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News Article | November 12, 2016
Site: www.eurekalert.org

WASHINGTON -- Patients with rheumatoid arthritis whose rheumatologists and primary-care physicians coordinate their care have a higher likelihood of being screened for hyperlipidemia, a key risk factor for coronary heart disease, according to new research findings presented this week at the 2016 ACR/ARHP Annual Meeting in Washington. Rheumatoid arthritis (RA) is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men. Patients with RA have an increased prevalence for coronary heart disease (CHD). Some data suggests that RA patients are not being screened properly for hyperlipidemia, so researchers at the University of Alabama at Birmingham conducted a study to evaluate lipid testing patterns among RA patients. They looked at whether patients screened for hyperlipidemia received care from a primary-care physician (PCP), a rheumatologist or both. The study was conducted to identify the extent of the screening and management gaps for hyperlipidemia among the RA patient population, said Iris Navarro-Millan, MD, Assistant Professor of Medicine at UAB and a lead author of the study. "You could argue that screening for hyperlipidemia, a traditional risk factor, should be addressed by primary-care physicians, but there are a number of patients with RA who only see a rheumatologist," she said. "Patients see a specialist for a comorbidity (in this case RA), and do not establish care with a PCP, and this results in gaps in standard of care, such as screening and management for hyperlipidemia. We decided to focus on hyperlipidemia because CHD is the most common cause of death among patients with RA. Therapies for RA also affect lipid profiles in these patients, which adds complexity to the issue of cardiovascular risk reduction in patients with RA." The study linked commercial and public health plan claims data together from 2006 to 2010. Participants in the study were required to have at least 12 months of continuous medical and pharmacy coverage at baseline, have two or more physician diagnoses plus relevant DMARD and/or biologic prescriptions to categorize them as having RA, plus two years of follow-up. Excluded were patients with prevalent myocardial infarction (MI), stroke or CHD at baseline, or those who had a diagnosis of hyperlipidemia or were using hyperlipidemia medications at baseline. The researchers organized the patterns of care at baseline as visited a PCP only, visited a rheumatologist only or visited both types of physicians. They used logistic regression to determine the how likely patients were to be screened for hyperlipidemia during two years of follow-up based on their pattern of care.The study measured hyperlipidemia screening in 13,319 RA patients, including 83 percent women. Twenty-six percent were between the ages of 41-60 and 74 percent were older than 65. Eighteen percent of the RA patients did not see a PCP at the 12-month baseline. The results showed that 42 percent of patients seeing a PCP only were screened for hyperlipidemia, 40 percent of patients seeing only a rheumatologist were screened, and 47 percent of patients seeing both a PCP and rheumatologist were screened. After controlling for multiple potential confounders, the researchers found that RA patients who received combined care had a 32 percent increase in the likelihood of being screened for hyperlipidemia. Rheumatologists may not always consider hyperlipidemia screenings as part of RA patient care, the researchers concluded. Improved coordination of care between PCPs and rheumatologists could help RA patients get necessary cardiovascular screenings. The study's findings help raise awareness that the RA patient population is inadequately screened and managed for hyperlipidemia, said Dr. Navarro-Millan. "Our goal is to develop an intervention that can facilitate communication between specialties with the goal of decreasing health care fragmentation and reduce CHD risk in these patients," she said. "We anticipate that patient activation and knowledge will be a key element for the success of such intervention, since patients with RA are less likely to be aware of their increased risk for CHD." This research was supported by funding from the Rheumatology Research Foundation and the NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases. About the American College of Rheumatology Headquartered in Atlanta, Ga., the American College of Rheumatology is an international medical society representing over 9,400 rheumatologists and rheumatology health professionals with a mission to Advance Rheumatology! In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases. For more information, visit http://www. . The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. With more than 450 sessions and thousands of abstracts, it offers a superior combination of basic science, clinical science, tech-med courses, career enhancement education and interactive discussions on improving patient care. For more information about the meeting, visit http://www. , or join the conversation on Twitter by following the official #ACR16 hashtag.


