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Biological Therapies (biological + therapy)
Selected AbstractsSystemic therapy of disseminated malignant melanoma: an evidence-based overview of the state-of-the-art in daily routineJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2007D Nashan Abstract Aims, In the metastatic stage, malignant melanoma is resistant to systemic treatment and carries a poor prognosis. A critical, evidence-based analysis of standard approaches based on an extended search of published literature and from different Internet sources is presented. Material and methods, A critical, evidence-based analysis of standard approaches and their variations to systemic therapy based on an extended search of published literature and from different Internet sources is presented. Few meta-analyses are available. Therefore, assessment of therapies is mainly based on randomized multicentre studies or clinical studies achieving an evidence level grade 1 or 2. Results, Monotherapy with DTIC (dacarbazine) is the standard. Based on overall survival data, polychemotherapies cannot be recommended. Combination of polychemotherapy with the cytokines interferon-, and interleukin-2 substantially augments chemotherapy induced response rates, but a meta-analysis for survival does not support its therapeutic superiority. Biological therapies such as vaccinations have not yet delivered results on a higher evidence level. Thus, immunotherapies as well as chemo-immunotherapies will have to be evaluated in further studies. Conclusions, Although the therapeutic efficacy is very limited, dacarbazine cannot be rejected as standard therapy for disseminated melanoma, because no other therapeutic regimen exhibits a survival benefit over DTIC in an evidence-based analysis. This lack of therapeutic progress over the past 40 years clearly calls for further clinical studies, and patients should be enrolled into clinical trials whenever possible. [source] Biological therapy in Crohn's disease: Is it an issue of how hard you strike or how fast you strike?INFLAMMATORY BOWEL DISEASES, Issue 2 2009Remo Panaccione MD No abstract is available for this article. [source] Prevention of relapse of Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2000Dr. Lloyd R. Sutherland Abstract Until a cure for Crohn's disease(s) is found, strategies that prolong the time spent in remission offer the greatest hope for reducing the morbidity and significant social costs associated with the disease. Medical therapy to date has been disappointing, and the search for a safe, effective therapy that could be offered at low cost continues. The aminosalicylates, so effective in ulcerative colitis, have shown, at best, minimal efficacy in maintaining remission in Crohn's disease. Conventional corticosteroids are not effective, and any reduction in time to relapse for budesonide-treated patients is measured in weeks not months. Azathioprine, 6-mercaptopurine, and methotrexate are effective in maintaining remission, but all three have significant side effects. Antibiotics may have a role to play. Biological therapy may be considered, but the issues of cost and long-term safety require evaluation. Future studies should segregate patients into two groups, those with a medically induced remission and patients whose concern is the prevention of postoperative recurrence. [source] Certolizumab pegol: a new option for rheumatoid arthritisFUTURE PRESCRIBER, Issue 4 2009MSc Rheumatology SpR, Margaret HY Ma MBBS Rheumatoid arthritis (RA) presents a significant burden to healthcare in the UK. New biological therapies have advanced treatment but at a high cost to the NHS. Certolizumab pegol is a new TNF inhibitor, providing an additional treatment option for RA. In this article Dr Ma and Dr Choy consider the efficacy of certolizumab pegol, and where it may fit into the RA armoury. Copyright © 2009 John Wiley & Sons, Ltd. [source] Current challenges of pharmacovigilance in bleeding disorders: converting the burden to benefitHAEMOPHILIA, Issue 2 2010R. LASSILA Summary., Safety surveillance studies have proven essential in research and development of new biological therapies for bleeding disorders as well as other diseases. Although product safety regarding HIV, hepatitis, and other blood-borne infections is currently excellent, potential new infectious agents require continued vigilant monitoring. Inhibitor development is the most common serious side effect of haemophilia replacement therapy. Several aetiological factors associated with inhibitors have been identified, but their true impact is still largely unknown. Moreover, whether plasma-derived and recombinant factor products differ in their immunogenic profiles is an unresolved issue. Coagulation factor products under development and those currently on the market require uniform, long-term surveillance. The European Haemophilia Safety Surveillance (EUHASS) project was recently established to meet these goals. The pharmaceutical industry and clinicians face common challenges complying with these requirements. In rare diseases like haemophilia, obtaining adequate patient numbers poses a challenge. Another challenge is a lack of methods for assessing disease severity, a surprising deficiency in the era of modern medical and laboratory technology. National and international registries can be used to gather required safety surveillance information. Simultaneously, clinicians benefit from well-organized registry data in their daily practice and harmonize the quality of comprehensive haemophilia care by homogeneous follow-up platforms. Experience with such registries comes, for example, from Europe (PEDNET), the USA (CDC/UDC), the UK (UKHCDO), and Sweden (Malmö). It is important to commit to future pharmacovigilance efforts, aiming at high-quality safety surveillance programmes at both the pharmaceutical research community and clinical levels. [source] Refining indications for contemporary surgical treatment of renal cell carcinoma metastatic to the pancreasHPB, Issue 2 2009Aram N. Demirjian Abstract Background:, The pancreas is a rare location for metastatic disease, with only 2,11% of all pancreatic tumours being of non-primary origin. It is also uncommon for renal cell carcinoma (RCC) to metastasize to the pancreas (1,3% of cases) and, when it does, it typically occurs substantially after index nephrectomy. It is not known whether all pancreatic metastases need be resected because today's chemo- and biological therapies are increasingly effective in controlling advanced disease. Methods:, Six