Research: Ten-Year Safety and Clinical Benefit from Open-Label Etanercept Treatment in Children and Young Adults with Juvenile Idiopathic Arthritis.

This is a summary of the original article 'Ten-year safety and clinical benefit from open label etanercept treatment in children and young adults with juvenile idiopathic arthritis'. Juvenile idiopathic arthritis (JIA) usually appears before the age of 16. JIA causes pain, swelling, and stiffness in the joints. People with JIA receive treatment for several years until the disease goes into prolonged remission. Therefore, the long-term safety of these treatments is an important topic. Etanercept is a treatment for JIA, which acts on the body's immune system to reduce arthritis. This summary of research article describes safety and how well etanercept works in children with JIA taking it for up to 10years.

Real-life data of etanercept efficacy and safety in juvenile idiopathic arthritis: a 24-month retrospective study at a single center

ABSTRACT Objective The aim of this study was to assess the efficacy and safety of etanercept (ETA) use in juvenile idiopathic arthritis (JIA). Methods The 24-month data of patients with JIA on etanercept in a single center were evaluated retrospectively. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), and JIA-American College of Rheumatology (ACR) improvement criteria. Safety assessments were based on adverse event (AE) reports. Results The study included 152 patients with JIA. The mean age at diagnosis of JIA was 8.5 ± 4.4 years, and treatment with ETA started at a mean age of 11.1 ± 4.4 years. The mean duration of ETA use was 16 ± 11.1 months. The mean JADAS10 score at baseline was 18.5 ± 5.9. By the third month, it had reduced to 8.6 ± 6.6 and by the sixth month to 5.7 ± 6. By the twelfth month, the JADAS10 score was 4.9 ± 6.7, and by the twenty-fourth month, it had worsened to 7.3 ± 7.8. ACR50 response was achieved in 79.6% of patients at 3 months, 67.1% at 6 months, 79.3% at twelfth months, 70.7% at the twenty-fourth month. During ETA treatment, 10 patients required hospitalization for serious infections. Conclusion Etanercept is a safe and effective option for patients with JIA. However, variations in response between JIA subtypes highlight the need for individualized treatment strategies.

Electrical stimulation of the arterial splenic nerve has durable therapeutic efficacy on murine collagen-induced arthritis.

Abstract Vagus nerve (VN) stimulation has anti-arthritic effects in animal models and in patients with rheumatoid arthritis (RA). However, VN stimulation may affect several physiological functions. The splenic nerve (SpN) has been implicated in VN-mediated immunomodulation. We tested the therapeutic efficacy of arterial SpN stimulation (SNS) on collagen-induced arthritis (CIA) in mice as a single treatment or in combination with etanercept or Jak inhibitor. SNS was evaluated in mice with CIA before or after disease onset and applied one or six times daily. Alternatively, mice were treated with etanercept or propranolol three times a week. SNS treatment of CIA mice before the onset of clinical symptoms prevented disease in a β1/β2-adrenoceptor-dependent manner. After SNS treatment, splenic inflammatory monocytes, B cells and autoantibody-secreting cells were reduced, as were serum levels of TNF and anti-collagen antibodies. When SNS was tested as a therapeutic modality in already diseased mice, clinical scores were significantly reduced compared to sham-treated animals. Importantly, the therapeutic efficacy of SNS was enhanced when combined with etanercept treatment. The results of this study suggest that SNS may have potent therapeutic anti-arthritogenic effects.

How Safe Are Biological Agents in Pediatric Rheumatology?

Biologic therapy has changed the prognosis of patients with rheumatologic disease. Despite all benefits of the biological agents, adverse events may occur due to their long-term use. The aim of this study is to analyze the adverse events observed in pediatric patients who received biological treatment. This retrospective observational cohort study was conducted between January 2010 and January 2022. File records of 139 patients used biological agents for rheumatologic diseases in a pediatric rheumatology clinic were evaluated. Diagnosis, received treatment, the rationale for stopping treatment, requirement of tuberculosis prophylaxis, presence of an adverse event, and results were recorded. The most used biological therapy was etanercept (41.7%). Anakinra, adalimumab, canakinumab were used in 30.9%, 27.3%, 23.7% of patients, and the others in less than 10%. Totally 491 adverse events (97.9/100 patient-years) were encountered during the duration of biological treatment. The most often adverse event was recurrent upper respiratory tract infection in the patients (31.9/100 patient-years). Elevated aminotransferase levels (10.4/100 patient-years), abdominal pain (7/100 patient-years), and headache (5.2/100 patient-years) were among the other common side effects. Isoniazid (INH) prophylaxis was needed before biological treatment in 20.9% of the patients. Tuberculosis developed in none of the patients followed-up for latent tuberculosis, however, it developed in a patient while receiving etanercept due to noncompliance with his scheduled outpatient visits during etanercept treatment. The most commonly used biological treatments were TNFi and IL-antagonists, and the majority of side effects were infections and laboratory abnormalities. Although the rate of serious adverse events is quite low, close follow-up of patients receiving biological therapy is very important.

