TNF Inhibitors Infliximab Research Articles

AB1159 Certolizumab in juvenile idiopathic arthritis (JIA): Experience of 12 patients treated

BackgroundBiological agents have demonstrated a favourable benefit-to-risk profile. Nevertheless, intolerance, lost of efficacy or adverse events has led to try other therapeutic options as the use of new TNF-inibithors. Since...

Extraction of Electronic Health Record Data in a Hospital Setting: Comparison of Automatic and Semi‐Automatic Methods Using Anti‐TNF Therapy as Model

There is limited experience and methods for extractions of drug therapy data from electronic health records (EHR) in the hospital setting. We have therefore developed and evaluated completeness and consistency of an automatic versus a semi-automatic extraction procedure applied on prescribing and administration of the TNF inhibitor infliximab using a hospital EHR system in Karolinska University Hospital, Sweden. Using two different extraction methods (automatic and semi-automatic), all administered infusions of infliximab between 2007 and 2010 were extracted from a database linked to the EHR system. Extracted data included encrypted personal identity number (PIN), date of birth, sex, time of prescription/administration, healthcare units, prescribed/administered dose and time of admission/discharge. The primary diagnosis (ICD-10) for the treatment with infliximab was extracted by linking infliximab infusions to their corresponding treatment episode. A total of 13,590 infusions of infliximab were administered during the period of 2007 to 2010. Of those were 13,531 (99.6%) possible to link to a corresponding treatment episode, and a primary diagnosis was extracted for 13,530 infusions. Information on encrypted PIN, date of birth, time of prescription/administration, time of admission/discharge and healthcare unit was complete. Information about sex was missing in one patient only. Calculable information about dosage was extracted for 13,300 (98.3%) of all linked infusions. This methodological study showed the potential to extract drug therapy data in a hospital setting. The semi-automatic procedure produced an almost complete pattern of demographics, diagnoses and dosages for the treatment with infliximab.

Biologic TNF inhibiting agents for treatment of inflammatory rheumatic diseases: dosing patterns and related costs in Switzerland from a payers perspective

BackgroundTo obtain detailed real-life data on costs and dosing patterns in the utilisation of the TNF inhibitors adalimumab, etanercept, and infliximab in patients treated in Switzerland.MethodsAdministrative claims processed by a major Swiss health insurer between 2005 and 2008 were analysed. Patients with inflammatory rheumatic diseases (IRDs) with at least one prescription for adalimumab, etanercept, or infliximab were identified. All-cause and disease-specific costs, as well as daily costs of treatment, were calculated. Dosing patterns and discontinuation rates were analysed.ResultsA total of 555 IRD patients were identified. All-cause costs during the 12 months after the index event were 20,555CHF in the etanercept group, 24,152CHF in the adalimumab group, and 27,614CHF in the infliximab group. The most important cost driver was mean TNF inhibitor drug cost, which was 15,613CHF in the etanercept group, 19,166CHF in the adalimumab group, and 21,313CHF in the infliximab group. Discontinuation rates during the first year after the index event were 46.8% in etanercept, 41.3% in adalimumab, and 51.2% in the infliximab group. Rates of dosage increase were 13.3% in the etanercept group, 13.0% in the adalimumab group, and 14.1% in the infliximab group. When time on treatment was considered, daily costs of treatment were similar for etanercept and adalimumab, but were higher for infliximab.ConclusionsMarked differences in costs between subcutaneous and intravenous therapies were observed. Among the three groups of patients defined by TNF inhibitor treatment, costs for the infliximab group were highest during the year after the index event.

Kronisk inflammatorisk artritt og svangerskap

Chronic inflammatory arthritis often appears first in women of fertile age. Their pregnancies are considered to be of low risk compared with pregnancies in women with systemic inflammatory connective tissue disease. The article is based on literature searches in PubMed for studies of the pregnancy outcomes of women with chronic inflammatory arthritis. Studies without a reference group or studies based on analyses of mixed populations of inflammatory arthritis and connective tissue disease patients were excluded. Recurrent findings in the published literature were: low mean birth weight, a higher proportion of children with a birth weight of less than 2500 grams, children born small for gestational age, preterm births and a higher proportion of Caesarean sections. A high level of disease activity is associated with the risk of low birth weight and preterm birth. However, serious complications are not frequently reported. Glucocorticosteroids and disease-modifying medicines such as sulphasalazine and hydroxychloroquine may be used during pregnancy. Non-steroidal anti-inflammatory drugs such as ibuprofen and naproxen may be used until gestational week 32. Methotrexate is contraindicated and must be terminated three months before conception. The TNF inhibitors adalimumab, etanercept and infliximab may be used until conception. Pregnancy is seldom absolutely contraindicated for women with inflammatory arthritis. Pregnancy should be planned carefully and preferably be confined to periods with a low level of disease activity. First pregnancies require special attention. Interdisciplinary collaboration between rheumatologists and gynaecologists is recommended for monitoring patients with active arthritis.