patients with a variety of symptoms are discussed. Four patients presented with recurrent gastrointestinal bleeding, ranging from occult to life-threatening in severity. Results:, The four patients with gastrointestinal bleeding had RCC metastases that had eroded into the duodenum and were successfully controlled by palliative pancreaticoduodenectomy or completion pancreatectomy. The other two patients were treated using different chemotherapeutic or biological agents. Conclusions:, Renal cell carcinoma metastases to the pancreas typically occur long after index nephrectomy. Although clinical presentation is variable, palliative resection should be reserved for those who develop complications, such as upper gastrointestinal bleeding, and, in other series, obstructive jaundice. Routine debulking resections do not appear to be indicated because current biological therapies effectively and reliably control disease over long periods. [source] Contribution of TNFSF15 gene variants to Crohn's disease susceptibility confirmed in UK populationINFLAMMATORY BOWEL DISEASES, Issue 6 2008Mark Tremelling MRCP Abstract Background: Identification of Crohn's disease (CD)-associated genetic variants is key to understanding pathogenic pathways underlying disease susceptibility. Recent reports of an association between TNFSF15 variants and CD have been modestly replicated in European populations, suggesting heterogeneity at this locus with stronger CD association in Japanese than European populations. Methods: We investigated the association between variants in TNFSF15 and CD in 756 CD patients and 636 controls. Disease subphenotype associations were also investigated. Results:TNFSF15 single nucleotide polymorphism (SNP) variants were associated with CD in our panel with peak odds ratio (OR) 1.2 (95% confidence interval [CI] 1.01,1.41) P = 0.033. The presence of a risk haplotype was replicated for the first time in a European population (frequency 67% in cases and 61% in controls) OR = 1.44 (95% CI 1.23,1.68) P = 0.00012. This result mirrors the UK panel in the index study (Yamazaki et al [2005] Hum Mol Genet 14:3499,3506) but is less significant than that reported in Japanese populations. There was no evidence of association with any individual CD subphenotype. Conclusions: Variants in TNFSF15 contribute to overall CD susceptibility in European populations, although to a lesser extent than that seen in the Japanese. Further studies to define the precise disease-causing variants as well as targeted functional studies are now required in human CD as TNFSF15 is a potential target for biological therapies. (Inflamm Bowel Dis 2008) [source] Antiadhesion molecule therapy in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2002Dr. Gert Van Assche Abstract Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. Some of these molecules such as MadCAM-1 are specific for the gastrointestinal endothelium, but in inflammatory bowel diseases most of the adhesion factors are up-regulated. Adhesion molecules also are involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. Recently, therapeutic compounds directed against trafficking of lymphocytes toward the gut mucosa have been designed, and are being developed as a novel class of drugs in the treatment of Crohn's disease (CD) and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Secondly, the changes in adhesion molecules and T-cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered in trials of biological therapies directed against adhesion molecules. Both antiintercellular adhesion molecule-1 (ICAM-1) and anti-,4 integrin strategies are being developed. Trials with the anti-ICAM-1 antisense oligonucleotide, ISIS-2302, in steroid-refractory CD have provided conflicting efficacy data. The anti-,4 integrin antibodies natalizumab (Antegren) and LDP-02 are in phase III and phase II trials, respectively. In the near future, these novel biological agents may prove valuable therapeutic tools in the management of refractory IBD. [source] Association between ulcerative colitis and multiple sclerosisINTERNAL MEDICINE JOURNAL, Issue 10 2007C. S. Pokorny Abstract An association between inflammatory bowel disease (IBD) and multiple sclerosis (MS) has been described. The current study was undertaken to explore this association further. Personal records of patients with IBD and MS were reviewed. In addition, a search of medical records at a large tertiary teaching hospital in Sydney was carried out for the years 1996,2006. Four patients (three women and one man) with both ulcerative colitis and MS were identified. MS did not occur in any of our patients with Crohn's disease. The association between ulcerative colitis and MS appears to be real and may help identify common factors involved in the cause of these two diseases. No association was found in this study between MS and Crohn's disease, sparking consideration why such difference should occur. With the increasing use of biological therapies in IBD and their reported propensity to cause demyelination, recognition of an association is all the more important. [source] Improving patient outlook in rheumatoid arthritis: Experience with abataceptJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 10 2008MA (Nurse Manager), Mary Coughlin RN Abstract Purpose: To examine the importance of improving patient outlook in rheumatoid arthritis (RA) and to discuss the role of the nurse practitioner (NP) who, through the assessment of patient-reported outcomes and in acting as an advocate for the patient with the wider healthcare team, has a crucial part to play in managing the overall well-being of the patient. This article will draw on the clinical experience to date with abatacept, a first-in-class therapy that has been approved for the treatment of RA in patients with an inadequate response to either traditional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, or biological DMARDs, such as tumor necrosis factor-, antagonists. Data sources: A comprehensive literature search was performed using the National Library of Medicine (MEDLINE), EMBASE, and BIOSIS databases (restricted to articles posted between January 2000 and February 2007) with the search terms CTLA-4Ig, abatacept, and primary clinical trial publications in patients with RA. The clinical data are summarized in this review along with safety data presented in the prescribing information. Conclusions: Recent changes in the approach to RA treatment, particularly the advent of biological therapies, have impacted the role of the NP. The role of the NP is integral to the management