ACR 2020 Highlights: Dr. Anthony Fauci, Gout Guidelines, Osteoarthritis & Promoting Physical Activity

Day three of the American College of Rheumatology’s annual meeting Saturday continued with sessions on biologics, osteoarthritis treatments, osteoporosis and more, a highlight was a lecture on COVID-19 by Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH), and a top advisor on COVID-19. 

Dr. Anthony Fauci on COVID-19 Background and Current Status
Dr. Fauci outlined the background and addressed the public health and scientific challenges of SARS-CoV-2, the novel coronavirus that causes COVID-19, and the pandemic in the U.S and around the world. Here are some highlights from his pre-recorded lecture: 

“We have had experience with coronaviruses now for decades and decades,” said Dr. Fauci“Here we are now with a global pandemic of historic proportions the likes of which we have not seen in the last 102 years, since the now iconic pandemic outbreak of 1918. 

Globally, there are currently 48.1 million cases of COVID-19 and the virus accounts for over 1.2 million deaths. 

“In the United States, we have been hit the hardest of any other country, with close to 10 million cases and over 230,000 deaths,” said Dr. FauciOn Nov. 4 the U.S. hit a new high with 100,000 cases in a single day. 

After much of Europe shut down, cases dropped and returned to a relatively low baseline. After the U.S. shut down, cases dropped, but never returned to a low baseline. Cases in the U.S. spiked after reopening, dropped again and now are steadily climbing. European cases have steadily climbed since reopening. Dr. Fauci pointed to significant differences in the degree to which the U.S. shut down compared to Europe.  

“The fundamentals to preventing the acquisition and transmission of SARS-CoV-2 are five-foldUniversal wearing of masks; maintain physical distance of at least 6 feet; avoid crowds; outdoors is better than indoors; frequent handwashing,” said Dr. Fauci. 

“If those five public health measures were adhered to universally and consistently over the country, it is clear from our previous experience with other nations and even regions in our own country that we would not have the degree of surging of cases that we are currently seeing,” said Dr. Fauci. 

Dr. Fauci expects a vaccine to be available within months. “The United States government has made major investments in the development of and facilitation of testing six [vaccine] candidates among the 11 [vaccine] candidates that are being tested worldwide,” he said. Five are in phase 3 trial, including two trials that are well advancedHe is cautiously optimistic that we will have a safe and effective vaccine by the end of this calendar year that we may be able to deploy early on in individuals with a high risk level,” he said, “That we will be able to give doses of vaccines beginning in 2021 and into the first few months of 2021.”BRYAN VARGO 

Biologics Then and Now
Gerd Burmester, MD, a professor of medicine in the Department of Rheumatology and Clinical Immunology at the Charité University Hospital in Berlin, discussed the evolution of biologics, beginning with the development of diphtheria antitoxin more than a century ago. This antibody therapy opened the door for the monoclonal antibodies used to treat rheumatoid arthritis (RA) and other autoimmune diseases today. 

Dr. Burmester also explained the stories behind individual biologics. The earliest, like infliximab, use a combination of mouse and human proteins. Later drugs, such as adalimumab (Humira), are fully human. Arthritis drug targets are changing, too, from tumor necrosis factor (TNF) to interleukin-6 (IL-6) and IL-17. Some, including the IL-6 inhibitor sarilumab (Kevzara) are being tested for use in COVID-19 patients. A staunch advocate of tried-and-true biologics, he thinks they should be used before newer oral drugs like janus kinase inhibitors. 

Although Dr. Burmester sees great progress in treating autoimmune disease with biologics, he is surprised that biosimilars haven’t made more inroads in the U.S. Biosimilars are FDA-approved drugs that are similar to already-approved biologics. They are widely used throughout Europe, where they have lowered treatment costs. As biosimilars gain even greater acceptance, costs are expected to come down even more. 

So far, 14 biologics have been approved in the U.S. for inflammatory disease, but only three biosimilars are available for doctors to prescribe. The rest tied up in courts with pharmaceutical company patent challenges and legal settlementsThose biosimilars that are on the market in the U.S. have had an unexpectedly lukewarm reception from both providers and patients, he said. Dr. Burmester stressed that wider acceptance of biosimilars could lower drug costs and help more patients receive treatment. LINDA RATH 

Men Need Osteoporosis Screening
While screening and treatment of osteoporosis in women as they age is common and widely accepted, it’s a harder battle for men  even after they’ve experienced a bone fracture due to osteoporosis, said rheumatologist Jeffrey Curtis, MD, professor of medicine at the University of Alabama in Birmingham. Approximately a quarter of patients who experience these fractures are men, and evidence suggests they experience worse outcomes. Fractures also can contribute to worsening comorbid conditions. 

