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    <recommendedItem id="20100101_19_404"
                     title="Tailor Etanercept to Symptoms in Psoriasis and Psoriatic Arthritis (CME/CE)"
                     score="0.009"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/18309?impressionId=1265801000355"
                     
      &lt;p&gt;The decision to use once-weekly or twice-weekly etanercept (Enbrel) in patients with both psoriasis and psoriatic arthritis should be determined by the cutaneous and joint symptoms of the patient, researchers said.&lt;/p&gt;
&lt;p&gt;In a blinded, multicenter study, 46% of patients who received the drug twice a week had cleared or almost cleared their skin manifestations of psoriasis at week 12, compared with 32% of those who received the drug only once each week (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001), according to Wolfram Sterry, MD, of Charite University Medicine in Berlin, and colleagues.&lt;/p&gt;
&lt;p&gt;In contrast, there were no differences in response for arthritis symptoms, with 77% of those in the twice-weekly group and 76% of those in the once-weekly group meeting predetermined psoriatic arthritis response criteria at week 12, the researchers reported online in the &lt;em&gt;BMJ&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;An estimated 30% of patients with psoriasis have an arthritic component to their disease, manifesting as chronic inflammation of the joints and entheses.&lt;/p&gt;
&lt;p&gt;&quot;The challenge of treating patients with both active psoriasis and active psoriatic arthritis is to optimize the treatment of both disease manifestations to give the best overall outcome,&quot; the investigators wrote.&lt;/p&gt;
&lt;p&gt;Etanercept, a fully human tumor necrosis factor (TNF) inhibitor, is approved for use in both conditions based on findings showing that TNF and other cytokines are upregulated in both inflamed joint and skin tissues.&lt;/p&gt;
&lt;p&gt;To determine the efficacy of two different treatment regimens in patients who had not previously received a TNF inhibitor but had moderate-to-severe skin symptoms and active arthritis, Sterry and colleagues recruited 752 patients from 98 centers for PRESTA (Psoriasis Randomized Etanercept STudy in subjects with psoriatic Arthritis).&lt;/p&gt;
&lt;p&gt;They paired rheumatologists and dermatologists to cooperatively assess effects of the drug.&lt;/p&gt;
&lt;p&gt;Patients were randomized to receive subcutaneous etanercept, 50 mg once or twice weekly for 12 weeks, and for an additional 12 weeks both groups received 50 mg once weekly.&lt;/p&gt;
&lt;p&gt;To maintain blinding, the once-weekly group also received a placebo injection during the first 12 weeks.&lt;/p&gt;
&lt;p&gt;Participants&apos; mean age was 46.5 years. Mean duration of psoriasis was 18.9 years, and mean duration of arthritis was seven years. Most were white men.&lt;/p&gt;
&lt;p&gt;For the joint symptoms, the proportions of patients who achieved American College of Rheumatology (ACR) responses were similar at weeks 12 and 24 in the two groups.&lt;/p&gt;
&lt;p&gt;At week 12, 66.4% and 60.8% of patients in the twice- and once-weekly groups, respectively, had achieved ACR20 responses (representing a 20% improvement). At week 24, the corresponding proportions were 69% and 71.7%.&lt;/p&gt;
&lt;p&gt;At week 12, the percentage reductions in physician&apos;s global assessment of arthritis were 60% and 62% for the twice- and once-weekly groups (&lt;em&gt;P&lt;/em&gt;=0.823), and at week 24 the corresponding percentages were 73% and 74% (&lt;em&gt;P&lt;/em&gt;=0.760).&lt;/p&gt;
&lt;p&gt;At baseline, enthesitis was found in 287 patients and dactylitis in 318. These two symptoms decreased comparatively in both groups at weeks 12 and 24.&lt;/p&gt;
&lt;p&gt;Skin findings included the following for the twice-weekly and once-weekly groups, respectively: &lt;ul&gt; &lt;li&gt;Improvement in physician&apos;s global assessment at week 12, 52% versus 45%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001&lt;/li&gt; &lt;li&gt;At week 24, 57% versus 55%, &lt;em&gt;P&lt;/em&gt;=0.420&lt;/li&gt; &lt;li&gt;Improvement in psoriasis area and severity index at week 12, 71% versus 62%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001&lt;/li&gt; &lt;li&gt;At week 24, 78% versus 74%, &lt;em&gt;P&lt;/em&gt;=0.110&lt;/li&gt; &lt;li&gt;75% improvement in psoriasis area and severity index at week 12, 55% versus 36%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001&lt;/li&gt; &lt;li&gt;At week 24, 70% versus 62%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.026&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Clearly there were differences in the optimal dosages for the skin lesions at week 12, but when the dosage was decreased to once weekly for the two groups, improvements in both joint and skin symptoms continued to improve, and at week 24 the responses were similar in the two groups, the investigators observed.&lt;/p&gt;
&lt;p&gt;&quot;We found that initial treatment of the psoriasis with etanercept 50 mg twice weekly may allow for more rapid clearance of skin lesions than a 50 mg weekly regimen,&quot; they wrote, noting that the higher dose therefore may be preferable for patients with more severe cutaneous involvement.&lt;/p&gt;
