<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <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=1265734513900"
                     
      &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_283"
                     title="Antibodies Predict Response to Biologics in RA (CME/CE)"
                     score="0.002"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/18141?impressionId=1265734513900"
                     
      &lt;p&gt;Patients with rheumatoid arthritis who develop antibodies against the tumor necrosis factor (TNF) antagonist infliximab (Remicade) are also likely to develop antibodies against adalimumab (Humira), a Dutch cohort study found.&lt;/p&gt;
&lt;p&gt;During 28 weeks of follow-up, 33% of patients with anti-infliximab antibodies also developed anti-adalimumab antibodies, compared with only 18% of patients who had never received a TNF blocker (&lt;em&gt;P&lt;/em&gt;=0.039), according to Geertje M. Bartelds, MD, of the Jan van Breemen Institute in Amsterdam, and colleagues.&lt;/p&gt;
&lt;p&gt;Patients who developed antibodies to both TNF blockers also had a smaller decrease in their disease activity score compared with TNF-naive patients (1.1 versus 1.7 points, &lt;em&gt;P&lt;/em&gt;=0.007), a difference that persisted after adjustment for baseline disease activity (95% CI &amp;#8722;1.166 to &amp;#8722;0.351, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), the researchers reported online in the &lt;em&gt;Annals of the Rheumatic Diseases&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Some 30% to 40% of patients with rheumatoid arthritis fail to respond to anti-TNF therapy. Some, though not all of this failure can be explained by immunogenic antibody responses to the drugs.&lt;/p&gt;
&lt;p&gt;When patients don&apos;t respond to one TNF antagonist, doctors frequently switch to another, the researchers noted, but the choice of drug is generally not evidence-based, and there is considerable variability in subsequent response.&lt;/p&gt;
&lt;p&gt;To investigate factors determining response after switching, Bartelds and colleagues prospectively followed a consecutive cohort of 235 patients with rheumatoid arthritis being treated with adalimumab.&lt;/p&gt;
&lt;p&gt;Mean age was 53 years and disease duration was about 10 years. About 80% were women. They had previously received a mean of four disease-modifying, anti-rheumatic drugs, and more than 80% also were receiving methotrexate.&lt;/p&gt;
&lt;p&gt;Baseline erythrocyte sedimentation rate (ESR) was approximately 30 mm/hour, and the mean disease activity score (DAS28) was 5.3. (A DAS28 of 3.2 or higher reflects active disease.)&lt;/p&gt;
&lt;p&gt;A total of 52 had previously received infliximab.&lt;/p&gt;
&lt;p&gt;In the overall cohort the mean DAS28 fell by 1.6 points during 28 weeks of follow-up.&lt;/p&gt;
&lt;p&gt;When responses were assessed according to the criteria used by the European League Against Rheumatism (EULAR), 24% were nonresponders, 43% were moderate responders, and 33% were good responders at 28 weeks.&lt;/p&gt;
&lt;p&gt;Among the TNF-naive patients, there were: &lt;ul&gt; &lt;li&gt;38% good responders&lt;/li&gt; &lt;li&gt;39% moderate responders &lt;/li&gt; &lt;li&gt;23% nonresponders&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;In contrast, among patients who had previously received infliximab, there were: &lt;ul&gt; &lt;li&gt;15% good responders&lt;/li&gt; &lt;li&gt;54% moderate responders&lt;/li&gt; &lt;li&gt;31% nonresponders&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Post-hoc analysis determined that only the percentage of good responders differed significantly between the TNF-naive patients and the infliximab switchers (&lt;em&gt;P&lt;/em&gt;=0.002).&lt;/p&gt;
&lt;p&gt;Among the 20% of patients who developed anti-adalimumab antibodies, the mean decrease in DAS28 was 0.6 points, compared with 1.8 points in those without the antibodies (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001). That difference remained significant after adjustment for baseline ESR (95% CI &amp;#8722;1.797 to &amp;#8722;0.908, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001).&lt;/p&gt;
&lt;p&gt;Previous studies have suggested that there may be differences between patients who are primary nonresponders and secondary nonresponders (who initially improve with treatment).&lt;/p&gt;
&lt;p&gt;In primary nonresponders, who never responded to anti-TNF therapy, TNF may not be the crucial cytokine responsible for the initiating events in rheumatoid arthritis, the investigators hypothesized.&lt;/p&gt;
&lt;p&gt;The findings of this study suggest that nonresponders could be treated according to their antibody status, with antibody-positive patients likely deriving greater benefit from switching to a less immunogenic drug acting on the same principle, or from optimizing concomitant methotrexate therapy.&lt;/p&gt;
&lt;p&gt;In nonresponders without antibodies, it may be more useful and cost-effective to try a drug with a different mechanism of action, they suggested.&lt;/p&gt;
&lt;p&gt;The study was limited by the small number of patients and the observational cohort design. The patient population also had severe, longstanding rheumatoid arthritis, which might have made it difficult to detect treatment effects.&lt;/p&gt;
&lt;p&gt;&quot;To our knowledge, this is the first study providing more information on the underlying mechanisms contributing to the possible success of switching,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;More research will be needed, however, to provide conclusive data on how immunogenicity could aid in clinical decision-making for individual patients.&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 Abbott, Wyeth, and the Netherlands Organization for Health Research and Development.&lt;/p&gt;&lt;p&gt;One co-author has served as consultant to Abbott, Amgen, Centocor, Schering-Plough, UCB, and Wyeth, and several others also are members of the advisory board of Abbott and have received honoraria for lectures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_8_387"
                     title="Biologics in Rheumatoid Arthritis Linked to Skin Cancer Only"
                     score="-0.005"
                     href="