 Dr. Curtis and colleagues studied men age 65 and older who had a “fragility fracture.” Of the 9,876 patients, fewer than 6% had been tested for bone mineral density in the two years before the fracture, although 63% had a history of musculoskeletal pan and 48% had used opioids (which increases the risk) in the year prior. About 93% had no osteoporosis diagnosis or treatment before the fracture, 2.8% were diagnosed but not treated, 2.3% were treated but not diagnosed, and only 2.1% were diagnosed and treated. 

“Men are being largely ignored for osteoporosis in the U.S.,”  Dr. Jeffrey Curtis. 

“There is a high level of underdiagnosis and undertreatment of osteoporosis, even in the most at-risk groups of men with comorbid conditions associated with falls.” 

A significant barrier is that policies and guidelines for screening for women don’t exist for men, and insurance companies don’t cover screening for men as they do for women – and may not reimburse the high costs of DXA scans (used to measure bone mineral density).  

“Clinicians aren’t recognizing them and screening them appropriately. They’re hardly being treated even if they break bones,” Dr. Curtis said. “Because osteoporosis is silent and people generally don’t have symptoms in the absence of a fracture, patients aren’t coming into doctors’ offices asking to be tested. 

“Even if they break bones, they may not know enough to ask how to prevent the next fracture,” he adds. “From the patient’s perspective, they may feel like the orthopedic surgeon did a great job repairing the broken bone, but nobody’s mentioning that, ‘Hey, there are medications that might help you avoid a future fracture.’”—JILL TYRER 

Methotrexate for Osteoarthritis
Inflammation plays a critical role in osteoarthritis (OA) symptoms, but there aren’t any medications that specifically target OA-related inflammation. While guidelines don’t recommend the use of methotrexate (a drug commonly used to treat inflammatory forms of arthritis) for OA, there seems to be some evidence for its use, said Biswadip Ghosh, MD, associate professor of rheumatology at the Institute of Post-Graduate Medical Education and Research in Kolkata, India.  

To find out if methotrexate would relieve knee OA, he and his colleagues identified patients with knee OA and tested them to see if they had elevated CRP or ESR, markers of inflammation. (They also screened the patients to make sure they did not have inflammatory forms of arthritis.)  

Of the patients who completed the study, 59 who had only local inflammation (no elevated CRP or ESR) received glucosamine as placebo, and 78 who had elevated markers of inflammation received methotrexate. At the end of three months, the methotrexate group showed statistically significant improvements not only in markers of inflammation but also in symptoms, including pain, stiffness and function, while the placebo group showed no significant improvement. 

Dr. Ghosh concluded that methotrexate may be a treatment option for knee OA patients with inflammation, especially those who have not gotten adequate response from other anti-inflammatory therapies. 

Do Steroid Shots Worsen OA?
A study last year that received a lot of attention found that corticosteroid (steroid) injections into joints can hasten joint damage by three-fold, raising alarms among doctors as well as patients. But while the authors accounted for a number of factors associated with worsening osteoarthritis (OA), one limitation of the study was that they did not compare steroid injections with a different type of joint injection – hyaluronic acid, or viscosupplementation – which is not associated with cartilage loss, said Justin Bucci, MD, an assistant professor of medicine at Boston University. 

To determine whether corticosteroid injections are associated with increased knee OA progression, he and his colleagues looked at data from two studies of knee OA patients who had received steroid or hyaluronic acid injections. Comparing X-rays from before the first reported injection and from the time of knee replacement, they looked at deterioration rates in 647 knees receiving steroid injection and 145 receiving hyaluronic acid. Results showed similar rates of OA progression between the two groups. 

Dr. Bucci concludes that the increased OA damage in the previous study was not from the corticosteroid injections but from more severe OA in those receiving injections of either kind. 

While more research is needed to confirm the results and get more information about the different injections, he said, “I think we can provide some reassurance to patients and clinicians treating OA that corticosteroid injections are not causing the OA to get worse. Patients with moderate to severe OA that is not responding to conservative measures should still be offered cortisone injections.”—JILL TYRER 

 Promoting Physical Activity and its Benefits
Patricia Katz, PhD, professor of medicine and health policy at University of California San Francisco, shared her insights and 25 years of rheumatology research experience on the statistically significant evidence on the effects of physical activity on arthritis.  