News Article | November 14, 2016
Site: www.sciencedaily.com

A Mayo Clinic study is shedding light on why some rheumatoid arthritis patients respond poorly when treated with tumor necrosis factor inhibitors, part of a class of drugs called biologics. It comes down to proteins: specifically, a protein in the body that drives inflammation in the disease, the research found. The discovery is an important step toward better personalizing rheumatoid arthritis treatment, helping to avoid trial and error when prescribing medications. The findings were presented at the American College of Rheumatology annual meeting in San Francisco. Researchers found that patients with a higher amount or higher proportion of an inflammatory protein called type 1 interferon beta compared with another inflammatory protein, type 1 interferon alpha, do not respond as well to tumor necrosis factor inhibitors as others. They looked at white blood cells called monocytes, a major cell type involved in rheumatoid arthritis, and found that those cells behaved differently in one group than in the other. The discovery paves the way for a more personalized approach to treatment in rheumatoid arthritis based on the biology of a particular patient's disease. "Investigating these pathways may identify other targets for therapy or other markers that predict treatment response," says first author Theresa Wampler Muskardin, M.D., a rheumatologist at Mayo Clinic in Rochester, Minn. "It will help rheumatologists find the right drug for each patient and spare patients medications that won't work for them." The Rheumatology Research Foundation funded the study. Mayo rheumatologist Timothy Niewold, M.D., was the study's senior author. In other studies presented at the meeting, Mayo Clinic researchers found: • Sarcoidosis, the growth of tiny clusters of inflammatory cells called granulomas, carries a higher risk of heart disease and venous thromboembolism. Researchers also found there is seasonal variation in the incidence of sarcoidosis: Rates are consistently lower in autumn. Physicians believe that sarcoidosis may be triggered by the body's immune response to environmental factors, such as something inhaled from the air. • The risk of coronary artery disease among patients with polymyalgia rheumatica is 70 percent higher than it is among others. • Heart and circulatory abnormalities are common in Takayasu's arteritis, a form of vasculitis in which large blood vessels become inflamed. Mayo rheumatologists and cardiologists formed the Mayo Clinic Cardio-Rheumatology Clinic to research and pioneer better prevention, detection and treatment of heart disease and other cardiovascular problems in patients with rheumatic diseases.