Patient self-reported experience and satisfaction with golimumab and etanercept treatments for rheumatic diseases: A cohort study.

Golimumab and etanercept both exhibit good efficacy in treating rheumatic diseases, while the patient self-reported measurement of treatment improvement and injection experience lacks sufficient evidence. Hence, this study aimed to compare the satisfaction with disease improvement and injection experience and the level of injection site reactions (ISRs) between golimumab-treated and etanercept-treated patients with rheumatic diseases. A total of 312 patients with rheumatic diseases were serially enrolled. Among them, 158 patients received golimumab (golimumab group); the other 154 patients were treated with etanercept (etanercept group) according to the actual disease status, physician advice, and patient willingness. Satisfaction with disease improvement was assessed using the 7-point Likert scale; satisfaction with injection experience and level of ISRs were both determined by the 5-point Likert scale. Satisfaction degrees with global injection experience (P = .025), injection device (P = .008), injection frequency (P = .010), and injection convenience (P = .003) were superior in the golimumab group to the etanercept group, while satisfaction degrees with global disease improvement, symptom relief, and speed of action did not vary (all P > .050) between the 2 groups. Discomfort (P = .005), swelling (P < .001), pain (P = .028), and burning (P = .035) levels were lower in the golimumab group than in the etanercept group. In addition, among 56 patients with a history of tumor necrosis factor inhibitor treatment before golimumab, 40 (71.4%) patients preferred golimumab to other tumor necrosis factor inhibitor. After switching to golimumab treatment, the level of ISRs in most patients was reduced or comparable. Golimumab achieves a satisfying injection experience and relieves the level of ISRs over etanercept in patients with rheumatic diseases.

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.

Adalimumab exhibits superiority over etanercept in terms of a numerically higher response rate and equivalent adverse events: A real-world finding.

Adalimumab (ADA) and etanercept (ETN) are the most commonly applied biologics for rheumatoid arthritis (RA) management in China; however, the evidence regarding their superiority is controversial. In addition, in real-world clinical settings, many factors may affect the application of these agents, such as dosage and administration period. Therefore, the present real-world study aimed to compare the efficacy and safety of ADA and ETN treatment in RA patients via the propensity score matching method. In total, 105 RA patients receiving ADA (n = 66) or ETN (n = 39) were reviewed in this retrospective study. The propensity score matching method was used to eliminate discrepancies in baseline features. Clinical response, low disease activity (LDA), and remission were evaluated based on the DAS28. Before propensity score matching, compared with ETN, ADA yielded higher rates of clinical response at W24 (97.0% vs. 84.6%, p = .021), LDA at W12 (78.8% vs. 51.3%, p = .003), and remission at W24 (75.8% vs. 46.2%, p = .002). After propensity score matching, compared with ETN, ADA only achieved a higher rate of clinical response at W24 (96.3% vs. 77.8%, p = .043), whereas the rates of LDA and remission were not different between ADA and ETN treatments at any time point (all p > .05). In addition, the incidence of adverse events was not significantly different between the ADA and ETN treatments (all p > .05). ADA shows superiority over ETN in terms of a numerically greater response rate and equivalent adverse events.

Etanercept induced erectile dysfunction

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial spine. Etanercept is a Tumor necrosis factor-alpha inhibitor (anti-TNF) that is widely used in the treatment of AS. The most common side effects of etanercept are infection, rash, and injection site reaction. Here, we reported an adverse event probably associated with etanercept. Case Presentation: A 30-year-old male patient with AS initiated etanercept due to uncontrolled back pain despite adequate doses of non-steroidal anti-inflammatory drugs. He developed erectile dysfunction (ED) within 1 month of etanercept treatment. ED disappeared after switching to secukinumab. Conclusion: There is limited data on the potential effects of anti-TNF on sexual function. ED might be a rare side effect of etanercept that resolves upon discontinuation of the drug. Secukinumab might be considered as an option in case of etanercept induced ED. Even though ED is not a life-threatening side effect, switching medications could significantly improve patients&amp;apos; quality of life.

A Case of Psoriasiform Dermatitis During Etanercept Treatment in a Patient with Rheumatoid Arthritis

A Case of Psoriasiform Dermatitis During Etanercept Treatment in a Patient with Rheumatoid Arthritis

Formation and clearance of TNF-TNF inhibitor complexes during TNF inhibitor treatment.