&lt;p&gt;In contrast, at no time was the twice-weekly regimen more effective in treating the articular symptoms, so 50 mg once weekly is a sufficient dose for the treatment of joint symptoms alone, they concluded.&lt;/p&gt;
&lt;p&gt;There were no differences in safety between the regimens.&lt;/p&gt;
&lt;p&gt;It is not clear why the higher dose cleared the skin symptoms more rapidly than the low dose but did not have an additional benefit for the joint symptoms.&lt;/p&gt;
&lt;p&gt;&quot;These two different organ systems may have dissimilar autoimmune inflammatory environments, allowing for differences in local concentrations of tumor necrosis factor or in disease burdens or a subtle difference in tissue penetration of drug, although little information is available to support any particular mechanism,&quot; the researchers noted.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Wyeth Research, which was acquired by Pfizer in October 2009, sponsored the trial.&lt;/p&gt;&lt;p&gt;Authors and sponsor were involved in study design, interpretation of data, manuscript preparation, and decision to publish.&lt;/p&gt;&lt;p&gt;Statistical analyses were done by the biostatistics department of Wyeth Research.&lt;/p&gt;&lt;p&gt;Several co-authors are employees of Pfizer, and others have received fees from multiple pharmaceutical companies including Wyeth.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_330"
                     title="Immune Cells Point to Skin Cancer Risk after Transplants (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/Nephrology/KidneyTransplantation/tb/18200?impressionId=1265801000355"
                     
      Monitoring two types of immune cells in kidney transplant recipients might identify patients with an increased risk of skin cancer, British investigators reported.&lt;br&gt;
&lt;br&gt;Increased levels of T-regulatory cells (Tregs) more than doubled the risk of squamous cell cancer of the skin. Decreased levels of natural killer (NK) cells were associated with more than a five-fold increased risk of skin cancer.&lt;br&gt;
&lt;br&gt;Both immune parameters had substantially greater predictive power than a history of squamous-cell skin cancer, according to an online report in the &lt;em&gt;Journal of the American Society of Nephrology&lt;/em&gt; by a team of Oxford University investigators.&lt;/p&gt;
&lt;p&gt;&quot;Squamous cell cancer of the skin affects about 30% of kidney transplant patients after 10 years of immunosuppression,&quot; Robert Carroll, MD, currently of Queen Elizabeth Hospital in Woodville, Australia, observed in a statement.&lt;/p&gt;
&lt;p&gt;&quot;A small number of patients develop multiple skin cancers per year, but there is no laboratory test to determine which transplant recipients will develop multiple skin cancers in the future.&quot;&lt;/p&gt;
&lt;p&gt;&quot;If a test can confirm high risk of skin cancer development, this may help clinicians to tailor immunosuppressive regimens for individual patients,&quot; he added.&lt;/p&gt;
&lt;p&gt;Long-term immunosuppression, such as that required for transplant recipients, confers an increased risk of squamous-cell skin cancer.&lt;/p&gt;
&lt;p&gt;Estimates of the magnitude have ranged as high as 200 times greater than the general population, the authors wrote. Additionally, 3% of organ transplant recipients require extensive plastic surgery each year as a result of skin cancer lesions.&lt;/p&gt;
&lt;p&gt;Age at transplantation and the immunosuppression dosage are the principal determinants of skin-cancer risk, and the dosage of immunosuppression also influences the risk of metastasis from squamous-cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;In the general population, cancer has been associated with increased levels of Tregs, including CDR&lt;sup&gt;+&lt;/sup&gt;CD25&lt;sup&gt;high&lt;/sup&gt;FOXP3&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt;CD28&lt;sup&gt;-&lt;/sup&gt; cells. The same types of cells could play a role in the risk of skin cancer among organ transplant recipients, the authors wrote.&lt;/p&gt;
&lt;p&gt;Within the tumor microenvironment, Tregs may impair the antitumor activity of CD8&lt;sup&gt;+&lt;/sup&gt; and NK cell. However, in organ transplant recipients, Tregs help control or prevent rejections and may help improve long-term outcomes.&lt;/p&gt;
&lt;p&gt;Different immunosuppressive drugs affect Tregs differently, the authors continued. Sirolimus (Rapamune), for example, increases the number of FOXP3&lt;sup&gt;+&lt;/sup&gt; cells, whereas cyclosporine decreases Treg numbers.&lt;/p&gt;
&lt;p&gt;&quot;Tregs have not been assessed in relation to cancer after transplantation,&quot; the authors wrote. &quot;We therefore investigated the hypothesis that squamous-cell cancer in kidney transplant recipients would be associated with an increased number of Tregs.&quot;&lt;/p&gt;
&lt;p&gt;To examine the hypothesis, investigators phenotyped peripheral blood from 65 kidney transplant recipients with squamous skin cancer and 51 recipients without skin cancer, matched for age, sex, and duration of immunosuppression.&lt;/p&gt;