News Article | November 12, 2016
Site: www.eurekalert.org

WASHINGTON -- Rheumatoid arthritis patients who keep using their disease-modifying antirheumatic drugs prior to surgery do not face an increased risk of infection after their procedures, according to new research findings presented this week at the 2016 ACR/ARHP Annual Meeting in Washington. Rheumatoid arthritis (RA) is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men. Because disease-modifying antirheumatic drugs (DMARDs), including methotrexate and biologic agents like tumor necrosis factor inhibitors (TNFi) suppress the immune system and can increase susceptibility of infections, RA patients often are advised to stop taking these drugs prior to surgery. To assess whether the risk of post-operative infections is greater for RA patients who continue their therapy through surgery compared to those who do not, a group of researchers examined data from 9,362 surgeries performed on 5,544 RA patients to assess the risk of infection. "Patients have higher chances of flare-ups if they discontinue their RA medication for a period of time prior to surgery," said Hsin-Husan Juo, MD, a rheumatology fellow the University of Washington School of Medicine and the lead author of the study. Patients who have flares usually are required to take prednisone for a period of time to calm down the inflammation, then it takes another two to three months for either DMARDs or TNF-inhibitors to be fully effective after restarting, she said. "Prednisone is well known for delaying wound healing and increasing the rate of infection, which would increase post-surgical complications. Therefore, whether discontinuing DMARDs or TNF-inhibitors prior to elective surgeries is necessary or not is an important issue." The researchers identified surgical procedures performed on RA patients between 1999 and 2009 by using the United States Department of Veterans Affairs (VA) databases and surgical quality registry. The patients selected were on at least one DMARD or biologic drug, such as TNFi drugs, prior to surgery. With the information provided by VA pharmacy database records, a previously validated algorithm was used to determine if these patients stopped their medication before surgery or stayed on therapy. Patients were grouped based on their therapy: methotrexate alone, hydroxychloroquine alone, leflunomide alone and methotrexate plus a TNFi. The researchers then measured total infectious complications and wound infections in each group. Many RA patients stay on therapy despite the perceived infection risk, said Dr. Juo. Out of 2,600 surgeries on patients taking methotrexate alone, therapy was continued in 1,961 procedures. Out of 2,012 surgeries on patients taking hydroxychloroquine alone, therapy was continued in 1,496 procedures. Out of 652 surgeries on patients taking leflunomide alone, therapy was continued in 508. Out of 386 surgeries on patients taking a combination of methotrexate and TNFi, both drugs were continued in 196 surgeries, while methotrexate was stopped and TNFi continued in 59 surgeries. In 72 surgeries, TNFi was stopped but methotrexate was continued. Both drugs were stopped in 59 surgeries. Continuation of therapy prior to surgery was not associated with increased rates of overall post-operative infections or wound infections in any of these treatment groups. "Our findings show that discontinuing methotrexate, hydroxychloroquine, leflunomide monotherapy and TNFi plus methotrexate therapy is not associated with increased risk of post- operative infectious complications," said Dr. Juo. "Therefore, surgeons and rheumatologists should consider continuing medication during the perioperative period to have better control over RA. This will decrease the possibility of requiring steroid therapy and maintain better post- operative functional status." In the future, these researchers plan to extend the study to 2015 and explore more sub-group analyses for specific surgeries as well as more biologics to gain more insight into infection risk with continuation of disease-modifying therapies. Headquartered in