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    <recommendedItem id="20100101_19_397"
                     title="AAPM: Nerve Growth Factor Antibody  May Reduce Pain (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18300?impressionId=1265729901833"
                     
      &lt;p&gt;SAN ANTONIO  --  A humanized monoclonal antibody against nerve growth factor provided relief in three chronic pain syndromes, according to a summary of small studies reported as an abstract here.&lt;/p&gt;
&lt;p&gt;Treatment with tanezumab led to statistically or clinically significant reductions in pain for patients with osteoarthritis, chronic lower back pain, and interstitial cystitis. The most common adverse events were transient abnormal peripheral sensations, which generally occurred only after the first infusion.&lt;/p&gt;
&lt;p&gt;&quot;Patients with these three different pain syndromes all had significant improvement when treated with tanezumab,&quot; Leslie Tive, PhD, of Pfizer, said in an interview at the American Academy of Pain Medicine meeting. &quot;The pain relief was sustained over time, and patient acceptance was good.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Nerve growth factor is increased in many types of chronic pain and therefore represents an attractive target for therapy,&quot; she added. &quot;Tanezumab is being evaluated in some of these other conditions in ongoing studies.&quot;&lt;/p&gt;
&lt;p&gt;A small phase I study showed that the humanized monoclonal antibody resulted in significant pain improvement in patients with osteoarthritis (&lt;em&gt;Arthritis Rheum&lt;/em&gt; 2005; 52: S461). Tive presented data from a phase II trial involving 400 patients with osteoarthritis of the knee. They were randomized to placebo or to one of five tanezumab doses, administered on day one and day 56.&lt;/p&gt;
&lt;p&gt;All five doses of tanezumab resulted in significant reductions (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05) versus placebo after one week and were sustained through 16 weeks. As assessed by a visual analog scale, the mean change in pain on walking from baseline to week 16 ranged from 30 to 45 points (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), a two- to threefold difference compared with placebo.&lt;/p&gt;
&lt;p&gt;The trial in chronic low back pain involved 217 adults with Quebec Task Force on Spinal Disorders category 1 or 2 pain for at least three months. The primary location of the pain was between the 12th thoracic vertebra and the lower gluteal folds.&lt;/p&gt;
&lt;p&gt;Eligibility criteria included a score of at least 4 on an 11-point pain scale on at least four occasions in the five days before randomization, as indicated by entries in an electronic pain diary.&lt;/p&gt;
&lt;p&gt;Patients were randomized 2:2:1 to a single infusion of tanezumab, to oral naproxen, or to placebo. The primary endpoint was the change in mean Lower Back Pain Index score from baseline to six weeks, averaged over the last seven days.&lt;/p&gt;
&lt;p&gt;Beginning at week one and continuing through week six, patients who were randomized to either dose of tanezumab had significantly greater improvement in pain than those who took the placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001), and compared with the naproxen group beginning at week two (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;/p&gt;
&lt;p&gt;The interstitial cystitis study included 64 men and women who had a score &amp;#8805;13 on Pelvic Pain Symptom/Frequency questionnaire, &amp;#8805;7 score on the O&apos;Leary-Sant Interstitial Cystitis index, and micturition frequency &amp;#8805;8 times a day, as recorded in an electronic diary for at least five consecutive days prior to randomization.&lt;/p&gt;
&lt;p&gt;Patients were randomized to intravenous tanezumab or matching placebo. The primary efficacy endpoint was change from baseline to six weeks in the 11-point pain scale. A difference of at least one point from placebo was considered clinically significant. Statistical significance was not evaluated.&lt;/p&gt;
&lt;p&gt;The mean difference between tanezumab and placebo was -0.7 at week two, increasing to -1.1 at week four and -1.4 at week six. The advantage versus placebo was maintained at week 10 (-0.9) and week 16 (-0.5).&lt;/p&gt;
&lt;p&gt;Adverse events were evaluated for all patients combined in the three studies. Adverse events were reported by 66.3% of tanezumab patients, 61.4% of naproxen patients, and 59.3% of placebo patients. Serious and severe adverse events occurred in 1.6% to 3.4% of patients and 4.8% to 5.7%, respectively.&lt;/p&gt;
&lt;p&gt;Tive said 14.4% of tanezumab patients reported abnormal peripheral sensations, the most common being paresthesia (7.1%), hyperesthesia (4.1%), and hypoesthesia (3.9%).&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 studies included in the summary were funded by Pfizer.&lt;/p&gt;&lt;p&gt;Investigators included several Pfizer employees.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_314"
                     title="Overall Mortality Down in Pediatric Rheumatology (CME/CE)"
                     score="0.004"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/18179?impressionId=1265729901833"
                     
      &lt;p&gt;Overall mortality for children with rheumatologic diseases is down, although the risk of death remains elevated in certain inflammatory disorders, analysis of data from a large registry found.&lt;/p&gt;