Millions of patients with inflammatory diseases are treated with tumour necrosis factor (TNF) inhibitors (TNFi). Individual treatment response varies, in part related to variable drug clearance. The role of TNF-TNFi complexes in clearance of the different TNFi is controversial. Moreover, mechanistic insight into the structural aspects and biological significance of TNF-TNFi complexes is lacking. We hypothesized a role for Fc-mediated clearance of TNF-TNFi immune complexes. Therefore, we investigated circulating TNF-TNFi complexes upon treatment with certolizumab-lacking Fc tails-in comparison with adalimumab, golimumab, infliximab and etanercept. Drug-tolerant ELISAs were developed and used to quantify TNF during adalimumab, golimumab, etanercept, certolizumab and infliximab treatment in patients with inflammatory arthritis or ulcerative colitis for a maximum follow-up of 1 year. Effects on in vitro TNF production and Fc-mediated uptake of TNF-TNFi complexes were investigated for all five TNFi. Circulating TNF concentrations were >20-fold higher during certolizumab treatment compared with adalimumab, reaching up to 23.1 ng·ml-1 . Internalization of TNF-TNFi complexes by macrophages depended on Fc valency, with efficient uptake for the full antibody TNFi (three Fc tails), but little or no uptake for etanercept and certolizumab (one and zero Fc tail, respectively). TNF production was not affected by TNFi. Total TNF load did not affect clearance rate of total TNFi. Differences in TNFi structure profoundly affect clearance of TNF, while it is unlikely that TNF itself significantly contributes to target-mediated drug disposition of TNFi.

Investigation of Glycosaminoglycans in Urine and Their Alteration in Patients with Juvenile Idiopathic Arthritis.

(1) Background: In this study, we evaluated the modulation of urine glycosaminoglycans (GAGs), which resulted from etanercept (ETA) therapy in patients with juvenile idiopathic arthritis (JIA) in whom methotrexate therapy failed to improve their clinical condition. (2) Methods: The sulfated GAGs (sGAGs, by complexation with blue 1,9-dimethylmethylene), including chondroitin-dermatan sulfate (CS/DS) and heparan sulfate (HS), as well as non-sulfated hyaluronic acid (HA, using the immunoenzymatic method), were determined in the blood of 89 children, i.e., 30 healthy children and 59 patients with JIA both before and during two years of ETA treatment. (3) Results: We confirmed the remodeling of the urinary glycan profile of JIA patients. The decrease in the excretion of sGAGs (p < 0.05), resulting from a decrease in the concentration of the dominant fraction in the urine, i.e., CS/DS (p < 0.05), not compensated by an increase in the concentration of HS (p < 0.000005) and HA (p < 0.0005) in the urine of patients with the active disease, was found. The applied biological therapy, leading to clinical improvement in patients, at the same time, did not contribute to normalization of the concentration of sGAGs (p < 0.01) in the urine of patients, as well as CS/DS (p < 0.05) in the urine of sick girls, while it promoted equalization of HS and HA concentrations. These results indicate an inhibition of the destruction of connective tissue structures but do not indicate their complete regeneration. (4) Conclusions: The metabolisms of glycans during JIA, reflected in their urine profile, depend on the patient's sex and the severity of the inflammatory process. The remodeling pattern of urinary glycans observed in patients with JIA indicates the different roles of individual types of GAGs in the pathogenesis of osteoarticular disorders in sick children. Furthermore, the lack of normalization of urinary GAG levels in treated patients suggests the need for continued therapy and continuous monitoring of its effectiveness, which will contribute to the complete regeneration of the ECM components of the connective tissue and thus protect the patient against possible disability.

201.2: No differences in long-term diabetes outcomes with etanercept or alpha-1 antitrypsin treatment in total pancreatectomy and islet autotransplantation: A randomized controlled pilot study

201.2: No differences in long-term diabetes outcomes with etanercept or alpha-1 antitrypsin treatment in total pancreatectomy and islet autotransplantation: A randomized controlled pilot study

Outcomes following switching from etanercept originator to etanercept biosimilar in 1024 patients with RA: a matched-analysis of the BSRBR-RA.