Atlanta, Ga., the American College of Rheumatology is an international medical society representing over 9,400 rheumatologists and rheumatology health professionals with a mission to Advance Rheumatology! In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases. For more information, visit http://www. . The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. With more than 450 sessions and thousands of abstracts, it offers a superior combination of basic science, clinical science, tech-med courses, career enhancement education and interactive discussions on improving patient care. For more information about the meeting, visit http://www. , or join the conversation on Twitter by following the official #ACR16 hashtag.


ZUG, Switzerland, Nov. 2, 2016 /PRNewswire/ -- A recent study of nearly 100 surveyed US rheumatologists reveals that after approximately nine months on the market, not only are current users of Novartis' Cosentyx reporting increased PsA initiations, but the brand has also made significant...


News Article | February 22, 2017
Site: www.marketwired.com

WAYNE, NJ--(Marketwired - February 22, 2017) - Konica Minolta Healthcare today announced the launch of its J5 Ultrasound System, a portable system with touch-screen intuitive navigation that produces high quality real-time images of the musculoskeletal (MSK) system. The new technology delivers the workflow benefits and diagnostic accuracy required to make critical point-of-care decisions during MSK evaluations. "The J5 release highlights our innovative approach to reinventing point-of-care ultrasound and increasing users' ability to do more with ultrasound," said Brian Noyes, Sr. Vice President and General Manager, Ultrasound Division at Konica Minolta. "It delivers a unique ease-of-use functionality unmatched by other technologies in the market, designed for securing clinical confidence in MSK scanning environments." The J5 Ultrasound System enables real-time examination of soft tissue without radiation exposure in a portable, ergonomic design. Orthopedists, sports medicine physicians, rheumatologists, podiatrists, and other MSK-focused physicians can provide immediate assessments of musculoskeletal ailments and help improve joint aspiration, biopsy, and injection accuracy with ultrasound. Needle visualization software allows for guidance during in-plane needle procedures. A three-second start-up time from standby, the J5 System boasts intuitive gesture controls and focused MSK presets to streamline the scanning process. The simple navigation, which includes one-touch image optimization, enhances efficient workflow for confident diagnoses and patient throughput. The new point-of-care ultrasound system provides excellent visualization via a 15" high-resolution, anti-glare screen with wide viewing angle that is touch-responsive through gloves and gel. The J5 can either be mounted on an ergonomically designed table stand, VESA plate for wall mounting, or height-adjustable mobile cart to accommodate facilities with limited space. The built-in battery supports over two hours of continuous scanning on the system, which includes wireless communication, and storage and archiving. "The engineers designed the J5 with the end user in mind, making operation seamless and simple. Combined with excellent image quality and an efficient workflow the J5 System demonstrates Konica Minolta's commitment to MSK physicians who want to incorporate ultrasound into their practices," concluded Noyes. Konica Minolta Healthcare is a world-class provider and market leader in medical diagnostic imaging and healthcare information technology. With over 75 years of endless innovation, Konica Minolta is globally recognized as a leader providing cutting-edge technologies and comprehensive support aimed at providing real solutions to meet customers' needs and helping make better decisions sooner. Konica Minolta Healthcare Americas, Inc., headquartered in Wayne, NJ, is a unit of Konica Minolta, Inc. ( : 4902). For more information on Konica Minolta Healthcare Americas, Inc., please visit www.konicaminolta.com/medicalusa.