of RA and in maximizing patient outcomes, through educating patients to make informed choices regarding their treatment, ensuring the safe administration of therapies and monitoring response to therapy, and in acting as an advocate for the patient within the wider healthcare team. Implications for practice: The use of more patient-centered measures of response are gaining increasing importance both in clinical trials and in clinical practice, and as such the NP has an important role in ensuring that both the physical and the psychological needs of patients are met. Clinical trials to date have shown that abatacept provides significant and clinically meaningful improvements in patient-reported outcomes, as well as demonstrating significant clinical benefits and a consistent safety profile, thus representing a valuable treatment option within the RA treatment armamentarium. [source] As tests evolve and costs of cancer care rise: reappraising stool-based screening for colorectal neoplasiaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2008M. PAREKH Summary Background, Colorectal cancer screening and treatment are rapidly evolving. Aims, To reappraise stool-based colorectal cancer screening in light of changing test performance characteristics, lower test cost and increasing colorectal cancer care costs. Methods, Using a Markov model, we compared faecal DNA testing every 3 years, annual faecal occult blood testing or immunochemical testing, and colonoscopy every 10 years. Results, In the base case, faecal occult blood testing and faecal immunochemical testing gained life-years/person and cost less than no screening. Faecal DNA testing version 1.1 at $300 (the current PreGen Plus test) gained 5323 life-years/100 000 persons at $16 900/life-year gained and faecal DNA testing version 2 (enhanced test) gained 5795 life-years/100 000 persons at $15 700/life-year gained vs. no screening. In the base case and most sensitivity analyses, faecal occult blood testing and faecal immunochemical testing were preferred to faecal DNA testing. Faecal DNA testing version 2 cost $100 000/life-year gained vs. faecal immunochemical testing when per-cycle adherence with faecal immunochemical testing was 22%. Faecal immunochemical testing with excellent adherence was superior to colonoscopy every 10 years. Conclusions, As novel biological therapies increase colorectal cancer treatment costs, faecal occult blood testing and faecal immunochemical testing could become cost-saving. The cost-effectiveness of faecal DNA testing compared with no screening has improved, but faecal occult blood testing and faecal immunochemical testing are preferred to faecal DNA testing when patient adherence is high. Faecal immunochemical testing may be comparable to colonoscopy every 10 years in persons adhering to yearly testing. [source] Review article: steroid resistance in inflammatory bowel disease , mechanisms and therapeutic strategiesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2007T. J. CREED Summary Background Steroid resistance in inflammatory bowel disease presents a difficult clinical challenge. The advent of biological therapies coupled with an increasing understanding of the pathogenesis of inflammatory bowel disease has provided new therapeutic options. Methods We review the available literature of the mechanisms behind steroid resistance. In addition, we outline some of the options available for treating those patients who fail to respond adequately to glucocorticoids. Results Approximately 30% of patients prescribed glucocorticoids will not achieve clinical remission. Many such patients are offered immunosuppressive or, recently, biological agents. However, these agents are ineffective in a large proportion of patients. Immunosuppressive agents only bring 40,60% of patients into remission, and biological agents typically induce remission in just 40% of patients. In this review, the possible explanations for glucocorticoid resistance are discussed. Recent evidence suggests that in many patients it is mediated by interleukin-2. Basiliximab, a biological agent that interrupts interleukin-2 signalling, has shown significant benefit in early clinical studies. Conclusions Patients who fail to respond to steroid therapy should have alternative agents introduced in a timely fashion. Steroid refractory inflammatory bowel disease remains a difficult condition to treat, but new therapies and managements are emerging. [source] Latest news and product developmentsPRESCRIBER, Issue 5 2008Article first published online: 3 APR 200 Newer antidepressants no better than placebo? A new meta-analysis suggests that newer antidepressants are no superior to placebo in most patients with depression , the exception being those with very severe depression, who can expect a small benefit. Writing in the online-only open access journal PLoS Medicine (5:e45.doi:10.1371/ journal.pmed.0050045), researchers from Hull and the US analysed published and unpublished trials submitted to the Food and Drug Administration in marketing applications for fluoxetine, paroxetine, venlafaxine (Efexor) and nefazodone (no longer available). Using the Hamilton Rating Scale for Depression (HRSD) score as an endpoint, meta-analysis of 35 trials involving 5133 patients and lasting six to eight weeks showed that mean HRSD score improved by 9.6 points with drug treatment and 7.8 with placebo. The authors say the difference of 1.8 was statistically significant but below the criterion for clinical significance (3.0) set by NICE in its clinical guideline on depression. A review of the study by the NHS Knowledge Service (www.nhs.uk) points out that it omits trials published after the drugs were licensed (1999) and those not sponsored by the pharmaceutical industry. It did not include any patients with severe depression and only one trial in patients with moderate depression. An earlier US study of data submitted to the FDA (N Eng J Med 2008;358:25260) showed that published trials of antidepressants were more likely to be positive (37/38) than unpublished ones (3/25). Further, FDA analysts concluded that 51 per cent of trials (published and unpublished) demonstrated positive findings compared with 94 per cent of those that were published. Audit reveals variations in hospital psoriasis care There are unacceptably large variations in the quality of care for patients with psoriasis in UK hospitals, a report by the British Association of Dermatologists and the Royal College of Physicians reveals. The audit of 100 hospital units found that 39 per cent restricted access to