<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_455"
                     title="Low Vitamin D Linked to Hip OA (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/18379?impressionId=1265746518075"
                     
      &lt;p&gt;Elderly men with low serum levels of vitamin D are at increased risk for developing hip osteoarthritis, a prospective cohort study found.&lt;/p&gt;
&lt;p&gt;Men whose levels of 25-hydroxyvitamin (OH)D were between 15.1 to 30 ng/mL had twice the likelihood of prevalent radiographic hip osteoarthritis than those whose levels were normal (OR 2.19, 95% CI 1.21 to 3.97), according to R. Krishna Chaganti, MD, of the University of California at San Francisco, and colleagues.&lt;/p&gt;
&lt;p&gt;Conversely, after adjusting for age, season at blood draw, and clinic site, higher vitamin D levels were associated with a lower prevalence of hip osteoarthritis (OR 1.39 per 1 SD decrease in 25(OH)D level, 95% CI 1.11 to 1.74), the researchers reported in the February issue of &lt;em&gt;Arthritis &amp;amp; Rheumatism&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Because the role vitamin D may play in the pathogenesis and progression of osteoarthritis is unclear, Chaganti and colleagues analyzed data from the Osteoporotic Fractures in Men Study, which enrolled a large cohort of elderly men between 2000 and 2002 from six centers across the U.S.&lt;/p&gt;
&lt;p&gt;A total of 1,104 men whose mean age was 77.2 years had baseline measurements of serum vitamin D, and about 4.5 years later pelvic radiographs were obtained.&lt;/p&gt;
&lt;p&gt;Radiographs were scored to reflect joint space narrowing, osteophyte formation, cysts, subchondral sclerosis, and femoral head deformity.&lt;/p&gt;
&lt;p&gt;Vitamin D levels were categorized as deficiency (&amp;#8804;15 ng/mL), insufficiency (15.1 to 30 ng/mL), and sufficiency (&amp;gt;30 ng/mL).&lt;/p&gt;
&lt;p&gt;Mean vitamin D level was 23.38 ng/mL in men who had radiographic hip osteoarthritis, compared with 26.04 ng/mL in men without radiographic abnormalities (&lt;em&gt;P&lt;/em&gt;=0.0002).&lt;/p&gt;
&lt;p&gt;Men with hip osteoarthritis had a higher prevalence of both vitamin D insufficiency (77% versus 65%, &lt;em&gt;P&lt;/em&gt;=0.002) and deficiency (10.2% versus 7.5%, &lt;em&gt;P&lt;/em&gt;=0.012).&lt;/p&gt;
&lt;p&gt;Moreover, they had slower six-meter walking speed (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001) and reported more hip pain (&lt;em&gt;P&lt;/em&gt;=0.0001).&lt;/p&gt;
&lt;p&gt;Men who were vitamin D deficient also tended to have an increased likelihood of hip osteoarthritis (OR 1.99, 95% CI 0.83 to 4.74), but after adjustment in multivariate models, statistical significance was lost with this level of the vitamin.&lt;/p&gt;
&lt;p&gt;&quot;The association of low 25(OH)D levels with prevalent radiographic hip [osteoarthritis] underscores the potentially important role of vitamin D in the pathogenesis of [osteoarthritis]. Vitamin D metabolites have been found to be associated with the regulation of the Wnt pathway, products of which play important roles in the development and maintenance of bone and cartilage,&quot; the investigators explained.&lt;/p&gt;
&lt;p&gt;Furthermore, in vitro studies have suggested that serum levels of 25-hydroxyvitamin D&lt;sub&gt;3&lt;/sub&gt; can affect the ratio of RANKL to osteoprotegerin and thereby influence bone deterioration and repair.&lt;/p&gt;
&lt;p&gt;Previous investigations have yielded conflicting results. One study found that low levels of vitamin D were not associated with worsening of knee osteoarthritis, as reflected in loss of articular cartilage on MRI.&lt;/p&gt;
&lt;p&gt;Another study, however, linked knee osteoarthritis with low vitamin D levels, particularly in patients who also had decreased bone mineral density in the lumbar spine.&lt;/p&gt;
&lt;p&gt;&quot;Vitamin D influences the mineralization of bone matrix, and low serum levels of vitamin D may result in poorly mineralized bone that might alter forces across the joint and reduce joint deterioration,&quot; the authors suggested.&lt;/p&gt;
&lt;p&gt;On the other hand, low levels may interfere with chondrocyte metabolism and thereby increase degeneration.&lt;/p&gt;
&lt;p&gt;Further studies will be needed to more fully clarify the effects of the vitamin on the development and progression of osteoarthritis, the investigators cautioned.&lt;/p&gt;