“The good news is we know exercise is recognized as safe and recommended for people with rheumatic and musculoskeletal diseases for quite some time,” says Katz. She cited a landmark study from 1989 by Marian Minor, PhD, that showed aerobic exercise reduced the number of tender joints and significantly improved functioning in people with arthritis, thus establishing exercise as both safe and helpful for arthritis patients. (Minor received the Arthritis Foundation’s Humanitarian of the Year award in 2000. 

In more recent study on high intensity interval training for patients with rheumatoid arthritis (RA), “They reported some pretty impressive results, with significant decreases in disease activity and swollen joints and they also reported improvements in physical function,” said Katz. 

She detailed the impact that physical activity can have on symptoms from reducing pain and fatigue to improving depression symptoms and cognitive function. She also discussed potential barriers to physical activity for people with rheumatic conditions, emphasizing a lack of education. 

“The most important reason people with rheumatic diseases are not exercising is they’re not getting the message that physical activity is a good thing for them, that it’s beneficial for their disease,” said Katz. “They’re not getting that message from their physicians or other health care providers.” —BRYAN D. VARGO 

Tapering Methotrexate in Remission
Patients with chronic conditions get tired of having to take a lot of medications for a long time, not only for the side effects and hassle, but also for the expense. Medication burden can lead some to stop taking them as prescribed, which can put their health at risk.  

Although guidelines for managing RA recommend tapering medications if possible, it isn’t clear how to go about that. So, in a recent study, rheumatologist Jeffrey Curtis, MD, professor of medicine in the Division of Clinical Immunology and Rheumatology at the University of Alabama at Birmingham, took a look at RA patients who were in remission while taking the biologic medication etanercept and methotrexate to find out if they could safely reduce or eliminate one or the other drug. 

People were determined to be in remission if both they and their physicians agreed that their disease was well controlled for at least six months – that they had few swollen or tender joints, that they were doing well overall, and that their C-reactive protein (CRP, a marker of inflammation) levels were low. The researchers randomized 253 of these patients to receive either etanercept alone, methotrexate alone or to continue the combination. Ninety percent completed the study. 

While similar proportions of the participants on etanercept alone and on combination therapy maintained remission – 49.5% and 52.9%, respectively – those on etanercept did not fare as well, with only 28.7% maintaining remission. Furthermore, those who failed remission on methotrexate did so sooner, about three to six months, than those on etanercept alone, about six months. Those who received “rescue therapy” were able to achieve remission again by the end of the year-long study. 

“The implication here is that probably if you’re doing that well on both treatments, you can continue etanercept, stop methotrexate, and the majority of those people are going to do just as well,” Dr. Curtis said. “As a clinician, the risk to try this is quite low because the likelihood that you can regain where you were before is quite good.”—JILL TYRER 

More Evidence for Gout Guidelines
Gout is a painful form of inflammatory arthritis affecting more than 8 million Americans, and it’s a condition that doctors in different specialties treat – but not all in the same ways. Gout occurs when uric acid levels build up in the blood, which can form needle-like crystals in joints – often a big toe – leading to acute pain and swelling. Patients often end up in the emergency room with a gout flare, and then to their primary care doctor rather than to a rheumatologist – and their treatment guidelines differ.  

The ACR (which updated its treatment guideline earlier this year) recommends long-term treatment with a urate-lowering drug, such as allopurinol, and treating to target, which means adjusting medication levels until the patient reaches a target level of uric acid in the blood. But other medical professional organizations, such as the American College of Physicians, disagree with the treat-to-target approach or that urate-lowering drugs should be used long-term, citing insufficient evidence. 

Robert Terkeltaub, MD, professor of medicine at the University of California, San Diego, chief of rheumatology at the VA Medical Center in San Diego and a leading gout expert, sought to bring more evidence to the table in a session Saturday. Citing several studies published in recent years, he presented evidence that urate-lowering therapy reduces gout flares and inflammation in the joint; that allopurinol and colchicine (another common gout medication) reduces urate levels as well as flares (compared to standard treatment from primary care); and that treat to target improves crystal deposits and limits joint erosion.  

Questions remain about how to treat gout in patients with comorbid conditions, such as cardiovascular or kidney disease. But evidence shows that ACR’s guidelines on urate-lowering therapy are sound and newer trial data support them for “clinically meaningful gout outcomes, he said. JILL TYRER 

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