biological therapies because of cost, and over one-third of pharmacies could not supply ,specials' such as topical coal tar preparations. More positively, the units are adequately resourced to provide timely communication with GPs. RCGP responds to Public Accounts Committee The Royal College of General Practitioners has agreed with the Commons Public Accounts Committee that drug package labelling should include the cost of the medication. The suggestion was made by the Committee in its report Prescribing Costs in Primary Care. While recognising the importance of generic prescribing, the RCGP cautions against frequent medication switches because it may unsettle patients. ,Any changes must be carried out for sound clinical reasons with good communication between GPs and their patients,' it adds. Statins for patients with kidney disease? Statins reduce cardiovascular risk in people with chronic kidney disease, a new study suggests, but their effects on renal function remain unclear (BMJ 2008; published online doi: 10.1136/bmj. 39472.580984.AE). The meta-analysis of 50 trials involving a total of 30 144 patients found that statins reduced lipids and cardiovascular events regardless of the severity of kidney disease. However, all-cause mortality was unaffected and, although proteinuria improved slightly, there was no change in the rate of decline of glomerular filtration rate. An accompanying editorial (BMJ 2008; published online doi:10.1136/ bmj.39483.665139.80) suggests that the indications for statin therapy to reduce cardiovascular risk in patients with chronic kidney disease should be the same as for those with normal renal function. New NICE guidance New clinical guidelines from NICE (see New from NICE, pages 14,15) include the diagnosis and management of irritable bowel syndrome in adults in primary care, the care and management of osteoarthritis in adults, and the diagnosis and treatment of prostate cancer. In a public health guideline on smoking cessation services, NICE endorses the use of nicotine replacement patches for 12,17 year olds. Suspect additives in children's medicines The Food Commission (www.foodcomm.org.uk) has drawn attention to the presence in children's medicines of food additives it says are linked with hyperactivity. The Commission, a national nonprofit organisation campaigning for ,the right to safe, wholesome food', says that seven common additives (including tartrazine, sodium benzoate and Ponceau 4R) are associated with hyperactivity in susceptible children. Checking the SPCs, it found that 28 of 70 children's medicines , including formulations of paracetamol, ibuprofen, amoxicillin, erythromycin and codeine phosphate throat linctus , contain at least one suspect additive. Digoxin may increase mortality in AF patients An observational study has suggested that digoxin may increase deaths in patients with atrial fibrillation (Heart 2008;94:191,6). The study was a planned subgroup analysis of a trial evaluating anticoagulant therapy in 7329 patients with atrial fibrillation. Of these, 53 per cent were treated with digoxin. Mortality was significantly higher among digoxin users than nonusers (4.22 vs 2.66 per cent per year); myocardial infarction and other vascular deaths (but not stroke, systemic embolic episodes and major bleeding events) were significantly more frequent with digoxin. Poor communications cause readmission Elderly hospital patients are often discharged with inadequate information or arrangements for care, causing almost three-quarters to be readmitted within a week, say investigators from Nottingham (Qual Safety Health Care 2008;17:71,5). Retrospective review of records for 108 consecutive patients aged over 75 found that readmission was related to medication in 38 per cent and, of these, 61 per cent were considered avoidable. Almost two-thirds had no discharge letter or were readmitted before the letter was typed; two-thirds of discharge letters had incomplete documentation of medication changes. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 22 2007Article first published online: 28 DEC 200 Glitazones: benefits outweigh the risks Following a review of the safety of rosiglitazone and pioglitazone, the European Medicines Agency (EMEA) has concluded that their benefits outweigh their risks in the approved indications. The review was prompted by reports of an increased risk of fractures in women and, in patients taking rosiglitazone, ischaemic heart disease. The EMEA concluded that prescribing information for rosiglitazone should now include a warning that, in patients with ischaemic heart disease, it should only be used after careful evaluation of each patient's individual risk, and the combination of rosiglitazone and insulin should only be used in exceptional cases and under close supervision. No change was considered necessary to the prescribing information for pioglitazone. Modern dressings no better? A systematic review has found only weak evidence that modern dressings are better than saline gauze or paraffin gauze for healing acute and chronic wounds (Arch Dermatol 2007;143: 1297-304). The analysis, which included 99 studies, found that only hydrocolloids were demonstrably better than older dressings for healing chronic wounds, and alginates were superior to other modern dressings for debriding necrotic wounds. There was no evidence that modern dressings offered superior overall performance to the older alternatives. Hospital inflation twice primary care level The cost of drugs prescribed in secondary care but dispensed in the community increased by 6.4 per cent in 2006 - twice the rate of inflation in primary care - according to the latest statistics on hospital prescribing in England. The increase follows a reduction in costs in 2005 after the introduction of the new PPRS scheme. Data from The Information Centre (www.ic.nhs.uk) show that hospital medicines make up about 24 per cent of the NHS drugs budget. Secondary care has a consistently better record than primary care in prescribing lower-cost alternatives within therapeutic categories, eg simvastatin and pravastatin among the statins, omeprazole and lansoprazole among PPIs, and ACE inhibitors among drugs acting on the renin angiotensin system. The most expensive drug prescribed by hospital specialists and dispensed in the community is interferon beta. MHRA limits the use of fibrates The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that fibrates should now be reserved for the treatment of isolated severe hypertriglyceridaemia. They should be considered for hypercholesterolaemia