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anti-TNF Treatment (anti-tnf + treatment)
Selected AbstractsReview article: chronic viral infection in the anti-tumour necrosis factor therapy era in inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010M. J. SHALE Summary Background, Anti-Tumour necrosis factor (TNF) therapy is now well established in the treatment of inflammatory bowel disease and the risk of opportunistic infection is recognized. However, specific considerations regarding screening, detection, prevention and treatment of chronic viral infections in the context of anti-TNF therapy in inflammatory bowel disease are not widely adopted in practice. Aim, To provide a detailed and comprehensive review of the relevance of chronic viral infections in the context of anti-TNF therapy in inflammatory bowel disease. Methods, Literature search was conducted using Medline, Pubmed and Embase using the terms viral infection, hepatitis, herpes, CMV, EBV, HPV, anti-TNF, infliximab, adalimumab, certolizumab pegol and etanercept. Hepatitis B and C and HIV had the largest literature associated and these have been summarized in Tables. Results, Particular risks are associated with the use of anti-TNF drugs in patients with hepatitis B infection, in whom reactivation is common unless anti-viral prophylaxis is used. Reactivation of herpes zoster is the most common viral problem associated with anti-TNF treatment, and may be particularly severe. Primary varicella infection may present with atypical features in patients on anti-TNF. Conclusion, Appreciation of risks of chronic viral disease associated with anti-TNF therapy may permit early recognition, prophylaxis and treatment. [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] The relationship between synovial lymphocyte aggregates and the clinical response to infliximab in rheumatoid arthritis: A prospective study,,ARTHRITIS & RHEUMATISM, Issue 11 2009Ruth Klaasen Objective Some patients with rheumatoid arthritis (RA) exhibit lymphocyte aggregates in the synovium. This study was undertaken to address whether the presence of lymphocyte aggregates before treatment could serve as a biomarker for the clinical response to tumor necrosis factor (TNF) blockade, and to confirm whether the aggregation of synovial lymphocytes is reversible after anti-TNF treatment. Methods Synovial tissue biopsy samples were obtained from 97 patients with active RA before the initiation of infliximab treatment. Lymphocyte aggregates in the synovial tissue were counted and also graded for size. Logistic regression analysis was performed to identify whether the presence of lymphocyte aggregates could be a predictor of the clinical response at week 16. Furthermore, the effects of TNF blockade on lymphocyte aggregates were compared between patients with RA and patients with psoriatic arthritis (PsA). Results Fifty-seven percent of RA synovial tissue samples contained lymphocyte aggregates, and 32% of the patients had large aggregates. Aggregates were found in 67% of clinical responders compared with 38% of nonresponders. The presence of aggregates at baseline was a highly significant predictor of the clinical response to anti-TNF treatment (R2 = 0.10, P = 0.008). Positivity for lymphocyte aggregates increased the power to predict the clinical response (R2 = 0.29), when analyzed in a prediction model that included baseline disease activity evaluated by the Disease Activity Score in 28 joints, anti,cyclic citrullinated peptide antibody positivity, and synovial TNF, expression. There was a reduction in lymphocyte aggregates after anti-TNF antibody therapy in both RA and PsA. Conclusion RA patients with synovial lymphocyte aggregates have, on average, a better response to infliximab treatment than those with only diffuse leukocyte infiltration. Moreover, the aggregation of synovial lymphocytes is reversible after anti-TNF antibody treatment. [source] Risk of tuberculosis is higher with anti,tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective french research axed on tolerance of biotherapies registry,ARTHRITIS & RHEUMATISM, Issue 7 2009F. Tubach Objective Tuberculosis (TB) is associated with anti,tumor necrosis factor (anti-TNF) monoclonal antibody (mAb) therapy, but whether this association is drug-specific remains a concern. Our objective was to describe cases of TB associated with anti-TNF mAb therapy, identify risk factors, and estimate the incidence. Methods We conducted an incidence study and a case,control analysis to investigate the risk of newly diagnosed TB associated with the use of anti-TNF agents. As part of the French Research Axed on Tolerance of Biotherapies (RATIO) registry, for 3 years we collected cases of TB among French patients receiving anti-TNF mAb therapy for any indication; for each