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    <recommendedItem id="20100101_19_350"
                     title="Leflunomide Equal to Methotrexate in Anti-TNF Combo for RA Treatment (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/18231?impressionId=1265756536847"
                     
      &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;
    </recommendedItem>
    <recommendedItem id="20100101_19_269"
                     title="Close Relationships Influence RA Inflammation (CME/CE)"
                     score="0.003"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/18125?impressionId=1265756536847"
                     
      &lt;p&gt;Women with rheumatoid arthritis whose close relationships are marked by mutuality  --  the reciprocal sharing of thoughts and feelings  --  have lower levels of inflammation, a prospective study found.&lt;/p&gt;
&lt;p&gt;After controlling for the effects of factors such as disease flares and the use of anti-inflammatory and disease-modifying drugs, mutuality accounted for 9% of the difference in levels of an inflammatory marker at six months, and an additional 12.5% at 12 months, according to Shelley Kasle, PhD, of the University of Arizona, Tucson.&lt;/p&gt;
&lt;p&gt;In contrast, levels of the marker (erythrocyte sedimentation rate, or ESR) had no effect on subsequent mutuality, suggesting that while mutuality influences inflammation, the reverse is not the case, the investigators reported in the Jan. 15 &lt;em&gt;Arthritis Care &amp;amp; Research&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Social relationships exert benefits on health through both biological and behavioral pathways. The impact of social relationships may be particularly great in patients with rheumatoid arthritis because they have been shown to be psychologically and physiologically reactive to interpersonal stressors.&lt;/p&gt;
&lt;p&gt;Previous studies have shown that heightened interpersonal stress in patients with rheumatoid arthritis led to increases in clinical disease activity and cellular inflammation.&lt;/p&gt;
&lt;p&gt;Specific aspects of close social relationships, such as marital status and quality, are also known to influence rheumatoid arthritis outcomes, with single patients becoming disabled more quickly than those who are married or partnered.&lt;/p&gt;
&lt;p&gt;Some researchers believe that mutuality, unlike similar constructs such as intimacy and emotional responsiveness, are important for women&apos;s psychological and physical health because mutuality emphasizes equal empowerment of both parties through empathic exchanges.&lt;/p&gt;
&lt;p&gt;To see whether mutuality simply correlates with health in patients with rheumatoid arthritis or has a possible causal role, Kasle and colleagues recruited 70 women with rheumatoid arthritis who completed questionnaires at baseline, six months, and 12 months, detailing demographics, medical history, and medications.&lt;/p&gt;
&lt;p&gt;In addition, couple mutuality was measured according to the Mutual Psychological Development Questionnaire.&lt;/p&gt;
&lt;p&gt;Their mean age was 57 years, mean disease duration was five years, and relationship duration was 24 years.&lt;/p&gt;
&lt;p&gt;Four regression analyses examined the cross-lagged effects of mutuality and other factors on ESR, as well as the possible effects of ESR on mutuality over two time spans  --  baseline to six months, and six months to 12 months.&lt;/p&gt;
&lt;p&gt;Variables included C-reactive protein, the use of disease-modifying anti-rheumatic drugs, nonsteroidal anti-inflammatory agents, and biologic response modifiers, arthritis disease flares, and negative affect.&lt;/p&gt;
&lt;p&gt;Mutuality remained constant across the two time spans, whereas mean ESR fell from 20.32 mm/hour at baseline to 13.32 mm/hour at 12 months.&lt;/p&gt;
&lt;p&gt;In step 1 of the regression predicting six-month ESR, baseline controls explained 42.7% of variance, with baseline ESR being the only significant predictor (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;In step 2 of this analysis, baseline mutuality demonstrated an inverse lagged effect on six-month ESR (&lt;em&gt;P&lt;/em&gt;=0.008), explaining 9% of the additional variance in ESR during that time span.&lt;/p&gt;
&lt;p&gt;In step 1 of the regression predicting 12 month ESR, six-month control variables accounted for 36.7% of variance, with six-month ESR and disease flares being marginally significant predictors.&lt;/p&gt;
&lt;p&gt;In step 2, six-month mutuality exerted an inverse lagged effect on 12-month ESR (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.02), explaining an additional 12.5% of the variance in ESR at that time point.&lt;/p&gt;