only when a statin or other treatment is contraindicated or not tolerated. In the latest Drug Safety Update, the MHRA says there is insufficient evidence of long-term benefits from fibrates, and first-line use is no longer justified because the evidence for the benefits of statins is robust. The MHRA also warns that some breastfeeding infants have increased susceptibility to the adverse effects of codeine taken by their mother, and that St John's wort may affect the hepatic metabolism of any anticonvulsant. Annual zoledronic acid infusion cuts mortality after hip fracture Once-yearly infusion of zoledronic acid (Aclasta) after hip fracture reduces deaths over a two-year period by 28 per cent compared with placebo, US investigators say (N Engl J Med 2007;357:1799-809). The HORIZON Recurrent Fracture Trial randomised 2127 men and women (mean age 75) within 90 days of surgery for hip fracture to zoledronic acid 5mg yearly or placebo. Mortality over 1.9 years of follow-up was 9.6 per cent with zoledronic acid and 13.3 per cent with placebo. Zoledronic acid also significantly reduced the rate of any new clinical fractures (by 35 per cent) and new clinical vertebral fractures(by 45 per cent),but the lower rate of hip fracture (2.0 vs 3.5 per cent with placebo) was not statistically significant. Rivastigmine patch for mild to moderate AD Rivastigmine (Exelon) is now available as a transdermal patch for the treatment of mild to moderate Alzheimer's disease. Applied once daily, the patch delivers 9.5mg per 24 hours and, says manufacturer Novartis, is associated with a lower incidence of nausea and vomiting than a comparable oral dose. The patch is available in two strengths: 4.6mg per 24hr is equivalent to oral doses of 3 or 6mg per day, and the 9.5mg per 24hr patch is equivalent to 9 or 12mg per day orally. The recommended dose of the patch is 9.5mg per day; both strengths cost £83.84 for 30 patches. Women more aspirin resistant than men? The cardioprotective effect of low-dose aspirin may be lower in women than men, say Canadian investigators (BMC Medicine 2007;5:29 doi: 10.1186/1741-70155-29). Their meta-analysis of 23 randomised trials involving a total of 113 494 participants found that aspirin significantly reduced the risk of nonfatal but not fatal myocardial infarction (MI). About one-quarter of the variation in its effects on nonfatal MI was accounted for by the sex mix of the trial population. Separating the results by sex showed the reduction in risk with aspirin use was statistically significant in men (relative risk, RR, 0.62) but not in women (RR 0.87). Look after physical health of mentally ill GPs and other primary care workers should take more responsibility for the physical health of their mentally ill patients, say advocacy groups. Mind and Body: Preventing and Improving Physical Health Problems in Patients With Schizophrenia points out that the mental health needs of patients with schizophrenia are met in secondary care, but their physical health needs should be met in primary care. In particular, the metabolic effects of antipsychotics may lead to obesity, diabetes and cardiovascular disease, and weight gain in particular is a frequent reason for nonadherence to treatment. The Mind and Body Manifesto was developed by SANE, The Mental Health Nurses Association, The National Obesity Forum and The Disability Rights Commission and sponsored by Bristol-Myers Squibb Pharmaceuticals Limited and Otsuka Pharmaceuticals (UK) Ltd. Copies are available from elizabeth.green@ ogilvyhealthworld.com. Health eCard costs Some costs quoted in our article on the Health eCard (The Health eCard: the way ahead for medical records?,5 October issue, pages 28-9) have been revised: the card and initial download will cost patients £39.50, and GPs will be entitled to charge patients £10 per annum for subsequent downloads. NICE appraisals of cytokine inhibitors in RA NICE has endorsed the use of the anti-TNF agents adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade), normally in conjunction with methotrexate, for the treatment of active RA when methotrexate and another DMARD have failed (also see New from NICE below). NICE has provisionally concluded, subject to consultation, that abatacept (Orencia) should not be recommended for the treatment of RA. Boots and BMJ launch health advice site www.askbootshealth.com is a new website providing information about health and medicines for the public produced by Boots using information provided by the BMJ Publishing Group. The website covers many of the topics already available from NHSDirect, with perhaps more information about available treatments. Diabetes care shows small improvement The third National Diabetes Audit in England and Wales has found that more people with diabetes were achieving the targets set by NICE for cholesterol levels, glycaemic control and blood pressure in 2005/06 - but younger patients were doing less well. Overall, the HbA1C target of ,7.5 per cent was achieved in 60 per cent of people with diabetes compared with 58 per cent in 2004/05. However, HbA1C was >9.5 per cent in 30 per cent of children and young people, of whom 9 per cent experienced at least one episode of ketoacidosis. More topics for NICE New topics referred to NICE include clinical guidelines on ovarian cancer, coeliac disease and stable angina, public health guidance on preventing cardiovascular disease, and technology appraisals on insulin detemir (Levemir) for type 1 diabetes, several treatments for cancer and hepatic and haematological disorders, and biological therapies for juvenile arthritis. New from NICE NICE appraisal on anti-TNFs for RA Since NICE published its first appraisal of agents acting against tumour necrosis factor-alpha (anti-TNFs) for the treatment of RA in 2002, the product licences for etanercept (Enbrel) and infliximab (Remicade) have changed and a new agent, adalimumab (Humira), has been introduced. The anti-TNFs act in different ways. Infliximab is a chimeric monoclonal antibody that binds to TNF-alpha, neutralising its activity. Etanercept, a recombinant human TNF-alpha receptor fusion protein, and adalimumab, a human-sequence antibody, both bind to TNF-alpha and block its interaction with cell surface receptors. Adalimumab also modulates some biological responses induced or regulated by TNF-alpha. These agents are recommended for adults with severe active RA (defined as a disease activity score - DAS28 - greater than 5.1) who have already tried two disease-modifying drugs, including methotrexate (if not contraindicated). Prior treatment should