&lt;p&gt;Strengths of the study include the large cohort of participants, careful classification of radiographic osteoarthritis, and reliance on the gold standard of vitamin D measurement, the 25(OH)D level.&lt;/p&gt;
&lt;p&gt;Limitations include the cross-sectional design, precluding the inference of causality, and the gap in time between measurement of serum vitamin D and radiography.&lt;/p&gt;
&lt;p&gt;The authors concluded that therapeutic interventions to increase vitamin D serum levels in the elderly &quot;are warranted,&quot; with the goal of improving skeletal health in this vulnerable age group.&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 study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging, the National Center for Research Resources, and the NIH Roadmap for Medical Research.&lt;/p&gt;&lt;p&gt;The lead author was supported by a grant from the American College of Rheumatology Research and Education Foundation.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_439"
                     title="Heart Often Affected in Churg-Strauss (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/tb/18353?impressionId=1265746518075"
                     
      &lt;p&gt;Cardiac involvement is common in patients with Churg-Strauss syndrome, even when their vasculitis is in clinical remission, a Dutch study found.&lt;/p&gt;
&lt;p&gt;Cardiac MRI detected abnormalities in 62% of patients with this rare, systemic disorder but in only 3% of matched controls (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001), according to Robert M. Dennert, MD, of Maastricht University in the Netherlands, and colleagues.&lt;/p&gt;
&lt;p&gt;Yet only 26% of the patients had clinical symptoms suggesting cardiac involvement, the researchers reported in February&apos;s &lt;em&gt;Arthritis &amp;amp; Rheumatism.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;Cardiac involvement is an important predictor of poor outcome in Churg-Strauss syndrome, with approximately half of the associated mortality being heart-related. Myocardial damage typically results from eosinophilic infiltration and granuloma formation.&lt;/p&gt;
&lt;p&gt;However, the cardiac manifestations are often subclinical. They remain undiagnosed, and the exact incidence is unclear.&lt;/p&gt;
&lt;p&gt;So Dennert and colleagues enrolled 32 patients with confirmed Churg-Strauss syndrome who were in complete clinical remission, performing detailed imaging assessments to determine the frequency and extent of heart involvement.&lt;/p&gt;
&lt;p&gt;About two-thirds were men. The mean age was 61 years, and disease duration was slightly over six years.&lt;/p&gt;
&lt;p&gt;A total of 41% had antineutrophil cytoplasmic antibodies (ANCA), and most were on maintenance steroids or immunosuppressants.&lt;/p&gt;
&lt;p&gt;On EKG, major abnormalities (atrial fibrillation and conduction disturbances) were detected in only 13% of patients. Minor abnormalities such as T wave abnormalities were seen in 50% of patients and in one control subject.&lt;/p&gt;
&lt;p&gt;Echocardiography identified abnormalities in 50% of patients and in 3% of controls (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001). These included wall motion and valvular abnormalities, pericardial effusion, and pulmonary hypertension.&lt;/p&gt;
&lt;p&gt;In the 62% of patients whose MRIs revealed abnormalities, findings included fibrosis, inflammation, wall motion and valvular abnormalities, pericardial effusion, and obliterated right ventricle.&lt;/p&gt;
&lt;p&gt;Previous reports had suggested that ANCA positivity in Churg-Strauss syndrome was more often associated with renal disease and peripheral neuropathy, while ANCA negativity was associated with fever and heart involvement.&lt;/p&gt;
&lt;p&gt;In this cohort, 74% of ANCA-negative patients had cardiac involvement, and in 64%, these were wall motion disturbances.&lt;/p&gt;
&lt;p&gt;In comparison, only 23% of ANCA-positive patients had heart involvement.&lt;/p&gt;
&lt;p&gt;Defects were identified with echocardiography or MRI in 88% of patients who had clinical symptoms, and in all who had major EKG abnormalities.&lt;/p&gt;
&lt;p&gt;But in the absence of symptoms and even with a normal EKG, abnormalities could still be detected on echocardiography or MRI in almost 40% of patients, according to the investigators.&lt;/p&gt;
