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Factor Antagonists (factor + antagonist)
Kinds of Factor Antagonists Selected AbstractsEfficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION)BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2008J.-H. Saurat Summary Background, Biologic therapies such as adalimumab, a tumour necrosis factor antagonist, are safe and effective in the treatment of moderate to severe chronic plaque psoriasis. Objectives, To compare a biologic agent with methotrexate, a traditional systemic agent, to define clearly the role of biologics in psoriasis. Methods, Patients with moderate to severe plaque psoriasis were randomized to adalimumab (80 mg subcutaneously at week 0, then 40 mg every other week, n = 108), methotrexate (7·5 mg orally, increased as needed and as tolerated to 25 mg weekly; n = 110) or placebo (n = 53) for 16 weeks. The primary efficacy endpoint was the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) after 16 weeks. Safety was assessed at all visits through week 16. Results, After 16 weeks, 79·6% of adalimumab-treated patients achieved PASI 75, compared with 35·5% for methotrexate (P < 0·001 vs. adalimumab) and 18·9% for placebo (P < 0·001 vs. adalimumab). Statistically significantly more adalimumab-treated patients (16·7%) than methotrexate-treated patients (7·3%) or placebo-treated patients (1·9%) achieved complete clearance of disease. The response to adalimumab was rapid, with a 57% improvement in mean PASI observed at week 4. Adverse events were similar across treatment groups. Adverse events leading to study discontinuation were greatest in the methotrexate group, primarily because of hepatic-related adverse events. Conclusions, After 16 weeks, adalimumab demonstrated significantly superior efficacy and more rapid improvements in psoriasis compared with either methotrexate or placebo. [source] Up-regulation of integrin ,3 in radioresistant pancreatic cancer impairs adenovirus-mediated gene therapyCANCER SCIENCE, Issue 10 2009Takuya Egami Adenovirus-mediated gene therapy is a promising approach for the treatment of pancreatic cancer. We previously reported that radiation enhanced adenovirus-mediated gene expression in pancreatic cancer, suggesting that adenoviral gene therapy might be more effective in radioresistant pancreatic cancer cells. In the present study, we compared the transduction efficiency of adenovirus-delivered genes in radiosensitive and radioresistant cells, and investigated the underlying mechanisms. We used an adenovirus expressing the hepatocyte growth factor antagonist, NK4 (Ad-NK4), as a representative gene therapy. We established two radioresistant human pancreatic cancer cell lines using fractionated irradiation. Radiosensitive and radioresistant pancreatic cancer cells were infected with Ad-NK4, and NK4 levels in the cells were measured. In order to investigate the mechanisms responsible for the differences in the transduction efficiency between these cells, we measured expression of the genes mediating adenovirus infection and endocytosis. The results revealed that NK4 levels in radioresistant cells were significantly lower (P < 0.01) than those in radiosensitive cells, although there were no significant differences in adenovirus uptake between radiosensitive cells and radioresistant cells. Integrin ,3 was up-regulated and the Coxsackie virus and adenovirus receptor was down-regulated in radioresistant cells, and inhibition of integrin ,3 promoted adenovirus gene transfer. These results suggest that inhibition of integrin ,3 in radioresistant pancreatic cancer cells could enhance adenovirus-mediated gene therapy. (Cancer Sci 2009; 100: 1902,1907) [source] Treatment of inflammatory dermatoses by tumour necrosis factor antagonistsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2006A Jacobi Abstract Background, The treatment of inflammatory skin diseases is at present often empirical as causal therapeutic approaches, based on an incomplete knowledge of the immune pathogenesis, are mostly unavailable. The currently applied treatments can in fact lead to remission of the disease; however, under certain circumstances undesirable side-effects must be expected. On the basis of experience gained in cytokine modulation therapy of chronic inflammatory diseases such as rheumatoid arthritis and psoriasis, the application of TNF-, inhibitors represents a novel, more specific, and effective therapeutic option for distinct chronic inflammatory diseases. Patients and methods, The current