&lt;p&gt;The overall standardized mortality ratio was 0.65 (95% CI 0.53 to 0.78, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001), Philip J. Hashkes, MD, of the Cleveland Clinic, and colleagues reported in the February issue of &lt;em&gt;Arthritis &amp;amp; Rheumatism&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;But the mortality ratio for systemic lupus erythematosus was 3.06 (95% CI 1.78 to 4.90, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and that for dermatomyositis was 2.64 (95% CI 0.86 to 6.17, &lt;em&gt;P&lt;/em&gt;=0.030), they wrote.&lt;/p&gt;
&lt;p&gt;In contrast, the standardized mortality ratio was significantly decreased in pain syndromes, at 0.41 (95% CI 0.21 to 0.72, &lt;em&gt;P&lt;/em&gt;=0.002).&lt;/p&gt;
&lt;p&gt;Earlier studies had identified increased mortality in a number of rheumatologic conditions. For example, estimates for systemic lupus erythematosus ranged from 83% to 95% for five-year survival and 76% to 95% for 10-year survival.&lt;/p&gt;
&lt;p&gt;However, most of those studies were limited in size and follow-up time and were conducted before the 1990s when new treatments became available.&lt;/p&gt;
&lt;p&gt;To get an updated picture, Hashkes and colleagues performed a systematic study of mortality outcomes using data from the Indianapolis Pediatric Rheumatology Disease Registry, which is the largest of its kind.&lt;/p&gt;
&lt;p&gt;They identified 110 deaths among 47,449 patients (0.23%, 95% CI 0.19 to 0.27), which is significantly lower than in the expected age- and sex-adjusted U.S. population.&lt;/p&gt;
&lt;p&gt;With a mean follow-up of 7.9 years, the five-year survival rates in all diagnoses were 99% or above.&lt;/p&gt;
&lt;p&gt;Ten-year survival rates were: &lt;ul&gt; &lt;li&gt;Entire cohort, 99.7% (95% CI 99.6 to 99.8)&lt;/li&gt; &lt;li&gt;Systemic lupus erythematosus, 98.2% (95% CI 97.2 to 99.2)&lt;/li&gt; &lt;li&gt;All connective tissue diseases, 98.8% (95% CI 98.2 to 99.3)&lt;/li&gt; &lt;li&gt;Systemic juvenile rheumatoid arthritis, 99.1% (95% CI 98.3 to 99.8)&lt;/li&gt; &lt;li&gt;Primary vasculitis, 96.7% (95% CI 93.2 to 100)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;In 35% of cases, the rheumatologic disease and its complications was the cause of death. Treatment complications was the cause in 10% of cases, non-natural causes in 23%, background disease in 21%. In 11% the cause of death was unknown.&lt;/p&gt;
&lt;p&gt;In a univariable survival analysis, the following disorders were significant predictors of increased risk of mortality: &lt;ul&gt; &lt;li&gt;All connective tissue diseases, HR 4.5 (95% CI 2.9 to 6.9)&lt;/li&gt; &lt;li&gt;Primary vasculitis, HR 9.2 (95% CI 3.4 to 25)&lt;/li&gt; &lt;li&gt;Genetic/chromosomal/metabolic diseases, HR 6.2 (95% CI 2 to 19.5)&lt;/li&gt; &lt;li&gt;Systemic lupus erythematosus, HR 6 (95% CI 3.6 to 10.1)&lt;/li&gt; &lt;li&gt;Dermatomyositis, HR 3.3 (95% CI 1.3 to 8)&lt;/li&gt; &lt;li&gt;Systemic juvenile rheumatoid arthritis, HR 2.5 (95% CI 1.1 to 5.7&lt;strong&gt;)&lt;/strong&gt;&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Other significant predictors of mortality included older age at the time of first visit to a rheumatologist and the use of systemic steroids and methotrexate.&lt;/p&gt;
&lt;p&gt;In a multivariable model, only connective tissue disease, other nonrheumatic diagnosis, male sex, and older age remained significantly predictive of mortality.&lt;/p&gt;
&lt;p&gt;A total of 58% of the deaths were in patients whose primary diagnosis was an inflammatory condition, and 41% were in patients whose primary diagnosis was noninflammatory. (The primary diagnosis was uncertain in one patient.)&lt;/p&gt;
&lt;p&gt;&quot;As expected, most of the patients with inflammatory disease died of their disease or disease complications. With longer follow-up this proportion may change, given the possibility of secondary malignancies or an increased rate of infections related to prolonged immunosuppression,&quot; the investigators cautioned.&lt;/p&gt;
&lt;p&gt;The study has limitations and may have underestimated mortality, the researchers acknowledged. Their ability to detect deceased patients in the registry was hampered by the limited identification (only birth date and initials were recorded).&lt;/p&gt;
&lt;p&gt;Also, identifying deaths through the Social Security Death Index may have missed some cases of children who had never received a Social Security number.&lt;/p&gt;
&lt;p&gt;The data also may not be entirely generalizable, because not all U.S. centers participate in the registry, and reporting compliance even in participating centers was variable.&lt;/p&gt;
&lt;p&gt;The study also had a relatively short follow-up, so it was unable to capture the complete extent of mortality, especially in early adulthood when premature cardiovascular disease develops in many patients with lupus and rheumatoid arthritis.&lt;/p&gt;
&lt;p&gt;&quot;While the results of our study are encouraging, with the mortality rate of our entire cohort similar to that of the age- and sex-matched U.S. population, it is important to follow up this cohort in the future for mortality trends, especially later deaths seen as sequelae in many rheumatic diseases,&quot; the investigators 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 study was supported by the Northeast Ohio Chapter of the Arthritis Foundation.&lt;/p&gt;&lt;p&gt;No disclosures were provided.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_2_695"
                     title="ACR: Marker Predicts Preeclampsia Risk in Lupus"
                     score="-0.006"
                     href="