Adults with RA are being switched from etanercept originator to biosimilar in non-medical/cost-saving switching. This analysis aims to investigate outcomes in these patients, including (i) drug survival and (ii) disease activity at 6 months and 12 months, compared with those who remain on the originator. Using BSRBR-RA, those who switched directly from etanercept originator to biosimilar were identified and matched to patients receiving the originator, based on gender, age, disease duration and originator start year. Drug survival was calculated; Cox-proportional hazard models assessed differences in drug persistence between those who switched vs remaining on originator. Change in DAS28 after 6months and 12months was compared between cohorts. Multiple imputation was used. A total of 1024 adults with RA switching from etanercept originator to biosimilar were included, with a matched cohort of patients remaining on the originator. Patients who switched onto a biosimilar product were no more likely to discontinue etanercept treatment vs those who remained on the originator; hazard ratio 1.06 (95%CI 0.89-1.26), with 65% of patients remaining on treatment at three years. Ninety-five (9%) patients switched back to the originator within the first year. After 6months and 12months, biosimilar patients were no more likely to have a worsening of DAS28 (>0.6units) compared with those who remained on the originator. This is the largest matched comparative effectiveness analysis showing patients switching from etanercept originator to biosimilar appearing to do just as well with regard to disease activity and drug persistence compared with those who remained on the originator. These data will be reassuring to clinicians and patients regarding non-medical switching.

Etanercept Mitigated Renal Injury in Male Rats Undergoing Global Renal Ischemia-Reperfusion

The kidneys are vulnerable to injury from ischemia-reperfusion (IR), a process that triggers inflammation and apoptosis, primarily mediated by tumor necrosis factor (TNF)-alpha. Numerous studies have investigated renal damage in this context. Etanercept, a soluble receptor for TNF-alpha, has demonstrated anti-inflammatory and anti-apoptotic properties. This study aims to assess the potential of etanercept in mitigating experimental renal IR injury and its capacity to protect against widespread renal ischemia/reperfusion injury. Methods: Male Sprague-Dawley (SD) rats were classified into four groups: sham, DMSO-treated, etanercept-treated, DMSO-treated IR, and etanercept-treated IR groups. After 24 hours following IR injury, renal levels of TNF-alpha and TLRs (Toll-like receptors) were assessed using ELISA and IHC methods, respectively. Histopathological analysis was employed to quantify the extent of renal cell injury. Results: Etanercept treatment significantly lowered tissue levels of TNF-alpha and TLRs in IR-damaged rats compared to DMSO-treated IR rats. Kidneys of DMSO-treated IR rats exhibited substantially elevated levels of TNF-alpha and TLRs when compared to DMSO-treated sham rats. Conversely, etanercept-treated IR rats displayed significantly reduced levels of TNF-alpha and TLRs compared to DMSO-treated IR rats. Pre-treatment with etanercept significantly alleviated the extent of damage in IR-injured rats compared to the control and DMSO groups. Etanercept further promoted the downregulation of TLRs and TNF-alpha, thereby enhancing resistance to renal damage during IR. Conclusion: In conclusion, etanercept shows promise in providing protection against renal ischemia-reperfusion injury by mitigating inflammation and apoptosis, as evidenced by reductions in TNF-alpha and TLR levels. This suggests its potential as a therapeutic intervention to mitigate renal damage resulting from ischemia-reperfusion injury.

Transcriptomic responses of peripheral blood mononuclear cells to cyclosporin and etanercept in a female infant with juvenile generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis. An early onset of the diseases is correlated with mutations among IL36RN, CARD14, AP1S3, MPO and SERPINA3 genes. Systemic biological agents including anti-TNF-α, anti-IL-17, anti-IL-12/IL-23, anti-IL1R, anti-IL1β and anti-IL-36R act as novel treatment methods for GPP. Herein we report a female infant clinically diagnosed with GPP since she was 10-month-old. Results of whole-exome sequencing (WES) and Sanger sequencing revealed a reported heterozygous IL36RN (c.115+6T>C) and another reported heterozygous SERPINA3 frame-shifting variant (c.1247_1248del). Initial cyclosporin treatment for the patient led to a partial remission of the symptoms. However, the patient reached nearly total remission of pustules and erythema after anti-TNF-α inhibitor etanercept treatment. Results of further RNA sequencing (RNA-seq) done on peripheral blood mononuclear cells correlated with the clinical responses, showing that cyclosporin suppressed a portion of the neutrophil-related genes, while most genes associated with neutrophil activation, neutrophil-mediated immunity and degranulation were downregulated by the subsequent etanercept treatment. We report this case to demonstrate WES and RNA-seq in combination could come in handy in reaching a precise diagnosis and in evaluating or even predicting the molecular alterations underlying clinical treatment effectiveness.

Occurrence of adverse events and change in disease activity after initiation of etanercept in paediatric patients with juvenile psoriatic arthritis in the CARRA Registry

ObjectiveEtanercept is commonly used to treat juvenile idiopathic arthritis, including juvenile psoriatic arthritis (JPsA); however, information on etanercept’s safety and effectiveness in clinical practice is limited. We used data from...

630 A multicenter single-arm study of etanercept treatment in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) and biomarkers of systemic steroid therapy resistance

630 A multicenter single-arm study of etanercept treatment in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) and biomarkers of systemic steroid therapy resistance