etanercept and sepsis

Adverse events were reported in various patients treated with etanercept, including infections (sepsis and tuberculosis), malignancies (e.g., lymphoma), demyelinating disorders, and autoimmune diseases. Only two adult patients with etanercept-related encephalopathy were previously reported. We describe a 7-year-old patient who developed encephalopathy immediately after his third dose of etanercept. To the best of our knowledge, ours is the first report of a pediatric patient with a diagnosis of systemic arthritis and who developed etanercept-related encephalopathy...

INTRODUCTION: The purpose of this observational study was to analyze the rates, characteristics and associated risk factors of severe infections in patients with systemic autoimmune diseases (SAD) who were treated off-label with biological agents in daily practice. METHODS: The BIOGEAS registry is an ongoing Spanish prospective cohort study investigating the long-term safety and efficacy of the off-label use of biological agents in adult patients with severe, refractory SAD...

INTRODUCTION: Necrotising fasciitis is a severe infection characterised by the fulminant destruction of tissue with associated systemic signs of sepsis and toxicity. Etanercept is a fully human fusion protein that inhibits tumor necrosis factor and the inflammatory cascade. It is effective in the treatment of many disorders but concerns regarding severe life threatening infections have been raised in multiple reports. CASE PRESENTATION: We present the case of a 39-year-old Caucasian man, who presented with sudden onset of severe and progressive neck and left shoulder pain, with a two-year history of seronegative rheumatoid arthritis treated with azathoprine and etanercept...

OBJECTIVE: To evaluate the long-term safety and efficacy of etanercept therapy in rheumatoid arthritis (RA) patients. METHODS: Adult patients with early RA or longstanding RA received etanercept in open-label extension studies following initial double-blind trials of etanercept. RESULTS: Of 558 early RA patients and 714 longstanding RA patients who received at least 1 dose of etanercept, a total of 194 early RA patients and 217 longstanding RA patients were treated with 25 mg of etanercept twice weekly through 10 years...

The biological treatments for psoriasis, mainly the tumor necrosis factor-alpha inhibitors (TNF-alpha), have demonstrated their efficacy and safety beginning with the clinical trials up to their subsequent marketing. However, pharmacovigilance studies have detected a mild increase in infections. For the management of infectious risk in patients with psoriasis being treated with etanercept or other anti-TNF medications, an evaluation should be made of the adequacy of its use in patients infected by HCV, HBV, HIV, with localized or generalized infections, with risk of sepsis (carriers of intravenous catheter and indwelling urinary catheter) or with underlying disorders that could predispose them to infections (diabetes, hemodialysis)...

BACKGROUND: TNF inhibitors have revolutionized the treatment of psoriasis vulgaris as well as psoriatic and rheumatoid arthritis and Crohn disease. Despite our understanding that these agents block TNF, their complex mechanism of action in disease resolution is still unclear. OBJECTIVE: To analyze globally the genomic effects of TNF inhibition in patients with psoriasis, and to compare genomic profiles of patients who responded or did not respond to treatment. METHODS: In a clinical trial using etanercept TNF inhibitor to treat psoriasis vulgaris (n = 15), Affymetrix gene arrays were used to analyze gene profiles in lesional skin at multiple time points during drug treatment (baseline and weeks 1, 2, 4, and 12) compared with nonlesional skin...

Acute graft-versus-host disease following orthotopic liver transplantation is a rare but feared complication arising in 1% to 2% of cases with a dismal prognosis. It most often presents as fever, rash, and diarrhea with or without pancytopenia. Patients die from complications of marrow failure such as sepsis or bleeding. Because of its low incidence, there is no clear treatment protocol for this complication. Both increasing and withdrawing immunosuppression have been attempted with variable success. Although anti-tumor necrosis factor alpha therapy has been widely used for the treatment of steroid-resistant acute graft-versus-host disease in the hematopoietic stem cell transplant setting, there previously have been no reported cases of its use in liver transplantation...

Mycobacterium mucogenicum is a recently characterized organism that rarely may cause human infections. This rapidly growing mycobacterium is commonly identified in tap water. Both immunosuppressed and immunocompetent patients may develop infections from Mycobacterium mucogenicum. Some patients have experienced lethal disease, including sepsis. Infections occurring in the skin and soft tissues have been described only after a preceding injury. We present the first case of infection with Mycobacterium mucogenicum occurring in a patient on the TNF-alpha antagonist etanercept and without any prior soft tissue injury...

Tumour necrosis factor (TNF) ligand members and their associated TNF receptor (TNFR) superfamilies have many diverse physiological roles. TNF is thought to play a critical role in the pathophysiology of a range of diseases including refractory asthma, sepsis, ankylosing spondylitis, lupus, type II diabetes, multiple sclerosis and psoriasis. The recent continued expansion of the novel anti-TNF therapeutic agents (etanercept and infliximab) has seen major improvements in the treatment of some inflammatory-based human diseases including notably rheumatoid arthritis and Crohn's disease, with other conditions currently being trialled using anti-TNF agents...

OBJECTIVE: To report the efficacy and adverse events with the use of anti-TNFalpha agents in pediatric patients with rheumatic diseases. PATIENTS AND METHODS: Retrospective, observational clinical case series of patients with rheumatic diseases refractory to the conventional treatment. Infliximab and etanercept were the the drugs used. RESULTS: Thirty patients received anti-TNFalpha therapy: Juvenile Idiopathic Arthritis (18), chronic idiopathic anterior uveitis (2), juvenile dermatomyositis (4), Blau syndrome (1), relapsing polychondritis (2), CINCA syndrome (1), and microscopic polyangiitis (1)...