Abstract 4132: Predictive classifiers for response to c-Met targeted therapies in lung and colon cancer

Abstract A fundamental challenge in the development of cancer therapies is the co-development of companion biomarkers to select patients most likely to respond to treatment prior to the availability of clinical outcomes data. We developed a methodology that leverages large scale public ‘omics data to identify candidate predictive biomarker panels to identify patients with a greater likelihood of responding to targeted therapies. We applied this approach to generate mechanism-based predictive biomarkers using our causal Knowledgebase as a substrate, as well as standard gene expression-based biomarkers for c-Met targeted therapy use in lung and colon cancers, and validated the methodology using clinical data. Gene signatures for c-Met activation in lung and colon were applied to individual lung and colon cancer training set patients to stratify them by c-Met activation levels. Data from patients identified as having high and low levels of c-Met activation were used to develop mechanism-based and gene expression-based classifiers to predict response to c-Met targeted therapies in lung and colon cancer. Validation of these classifiers requires transcriptomic data with associated clinical outcomes from c-Met inhibitor trials. In the absence of such, we verified this general approach using data from Inflammatory Bowel Disease (IBD) patients treated with the TNF inhibitor Infliximab, for which published colon transcriptomic data and associated clinical outcomes data are available {GSE16879} We developed a gene signature to assess TNF pathway activation and stratify a training set of IBD patients, then generated gene expression and mechanism-based classifiers from patients with high and low TNF signaling. These classifiers were tested on an independent test set of IBD patients treated with Infliximab {GSE12251}; the mechanism and gene expression-based classifiers predicted responders with positive and negative predictive values of 85%/88% and 70%/100% respectively. This method can be applied to other targets, pathways and diseases and may facilitate companion diagnostic development by enabling the selection of appropriate patient populations prior to treatment and clinical trial participation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4132. doi:10.1158/1538-7445.AM2011-4132

Advances in the development and application of biological therapies for rheumatoid arthritis: review of the latest clinical evidence

Since the introduction of the first biological therapies for rheumatoid arthritis – the TNF inhibitors (TNFi) etanercept, infliximab and adalimumab – other biologic agents have been developed and are now approved for use. This article summarizes the evidence for new TNFi (certolizumab and golimumab), B-cell-depleting therapy (rituximab), T-cell co-stimulation modulating therapy (abatacept) and an IL-6 receptor inhibitor (tocilizumab). A proportion of patients may not be suitable for these or may remain resistant to multiple therapies; thus, new biological agents in development will be discussed. Advances in the application of biologic therapies will be explored, including the use of biologics in early rheumatoid arthritis, towards achieving predefined targets, and the emergence of biomarkers introducing the prospect of personalized therapy.

Infliximab for the treatment of refractory scleritis

BackgroundScleritis is a potentially blinding inflammatory disorder. Standard care consists of systemic corticosteroids and immunosuppresants. The authors describe a series of 10 patients suffering from scleritis treated with the TNF...

Sudden loss of the GVL effect following use of the TNF inhibitor infliximab in a chronic myelogenous leukemia patient with chronic GVHD

Sudden loss of the GVL effect following use of the TNF inhibitor infliximab in a chronic myelogenous leukemia patient with chronic GVHD

Rituximab Therapy Produced Rapid and Sustained Clinical Improvement in a Patient With Systemic Onset Juvenile Idiopathic Arthritis Refractory to TNF Alpha Antagonists

We describe a patient with systemic onset juvenile idiopathic arthritis refractory to disease-modifying antirheumatic drugs, intravenous gamma globulin, and TNF inhibitors (etanercept and infliximab), in whom treatment with rituximab resulted in remission of systemic symptoms (rash and fever), a fall in erythrocyte sedimentation rate, C-reactive protein, and ferritin serum levels, with recovery in disability index and improvement of arthritis. A total of 4 cycles of rituximab were given over 18 months because of relapses. Since her last course, she remains stable and asymptomatic. To our knowledge, this is the first case reported on a long-lasting beneficial effect of rituximab in a patient with soJIA.