News Article | November 12, 2016
Site: www.eurekalert.org

WASHINGTON -- Injection of a Wnt inhibitor drug showed promise to ease pain, improve joint function, and even slow or reverse cartilage loss in patients with knee osteoarthritis, according to new research findings presented this week at the 2016 ACR/ARHP Annual Meeting in Washington. Osteoarthritis, or OA, is the most common joint disease affecting middle-aged and older people. It is characterized by progressive damage to the joint cartilage--the cushioning material at the end of long bones--and causes changes in the structures around the joint. Existing OA therapies address joint pain and function, but they may only have limited efficacy. There are also questions about their long-term safety for patients, said Yusuf Yazici, MD, Chief Medical Officer of Samumed, LLC, a biotech in San Diego, Calif., which conducted new research about Wnt inhibitors. Recent research shows that the Wnt signaling pathway plays a role in the formation of joint tissues, and suggests that an altered Wnt pathway is associated with cartilage loss. "Osteoarthritis is a debilitating disease affecting nearly 30 million patients in the U.S. alone," said Dr. Yazici. The goals for his laboratory's research are "to develop a disease-modifying treatment which will regrow cartilage, while also safely treating the signs and symptoms of this significant patient population." In a 24-week, multicenter, single-dose-escalation, randomized controlled trial, the researchers measured the impact of a single, intra-articular injection of SM04690, a Wnt inhibitor, on pain and function in 61 patients with moderate to severe knee OA. The drug's efficacy was analyzed through Outcomes Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) strict responder data. "Our impetus for the trial was to analyze OMERACT-OARSI responses to further test the clinical relevance of the signs and symptoms data we had observed," said Dr. Yazici. "SM04690 has the potential for true disease modification, and relief of signs and symptoms for OA patients." The average age of the study subjects was 62.6 (±5.7) years, 67 percent were female, and their average body-mass index was 30.4 (±4.7). Escalation cohorts of 20 patients each, including 16 active and four placebo) were given a dose of SM04690 at 0.03 mg, 0.07 mg and 0.23 mg in a 2 mL injection. Subjects were given one injection into their affected knee on the first day, and participated in a follow-up period of 24 weeks. The researchers collected safety, pharmacokinetics, biomarker and preliminary effectiveness data, including Western Ontario McMasters Universities Arthritis Index (WOMAC Likert v3.1) measures. They evaluated the percentage of OMERACT-OARSI strict responders in the modified Intention-to-Treat (mITT) population. These responders were patients reporting either WOMAC pain or function subscores improvement of ?50 percent, coupled with a reduction in the given subscore of at least 20 points, scaled to [0-100]. Compared to placebo, the researchers found statistically more OMERACT-OARSI strict responders in the 0.07 mg cohort at week 12, or 76 percent versus 36 percent, P=0.04. Numerically, there were more strict responders in the 0.03 mg cohort at week 24, or 73 percent versus 36 percent, P=0.07. More patients in the 0.07 mg cohort met both the pain and function criteria versus placebo at 12 and 24 weeks. Responses in the 0.23 mg cohort were 44 percent at week 12 and 25 percent at week 24. These results are evidence that SM04690 has a potentially therapeutic effect on knee OA pain and function compared with placebo, Dr. Yazici said. "More patients treated with a single, intra-articular injection of SM04690 than placebo achieved a significant OMERACT-OARSI strict response, a composite score of clinical efficacy requiring both absolute and relative improvement," he said. "Through further analysis, we saw that the clinical response was driven by improvements in both pain and function measurements from baseline as 12 and at 24 weeks, and not solely by one or the other, suggesting clinically relevant, multidimensional improvement." The researchers also explored the potential efficacy of Wnt inhibitors on joint space narrowing and cartilage loss, two signs of worsening arthritis. "A therapy with the potential to not only decrease pain and improve function for patients with knee OA, but also to halt or reverse the processes that are driving disease progression, would be a welcome addition to the OA treatment armamentarium," said Dr. Yazici. The researchers examined their data to evaluate the change from baseline in joint space width (JSW) on X-rays, and then conducted an analysis of JSW change using repeated measures analysis of covariance, or ANCOVA, adjusting for baseline JSW in the modified intention-to-treat (mITT) population. In the mITT population at 24 weeks, subjects in the 0.07 mg cohort showed statistically significant increase in mean medial JSW of 0.49 mm (SD ±0.75 mm, P=0.02) from baseline compared to placebo. No change in mean medial JSW was observed in the 0.03 mg cohort (mean 0.00 mm, SD ±0.69 mm), a decrease in mean medial JSW of 0.15 mm (SD ±1.07 mm) observed in the 0.23 mg cohort and a mean decrease of 0.33 mm (SD ±0.87 mm) observed in the placebo cohort. These results, based on exploratory X-ray outcomes from the study, suggest that treatment with SM04690 may maintain or increase joint space width compared to placebo, said Dr. Yazici. "SM04690 has a novel mechanism of action, and the findings so far suggest that it's safe and has the potential for true disease modification, as well as relief of signs and symptoms of OA after a single injection," he said. "Radiographs (X-rays) taken at baseline and at 24 weeks post-injection suggested that mean joint space width was maintained in one dose, and even increased in another dose." The next steps are to further assess Wnt inhibitors' safety and efficacy, said Dr. Yazici. The researchers are now conducting a Phase II trial on patients with moderate to severe knee OA. "Most importantly, we hope that SM04690 will continue to show positive safety and efficacy so that the millions of patients with knee OA will have a new treatment option," he said. About the American College of Rheumatology Headquartered in Atlanta, Ga., the American College of Rheumatology is an international medical society representing over 9,400 rheumatologists and rheumatology health professionals with a mission to Advance Rheumatology! In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases. For more information, visit http://www. . The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. With more than 450 sessions and thousands of abstracts, it offers a superior combination of basic science, clinical science, tech-med courses, career enhancement education and interactive discussions on improving patient care. For more information about the meeting, visit http://www. , or join the conversation on Twitter by following the official #ACR16 hashtag.


