<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_463"
                     title="AAPM: Online Program Helps Manage Pain (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18393?impressionId=1265799779073"
                     
      &lt;p&gt;SAN ANTONIO  --  A personalized, online self-management program helped patients with pain syndromes improve coping skills and reduce stress and depression in two studies reported here.&lt;/p&gt;
&lt;p&gt;Patients randomized to the self-management program demonstrated significant improvement in multiple social, emotional, and behavioral outcomes after six months (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01). Improvement in some parameters occurred within one month. A control group that was not exposed to the program showed no significant improvement.&lt;/p&gt;
&lt;p&gt;&quot;Our goal is to help people communicate better with providers, understand better how they can use social support, understand the comorbid conditions, like anxiety and depression, and develop cognitive skills to help get them through their pain episodes,&quot; said Emil Chiauzzi, PhD, of Inflexxion, the Newton, Mass. company that developed the program.&lt;/p&gt;
&lt;p&gt;Although the studies involved patients with migraine or low-back pain, programs are being developed for other types of pain condition, including several forms of neuropathic pain.&lt;/p&gt;
&lt;p&gt;The online program, demonstrated at &lt;a href=&quot;http://www.painACTION.com&quot; mce_href=&quot;http://www.painACTION.com&quot; target=&quot;_blank&quot;&gt;www.painACTION.com&lt;/a&gt;, employs patient-specific information to generate individualized self-management strategies.&lt;/p&gt;
&lt;p&gt;Patient responses to assessments are analyzed by a &quot;recommendation engine,&quot; which produces content recommendations designed to address each patient&apos;s informational and self-management needs.&lt;/p&gt;
&lt;p&gt;Elements on the Web site include multimedia education units, a pain inventory, interactive tools that provide information based on patient-provider communication, and medication risk management.&lt;/p&gt;
&lt;p&gt;&quot;The content on the Web site is focused on teaching people practical skills to manage the behavioral side of pain,&quot; Jonas Bromberg, PsyD, also of Inflexxion, said in an interview.&lt;/p&gt;
&lt;p&gt;Bromberg presented results of a randomized study involving 210 patients, all of whom met International Headache Society diagnostic criteria for migraine, with or without aura.&lt;/p&gt;
&lt;p&gt;Patients assigned to the online program completed at least eight 30-minute session during the first month of the study and at least five more 30-minute sessions during the five-month follow-up period. Patients in the control group continued to receive usual care without exposure to the Web site.&lt;/p&gt;
&lt;p&gt;Participants assigned to the online program had a minimum set of requirements for each session, which were provided at log-in. Follow-up assessments occurred at one, three, and six months.&lt;/p&gt;
&lt;p&gt;The two groups were balanced with respect to sex and headache frequency and severity, the researchers said.&lt;/p&gt;
&lt;p&gt;Bromberg reported that patients assigned to the self-management program demonstrated significant improvement in: &lt;ul&gt; &lt;li&gt;Headache self-efficacy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01 compared with baseline)&lt;/li&gt; &lt;li&gt;Use of relaxation (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Use of social support (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Pain catastrophizing (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Depression (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Stress (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Chiauzzi presented results from a randomized study of 209 patients with low-back pain. The design was similar to that of the migraine study, except results were analyzed for between-group differences.&lt;/p&gt;
&lt;p&gt;The results showed significant improvement in the study group versus control group with respect to: &lt;ul&gt; &lt;li&gt;Stress (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Coping (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Social supports (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The data showed significant effects of both treatment (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01) and time (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01) favoring the Web site versus control. Chiauzzi said patients assigned to the Web site had greater mean improvement at posttest, three months, and six months.&lt;/p&gt;
&lt;p&gt;Qualitative analysis suggested that Web site participants had clinically meaningful improvement in depression, anxiety, and stress.&lt;/p&gt;
&lt;p&gt;Additionally, patients in the self-management program reported a 12.3% decrease in pain from baseline, versus 7% in the control group.&lt;/p&gt;
&lt;p&gt;Access to the Web site did not improve physical functioning.&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 were funded by the National Institutes of Health.&lt;/p&gt;&lt;p&gt;Chiauzzi and Bromberg are employees of Inflexxion, developer of the online program.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <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=1265799779073"
                     
      &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_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=1265799779073"
                     
      &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_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=1265799779073"
                     
      &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_375"
                     title="Rituximab Safe Long-Term in RA (CME/CE)"
                     score="0.008"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/18267?impressionId=1265799779073"
                     