have been of at least six months' duration, including two months at the standard dose (unless limited by toxicity). Anti-TNFs should normally be prescribed with methotrexate; when this is not appropriate, etanercept and adalimumab may be prescribed as monotherapy. Treatment with an anti-TNF should be continued beyond six months only if there is an adequate response (defined as an improvement in DAS28 of at least 1.2). Data from the British Rheumatology Society Biologics register show that, after six months, 67 per cent of patients met NICE criteria for an adequate response; this declined to 55 per cent at 18 months. The basic annual cost of treatment is £9295 for adalimumab 40mg on alternate weeks or etanercept 25mg twice weekly; infliximab costs £3777 for a loading dose, then £7553-£8812 depending on dose. Assuming no progression of disability, the incremental costs per QALY (compared with sequential DMARDs) were £30 200 for adalimumab, £24 600 for etanercept and £39 400 for infliximab. There are no direct comparative trials of the anti-TNFs, and their clinical trial findings are not directly comparable. Unless other factors determine treatment choice, NICE therefore recommends the least expensive. If the first anti-TNF is withdrawn within six months due to an adverse event, a second may be tried. [source] 3413: Treatment options of macular edema in uveitisACTA OPHTHALMOLOGICA, Issue 2010Y GUEX-CROSIER Purpose To summarize current concepts on therapeutic approach in inflammatory cystoid macular edema (ICME). Methods A review of relevant literature concerning treatment options of ICME was performed. Results ICME is a major factor related to poor visual acuity in long term follow-up of uveitis. Topical corticosteroids administration has a minor therapeutic effect on ICME. Local therapies consist mostly of posterior sub-tenon's, intraocular corticosteroids injections or drug delivery systems. The effect of systemic corticosteroids, immunosuppressive agents or biological therapies will be discussed. Conclusion The recent development of drug delivery systems and biological therapies has considerably improved the prognosis of ICME. [source] What's new in psoriasis?CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 7 2010Analysis of the clinical significance of new guidelines, systematic reviews on psoriasis published in 200 Summary This review summarizes the clinical importance of 18 systematic reviews and guidelines on psoriasis published or indexed between November 2008 and October 2009. The topics covered include guidance on the use of topical, systemic and biological therapies for the treatment of psoriasis; comorbidities associated with psoriasis; and complementary therapies for psoriasis. A similar and more detailed review to this appeared in the 2009 Annual Evidence Update on Psoriasis from NHS Evidence , Skin Disorders in November 2009. [source] Methotrexate for psoriasis in the era of biological therapyCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 5 2008R. B. Warren Summary Methotrexate's traditional role as a first line agent for moderate to severe psoriasis is being challenged by the rapid and growing use of biological therapies. A recent study comparing adalimumab with methotrexate showed significantly superior efficacy of adalimumab over methotrexate over 16 weeks. Although it is inexpensive, the future use of methotrexate may be compromised by its unpredictable response and toxicity, and by the introduction of newer, more effective biological therapies. However, recent advances in the screening of liver fibrosis by monitoring serum levels of the aminoterminal peptide fragment of type III procollagen have reduced the need for liver biopsy. Furthermore, the potential for personalized methotrexate use by application of modern pharmacogenetics and pharmacokinetics may ensure its place as a first-line agent for the treatment of psoriasis for the foreseeable future. [source] Management of metastatic carcinoma of the uveal tract: an evidence-based analysisCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 6 2007Gowri L Kanthan MBBS Abstract Uveal metastasis from carcinoma is the most common cause of ocular malignancy in adults and represents an increasing problem in the context of an ageing population and enhanced survival of stage IV cancer patients. The reported prevalence of clinically evident uveal metastases in carcinoma patients ranges from 2% to 9%, with breast and lung cancer together accounting for between 71% and 92% of cases. Most patients (66,97%) have a known history of cancer and, although the majority have metastatic lesions elsewhere, up to 33% may present with an isolated ocular metastasis. These lesions may progress rapidly and are potentially sight-threatening. Early diagnosis and appropriate timely treatment are therefore of paramount importance to maintain patients' quality of life. The diagnosis is usually clinical and detailed descriptions of symptomatology and physical characteristics are provided. In 21,50% of patients, involvement is bilateral. External beam radiotherapy (EBRT), chemotherapy, hormone and biological therapies, brachytherapy, transpupillary thermotherapy, laser photocoagulation/photodynamic therapy and enucleation are therapeutic modalities described in the literature for the management of uveal metastases. The strongest evidence favours timely EBRT for the management of sight-threatening uveal metastases. The published evidence supporting EBRT for sight-threatening uveal metastases was given a grade B (strong support for recommendation). Newer alternative therapies are emerging and may have a role in selected patients; however, there are unfortunately few large studies examining such treatments for carcinoma metastatic to the eye. The role of these modalities will be further clarified with the results of larger comparative trials. [source] Treatment of erythrodermic psoriasis in HCV+ patient with adalimumabDERMATOLOGIC THERAPY, Issue 2009Antonio Giovanni Richetta ABSTRACT Erythrodermic psoriasis is a severe and disabling variant of psoriasis. The authors present the case of a 48-year-old man with psoriasis and hemophilia presented with a history of hepatitis C virus (HCV) infection treated with pegylated interferon alpha-2a and ribavirin therapy. At the end of antiviral therapy, skin manifestation progressively worsened, becoming erythrodermic, with lack of efficacy of steroid therapy. The authors decided to start biological therapy with induction dose of adalimumab (Humira, Abbott Laboratories, Abbott Park, Chicago, IL) 80 mg at