Anakinra in the treatment of rheumatic disease

Anakinra is a specific receptor antagonist of interleukin-1 that differs from naturally occurring interleukin-1 receptor antagonist by the presence of a methionine group. It is administered by daily subcutaneous injection. Anakinra improves the clinical signs and symptoms of rheumatoid arthritis, slows radiographic progression and improves patient physical function. The most common adverse event is an injection site reaction. Anakinra has been associated with an increased incidence of serious infections and has an increased standardized incidence ratio for lymphoma. It has not been found to be associated with the development of opportunistic infections, worsening of congestive heart failure or the development of demyelinating disease. It appears to be effective in treating adult Stills disease, systemic-onset juvenile idiopathic arthritis and chronic infantile neurological cutaneous and articular syndrome (also known as neonatal-onset multisystem inflammatory disease syndrome).     

The use of biologics and small molecules in pregnant patients with rheumatic diseases

ABSTRACT

Introduction: Biological agents have radically changed the prognosis of rheumatic patients. Current evidence demonstrates that tight disease control during pregnancy is mandatory to minimize adverse outcome risk. As the new therapeutic tools are pivotal to maintain appropriate disease activity, it is timely to review available evidence about the safety of biologics and small molecules in pregnancy.

Areas covered: A comprehensive literature review has been performed, reporting available data about the passage into breast milk, rate of pregnancy loss and fetal malformations, and long-term complications due to in utero exposure to biological agents and small molecules.

Expert commentary: Data about the safety of agents against tumor necrosis factor in pregnancy are reassuring. Even rituximab, tocilizumab, belimumab, ustekinumab, secukinumab, and abatacept have not been associated with an increased rate of fetal abnormalities or adverse pregnancy outcome. Experience with small molecules is too small to draw any conclusion. Even if further data are warranted to define the possible long-term effects of in utero biologic exposure on the infant immune system development, it is reasonable to speculate that in the next future the use of biologics during pregnancy will continue to expand, at least when maternal benefit justifies the potential risk to the fetus.     

阿那白滞素对缺氧-复氧和兴奋性氨基酸所致神经细胞损伤的保护作用

用缺氧-复氧环境和兴奋性氨基酸谷氨酸诱导培养神经元细胞损伤和坏死,观察阿那白滞素(1)对体外培养大鼠脑神经元细胞坏死的保护作用,以研究其抗缺血性脑损伤的作用机制.结果表明,1的3个剂量组(25、50、100μg/ml)均能明显减轻缺氧-复氧所致的神经元细胞损伤,浓度效应呈正相关.定性观察表明,1的3个剂量组对谷氨酸致神经元细胞损伤亦有改善作用,且与浓度相关.提示在缺氧-复氧和兴奋性氨基酸导致的大鼠神经元细胞损伤中可能有IL-1炎症通路参与.     

Therapeutic options for rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder primarily targeting the synovium. Unchecked disease activity is associated with significant morbidity and an increased mortality. Recent advances in the understanding of the pathogenesis of RA and the capability of biologically engineered treatments for RA have expanded the armamentarium of antirheumatic agents. Methods: A systematic literature review was conducted through PubMed. Results/conclusions: At present, a common strategy for the treatment of RA uses methotrexate either as monotherapy or in combination with a variety of conventional and/or biologic disease-modifying antirheumatic drugs (DMARDs), with the goal of inducing remission of active disease. The choice of which agent(s) to use is based upon patient-specific criteria (activity of disease, comorbidities, patient preferences, costs etc.). Emerging therapies that target specific cytokines and growth factors in the inflammatory cascade of RA offer a potent new means of modifying disease activity, but many questions regarding their use remain unanswered.     

Emerging drugs for rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic, autoimmune disease characterized by symmetric arthritis of diarhthrodial joints leading to progressive erosion of cartilage and bone. The individual and social impacts of RA are of great importance. Objective: To investigate the development of new therapies for RA treatment. Methods: Various databases have been searched for new drugs in clinical trials (Phase I – III) and experimental future therapeutic agents for RA. Results/conclusion: The current management of the disease includes the use of disease modifying anti-rheumatic drugs and the biologic therapies. Progress in our understanding of RA pathophysiology led to the identification of new therapeutic targets. These include pro-inflammatory cytokines, T and B cells, adhesion molecules, chemokines and intra- and extracellular signaling pathways. Therapeutic modulation of the above targets can provide new treatment strategies. This article reviews a few of the new treatment strategies currently being evaluated.     

Schnitzler syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment

OBJECTIVE: Schnitzler syndrome is a rare disorder characterized by a chronic urticarial rash and monoclonal gammopathy, accompanied by intermittent fever, arthralgia or arthritis, bone pain, and lymphadenopathy. Our objectives are to systematically review disease characteristics of Schnitzler syndrome and collect follow-up information to gain insight into treatment efficacy and long-term prognosis. METHODS: PubMed and MEDLINE databases (1966-2006) were searched, using the key words "Schnitzler syndrome," and the combination of "urticaria" with "monoclonal gammopathy," "immunoglobulin M (IgM)," or "paraproteinemia," as well as secondary references. Data on a total of 94 patients who met the criteria for Schnitzler syndrome were reviewed. Questionnaires sent to all authors retrieved additional follow-up data on 43 patients, resulting in a mean follow-up of 9.5 years after onset of symptoms, and a follow-up of 20 years or more in 10 patients. RESULTS: Symptoms, signs, and laboratory findings as found in the 94 patients are reviewed in detail. There have been promising developments in therapeutic options, especially antiinterleukin-1 treatment, which induced complete remission in all 8 patients treated so far. To date, no spontaneous complete remissions have been reported. Patients with Schnitzler syndrome showed no increased mortality during the present follow-up. However, they had a 10-year risk of 15% of developing a lymphoproliferative disorder, most notably Waldenstr?m's macroglobulinemia. Three cases of type amyloid A (AA) amyloidosis associated with Schnitzler syndrome were reported. CONCLUSIONS: Schnitzler syndrome is a disabling disorder which affects multiple systems and which can be considered as an autoinflammatory syndrome. There are new, effective treatment options, but close monitoring remains warranted because of the increased risk of lymphoproliferative disease.