&lt;p&gt;They also quantified lymphocyte populations in skin cancer lesions from a subset of 25 patients and matched them with 25 other nontransplant patients with squamous cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;The kidney transplant recipients had a median follow-up of 340 days. The investigators found that a concentration of &amp;gt;35 peripheral FOXP3&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt;CD127&lt;sup&gt;low&lt;/sup&gt; regulatory T cells/&amp;#181;L was associated with a hazard ratio for squamous cell skin cancer of 2.48 (95% CI 1.04 to 5.98).&lt;/p&gt;
&lt;p&gt;An NK cell count &amp;lt;100 cells/&amp;#181;L was associated with a skin cancer hazard ratio of 5.6 (95% CI 1.31 to 24). A history of squamous cell cancer of the skin increased the risk of skin cancer recurrence by a third (HR 1.33, 95% CI 1.15 to 1.53).&lt;/p&gt;
&lt;p&gt;&quot;If similar immune phenotypes are predictive in other kidney transplant recipient populations, then immune phenotype method has the potential to inform immunosuppressive regimen manipulation in kidney transplant recipients at high risk for developing multiple squamous cell cancers,&quot; the authors concluded.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The authors had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_190"
                     title="Rising Costs -- the Real Heartbreak of Psoriasis (CME/CE)"
                     score="-0.006"
                     href="http://www.medpagetoday.com/Dermatology/Psoriasis/tb/18028?impressionId=1265801000355"
                     
      &lt;p&gt;The heartbreak of psoriasis used to be the disease itself. Now it&apos;s the skyrocketing cost of treatment.&lt;/p&gt;
&lt;p&gt;From 2000 through 2008, the cost of brand-name drugs increased 66% on average, according to Vivianne Beyer, MD, and Stephen Wolverton, MD, of the Indiana University School of Medicine in Indianapolis (Beyer is currently at St. Vincent Hospital in Indianapolis).&lt;/p&gt;
&lt;p&gt;The cost of several of the drugs &quot;greatly outpaced&quot; both general inflation and the overall increase in cost of prescription medicines, the researchers reported in the January issue of &lt;em&gt;Archives of Dermatology.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;The disease, a chronic autoimmune illness, affects between 4.5 million and 7.5 million people in the U.S., the researchers noted.&lt;/p&gt;
&lt;p&gt;Up to a third of those do not respond to topical therapy. However, more effective systemic treatments appear to be underused, they said  --  perhaps in part because of cost, a major issue with newer biologic drugs.&lt;/p&gt;
&lt;p&gt;Analysis showed that current annual costs ranged from $1,197 for methotrexate (Rheumatrex, Trexall), at 7.5 milligrams a week, to $27,577 for two 12-week courses of alefacept (Amevive).&lt;/p&gt;
&lt;p&gt;Phototherapy costs ranged from $3,083 for a year of UV-B therapy to $7,288 annually for psoralen-UV-A treatment, including induction and maintenance.&lt;/p&gt;
&lt;p&gt;Acitretin (Soriatane) at 25 milligrams a day cost $9,163, comparable to the $9,999 for 400 milligrams daily of cyclosporine. But some patients need twice the dose of acitretin, which increases the annual cost to $17,613, the researchers said.&lt;/p&gt;
&lt;p&gt;The annual costs of the biologics used to treat psoriasis ranged from $18,384 to $27,577, but those requiring a loading dose  --  such as adalimumab (Humira) and infliximab (Remicade)  --  were more costly during the first year of treatment than in following years, they said.&lt;/p&gt;
&lt;p&gt;To obtain information about trends, the researchers compared year-over-year average wholesale prices for the various treatments.&lt;/p&gt;
&lt;p&gt;They found that percentage changes in drug prices between 2000 and 2008 ranged from a drop of 24.1% for methotrexate to an increase of 316% for the brand-name version of methoxsalen  --  Oxsoralen-Ultra.&lt;/p&gt;
&lt;p&gt;The second-largest increase was 157.5% for acitretin, they said.&lt;/p&gt;
&lt;p&gt;The biologics also increased in price, but not all were available for the entire period. For example, the cost of efalizumab (Raptiva) increased by 35.1% over a four-year period, while adalimumab&apos;s cost increased by 27.2% during a five-year interval, the researchers said.&lt;/p&gt;
&lt;p&gt;On average the increase was 66%, they said, which is markedly higher than inflation. Over the same period, the consumer price index-urban for all items rose 25.8%, and 30.1% for prescription drugs.&lt;/p&gt;
&lt;p&gt;The researchers did not include indirect costs, such as time away from work, direct costs such as inpatient care, or costs that arose because of adverse effects.&lt;/p&gt;
&lt;p&gt;One clinical implication of the findings is that physicians should consider cost as well as efficacy and tolerability when prescribing drugs for psoriasis, the researchers concluded.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The researchers did not report external support for the study. Wolverton reported financial links with Eli Lilly and Amgen.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_10_772"
                     title="WHO Just Says No to Tanning Beds for Teens"
                     score="-0.006"
                     href="