&lt;p&gt;Then, in a regression analysis predicting six-month mutuality, baseline mutuality was the only significant predictor in both steps 1 and 2 (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for both), with negative affect being marginally significant.&lt;/p&gt;
&lt;p&gt;In step 2, baseline ESR failed to exert any lagged effect on six-month mutuality.&lt;/p&gt;
&lt;p&gt;In the regression analysis predicting 12-month mutuality, baseline mutuality again was the only significant predictor in steps 1 and 2 of the model (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for both).&lt;/p&gt;
&lt;p&gt;And in step 2, six-month ESR failed to exert any lagged effect on 12-month mutuality.&lt;/p&gt;
&lt;p&gt;&quot;The current study provides initial evidence that the relational behaviors measured as mutuality (engaged, authentic, empathic, and validating responses) exert a beneficial effect relative to inflammation for female patients with [rheumatoid arthritis], suggesting their potential usefulness as therapeutic targets,&quot; the investigators wrote.&lt;/p&gt;
&lt;p&gt;For instance, developing interventions to enhance couple mutuality could contribute to the maintenance of health and quality of life for these patients.&lt;/p&gt;
&lt;p&gt;The study findings also suggest that exclusive reliance on pharmacotherapy may represent less than optimal care, particularly since many of the disease modifying drugs and biologic response modifiers have potentially serious adverse effects and are not effective in all patients.&lt;/p&gt;
&lt;p&gt;Strengths of the study include its prospective design and replication of findings over two time spans, the authors reported.&lt;/p&gt;
&lt;p&gt;&quot;In addition, the linkage of a self-report measure of relationship quality with an objective medical measure of inflammation argues persuasively for the importance of psychosocial factors for physical health.&quot;&lt;/p&gt;
&lt;p&gt;Study limitations were inherent in its design, wherein cross-lagged effects provide a starting point for determining causality, but effects must then be tested experimentally.&lt;/p&gt;
&lt;p&gt;Moreover, other factors, such as personality traits and disease severity, and other disease measures, such as disability and pain, were not accounted for.&lt;/p&gt;
&lt;p&gt;Nonetheless, the investigators concluded, &quot;Our findings join an accumulating body of evidence linking social relationships with health.&quot;&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 lead investigator was supported by a grant from the Arthritis Foundation.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_268"
                     title="No Meds Needed for Two Effective OA Regimens (CME/CE)"
                     score="0.003"
                     href="http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/tb/18119?impressionId=1265756536847"
                     
      &lt;p&gt;Middle-aged patients with early knee osteoarthritis can benefit from either a self-managment program or strength training, but a combination of the two did not provide additional gains, a study found.&lt;/p&gt;
&lt;p&gt;During a two-year trial, roughly two-thirds of participants randomized to one of three groups achieved clinically meaningful improvements in functioning, defined as a 26% change from baseline, according to a new report in the Jan. 15 &lt;em&gt;Arthritis Care &amp;amp; Research&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Patients also achieved clinically meaningful improvements in pain -- defined as a 40% change from baseline -- regardless of treatment group, wrote Patrick E. McKnight, PhD, of George Mason University in Fairfax, Va., and colleagues.&lt;/p&gt;
&lt;p&gt;The functional improvements were 70% for patients in the strength training group, 64% for those in the self-management group, and a 66% improvement in the combined treatment group. For pain, the breakdown was as follows: &lt;ul&gt; &lt;li&gt;Strength training, 65%&lt;/li&gt; &lt;li&gt;Self-management, 56%&lt;/li&gt; &lt;li&gt;Combined treatment, 65%&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;McKnight and colleagues wrote that studies in older patients have reported positive changes for both strength training and self-management.&lt;/p&gt;
&lt;p&gt;To see if these modalities also could benefit younger patients with milder disease, and whether combining the two would lead to additional benefits, the investigators recruited 273 subjects ages 35 to 64 years.&lt;/p&gt;
