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Severe Plaque Psoriasis (severe + plaque_psoriasis)
Selected AbstractsAdalimumab for treatment of moderate to severe psoriasis and psoriatic arthritisDERMATOLOGIC THERAPY, Issue 2008M. R. Bongiorno ABSTRACT: Psoriasis and psoriatic arthritis are common diseases associated with considerable morbidity and disability. Their pathophysiology comprises similar processes leading to inflammation of skin, entheses, and joints. Although traditional systemic agents can be effective, their use may be limited by lack of efficacy and concerns regarding adverse effects. The objective of this study was to assess the efficacy and safety of adalimumab, a fully human antitumor necrosis factor (anti-TNF) monoclonal antibody, over 16 weeks. The present authors report their personal experience in 15 patients with severe plaque psoriasis and psoriatic arthritis, refractory to other treatments, in which a decisive regression of joint/skin involvement was obtained. Psoriasis and psoriatic arthritis are chronic inflammatory disorders resulting from a combination of genetic and environmental factors. [source] Safety of efalizumab in adults with chronic moderate to severe plaque psoriasis: A phase IIIb, randomized, controlled trialINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2006Kim A. Papp MD Background, To provide safety data for efalizumab, a recombinant humanized monoclonal IgG1 antibody, in adults with chronic plaque psoriasis. Methods, A 12-week, Phase IIIb, randomized, double-blind, parallel-group, placebo-controlled trial. At 58 study sites in the USA and Canada, 686 patients with moderate to severe chronic plaque psoriasis received an initial conditioning dose of efalizumab 0.7 mg/kg subcutaneously (SC) followed by either 11 weekly doses of efalizumab 1 mg/kg SC or matching placebo. Main outcome measures were safety and tolerability outcomes (primary) and efficacy outcomes (secondary). Results, During 12 weeks of therapy with efalizumab or placebo, the incidence of clinical adverse events was 82.2% and 72.9%, respectively; the incidence of serious adverse events was 1.8% and 3.4%, respectively; and the incidence of nonserious adverse events leading to withdrawal was 1.8% and 1.7%, respectively. In the efalizumab group, there were no clinically significant changes in vital signs or laboratory parameters and no evidence of end-organ toxicities. A significantly higher proportion of patients receiving efalizumab than those receiving placebo achieved , 75% improvement in the Psoriasis Area and Severity Index (PASI) (P < 0.001), , 50% improvement in PASI (P < 0.001), and a static Physician's Global Assessment rating of Minimal or Clear (P < 0.001). The mean improvement in the Psoriasis Symptom Assessment was significantly greater in the efalizumab group (P < 0.001). Conclusions, Efalizumab treatment SC for 12 weeks was safe, well tolerated, and effective in patients with moderate to severe chronic plaque psoriasis. [source] Rapid response to infliximab in severe pustular psoriasis, von Zumbusch typeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2002Meggan R. Newland MD Tumor necrosis factor-alpha (TNF-,) is a chemokine secreted by T cells which is thought to play a critical role in the pathophysiology of psoriasis. The monoclonal antibody, infliximab, complexes with TNF-,, rendering it inactive. A recent clinical trial has reported the clinical benefit and safety of infliximab in moderate to severe plaque psoriasis. We report a case of rapid response and clinical benefit using infliximab in severe pustular psoriasis of von Zumbusch. [source] Cost-effectiveness of psoriasis therapy with etanercept in GermanyJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 9 2007Tatjana Heinen-Kammerer Summary Background: We estimated the cost-effectiveness of intermittent therapy with etanercept in patients with moderate-to-severe plaque-type psoriasis in comparison to non-systemic therapy in Germany. Patients and Methods: We performed a cost-utility analysis using the endpoint costs per quality-adjusted life year gained (costs/QALY). For this purpose, we adapted a UK-based Markov model by means of resource use data that we derived from a German cost study. Efficacy data, information on frequency of adverse events and changes in quality of life were derived from three pooled clinical trials. We extrapolated the further course of the disease and its treatment over a 10 year course. Results: For patients with an initial Psoriasis Area and Severity Index (PASI) > 10 and a Dermatology Life Quality Index (DLQI) > 10 the incremental cost-effectiveness ratio (ICER) for etanercept compared to non-systemic therapy was 45,491 ,/QALY. For patients with PASI and DLQI > 15 costs/QALY were 32,058 , and among patients with severe plaque psoriasis (DLQI and PASI > 20) 18,154 , . Conclusions: According to internationally accepted levels of cost-effectiveness thresholds, the intermittent treatment of (moderate to) severe plaque-type psoriasis with etanercept is a cost-effective measure within the German healthcare system. [source] Latest news and product developmentsPRESCRIBER, Issue 3 2008Article first published online: 26 FEB 200 Higher risk of CV events in aspirin resistance More than one in four patients may have aspirin resistance, a new metaanalysis shows, and they face a four-to sixfold increased risk of a major cardiovascular event or death compared with aspirin-sensitive patients taking low-dose aspirin (BMJ online: 17 Jan 2008; doi:10. 