Sulfasalazine and Pentoxifylline: Potential for Adjunctive Treatment of Pemphigus Vulgaris

Evidence shows that tumor necrosis factor α (TNF-α) contributes to acantholysis in pemphigus, and several reports document the efficacy of the TNF inhibitors infliximab and etanercept in autoimmune blistering disease. Sulfasalazine and pentoxifylline both inhibit TNF-α, although by different mechanisms: Pentoxifylline reduces its production, whereas sulfasalazine inhibits TNF-α mRNA levels and binds to circulating TNF-α. In this study, researchers examined sulfasalazine plus …

Tumour necrosis factor inhibitors

The cytokine, tumour necrosis factor-alpha (TNF-alpha) plays a key role in the pathogenesis of many chronic inflammatory and rheumatic diseases, in particular, Crohn's disease, rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Controlled trials have shown that the TNF inhibitors (etanercept, infliximab and adalimumab) significantly reduce symptoms and signs, improve function and quality of life, and reduce radiologically evident damage in patients with rheumatoid diseases. For reasons that are not entirely clear, etanercept does not work in Crohn's disease. Injection site and intravenous reactions and increased risk of infection (in particular, reactivation of tuberculosis) are associated with the use of these agents. Increased risk of lymphoproliferative disease, the development of lupus-like syndromes and demyelination, including optic neuritis and reactivation of multiple sclerosis, are under evaluation in long-term follow-up studies. The TNF inhibitors are expensive (about $18000 per year), and in some patients need to be given continuously to maintain benefit, even in the presence of other immunosuppressive therapy.

The impact of new biologicals in the treatment of rheumatoid arthritis.

The past decade has seen a shift in the paradigm for RA management. DMARDs have been introduced at earlier stages of disease in an effort to slow or stop radiographic disease progression before irreversible joint damage, work disability, functional decline and other adverse outcomes are seen. Although often effective, DMARDs have been limited in treatment durability over the long term due to side-effects and declining efficacy. Combination regimens, often involving weekly methotrexate as the anchor drug, have been used increasingly to overcome the limitations of DMARD monotherapy. The advent of biological therapies that specifically target key proinflammatory cytokines, believed to be important in disease pathogenesis, provides several new treatment options. In controlled clinical trials, the IL-1 blocker anakinra (r-metHuIL-1ra) significantly reduced the clinical signs and symptoms of RA when used alone or in combination with weekly methotrexate. The TNF inhibitors etanercept, infliximab and adalimumab have shown similar efficacy; indeed, higher response rates for clinical and radiological parameters have been seen with the TNF blockers. Importantly, each of these biological response modifiers significantly reduced radiographic disease progression in 6- to 12-month studies, and some radiographic data extend to 24 months. Despite these promising findings, it remains to be determined whether slowing radiographic progression will translate into significant improvements in long-term outcomes.

Differentiating the New Rheumatoid Arthritis Biologic Therapies

Current understanding of the mechanisms behind the pathogenesis of rheumatoid arthritis (RA) has led to the development of therapies involving biologic agents that target specific mediators of the disease process. Although the biologic agents used to treat RA share the ability to alter the cytokine cascade, they differ in ways that are clinically important. For example, they vary with regard to how they block cytokine activity (ie, as receptors, as receptor blockers, or as anticytokine antibodies) and the particular cytokine they target (eg, tumor necrosis factor [TNF] versus interleukin-1). Biologic therapies for RA also differ in mode of administration. Several are administered subcutaneously, whereas others are given intravenously. They also have molecular dissimilarities that result in differences in pharmacokinetics (ie, long versus medium half-life) and that may influence their safety profiles.Some biologic agents, such as the TNF inhibitors etanercept and infliximab, have been rigorously examined for long-term safety and efficacy, whereas other agents, like the TNF inhibitor adalimumab, have not. Differences between the various biologic agents may relate to the usefulness of each individual drug as a long-term treatment in RA. For example, the need for physician visits may impact the practicality of drugs that are administered intravenously. Also, physicians should be aware that use of cytokine inhibitors increases the risk of infection. The prevalence of tuberculosis during therapy with infliximab exceeds the background rate in patients with RA. Accordingly, physicians should be familiar with the updated warnings in the package inserts that accompany these drugs.

Juvenile spondyloarthropathies and related arthritis.

This article reviews recent publications related to the classification and treatment of juvenile spondyloarthropathies. We have included studies on adult onset spondyloarthropathies that are particularly relevant to childhood onset disease. Significant questions concerning classification of juvenile spondyloarthropathies remain unresolved. Diagnostic criteria that are both sensitive and specific for identifying undifferentiated spondyloarthropathies in adults have been developed, and while separate criteria have been proposed for juvenile onset disease, they remain to be validated. The most significant recent advances have occurred in the area of treatment. A small number of studies suggest that bisphosphonates such as pamidronate may be efficacious. Several studies using the TNF inhibitors infliximab and etanercept suggest that these agents hold great promise for ameliorating symptoms and improving function, while long-term effects on disease progression remain to be evaluated.