      &lt;p&gt;Multiple courses of rituximab (Rituxan) were safe for patients with advanced rheumatoid arthritis, with no increase in serious adverse events or serious infections, an analysis of data from an international follow-up program demonstrated.&lt;/p&gt;
&lt;p&gt;The rate of serious adverse events was 17.85 per 100 patient-years (95% CI 16.72 to 19.06), remaining stable following each course of treatment for up to five years, according to Ronald F. van Vollenhoven, MD, of Karolinska University Hospital in Stockholm, and colleagues.&lt;/p&gt;
&lt;p&gt;Serious infections such as pneumonia, cellulitis, and urinary tract infections were reported in 170 patients (7%), for an overall serious infection rate of 4.31 per 100 patient-years (95% CI 3.77 to 4.92), the investigators reported online in &lt;em&gt;The Journal of Rheumatology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Time and experience have made clear that the immunomodulatory nature of biologic therapies in patients with rheumatoid arthritis requires careful safety vigilance.&lt;/p&gt;
&lt;p&gt;In addition to treatment-related risks, patients with rheumatoid arthritis already are at increased risk of infections, malignancies, and cardiovascular disease.&lt;/p&gt;
&lt;p&gt;Rituximab acts by binding to the CD20 antigen, resulting in depletion of CD20-positive B cells. It is licensed in the U.S. for use in combination with methotrexate in rheumatoid arthritis patients who have had an inadequate response to one or more tumor necrosis factor inhibitors.&lt;/p&gt;
&lt;p&gt;To identify adverse events possibly attributable to B-cell depletion, and of particular concern for RA patients, van Vollenhoven and colleagues analyzed long-term follow-up from patients who had been treated in nine clinical trials and two open-label extension studies.&lt;/p&gt;
&lt;p&gt;&quot;This analysis involves a larger number of rituximab-treated patients than previously reported, followed for multiple courses,&quot; they observed.&lt;/p&gt;
&lt;p&gt;A single course of treatment consisted of infusions of 2 X 500 mg or 2 X 1,000 mg, given two weeks apart.&lt;/p&gt;
&lt;p&gt;In the overall cohort there were patients who had undergone up to 10 courses of rituximab. This analysis, however, only included patients with up to five courses, because the numbers of patients having more than five were small and the confidence intervals of point estimates were wide.&lt;/p&gt;
&lt;p&gt;A total of 2,578 patients were included, with 5,013.5 patient-years of observation.&lt;/p&gt;
&lt;p&gt;Most study participants were women, mean age was 53 years, and disease duration averaged 10 years.&lt;/p&gt;
&lt;p&gt;They had received a mean of three previous biologic or disease-modifying drugs (other than methotrexate), and more than half had previously been treated with a tumor necrosis factor inhibitor.&lt;/p&gt;
&lt;p&gt;A total of 123 patients (5%) withdrew from the study because of adverse events.&lt;/p&gt;
&lt;p&gt;The overall rate of adverse events was 359.6 per 100 patient-years, being highest for the first course, declining with the second course, and remaining stable thereafter.&lt;/p&gt;
&lt;p&gt;The most common adverse events were infusion-related reactions, observed in 25% of patients during the first course, typically manifesting as mild-to-moderate headache, pruritus, hypertension, and rash.&lt;/p&gt;
&lt;p&gt;Some 9% of patients required slowing or stopping the infusion because of these reactions during the first course.&lt;/p&gt;
&lt;p&gt;By the fifth course, all patients were tolerating the infusion. &quot;This pattern is consistent with the hypothesis that cytokine release syndrome is less likely with additional courses because of a lower B-cell load,&quot; the investigators wrote.&lt;/p&gt;
&lt;p&gt;For serious adverse events, the most frequently reported were: &lt;ul&gt; &lt;li&gt;Pneumonia, 1%&lt;/li&gt; &lt;li&gt;Falls, 1%&lt;/li&gt; &lt;li&gt;Myocardial infarction, 0.9%&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The rate of myocardial infarction was an expected 0.56 per 100 patient-years, generally occurring in patients with risk factors. This was consistent with rates reported for other rheumatoid arthritis populations, according to the authors.&lt;/p&gt;
&lt;p&gt;A total of 65% of patients experienced some type of infection  --  most commonly nasopharyngitis and upper respiratory tract infection  --  with a rate of 97.7 per 100 patient-years.&lt;/p&gt;
&lt;p&gt;There were no cases of serious opportunistic infections during the analysis period.&lt;/p&gt;
&lt;p&gt;Overall serum immunoglobulin levels decreased during follow-up, with 5% of patients having levels of IgG below the lower limit of normal on at least one occasion.&lt;/p&gt;
&lt;p&gt;&quot;Classical observations have shown that IgG is the most important among serum immunoglobulins for protective immunity and that patients with low levels of IgG are at increased risk of serious infections,&quot; the investigators said.&lt;/p&gt;
&lt;p&gt;In this patient cohort, the rates of serious infections did not significantly increase when low IgG levels were detected.&lt;/p&gt;
&lt;p&gt;Older age and the concomitant use of steroids can contribute to decreases in IgG, and because corticosteroids were permitted in the clinical trials, it&apos;s unclear to what degree rituximab caused the fall in immunoglobulins.&lt;/p&gt;
&lt;p&gt;&quot;Irrespective of the underlying mechanisms for patients who had low IgG levels, this subset of patients may be at higher risk for infections and should be monitored closely,&quot; they cautioned.&lt;/p&gt;
&lt;p&gt;The overall incidence of malignancies other than nonmelanoma skin cancer was 0.84 per 100 patient-years, and the adjusted standardized incidence ratio compared with the general U.S. population was 1.05 (95% CI 0.76 to 1.42).&lt;/p&gt;
&lt;p&gt;Thirty deaths occurred, and the adjusted standardized mortality rate compared with the overall U.S. population was 0.83 (95% CI 0.56 to 1.18).&lt;/p&gt;
&lt;p&gt;The study had limitations, the authors&lt;strong&gt; &lt;/strong&gt;acknowledged, such as pooling of information from trials in which number of treatment courses, disease status, and doses of rituximab differed.&lt;/p&gt;
&lt;p&gt;The data were also constrained by the inclusion and exclusion criteria of the clinical trials.&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;Several co-authors are employees of Biogen Idec, Genentech, or Roche.&lt;/p&gt;&lt;p&gt;Writing assistance was provided and supported by Genentech, Biogen Idec, and F. Hoffmann La Roche.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
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