Week 0 and 40 mg weekly. In our case, this resulted in a highly effective and safe treatment. [source] Inflammatory bowel disease in young people: The case for transitional clinicsINFLAMMATORY BOWEL DISEASES, Issue 6 2010J. Goodhand MRCP Abstract Background: The incidence of inflammatory bowel disease (IBD) is increasing among adolescents. In all, 25% of patients are diagnosed before the age of 16, when they are traditionally transferred from the pediatric to the adult service. Methods: We conducted a retrospective case-controlled study to characterize patients treated in a novel transitional adolescent,young adult IBD clinic. This compared disease extent, radiation exposure, therapeutic strategy, and requirement for surgery in 100 adolescents with controls from our adult IBD clinic matched for disease duration. Results: The median (range) ages for the adolescent and adult population was 19 (16,28) and 43 (24,84), with a median age at diagnosis of 15 (3,26) and 39 (13,82) respectively (P < 0.001). Crohn's disease was significantly more common in the adolescents. Disease distribution was ileocolonic in 69% of adolescents and 28% of adults, restricted to the ileum in 20% of adolescents and 47% of adults, and colonic only in 11% and 22%, respectively. Upper gastrointestinal involvement occurred in 23% of adolescents, but was not seen in adults (P < 0.01). Total ulcerative colitis was seen in 67% of adolescents and 44% of adults (P < 0.01). Contrary to previous data adolescents did not receive more ionizing radiation than adults. Requirement for immunosuppressive therapy was higher in the adolescent group (53% versus 31%, respectively, P < 0.01). Likewise, 20% of adolescents had required biological therapy compared to only 8% in the adult cohort (P < 0.05). Conclusions: Gastroenterologists should recognize that IBD is more complex when presenting in adolescence and our data support the creation of specific adolescent transitional clinics. Inflamm Bowel Dis 2009 [source] Crohn's disease, hepatosplenic T-cell lymphoma and no biological therapy: Are we barking up the wrong tree?INFLAMMATORY BOWEL DISEASES, Issue 9 2009Dr. Gordon Moran MD No abstract is available for this article. [source] Un-promoted issues in inflammatory bowel disease: opportunities to optimize careINTERNAL MEDICINE JOURNAL, Issue 3 2010J. M. Andrews Abstract Inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the gut, which lead to significant morbidity and impaired quality of life (QoL) in sufferers, without generally affecting mortality. Despite CD and UC being chronic, life-long illnesses, most medical management is directed at acute flares of disease. Moreover, with more intensive medical therapy and the development of biological therapy, there is a risk that management will become even more narrowly focused on acute care, and be directed only at those with more severe disease, rather than encompassing all sufferers and addressing important non-acute issues. This imbalance of concentration of medical attention on ,high-end' care is in part driven by the need to perform and publish randomized clinical trials of newer therapies to obtain registration and licensing for these agents, which thus occupy a large proportion of the recent IBD treatment literature. This leads to less attention on relatively ,low-technology' issues including: (i) the psychosocial burden of chronic disease, QoL and specific psychological comorbidities; (ii) comorbidity with functional gastrointestinal disorders (FGIDs); (iii) maintenance therapy, monitoring and compliance; (iv) smoking (with regard to CD); (v) sexuality, fertility, family planning and pregnancy; and (vi) iron deficiency and anaemia. We propose these to be the ,Un-promoted Issues' in IBD and review the importance and treatment of each of these in the current management of IBD. [source] Denaturing capillary electrophoresis for automated detection of L858R mutation in exon 21 of the epidermal growth factor receptor gene in prediction of the outcome of lung cancer therapyJOURNAL OF SEPARATION SCIENCE, JSS, Issue 15 2010Lucie Benesova Abstract The presence of activating mutations within the tyrosine kinase domain of the epidermal growth factor receptor gene has been attributed to a positive response to biological therapy of lung cancer by small-molecular tyrosine kinase inhibitors, gefitinib and erlotinib. Among the two most significant mutation types are deletions in exon 19 and a single point substitution in exon 21 (termed L858R). The exon 19 deletions can readily be examined by fragment analysis, due to the characteristic length difference between the normal and mutated PCR product. Analysis of the L858R point mutation, however, presents a greater challenge. The current paper is aimed at developing a sensitive, yet simple, low-cost mutation detection assay directed at the L858R mutation using a method based on CE of heteroduplexes under partial denaturing conditions. We perform optimization of separation conditions on different commercial instruments including ones equipped with 8, 16 and 96 capillaries. We present normalized migration reproducibility in the range from 1 (8 and 16) to 5% (96) RSD. A reliable distinction of the R836R silent polymorphism from a potential presence of the L858R mutation is also demonstrated. In its implementation, the presented assay is just another application running on a conventional CE platform without the need of dedicated instrumentation. [source] From bench to bedside , translational research in psoriasisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2010JC Prinz Abstract For many years, psoriasis was firmly believed to be a disease of epidermal keratinocytes, but now is attributed to a combination of genetic and environmental factors that promote a T-cell mediated immune response in the skin. Psoriasis is now understood to be a systemic T-cell mediated autoimmune disease with the innate immune system playing an important role. Progress in understanding the pathogenesis of psoriasis has shown that following a stimulus, dendritic and T cell activation leads to the release of cytokines, chemokines and growth factors that initiate the proliferation and altered differentiation of keratinocytes. These factors subsequently lead to continuous activation of T cells and antigen-presenting cells, particularly dendritic cells, within the psoriatic plaque. This vicious cycle of psoriasis, in which the cytokines interleukin 12 (IL-12) and IL-23 play a pivotal role, is a logical target for biological therapy. [source] Cost-effectiveness of biological therapy