&lt;p&gt;&quot;We therefore recommend that the evaluation for cardiac involvement in patients with [Churg-Strauss syndrome] should include not only detailed history of cardiac symptoms and EKG, but also imaging with echocardiography or cardiac MRI,&quot; they stated.&lt;/p&gt;
&lt;p&gt;The high prevalence of heart abnormalities could not be attributed to concomitant heart disease such as coronary artery disease or hypertension, because the prevalence of these diseases among patients was comparable to that in controls.&lt;/p&gt;
&lt;p&gt;Churg-Strauss syndrome typically develops in three phases, beginning with asthma, followed by peripheral and tissue eosinophilia accompanied by pulmonary infiltrates, and finally the systemic small-vessel vasculitis.&lt;/p&gt;
&lt;p&gt;During this late phase the vasculitic lesions in the coronary vessels and myocardium can lead to myocardial infarction, heart failure, and cardiac tamponade.&lt;/p&gt;
&lt;p&gt;Studies have shown that long-term treatment with immunosuppressive drugs can improve survival and resolve the cardiac abnormalities, so early diagnosis is needed.&lt;/p&gt;
&lt;p&gt;The authors acknowledged that their study was cross-sectional, and that a longitudinal study could have provided more detailed data.&lt;/p&gt;
&lt;p&gt;Nonetheless, the study revealed a high incidence of cardiac involvement, which was often unrecognized, and they concluded that a multidisciplinary approach to management therefore should include a cardiologist.&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 study was funded by the Netherlands Heart Foundation and the Dutch Organization for Scientific Research.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_410"
                     title="Most Adults Are Not Getting Necessary Vaccinations"
                     score="0.01"
                     href="http://www.medpagetoday.com/InfectiousDisease/Pneumonia/tb/18317?impressionId=1265746518075"
                     
      &lt;p&gt;Public health experts say they&apos;re concerned about the low number of U.S. adults who receive recommended vaccinations  --  and in particular about seniors who aren&apos;t immunized against pneumonia.&lt;/p&gt;
&lt;p&gt;As of 2008, one-third of people 65 and older had not received the pneumococcal vaccine, according to a report issued by the Trust for America&apos;s Health (TFAH), the Infectious Diseases Society of America (IDSA), and the Robert Wood Johnson Foundation.&lt;/p&gt;
&lt;p&gt;In 36 states, 30% or more of their older residents had not received the vaccine.&lt;/p&gt;
&lt;p&gt;The worst coverage was in the District of Columbia, where 45.6% of seniors had not been vaccinated. Even in the best performing state, Oregon, more than a quarter (26.8%) of older people had not received the one-time shot.&lt;/p&gt;
&lt;p&gt;Among all adults, the investigators also found extremely low rates of immunization against tetanus, diphtheria, and pertussis (2.1%), shingles (&amp;lt;2%), human papillomavirus (10%), and seasonal influenza (36.1%).&lt;/p&gt;
&lt;p&gt;&quot;The vaccination efforts around the 2009 H1N1 outbreak actually showed how well our public health system can react to vaccinate millions of people in a very short amount of time,&quot; L.J. Tan, PhD, director of medicine and public health for the American Medical Association, told reporters in a conference call.&lt;/p&gt;
&lt;p&gt;&quot;But I think our response also clearly demonstrated that we do have a lack of a strategy and a system for vaccinating adults.&quot;&lt;/p&gt;
&lt;p&gt;Added Jeffrey Levi, PhD, executive director of TFAH, &quot;We need a national strategy to make vaccines a regular part of medical care and to educate Americans about the effectiveness and safety of vaccines.&quot;&lt;/p&gt;
&lt;p&gt;Doing so could avoid 40,000 to 50,000 deaths from vaccine-preventable illnesses and save about $10 billion in healthcare costs each year, he said.&lt;/p&gt;
&lt;p&gt;But, according to William Schaffner, MD, chair of IDSA&apos;s immunization working group and a co-author of the report, there are many obstacles to adult vaccination efforts.&lt;/p&gt;
&lt;p&gt;First, unlike children in school, adults lack widespread institutional access to immunizations nor is there a way to require most adults to undergo vaccination.&lt;/p&gt;
&lt;p&gt;In addition, there are limited interactions with the healthcare system because, also unlike in children, care in adults generally revolves around acute care and not well care visits.&lt;/p&gt;