1136/bmj.39430.529549.BE). The analysis included 20 studies involving a total of 2930 patients with cardiovascular disease. Of these, 28 per cent were defined as having aspirin resistance (according to the various definitions in each study). Compared with aspirin-sensitive patients, the odds ratio of any cardiovascular event or acute coronary syndrome was about 4 and the odds ratio of death was 6. Aspirin-resistant patients did not benefit from other antiplatelet treatment. ADOPT: rosiglitazone fracture risk in women A new analysis of the ADOPT trial (N Engl J Med 2006;355: 2427-43) has found that the risk of fractures during treatment with rosiglitazone (Avandia) is approximately twice as high as with metformin or glibenclamide, but mainly in women (Diabetes Care online: 25 Jan 2008; doi: 10.2337/dc07-2270). The study found a significant difference in risk between the drugs only for women, with a cumulative incidence of 15.1 per cent with rosiglitazone, 7.3 per cent with metformin and 7.7 per cent with glibenclamide after five years. No risk factors were identified although the incidence of fractures was higher among postmenopausal than premenopausal women. New from NICE Infliximab for the treatment of adults with psoriasis. Technology Appraisal Guidance No. 134, Jan 2008 Infliximab (Remicade), a monoclonal antibody against TNF-alpha, should be an option for treating very severe plaque psoriasis in adults, NICE recommends. Using its fast-track single technology appraisal procedure, NICE concluded that infliximab should be considered when standard therapies,methotrexate or ciclosporin (Neoral), or PUVA , have failed or are unsuitable. The criteria for disease severity are defined by the Psoriasis Area Severity Index (PASI) score (,20) and the Dermatology Life Quality Index (DLQI) score (>18). Treatment response is also defined by these measures and infliximab should be continued for longer than 10 weeks only when predefined thresholds are met. Infliximab costs an average of £11 750 annually. In 2006, NICE recommended etanercept (Enbrel) and efalizumab (Raptiva) for patients with severe psoriasis (PASI ,10 and DLQI >10). Commons committee wants tougher targets Most GPs get full QOF points for medicines management even though there is inexplicably large variation in good prescribing practice between PCTs, the Public Accounts Select Committee points out in its latest report, Prescribing Costs in Primary Care. The Committee wants to see tougher QOF targets among several initiatives to reduce prescribing costs. Although most publicity centred on its endorsement of the National Audit Office claim that GPs could save £200 million by prescribing lower-cost drugs, the report contains some more far-reaching proposals. GPs should prescribe generic alternatives within a therapeutic category, so when a brand is not available generically, eg Lipitor, a different drug that is, eg simvastatin, should be used when clinically appropriate. Further, this form of substitution should be rewarded via QOF targets. There should be greater uniformity in the appearance, labelling and packaging of generic and branded equivalents. The Department of Health should consider raising awareness of the value of medicines by printing the cost on packaging, and to reduce the £100 million wasted annually in dumped medicines, it should investigate which drugs aren't used and why patients won't take them. Strategic health authorities should work with the National Prescribing Centre to develop more prescribing indicators with which to measure PCT performance and support PCTs to promulgate best practice. They should also collaborate on promoting joint primary-secondary care formularies and increase the consistency of prescribing, not only between hospital specialists and GPs but also between PCTs. To monitor the influence of the pharmaceutical industry, PCTs should keep a record of gifts and hospitality and publish a register. Questions to ask about mental health treatment The Department of Health has published a booklet designed to raise awareness of medicines management issues affecting people using mental health services and their carers, and professionals in the health and social services. Although one aim of Medicines Management: Everybody's Business is to empower people with mental health problems to ask about their medication, its formal style is better suited to staff who need to improve their person-centred approach to care. It covers what information people should expect and what questions to ask when drug treatment is being considered, what to expect at review and issues to consider when contemplating stopping treatment. Copies can be downloaded at www.dh.gov.uk. Consider statins for all patients with diabetes Treatment with a statin should be considered for all patients with diabetes unless their risk is low, say the authors of a new study (Lancet 2008;371:117-25). Their meta-analysis of 14 randomised trials involving 18 686 people with diabetes and an average follow-up of 4.3 years found that statins reduced vascular events and vascular mortality as much as in nondiabetic populations. The overall benefit was 42 fewer major events per 1000 people treated for five years. This was independent of a history of vascular disease or other baseline characteristics. No evidence for OTC cough medicines There is no evidence that over-the-counter cough medicines for adults and children are effective in relieving acute