case, 2 patients treated with anti-TNF agents served as control subjects. Results We collected 69 cases of TB in patients treated for rheumatoid arthritis (n = 40), spondylarthritides (n = 18), inflammatory colitis (n = 9), psoriasis (n = 1) and Behçet's disease (n = 1) with infliximab (n = 36), adalimumab (n = 28), and etanercept (n = 5). None of the patients had received correct chemoprophylactic treatment. The sex- and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The standardized incidence ratio (SIR) was 12.2 (95% confidence interval [95% CI] 9.7,15.5) and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (SIR 18.6 [95% CI 13.4,25.8] and SIR 29.3 [95% CI 20.3,42.4] versus SIR 1.8 [95% CI 0.7,4.3], respectively). In the case,control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB (odds ratio [OR] 13.3 [95% CI 2.6,69.0] and OR 17.1 [95% CI 3.6,80.6], respectively). Other risk factors were age, the first year of anti-TNF mAb treatment, and being born in an endemic area. Conclusion The risk of TB is higher for patients receiving anti-TNF mAb therapy than for those receiving soluble TNF receptor therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylactic treatment favor the reactivation of latent TB. [source] Improvement of lipid profile is accompanied by atheroprotective alterations in high-density lipoprotein composition upon tumor necrosis factor blockade: A prospective cohort study in ankylosing spondylitisARTHRITIS & RHEUMATISM, Issue 5 2009I. C. van Eijk Objective Cardiovascular mortality is increased in ankylosing spondylitis (AS), and inflammation plays an important role. Inflammation deteriorates the lipid profile and alters high-density lipoprotein cholesterol (HDL-c) composition, reflected by increased concentrations of serum amyloid A (SAA) within the particle. Anti,tumor necrosis factor (anti-TNF) treatment may improve these parameters. We therefore undertook the present study to investigate the effects of etanercept on lipid profile and HDL composition in AS. Methods In 92 AS patients, lipid levels and their association with the inflammation markers C-reactive protein (CRP), erythrocyte sedimentation rate, and SAA were evaluated serially during 3 months of etanercept treatment. HDL composition and its relationship to inflammation markers was determined in a subgroup of patients, using surface-enhanced laser desorption/ionization time-of-flight analysis. Results With anti-TNF treatment, levels of all parameters of inflammation decreased significantly, whereas total cholesterol, HDL-c, and apolipoprotein A-I (Apo A-I) levels increased significantly. This resulted in a better total cholesterol:HDL-c ratio (from 3.9 to 3.7) (although the difference was not statistically significant), and an improved Apo B:Apo A-I ratio, which decreased by 7.5% over time (P = 0.008). In general, increases in levels of all lipid parameters were associated with reductions in inflammatory activity. In addition, SAA was present at high levels within HDL particles from AS patients with increased CRP levels and disappeared during treatment, in parallel with declining plasma levels of SAA. Conclusion Our results show for the first time that during anti-TNF therapy for AS, along with favorable changes in the lipid profile, HDL composition is actually altered whereby SAA disappears from the HDL particle, increasing its atheroprotective ability. These findings demonstrate the importance of understanding the role of functional characteristics of HDL-c in cardiovascular diseases related to chronic inflammatory conditions. [source] Inflammatory lesions of the spine on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis: Evidence of a relationship between inflammation and new bone formationARTHRITIS & RHEUMATISM, Issue 1 2009Walter P. Maksymowych Objective To determine whether a vertebral corner that demonstrates an active corner inflammatory lesion (CIL) on magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS) is more likely to evolve into a de novo syndesmophyte visible on plain radiography than is a vertebral corner that demonstrates no active inflammation on MRI. Methods MRI scans and plain radiographs were obtained for 29 patients recruited into randomized placebo-controlled trials of anti,tumor necrosis factor , (anti-TNF,) therapy. MRI was conducted at baseline, 12 or 24 weeks (n = 29), and 2 years (n = 22), while radiography was conducted at baseline and 2 years. A persistent CIL was defined as a CIL that was found on all available scans. A resolved CIL was defined as having completely disappeared on either the second or third scan. A validation cohort consisted of 41 AS patients followed up prospectively. Anonymized MRIs were assessed independently by 3 readers who were blinded with regard to radiographic findings. Results New