WASHINGTON -- Patients with ankylosing spondylitis or psoriatic arthritis who take statins may have as much as a 33 percent lower mortality risk, according to new research findings presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington. Ankylosing spondylitis (AS) is arthritis of the spine that can resemble rheumatoid arthritis. It more often affects males, with HLA antigen present but rheumatoid factor absent. Psoriatic arthritis (PsA) is a chronic form of arthritis that can affect the skin and joints. It can lead to joint damage if not treated. Researchers at Massachusetts General Hospital in Boston set out to explore the potential benefits of statins, which can both lower lipids and reduce inflammation, in patients with AS or PsA, which are both seronegative spondyloarthropathies. Both AS and PsA are associated with increased cardiovascular mortality risk. The goal of the study was to see if initiation of statins might be associated with a lower mortality risk in this patient population. "The expanding literature on the dual-role of statins to lower both inflammation and cholesterol levels has naturally led to interest in the role of statins in inflammatory arthritis," said Amar Oza, MD, a rheumatologist at Massachusetts General and a lead author of the study along with Na Lu, MD and Hyon Choi, MD. "A randomized trial found such a dual benefit among patients with rheumatoid arthritis (RA), and a population-based study of patients with RA found a survival benefit associated with statin use as well. As such, we hoped to quantify the potential impact of statins in the seronegative spondyloarthropathies, as the risk of all-cause mortality and even cardiovascular-specific mortality has shown to be elevated in these conditions." Using a United Kingdom (UK) general population database, the researchers studied both AS and PsA patients between January 1, 2000 and December 31, 2014. They also used 50 different variables to create propensity scores, including disease duration, socioeconomic status, body-mass index, lifestyle factors and medication use. Of 2,904 patients with either AS or PsA who started statins, 271 died during the follow-up, a mean of 5.3 years. Of 2,904 propensity-matched AS or PsA patients who did not start statins, 376 died during the follow-up, a mean of 5.15 years. Baseline characteristics between the two groups were well balanced. Statin initiation was associated with 33 percent reduction in all-cause mortality. The inverse association of statin initiation and mortality risk among AS and PsA patients appears to be larger than that observed in other population-based cohort studies of rheumatoid arthritis patients, the study noted. Statins' dual benefits of lowering lipids and reducing inflammation, both contributors to cardiovascular disease risk, could be the reason for this significant benefit. "Given the increased risk of mortality and cardiovascular disease compared to the general population, patients with seronegative spondyloarthropathies like AS and PsA may benefit from the dual anti-inflammatory and lipid-lowering properties of statins, perhaps even more than in the general population," said Dr. Oza. "This observational study raises the possibility that clinicians may have a lower threshold for starting their patients on statins to mitigate this mortality risk. To that effect, it sets the groundwork for potential clinical trials to come, which will provide high-level evidence about the impact statins have on their health." More research is needed to explore the potential benefits of statins to prevent mortality due to cardiovascular and other causes, he concluded. This research was supported by funding from the NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases. About the American College of Rheumatology Headquartered in Atlanta, Ga., the American College of Rheumatology is an international medical society representing over 9,400 rheumatologists and rheumatology health professionals with a mission to Advance Rheumatology! In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases. For more information, visit http://www. . The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. With more than 450 sessions and thousands of abstracts, it offers a superior combination of basic science, clinical science, tech-med courses, career enhancement education and interactive discussions on improving patient care. For more information about the meeting, visit http://www. , or join the conversation on Twitter by following the official #ACR16 hashtag.