&lt;p&gt;Insurance coverage also plays a major role in low vaccination rates among adults, and not just in the uninsured or underinsured.&lt;/p&gt;
&lt;p&gt;Most insurance plans do not cover routine vaccination, Schaffner said, a situation that would change under pending healthcare reform legislation in Congress. That would require insurers to pay for all vaccinations recommended by the CDC&apos;s Advisory Committee on Immunization Practices.&lt;/p&gt;
&lt;p&gt;Schaffner also cited what he called misunderstandings and misinformation regarding the safety and effectiveness of vaccines, and the limited support for research, development, and production of vaccines as reasons for low immunization rates among adults.&lt;/p&gt;
&lt;p&gt;&quot;It&apos;s a shame that we aren&apos;t focusing enough resources on the science to prevent disease and we don&apos;t have a system where we can better protect people by getting them all of the vaccines that are currently available,&quot; he said.&lt;/p&gt;
&lt;p&gt;Tan outlined several recommendations the report makes to increase adult vaccination rates, starting with the creation of a program to provide vaccine coverage to uninsured individuals.&lt;/p&gt;
&lt;p&gt;Also, he said, the CDC and local and state health departments should be given more funding to conduct public education campaigns to increase awareness about the importance of vaccination.&lt;/p&gt;
&lt;p&gt;For their part, physicians should adopt practices to enable them to offer their adult patients vaccines at appropriate visits, like general physicals and cancer screenings, and to make a review of vaccination history a part of standard care.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_404"
                     title="Tailor Etanercept to Symptoms in Psoriasis and Psoriatic Arthritis (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/18309?impressionId=1265746518075"
                     
      &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_350"
                     title="Leflunomide Equal to Methotrexate in Anti-TNF Combo for RA Treatment (CME/CE)"
                     score="0.009"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/18231?impressionId=1265746518075"
                     
      &lt;p&gt;Treatments combining leflunomide (Arava) with an antitumor necrosis factor (TNF) agent were as effective in rheumatoid arthritis as regimens combining methotrexate with the biologics, a randomized Italian study found.&lt;/p&gt;
&lt;p&gt;After 24 weeks of therapy, patients receiving a methotrexate-based regimen achieved a mean Disease Activity Score (DAS)28 of 3.3, while those receiving leflunomide-based treatment had a mean DAS28 of 3.5, according to Renato De Stefano, MD, and colleagues from the Siena (Italy) University Hospital.&lt;/p&gt;
&lt;p&gt;Remission was achieved by 21.6% of patients in the methotrexate group and 16.6% of those in the leflunomide group. Neither of these differences was statistically significant, the investigators reported online in &lt;em&gt;Clinical Rheumatology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Multiple clinical trials have now demonstrated the efficacy of TNF blocking agents in combination with methotrexate for rheumatoid arthritis, but some patients can&apos;t tolerate or don&apos;t respond to methotrexate.&lt;/p&gt;
&lt;p&gt;Some data suggested leflunomide as an alternative to methotrexate, particularly if the TNF blocker is not begun for at least 12 weeks after the initiation of leflunomide.&lt;/p&gt;
&lt;p&gt;The mechanism of action of leflunomide is not fully understood, but it may be related to its ability to inhibit de novo pyrimidine biosynthesis through the inhibition of the enzyme dihydroorotate dehydrogenase, researchers say. Laboratory studies have demonstrated that it also affects stimulated T cells.&lt;/p&gt;
&lt;p&gt;So De Stefano and colleagues undertook a prospective trial that included 120 patients whose disease activity was high (DAS28 &amp;gt;5.1) despite treatment with methotrexate at 15 mg/week or leflunomide at 20 mg/day.&lt;/p&gt;
&lt;p&gt;These two groups of 60 patients each were then divided into three subgroups, with patients being randomized to receive etanercept (Enbrel), 25 mg twice weekly, adalimumab (Humira), 40 mg every two weeks, or infliximab (Remicade) at 5 mg/kg/week at baseline, weeks two and six, and every six to eight weeks thereafter.&lt;/p&gt;