&lt;p&gt;Participants all had pain on most days in at least one knee, had symptoms for less than five years, had radiographic evidence of osteoarthritis, and had self-reported disability.&lt;/p&gt;
&lt;p&gt;The strength training program consisted of two phases, the first being nine months focused on stretching and balance, range of motion and flexibility, and isotonic muscle strengthening in three sessions each week.&lt;/p&gt;
&lt;p&gt;Phase two involved the development of self-directed long-term exercising habits, following the guidance and advice of trainers.&lt;/p&gt;
&lt;p&gt;The self-management program also included two phases. During the first nine-month phase, participants attended 12 weekly 90-minute classroom sessions addressing coping and self-efficacy skills, promoting active adaptive strategies and increasing perception of control for physical function and pain management.&lt;/p&gt;
&lt;p&gt;Phase two consisted of telephone calls from instructors and problem-solving discussions.&lt;/p&gt;
&lt;p&gt;The combined treatment group concurrently participated in both strength training and self-management programs, adjusted to maintain equivalent contact time with the other two groups.&lt;/p&gt;
&lt;p&gt;Overall compliance was modest, with 55.8% of those in the strength training group completing the study, along with 69.1% and 59.6% of the self-management and combined groups, respectively.&lt;/p&gt;
&lt;p&gt;Objective measures of physical functioning consisted of five physical performance tests measured at baseline and at months nine and 24. Pain and disability were self-reported.&lt;/p&gt;
&lt;p&gt;All of these outcomes showed significant changes over time in all three treatment groups, with effect sizes computed using the standard Cohen&apos;s d units: &lt;ul&gt; &lt;li&gt;Leg press, d=0.85&lt;/li&gt; &lt;li&gt;Range of motion, d=1.00&lt;/li&gt; &lt;li&gt;Work capacity, d=0.60&lt;/li&gt; &lt;li&gt;Balance, d=0.59&lt;/li&gt; &lt;li&gt;Stair climbing, d=0.59&lt;/li&gt; &lt;li&gt;Pain, d= &amp;#8722;0.51&lt;/li&gt; &lt;li&gt;Disability, d= &amp;#8722;0.55&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Both men and women improved, although benefits were greater among men, who gained more large muscle mass strength. Study-related adverse effects included accident, injury, or increased pain with strength training.&lt;/p&gt;
&lt;p&gt;Within-group and between-group effect sizes were also computed. All within-group effect sizes differed significantly from zero, with the exception of the pain outcome in the strength training group, but none of the between-group effects were significant.&lt;/p&gt;
&lt;p&gt;&quot;The logic behind the combined treatment was that the different factors addressed in physical and psychological treatments might produce an additive effect if administered together. These results suggest otherwise,&quot; the investigators conceded.&lt;/p&gt;
&lt;p&gt;As to why there were no differences between the three treatment arms, the length of the study and the relative youth of the participants may have contributed.&lt;/p&gt;
&lt;p&gt;The sample was younger than are included in typical osteoarthritis studies and were higher functioning at baseline, which could mean that there was less opportunity to produce a significant effect, the investigators suggested.&lt;/p&gt;
&lt;p&gt;Also, the increased burden of the combined treatment may have diluted the effects of the two programs.&lt;/p&gt;
&lt;p&gt;Despite the fact that combined treatment in this study had negligible benefits beyond that seen with strength training and self-management, other long-term outcomes such as physical activity level might show a greater response. This remains speculative, but deserves further study, according to the investigators.&lt;/p&gt;
&lt;p&gt;Limitations of the study include the fact that the researchers did not assess effects of the treatment on articular cartilage or inflammation, and they did not include a no-treatment arm.&lt;/p&gt;
&lt;p&gt;Also, there may have been differences in self-medication practices between the groups.&lt;/p&gt;
&lt;p&gt;Nonetheless, the study findings suggest that the two nonpharmacologic approaches can produce gains in middle-age patients with osteoarthritis, and both can be recommended.&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.&lt;/p&gt;&lt;p&gt;One co-author is an employee of Bristol-Myers Squibb and holds stock and/or stock options in the company.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_5_213"
                     title="Rofecoxib (Vioxx) Studies on Mortality Were Controlled by Drug Company"
                     score="-0.005"
                     href="