News Article | November 12, 2016
Site: www.eurekalert.org

WASHINGTON -- Three gene expression signatures can help rheumatologists predict which patients are more likely to respond to tumor necrosis factor inhibitors (TNFi) or B-cell depletion therapies in patients with moderate to severe rheumatoid arthritis, according to new research findings presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington. Rheumatoid arthritis (RA) is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men. Drawing on data from the ORBIT study, a randomized, controlled trial of RA patients in the United Kingdom, researchers looked for gene expression markers that would help predict responses to either TNFi drugs or the B-cell therapy rituximab, or both. The ORBIT data "showed that patients who have seropositive rheumatoid arthritis are just as likely to respond to rituximab therapy when compared to anti-TNF therapy," said Duncan Porter, MD, Honorary Associate Professor and a consultant rheumatologist at Queen Elizabeth University Hospital in Glasgow, Scotland, and one of the lead authors of the study. "However, a significant proportion of patients failed to respond to their first biologic drug, but responded when they were switched to the alternative. If we could identify markers in the blood that predicted which drug patients were most likely to respond to, that would allow us to choose the best treatment for that patient at the start, rather than rely on a trial-and-error approach." Dr. Porter and his fellow researchers sequenced the RNA from the peripheral blood of 241 RA patients recruited for the ORBIT study, after first depleting ribosomal and globin RNA. They used 70 percent of the samples to develop response prediction models, and reserved 30 percent for validation. Clinical response to the therapies was defined as a drop in DAS28-ESR (disease activity score) of 1.2 units between the baseline and at three months. They used multiple machine learning tools to predict general responsiveness and differential responses to TNFi and rituximab. They also used tenfold cross validation to train the models for responsiveness, and then tested these on the validation samples as well. Using support vector machine recursive feature elimination, the researchers identified three gene expression signatures that predicted therapy responses. Eight genes predicted general responsiveness to both TNFi and rituximab, 23 genes predicted responsiveness to TNFi and 23 genes predicted responsiveness to rituximab. The researchers also tested their prediction models on the validation set, and this resulted in ROC (receiver operating characteristic) plot points with an AUC (area under the curve) of 91.6 percent for general responsiveness, 89.7 percent for TNFi response and 85.7 percent for rituximab response. "There are indeed gene expression markers that predict drug-specific response," said Dr. Porter. "If confirmed, this will allow stratification of patients into groups more likely to respond to one drug rather than another. This would lead to higher response rates, and reduced likelihood of receiving a trial of an ineffective drug. Because ineffective treatment is associated with pain, stiffness, disability and reduced quality of life, this will lead to better patient care." Confirmation of these models is the next step for research in this area, said Dr. Porter. "The findings need to be confirmed using targeted RNA sequencing, or internal validation, and then tested in a new cohort of patients, or external validation. Ultimately, a commercial testing kit would be developed to allow clinicians to test patients before they receive treatment to guide them to the most effective treatment," he said. About the American College of Rheumatology Headquartered in Atlanta, Ga., the American College of Rheumatology is an international medical society representing over 9,400 rheumatologists and rheumatology health professionals with a mission to Advance Rheumatology! In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases. For more information, visit http://www. . The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. With more than 450 sessions and thousands of abstracts, it offers a superior combination of basic science, clinical science, tech-med courses, career enhancement education and interactive discussions on improving patient care. For more information about the meeting, visit http://www. , or join the conversation on Twitter by following the official #ACR16 hashtag.


News Article | November 14, 2016
Site: www.sciencedaily.com

Three gene expression signatures can help rheumatologists predict which patients are more likely to respond to tumor necrosis factor inhibitors (TNFi) or B-cell depletion therapies in patients with moderate to severe rheumatoid arthritis, according to new research findings presented this week at the 2016 ACR/ARHP Annual Meeting in Washington. Rheumatoid arthritis (RA) is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men. Drawing on data from the ORBIT study, a randomized, controlled trial of RA patients in the United Kingdom, researchers looked for gene expression markers that would help predict responses to either TNFi drugs or the B-cell therapy rituximab, or both. The ORBIT data "showed that patients who have seropositive rheumatoid arthritis are just as likely to respond to rituximab therapy when compared to anti-TNF therapy," said Duncan Porter, MD, Honorary Associate Professor and a consultant rheumatologist at Queen Elizabeth University Hospital in Glasgow, Scotland, and one of the lead authors of the study. "However, a significant proportion of patients failed to respond to their first biologic drug, but responded when they were switched to the alternative. If we could identify markers in the blood that predicted which drug patients were most likely to respond to, that would allow us to choose the best treatment for that patient at the start, rather than rely on a trial-and-error approach." Dr. Porter and his fellow researchers sequenced the RNA from the peripheral blood of 241 RA patients recruited for the ORBIT study, after first depleting ribosomal and globin RNA. They used 70 percent of the samples to develop response prediction models, and reserved 30 percent for validation. Clinical response to the therapies was defined as a drop in DAS28-ESR (disease activity score) of 1.2 units between the baseline and at three months. They used multiple machine learning tools to predict general responsiveness and differential responses to TNFi and rituximab. They also used tenfold cross validation to train the models for responsiveness, and then tested these on the validation samples as well. Using support vector machine recursive feature elimination, the researchers identified three gene expression signatures that predicted therapy responses. Eight genes predicted general responsiveness to both TNFi and rituximab, 23 genes predicted responsiveness to TNFi and 23 genes predicted responsiveness to rituximab. The researchers also tested their prediction models on the validation set, and this resulted in ROC (receiver operating characteristic) plot points with an AUC (area under the curve) of 91.6 percent for general responsiveness, 89.7 percent for TNFi response and 85.7 percent for rituximab response. "There are indeed gene expression markers that predict drug-specific response," said Dr. Porter. "If confirmed, this will allow stratification of patients into groups more likely to respond to one drug rather than another. This would lead to higher response rates, and reduced likelihood of receiving a trial of an ineffective drug. Because ineffective treatment is associated with pain, stiffness, disability and reduced quality of life, this will lead to better patient care." Confirmation of these models is the next step for research in this area, said Dr. Porter. "The findings need to be confirmed using targeted RNA sequencing, or internal validation, and then tested in a new cohort of patients, or external validation. Ultimately, a commercial testing kit would be developed to allow clinicians to test patients before they receive treatment to guide them to the most effective treatment," he said.