syndesmophytes developed significantly more frequently in vertebral corners with inflammation (20%) than in those without inflammation (5.1%) seen on baseline MRI (P , 0.008 for all reader pairs). They also developed more frequently in vertebral corners where inflammation had resolved than in those where inflammation persisted after anti-TNF treatment. This was confirmed in the analysis of the prospective cohort, in which significantly more vertebral corners with inflammation (14.3%) compared with those without inflammation (2.9%) seen on baseline MRI developed new syndesmophytes (P , 0.003 for all reader pairs). Conclusion Our findings indicate that a syndesmophyte is more likely to develop from a prior inflammatory lesion, supporting a relationship between inflammation and ankylosis. [source] Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: A multicenter active-surveillance reportARTHRITIS & RHEUMATISM, Issue 8 2003Juan J. Gómez-Reino Objective The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. Methods We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. Results Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). Conclusion Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event. [source] Tumor necrosis factor antagonist therapy and lymphoma development: Twenty-six cases reported to the Food and Drug Administration,ARTHRITIS & RHEUMATISM, Issue 12 2002S. Lori Brown PhD Objective Etanercept and infliximab are tumor necrosis factor (TNF) antagonists that have been recently approved for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). This study was undertaken to investigate the occurrence of lymphoproliferative disorders in patients treated with these agents. Methods Relevant data in the MedWatch postmarket adverse event surveillance system run by the US Food and Drug Administration were reviewed. Results We identified 26 cases of lymphoproliferative disorders following treatment with etanercept (18 cases) or infliximab (8 cases). The majority of cases (81%) were non-Hodgkin's lymphomas. The interval between initiation of therapy with etanercept or infliximab and the development of lymphoma was very short (median 8 weeks). In 2 instances (1 infliximab, 1 etanercept), lymphoma regression was observed following discontinuation of anti-TNF treatment, in the absence of specific cytotoxic therapy directed toward the lymphoma. Conclusion Although data from a case series such as this cannot establish a clear causal relationship between exposure to these medications and the risk of lymphoproliferative disease, the known predisposition of patients with RA and CD to lymphoma, the known excess of lymphoma in other immunosuppressed populations, and the known immunosuppressive effects of the anti-TNF drugs provide a biologic basis for concern and justification for the initiation of additional epidemiologic studies to formally evaluate this possible association. [source] Tumor necrosis factor , blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cellsARTHRITIS & RHEUMATISM, Issue 2 2010Hak-Ling Ma Objective Patients with psoriasis and psoriatic arthritis respond well to tumor necrosis factor , (TNF,) blockers in general; however, there is now mounting evidence that a small cohort of patients with rheumatoid arthritis who receive TNF, blockers develop psoriasis. This study was undertaken to explore the mechanisms underlying TNF, blockade,induced exacerbation of skin inflammation in murine psoriasis-like skin disease. Methods Skin inflammation was induced in BALB/c scid/scid mice after they received CD4+CD45RBhighCD25, (naive CD4) T cells from donor mice. These mice were treated with either anti,interleukin-12 (anti,IL-12)/23p40 antibody or murine TNFRII-Fc fusion protein and were examined for signs of disease, including histologic features, various cytokine levels in the serum, and cytokine or FoxP3 transcripts in the affected skin and draining lymph node (LN) cells. In a separate study, naive CD4+ T cells were differentiated into Th1 or Th17 lineages with anti-CD3/28 magnetic beads and appropriate cytokines in the presence or absence of TNF,. Cytokine gene expression from these differentiated cells was also determined. Results Neutralization of TNF, exacerbated skin inflammation and markedly enhanced the expression of the proinflammatory cytokines IL-1,, IL-6, IL-17, IL-21, and IL-22 but suppressed FoxP3 expression in the skin and reduced the number of FoxP3-positive Treg cells in the draining LNs. TNF, also demonstrated a divergent role during priming and reactivation of naive T cells. Conclusion These results reveal a novel immunoregulatory role of TNF, on Th17 and Treg cells in some individuals, which may account for the exacerbation of skin inflammation in some patients who receive anti-TNF treatments. [source] | ||||||||||