status of the therapeutic effect of TNF-, blockers is discussed based on our own observations and a review of the current literature. Also discussed are potential undesirable side-effects and possible contraindications of this therapy. Results and conclusions, Based on recent findings, the use of TNF-, blockers seems to be promising in the treatment of therapy-resistant inflammatory dermatoses. At present, guidelines for indications and contraindications of anti-TNF-, treatment of inflammatory skin disorders are rare. Such guidelines are necessary to improve the efficacy of anticytokine treatment and the reduction of side-effects. [source] Tumour necrosis factor antagonists and inflammatory bowel diseases: a national practice surveyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2009A. OUSSALAH Aliment Pharmacol Ther,30, 854,863 Summary Background, Although the use of tumour necrosis factor (TNF) antagonists is increasingly codified, several unresolved issues remain. Aim, To conduct a French national survey on TNF antagonists use in inflammatory bowel disease (IBD). Methods, A postal questionnaire was sent to all French gastroenterologists among whom 450 prescribe TNF antagonists for IBD. Only anti-TNF prescribers were invited to respond. Results, A total of 333 questionnaires could be analysed, which represented a rate of survey completeness of 74%. Scheduled maintenance infliximab treatment was prescribed by 92% of gastroenterologists. In Crohn's disease in remission after 1 year of TNF antagonists, 77.4% of physicians continued treatment. In luminal Crohn's disease, 97% of hospital practitioners introduced infliximab as first-line anti-TNF therapy vs. 78% of physicians with nonhospital activity (P = 0.002); only 22.5% of gastroenterologists opted for adalimumab as first-line therapy. In Crohn's disease in remission after 6 months of azathioprine in combination with infliximab, 63.8% of practitioners discontinued azathioprine. In case of pregnancy during anti-TNF treatment, 35.1% of physicians discontinued therapy at the time of conception and did not administer anti-TNF therapy during pregnancy. Conclusions, The attitudes of French gastroenterologists generally reflect the recommendations regarding the use of anti-TNF and concomitant immunosuppressive therapy in IBD. [source] Association of the response to tumor necrosis factor antagonists with plasma type I interferon activity and interferon-,/, ratios in rheumatoid arthritis patients: A post hoc analysis of a predominantly Hispanic cohortARTHRITIS & RHEUMATISM, Issue 2 2010Clio P. Mavragani Objective Despite the substantial clinical efficacy of tumor necrosis factor , (TNF,) antagonist therapy in patients with rheumatoid arthritis (RA), some patients respond poorly to such agents. Since an interferon (IFN) signature is variably expressed among RA patients, we investigated whether plasma type I IFN activity might predict the response to TNF antagonist therapy. Methods RA patients (n = 35), the majority of whom were Hispanic, from a single center were evaluated before and after initiation of TNF antagonist therapy. As controls, 12 RA patients from the same center who were not treated with a TNF antagonist were studied. Plasma type I IFN activity was measured using a reporter cell assay, and disease status was assessed using the Disease Activity Score in 28 joints (DAS28). Levels of interleukin-1 receptor antagonist (IL-1Ra) were determined in baseline plasma samples using a commercial enzyme-linked immunosorbent assay. The clinical response was classified according to the European League Against Rheumatism criteria for improvement in RA. Results Plasma type I IFN activity at baseline was significantly associated with clinical response (odds ratio 1.36 [95% confidence interval 1.05,1.76], P = 0.020), with high baseline IFN activity associated with a good response. Changes in DAS28 scores were greater among patients with a baseline plasma IFN,/, ratio >0.8 (indicating elevated plasma IFN, levels). Consistent with the capacity of IFN, to induce IL-1Ra, elevated baseline IL-1Ra levels were associated with better therapeutic outcomes (odds ratio 1.82 [95% confidence interval 1.1,3.29], P = 0.027). Conclusion The plasma type I IFN activity, the IFN,/, ratio, and the IL-1Ra level were predictive of the therapeutic response in TNF antagonist,treated RA patients, indicating that these parameters might define clinically meaningful subgroups of RA patients with distinct responses to therapeutic agents. [source] | ||||||||||