cough, a new Cochrane review has concluded (Cochrane Database of Systematic Reviews 2008, Issue 1). The review of 17 randomised trials involving 2876 adults and eight involving 616 children reported conflicting findings of uncertain clinical relevance. The trials were heterogeneous and of low quality. Copyright © 2008 Wiley Interface Ltd [source] Interleukin-20 plays a critical role in maintenance and development of psoriasis in the human xenograft transplantation modelBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2009K. Stenderup Summary Background, Interleukin (IL)-20 is a recently discovered cytokine displaying increased levels in psoriatic lesions. Interestingly, IL-20 levels decrease with antipsoriatic treatment, correlating with clinical improvement. However, the role of IL-20 in the aetiology of psoriasis is unknown. Objectives, In this study, we investigate the effects both of blocking IL-20 signalling in psoriatic plaques and of adding IL-20 to nonlesional psoriasis skin. Methods, We employed the human skin xenograft transplantation model in which psoriatic plaques and nonlesional keratome skin biopsies obtained from donors with moderate to severe plaque psoriasis were transplanted on to immuno-deficient mice. The transplanted mice were treated with anti-IL-20 antibodies or recombinant human IL-20. Results, We demonstrate that blocking IL-20 signalling with anti-IL-20 antibodies induces psoriasis resolution and inhibits psoriasis induction. We also demonstrate that continuous IL-20 infusion, together with injection of additional nonactivated leucocytes, promotes induction of psoriasis in nonlesional skin from patients with psoriasis. Conclusions, The results suggest that IL-20 plays a critical role in the induction and maintenance of psoriasis, and IL-20 is suggested as a new possible specific target in psoriasis treatment. [source] Effects of etanercept on C-reactive protein levels in psoriasis and psoriatic arthritisBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2008B. Strober Summary Background, C-reactive protein (CRP), an inflammation biomarker, indicates cardiovascular risk and is elevated in psoriasis. The effect of etanercept on CRP in psoriasis has not been previously examined. Objectives, The primary objective was to examine the effect of etanercept on CRP levels from baseline to week 12 compared with placebo. Secondary objectives included assessment of baseline CRP and relationships between CRP and body mass index (BMI), statin drug use, and Psoriasis Area and Severity Index (PASI) scores. Methods, A retrospective analysis was conducted of CRP levels from patients with psoriasis who participated in a randomized, double-blind, placebo-controlled, U.S. registrational study. Data were analysed separately if patients self-reported psoriatic arthritis. Results, Baseline CRP levels were elevated in patients with psoriasis with and without psoriatic arthritis. CRP was significantly reduced in both groups after 12 weeks of etanercept treatment. Patients with psoriasis with psoriatic arthritis and patients with higher BMIs had higher median baseline CRP values and greater reduction of CRP values compared with those without psoriatic arthritis and those with lower BMIs. Etanercept lowered CRP levels in statin users and nonusers. Regression analyses revealed an association between baseline PASI score and baseline CRP independent of BMI in patients with psoriasis. Conclusions, Patients with moderate to severe plaque psoriasis, with or without psoriatic arthritis, have increased systemic inflammation demonstrated by elevated CRP levels. In psoriasis without psoriatic arthritis, skin disease activity is associated significantly with CRP elevation, independent of BMI, age and sex. Etanercept reduced CRP levels in all but the normal weight psoriasis group without psoriatic arthritis. [source] Impact of adalimumab treatment on health-related quality of life and other patient-reported outcomes: results from a 16-week randomized controlled trial in patients with moderate to severe plaque psoriasisBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2008D. Revicki Summary Background, Health-related quality of life (HRQOL) and other patient-reported outcomes (PROs) are important in evaluating the impact of psoriasis and its treatment. Objectives, To assess the impact of adalimumab treatment on HRQOL and other PROs in patients with moderate to severe psoriasis. Methods, A 16-week, double-blind, double-dummy, randomized controlled trial evaluated the efficacy and safety of adalimumab in 271 adults with moderate to severe chronic plaque psoriasis. Patients were randomized in a 2 : 2 : 1 ratio to adalimumab, methotrexate (MTX) or placebo. PROs were evaluated throughout the study and included the Dermatology Life Quality Index (DLQI), Patient's Global Assessment of disease severity, plaque psoriasis and psoriatic arthritis pain visual analogue scale (VAS), Psoriasis-Related Pruritus Assessment and EuroQOL 5D (EQ-5D). Results, Statistically significant differences were observed between the adalimumab- and placebo-treated and the MTX-treated groups on mean DLQI total scores during the 16-week double-blind study (both P < 0·001). Significant differences, favouring adalimumab compared with placebo, were also observed on the Patient's Global Assessment of disease severity (P < 0·001), VAS for pain (P < 0·001), Psoriasis-Related Pruritus Assessment (P < 0·001), EQ-5D VAS (P < 0·001) and EQ-5D index score (P < 