&lt;p&gt;Treatment was discontinued in patients whose DAS28 score did not change more than 1.2 points or if they had an insufficient ACR20 response (20% improvement on American College of Rheumatology criteria) by 12 weeks.&lt;/p&gt;
&lt;p&gt;Most patients were women, with an average age of 52.&lt;/p&gt;
&lt;p&gt;In the methotrexate group, therapy was discontinued prematurely in 30%. The reasons were lack of efficacy in 18.3% and serious adverse effects in 11.6%.&lt;/p&gt;
&lt;p&gt;Serious adverse effects associated with methotrexate use included vasculitis in a patient receiving etanercept, elevated liver enzymes in one patient receiving etanercept and another receiving infliximab, and a diffuse rash in one patient on etanercept and in another on adalimumab.&lt;/p&gt;
&lt;p&gt;In the leflunomide group, therapy was discontinued in 30%, in 15% because of lack of efficacy and in 15% because of adverse effects.&lt;/p&gt;
&lt;p&gt;Serious adverse events in the leflunomide patients included one case each of thrombocytopenia and leukopenia in patients receiving etanercept, and diffuse rash in one patient on infliximab and in another on adalimumab.&lt;/p&gt;
&lt;p&gt;Mild adverse events, such as nausea and arthromyalgia, occurred much more frequently in the methotrexate group (43.3% versus 20%, &lt;em&gt;P&lt;/em&gt;=0.032), the investigators reported.&lt;/p&gt;
&lt;p&gt;By week 24, antinuclear antibodies had appeared in titers exceeding 1:160 in seven patients undergoing methotrexate treatment and in five taking leflunomide.&lt;/p&gt;
&lt;p&gt;In one patient taking leflunomide in combination with etanercept, anticardiolipid and anti-SS-A antibodies also appeared, but no patients developed clinical signs of connective tissue disease.&lt;/p&gt;
&lt;p&gt;Efficacy was similar among all groups. At week 24, methotrexate patients in the three coordinated-drug subgroups had these DAS28 scores: &lt;ul&gt; &lt;li&gt;Etanercept, 2.93&lt;/li&gt; &lt;li&gt;Adalimumab, 3.2&lt;/li&gt; &lt;li&gt;Infliximab, 3.7&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Leflunomide patients had these scores: &lt;ul&gt; &lt;li&gt;Adalimumab, 3.3&lt;/li&gt; &lt;li&gt;Infliximab, 3.6&lt;/li&gt; &lt;li&gt;Etanercept, 3.7&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;There were no significant differences in DAS28 scores between the leflunomide and methotrexate groups or in the six subgroups.&lt;/p&gt;
&lt;p&gt;At week 24, the ACR responses in the methotrexate group were: &lt;ul&gt; &lt;li&gt; ACR20, 63.3%&lt;/li&gt; &lt;li&gt;ACR50, 51.2%&lt;/li&gt; &lt;li&gt;ACR70, 32.1%&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Corresponding responses in the leflunomide group were &lt;ul&gt; &lt;li&gt;ACR20, 66.6%&lt;/li&gt; &lt;li&gt;ACR50, 47.4%&lt;/li&gt; &lt;li&gt;ACR70, 26.3%&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Differences in ACR scores were not significant between the leflunomide and methotrexate groups, or in the six subgroups.&lt;/p&gt;
&lt;p&gt;Improvements in health assessment questionnaire scores, reflecting levels of disability, were seen throughout the study for both groups, and by week 24 (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001) were most pronounced for the methotrexate-etanercept subgroup (median 0.11) and for the leflunomide-etanercept subgroup (median 0.3).&lt;/p&gt;
&lt;p&gt;The results of the study seem to confirm that TNF-blocker combination therapy with leflunomide is associated with a similar likelihood of achieving significant clinical response as with methotrexate, and without a significantly greater risk of adverse effects.&lt;/p&gt;
&lt;p&gt;In fact, treatment with leflunomide was more readily tolerated, lacking the minor dyspeptic and arthromyalgic side effects associated with methotrexate.&lt;/p&gt;
&lt;p&gt;That tolerability, and the fact that the drug can be administered orally, &quot;undoubtedly represent points in its favor as far as patients are concerned,&quot; the investigators noted.&lt;/p&gt;
&lt;p&gt;However, leflunomide is much more expensive than methotrexate, they pointed out.&lt;/p&gt;
&lt;p&gt;They called for further research on the use of leflunomide in this context, with greater numbers of patients and longer duration to better assess the persistence of efficacy, potential safety concerns with long-term use, and effects on structural joint damage.&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 disclosed no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
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