for Crohn's disease: Markov cohort analyses incorporating United Kingdom patient-level cost dataALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009K. BODGER Summary Background, Anti-TNF-alpha agents for Crohn's disease (CD) have good clinical efficacy but high acquisition cost compared to rival drugs. Aim, To assess the cost-effectiveness of infliximab and adalimumab for Crohn's disease from the perspective of the UK NHS, incorporating recent trial and observational data. Methods, Lifetime Markov analyses constructed to simulate quality-adjusted life-years (QALYs) and costs. CD was represented by four health-states representing: Full response, partial response, nonresponse, surgery and death. The course of CD under standard care was based on the Olmsted county cohort. Systematic review identified ACCENT I (infliximab) and CHARM (adalimumab) as sources for efficacy data. We modelled an intention-to-treat strategy for biologics including surgical rates based on observational data, cost estimates from our UK dataset and utilities from an algorithm converting CDAI to EQ-5D utilities. Results, The incremental cost-effectiveness ratios (ICERs) compared to standard care for 1-year of treatment with infliximab or adalimumab were £19 050 and £7190 per QALY gained, respectively. Lifetime therapy was dominated by standard care. Analyses over shorter time horizons, matched to treatment duration, resulted in unfavourable ICERs. Conclusion, The model suggests acceptable ICERs for biological agents when considering a lifetime horizon with periods of up to 4 years continuous therapy. As with all economic evaluations, the results may not be generalizable beyond the perspective of analysis. [source] Surgery for gastrointestinal stromal tumour in the post-imatinib eraANZ JOURNAL OF SURGERY, Issue 3 2005Susan J. Neuhaus Gastrointestinal stromal tumour (GIST) is a rare tumour. Historically, surgery has been the only effective treatment. The prognosis of patients with gastrointestinal stromal tumour is poor. Even after apparently ,curative' surgical resection more than 50% of patients relapse. The development of an effective novel targeted therapy against GIST (imatinib mesylate) is a success story of molecular biology that has dramatically altered the management of patients with these tumours. However, as follow up of patients who have initially responded to imatinib has increased, it has become evident that such hopes of cure were premature because responses to imatinib are of limited duration. Unresolved issues include the role of imatinib as an induction (neo-adjuvant) therapy prior to surgery, or as adjuvant treatment after surgery, the role of surgery in patients with a differential or partial response and the role of surgery in patients with isolated metastatic disease. In the present paper the biology and natural history of GIST are reviewed, and the complexities of surgical management that exist in the context of an effective, but not curative, biological therapy, are addressed. [source] Outcome and survival with nonsurgical management of renal cell carcinomaBJU INTERNATIONAL, Issue 7 2003A.D. Baird OBJECTIVE To document long-term survival in patients with renal cell carcinoma (RCC) in whom the primary tumour was left in situ and treatment limited to palliative and symptomatic measures. PATIENTS AND METHODS All patients with a diagnosis of RCC from January 1994 to January 1999 and in whom the primary tumour was left in situ were identified from hospital records (nine women and 16 men, mean age 69 years). The tumour stage was T1,T4. RESULTS The mean survival overall was 19.3 months; patients with locally advanced disease, i.e. stage , T3a, had a mean survival of 16.9 months. CONCLUSIONS There is renewed interest in the management of advanced RCC, with data supporting cytoreductive nephrectomy with systemic biological therapy. These results confirm that such patients with or without metastatic disease can survive for a considerable period with no aggressive surgical or systemic measures, and such intervention may offer no significant advantage in outcome and survival over supportive treatment alone. [source] Methotrexate for psoriasis in the era of biological therapyCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 5 2008R. B. Warren Summary Methotrexate's traditional role as a first line agent for moderate to severe psoriasis is being challenged by the rapid and growing use of biological therapies. A recent study comparing adalimumab with methotrexate showed significantly superior efficacy of adalimumab over methotrexate over 16 weeks. Although it is inexpensive, the future use of methotrexate may be compromised by its unpredictable response and toxicity, and by the introduction of newer, more effective biological therapies. However, recent advances in the screening of liver fibrosis by monitoring serum levels of the aminoterminal peptide fragment of type III procollagen have reduced the need for liver biopsy. Furthermore, the potential for personalized methotrexate use by application of modern pharmacogenetics and pharmacokinetics may ensure its place as a first-line agent for the treatment of psoriasis for the foreseeable future. [source] Cytokine and anti-cytokine therapy in asthma: ready for the clinic?CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2009D. Desai Summary Asthma is a common disease with an increasing prevalence worldwide. Up to 10% of these patients have asthma that is refractory to current therapy. This group have a disproportionate use of health care resources attributed to asthma, have significant morbidity and mortality and therefore represent an unmet clinical need. Asthma is a complex heterogeneous condition that is characterized by typical symptoms and disordered airway physiology set against a background of airway inflammation and remodelling. The inflammatory process underlying asthma is co-ordinated by a cytokine network. Modulating this network with biological therapy presents a new paradigm for asthma treatment. Clinical trials undertaken to date have underscored the complexity of the inflammatory profile and its relationship to the clinical features of the disease and have raised the importance of safety considerations related to these novel therapies. T helper type 2 cytokine blockade remains the most promising strategy, with anti-interleukin-5 reducing asthma exacerbations. Although anti-cytokine therapy is not yet ready for the clinic, the long-awaited possibility of new treatments for severe asthma is moving ever closer. [source] | ||||||||||||||||||||||