0·01). Compared with MTX, adalimumab resulted in statistically significantly greater improvements in the Patient's Global Assessment of disease severity (P < 0·001), the VAS for pain (P < 0·01) and the Psoriasis-Related Pruritus Assessment (P < 0·001). Conclusions, Adalimumab was efficacious in improving dermatology-specific HRQOL, disease control and symptom outcomes in patients with moderate to severe psoriasis. [source] Efficacy 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] Infliximab treatment results in significant improvement in the quality of life of patients with severe psoriasis: a double-blind placebo-controlled trialBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2005S.R. Feldman Summary Background, Psoriasis is a chronic disease that significantly diminishes the health-related quality of life (HRQOL). Infliximab is a chimeric, tumour necrosis factor , monoclonal antibody that has been shown to improve the signs and symptoms of plaque psoriasis. Objectives, The objective of this study was to evaluate the effect of infliximab induction therapy on the HRQOL of patients with severe plaque psoriasis. Methods, In this double-blind, placebo-controlled trial, 249 patients were randomly assigned to receive intravenous infusions of 3 or 5 mg kg,1 of infliximab or placebo and were treated at weeks 0, 2 and 6. Patients completed the Dermatology Life Quality Index (DLQI) at baseline and week 10. Results, Infliximab induction therapy resulted in a substantial improvement in HRQOL. At week 10, patients in the infliximab 3- and 5-mg kg,1 groups showed a median percentage improvement in DLQI scores of 84·0% and 91·0%, respectively, compared with 0% in the placebo group (P < 0·001). The median decrease from baseline in DLQI score at week 10 was 8·0 and 10·0 for the 3 and 5 mg kg,1 infliximab groups, respectively, compared with 0 in the placebo group (P < 0·001). Thirty-three per cent and 40% of patients in the 3 and 5 mg kg,1 infliximab groups, respectively, had a DLQI score of 0 at week 10, compared with 2% in the placebo group (P < 0·001). There was a strong correlation between the percentage change from baseline at week 10 in Psoriasis Area and Severity Index (PASI) scores and the percentage change in DLQI scores during the same period (Spearman's correlation, 0·61, P < 0·001). When the infliximab and placebo treatment groups were combined, patients with at least 75% improvement in PASI scores between baseline and week 10 had a greater mean improvement in DLQI scores (81%) than those with 50,75% improvement in PASI during the same period (60%). Conclusions, Infliximab induction therapy resulted in significant improvement in HRQOL in patients with severe psoriasis. [source] A multiparameter flow cytometric analysis of the effect of bexarotene on the epidermis of the psoriatic lesionBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2003M.E.J. Franssen Summary Background A new retinoid, bexarotene (Targretin®), was recently investigated in a large multicentre trial for its efficacy and safety in psoriasis. Bexarotene is a novel retinoid X receptor (RXR)-selective ligand. Objectives The aim was to study the effect of bexarotene in psoriasis by analysing markers for epidermal differentiation, proliferation and inflammation in epidermal single cell suspensions from lesions of patients with psoriasis treated with various doses of bexarotene. Methods Thirty-four patients with moderate to severe plaque psoriasis participated in this study and were assigned in sequence to four different dose regimens: 0·5, 1, 2 and 3 mg kg,1 once daily. Before and after 12 weeks of bexarotene treatment, punch biopsies were taken from lesional skin from which epidermal single cell suspensions were prepared using an optimized thermolysin protocol. A sum of scores was determined for each biopsy site, based on a four-point scale for erythema, induration and desquamation. An improved multiparameter flow cytometric assay was used that enabled simultaneous assessment of epidermal proliferation, various aspects of differentiation and epidermal inflammation. The following variables were measured simultaneously: relative DNA content, relative cell size, keratin (K) 10, K6 and vimentin expression. Results The psoriasis area and severity index (PASI) and sum of scores for the individual psoriatic lesion each showed a statistically significant decrease of 28% after 12 weeks of bexarotene treatment (P < 0·001). However, no significant dose,response effect was found. The total percentage of K10+ cells showed a significant increase of 43% (P < 0·01). The total population of K6 expressing cells did not show significant changes. Regarding the subpopulations of K6 single, K10 single and K6 and 10 co-expressing cells, a significant increase of 77% was seen in the K10+ K6, cells (P < 0·05), a significant decrease of 33% in K10, K6+ cells (P < 0·01), and no significant changes in the remaining population of K10+ K6+ cells. After 12 weeks of treatment with bexarotene no significant changes in epidermal proliferation and inflammation were shown. Conclusions The present study indicates a direct effect of RXR activation by bexarotene on the transition of proliferation-associated keratinization into normal keratinization. Although no direct effect of bexarotene on DNA content in the total K10, cells was shown, further studies on subpopulations within the germinative layer such as stem cells and transit amplifying cells might be worthwhile. [source] | ||||||||||