BACKGROUND: Clinical improvement during the treatment of rheumatoid arthritis (RA) with the TNFalpha antagonists has been well documented. Our knowledge of uncommon adverse drug reactions (ADRs) with these new drugs is more restricted. Concerns have been raised that these types of drugs could cause an increased frequency of infections, and already existing infections are named as contraindications in the product labels. METHODS: In Sweden, it is compulsory for healthcare professionals with permission to prescribe drugs to report suspected ADRs to the regulatory authority, the Medical Product Agency (MPA)...

Conventional systemic treatments for patients with psoriasis are associated with multiple adverse effects that require continuous monitoring. The introduction of new biological agents such as etanercept, a fully human fusion protein, has permitted individualisation of patients' treatment according to disease stage. The drug is a competitive inhibitor of tumour necrosis factor-alpha (TNFalpha) that prevents interaction between this cytokine and its cell surface receptors. Etanercept also modulates the activity of other inflammatory cytokines and does not induce complement-mediated cell lysis in vitro...

UNLABELLED: Macrophage activation syndrome (MAS) is a rare and potentially lethal complication of chronic rheumatic diseases of childhood, in particular of systemic-onset juvenile idiopathic arthritis (s-JIA), resulting from uncontrolled activation and proliferation of T lymphocytes and macrophages. The onset, acute and dramatic, may mimic a flare of the underlying disease or a severe sepsis. Diagnosis is difficult and, until now, no specific criteria have been developed. Laboratory data show pancytopenia, coagulopathy, low ESR and low concentrations of serum albumin, and high levels of ferritin, liver enzymes and triglycerides...

Tumor necrosis factor alpha (TNF-alpha) blocking drugs improve therapy for rheumatic diseases, but the risk of additional immunosuppression and infection is unclear. We report on a patient with rheumatoid arthritis treated with etanercept for 2 years, in addition to methotrexate and prednyliden, who developed fulminant pneumococcal pneumonia with rapid progression to fatal acute respiratory distress syndrome (ARDS) and septic shock. In patients receiving anti-TNF-alpha therapy, especially in combination with corticosteroids, signs of pulmonary infection should be regarded as very serious, as fulminant pneumonia with ARDS and severe sepsis may develop within 24 h...

The tumor necrosis factor blocking agent etanercept is effective in the treatment of chronic inflammatory diseases. Previously published studies provided no evidence for an elevated frequency of severe adverse events under therapy. The present work documents efficacy and safety of long-term treatment with etanercept up to four years in 29 patients with rheumatoid arthritis in single German study center. Follow-up examinations were conducted at monthly intervals. The response was assessed in an intention-to-treat analysis (last observation carried forward) according to the ACR and EULAR criteria...

Upregulation of tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of several inflammatory conditions, including rheumatoid arthritis. Therapeutic agents such as antibodies or soluble TNF-alpha receptor analogs, which block TNF-alpha activity are a recent addition to the therapeutic armamentarium for the conditions. We describe a patient who developed aplastic anemia complicated by sepsis after receiving etanercept, a TNF-alpha receptor analog, for the treatment of rheumatoid arthritis...

The ongoing evaluation of the cytokine-cascade and the steadily growing knowledge about cytokine mediated processes seem to open striking therapeutical options in the fields of sepsis, autoimmune and chronic inflammatory joint or bowel diseases via modulation or inhibition of the cytokine-cascade. There is no doubt about the efficacy of the various anticytokine-treatments in the therapy of chronic inflammatory rheumatic diseases. A large number of preclinical and clinical studies forms the scientific basis for these almost widely established therapies...

OBJECTIVE: With rising numbers of anti-tumour necrosis factor alpha (TNF-alpha) treatments for rheumatoid arthritis (RA), Crohn's disease and other conditions, physicians unaware of potential pitfalls are increasingly likely to encounter associated severe infections. Our purpose was to assess the incidence and nature of severe infections in our RA patients under anti-TNF-alpha therapy. METHODS: We reviewed patient charts and records of the Infectious Disease Unit for serious infections in patients with RA in the 2 yr preceding anti-TNF-alpha therapy and during therapy...

The management of rheumatoid arthritis (RA) with biological response modifiers (BRMs) is reviewed. RA, an autoimmune disorder affecting 1-2% of the world's population, is characterized by inflammation of synovial tissues, joint swelling, stiffness, and pain that may progress to joint erosion. There is strong evidence that inflammatory mediators, such as tissue necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), play a critical role in the pathogenesis of this disorder. IL-1-receptor antagonist (IL-1Ra) is produced in healthy subjects and helps to protect against the adverse effects associated with IL-1 overexpression...

The impressive anti-inflammatory effects of the tumor necrosis factor (TNF)alpha blockers etanercept and infliximab have led to their use in multiple inflammatory diseases besides their original indication, rheumatoid arthritis (RA). The well-studied clinical effects of both agents in RA are the reduction of signs and symptoms of joint inflammation as well as the arrest of bone destruction. Infliximab has also been Food and Drug Administration-approved in the treatment of Crohn disease; etanercept is now FDA-approved for juvenile chronic arthritis and psoriatic arthritis...