News Article | November 12, 2016
Site: www.eurekalert.org

WASHINGTON -- Chronic kidney disease patients who take urate-lowering therapy and achieve target urate levels show improvement in kidney function, according to new research findings presented this week at the 2016 ACR/ARHP Annual Meeting in Washington. Chronic kidney disease (CKD) is a gradual loss of kidney function that can lead to fluid, electrolyte and waste build-up in its advanced stages. Gout, a condition marked by high levels of uric acid that can crystallize through the body, can lead to CKD in some patients. Could patients with chronic kidney disease benefit from therapies that lower their serum uric acid levels to reach a target goal associated with better organ function? A group of researchers set out to examine whether this therapy, widely used for gout treatment, help CKD patients who achieve the ACR target serum urate level of "Progressive kidney disease leading to dialysis impacts patients on a daily basis and represents a major cost to the health care system," said Gerald Levy, MD, MBA, a rheumatologist at Kaiser Permanente in Downey, California, and a lead author of the study. "Controlling diabetes and hypertension are the primary tools to prevent end stage kidney disease. Normalizing serum uric acid level potentially is another tool to help prevent worsening kidney disease." In this retrospective cohort study conducted from 2008 to 2014, the researchers identified 12,751 patients with serum urate levels of >7mg/dl. Patients' index date for the study was the first time they achieved this test result. In addition, patients included in the study had an estimated glomerular filtration rate (eGFR), a test used to measure kidney function and how well the kidneys are filtering blood, in the six months prior to that index date. They also had to be ULT-naïve, 18 years of age or older, and have either CKD Stages 2, 3 or 4 at the index date. The researchers also only included patients who had continuous health coverage with drug benefits during the entire study period. They defined outcomes in the study as either 30 percent decrease or 30 percent improvement in the patients' eGFR test results from baseline to the last available result. During the study's span, 2,690 patients received ULT and 10,061 patients did not. Serum urate level goals were met in 42 percent of the patients who were on ULT. Of those achieving this goal, 17.1 percent also showed a 30 percent improvement in their eGRF, compared to only 10.4 percent of those patients who did not meet the serum urate goal. As for the influence of CKD stage at the onset of ULT, 7.1 of Stage 2 patients, 19.9 percent of Stage 3 patients, and 30 percent of Stage 4 patients all met the goal of 30 percent improvement in eGRF. Stage 3 patients had the most pronounced effect from ULT on their kidney function. The study's findings suggest that CKD patients who achieve the ACR serum urate goal of "This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. In patients with significantly elevated serum uric acid and moderate kidney failure, the addition of urate lowering therapy may help stabilize or improve kidney function," said Dr. Levy. Headquartered in Atlanta, Ga., the American College of Rheumatology is an international medical society representing over 9,400 rheumatologists and rheumatology health professionals with a mission to Advance Rheumatology! In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases. For more information, visit http://www. . The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. With more than 450 sessions and thousands of abstracts, it offers a superior combination of basic science, clinical science, tech-med courses, career enhancement education and interactive discussions on improving patient care. For more information about the meeting, visit http://www. , or join the conversation on Twitter by following the official #ACR16 hashtag.

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