Day three of theAmerican College of Rheumatology’s annual meetingSaturdaycontinued with sessions onbiologics, osteoarthritis treatments, osteoporosis and more,a highlight was a lecture on COVID-19byAnthonyFauci, 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.AnthonyFaucion COVID-19Background and Current Status
Dr.Faucioutlined thebackgroundand addressed the public health and scientific challenges of SARS-CoV-2, the novel coronavirusthat causesCOVID-19, and thepandemic in the U.S and around the world.Here aresomehighlights 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.”
全球目前有4810万例COVID-19病例，该病毒造成120多万人死亡。
“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.Fauci.OnNov. 4the U.S. hit a new highwith100,000 cases in a single day.
在欧洲大部分地区关闭后，病例下降并回到相对较低的基线。美国政府关闭后，病例有所下降，但从未回到低基线水平。Cases in the U.S. spiked after reopening, droppedagainand now are steadily climbing. European cases have steadily climbed since reopening. Dr.Faucipointed tosignificant 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-fold:Universal wearing of masks; maintain physical distanceofat 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 regionsin our own country that we would not have the degree of surging of cases that we are currently seeing,” said Dr.Fauci.
Dr.Fauciexpects 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,”hesaid. Five are in phase 3 trial, including two trials that are well advanced.He 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
GerdBurmester, MD, a professor of medicine in theDepartment of Rheumatology and Clinical Immunology at theCharitéUniversity 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还解释了个别生物背后的故事。最早的类似英夫利昔单抗，使用的是小鼠和人类蛋白质的结合。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 inhibitorsarilumab(Kevzara) are being tested for use in COVID-19patients. A staunch advocate of tried-and-true biologics, he thinks they should be used before newer oral drugs likejanuskinase inhibitors.
Although Dr.Burmestersees great progress in treating autoimmune disease with biologics, he is surprised that biosimilarshaven’tmade 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 threebiosimilarsare available for doctors to prescribe. The rest tied up in courtswith pharmaceutical companypatent challenges and legal settlements.Thosebiosimilarsthat are onthe marketin the U.S. havehad an unexpectedly lukewarm reception from both providers and patients, he said. Dr.Burmesterstressed 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.JeffreyCurtis.
“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 andguidelines对女性的筛查并不适用于男性，保险公司不像对女性那样为男性筛查提供保险——而且可能不会报销DXA扫描(用于测量骨密度)的高额费用。
“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 generallydon’thave symptoms in the absence of a fracture, patients aren’t coming into doctors’ offices asking to be tested.
他补充说:“即使他们骨折了，他们可能也不知道如何防止下一次骨折。”“从患者的角度来看，他们可能会觉得骨科医生修复骨折的工作做得很好，但没有人会提到，‘嘿，有些药物可能会帮助你避免未来的骨折。’”—JILL TYRER
Methotrexate for Osteoarthritis
Inflammation plays a critical role in osteoarthritis (OA) symptoms, but therearen’tany 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, saidBiswadipGhosh,MD,associate professor ofrheumatology at theInstitute 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,stiffnessand 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 otheranti-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, orviscosupplementation– 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 damagein the previous studywas 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.
卡茨说:“好消息是，我们知道运动在相当一段时间内被认为是安全的，并被推荐给患有风湿病和肌肉骨骼疾病的人。”She cited a landmark study from 1989 by Marian Minor, PhD, that showed aerobic exercise reduced the number oftenderjoints 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.)
Inamore 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.
Shedetailed the impactthatphysical activity can have on symptoms fromreducing pain and fatigue toimproving depression symptoms and cognitive function.She alsodiscussed potential barriers to physical activity for people with rheumatic conditions, emphasizinga 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, itisn’tclear 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 theyand 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, andit’sa 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 meansadjusting 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.
RobertTerkeltaub, 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