University of Colorado wins the ACR Knowledge Bowl

The University of Colorado upset last year’s winning team from Ochsner Medical Center to take the 2012 ACR Knowledge Bowl on Monday. The University of Michigan team finished third.

“You get the Knowledge Bowl trophy with your names engraved,” said competition moderator Zsuzsanna McMahan, MD, MHS, Assistant Professor of Medicine at Johns Hopkins University. “And you get eternal bragging rights!”

Based on the ever-popular television game show Jeopardy!, the Knowledge Bowl pitted six teams of two fellows and an attending against each other in a test of knowledge, trivia, and quick reflexes. The winners of Sunday’s qualifying rounds, “Know Bones About It” from the University of Colorado and “Growing Rheum” from the University of Minnesota, met the 2011 champion, “New Orleans Mardi Gras” from Ochsner Medical Center. The final showdown featured four rounds and a win-or-lose final question.

The first round ended with Colorado in a strong lead with 2,400 points to 1,600 for Minnesota and 1,300 for Ochsner. Round two featured several incorrect answers by all three teams that left Ochsner in the lead with 1,800 points, followed by Minnesota with 1,600 and Colorado with 1,300.

The scores began to separate in the third round. Colorado pulled ahead with 5,000 points to 4,400 for Ochsner and 2,000 for Minnesota. By the end of the fourth and final round, Colorado held a commanding lead with 10,400. Ochsner was in second place with 7,200 and Minnesota trailed at 3,800.

All three teams knew the correct question for the final-round clue: “Injury to THIS cranial nerve produces the characteristic phenotype features in Cogan’s Syndrome.” (“What is the 8th cranial (audiovestibular) nerve?”)

The Growing Rheum team wagered all 3,800 points to bring their final score to 7,800. The New Orleans Mardi Gras put 4,000 of their 7,200 points on the line to end the round with 11,200 points. And Know Bones About It risked 4,500 of their 10,400 points to finish with 14,900.

The ACR Knowledge Bowl will be back next year, Dr. McMahan promised, bigger and better than ever. Any medical school in the world with fellows and attendings in rheumatology is welcome to enter. See you in San Diego!

 

New tools facilitate use of disease activity measures

Defining targets to achieve in the management of rheumatoid arthritis can result in superior outcomes. So why don’t all rheumatologists use the tools available to measure disease activity?

That question, along with how to best use the new tools available from the ACR, will be addressed by several experts Wednesday during the ACR Clinical Symposium Rheumatoid Arthritis – Treating to Target: How to Incorporate Rheumatoid Arthritis Disease Activity Measures into Routine Practice. The session will be held from 11:00 am – 12:30 pm in Hall E of the convention center.

James R. O’Dell, MD, Professor of Internal Medicine in the Division of Rheumatology at the University of Nebraska Medical Center, will begin the session by explaining “why the time has come for all rheumatologists to routinely measure rheumatoid arthritis disease activity in their practices.”

“Clinicians have long treated diabetes, hypertension, and elevated cholesterol to specific targets with great success,” Dr. O’Dell said. “It is gratifying that we now have similar approaches in RA. Patients with rheumatoid arthritis clearly have better outcomes if their disease is treated to a goal or target.”

Kaleb Michaud, PhD, will then describe “which rheumatoid arthritis disease activity measures to use in practice and why.” Dr. Michaud is Co-Director of the National Data Bank for Rheumatic Diseases and Assistant Professor of Rheumatology & Immunology at the University of Nebraska Medical Center.

“There are over 50 different measures for documenting disease activity in patients with rheumatoid arthritis. I’ll be covering the top 10 of these, and will provide the pros and cons of each for use in the clinic,” Dr. Michaud said.

Charles M. King II, MD, who practices at North Mississippi Medical Center, will then provide tips for integrating these measures into practice. Some measures, such as the disease activity score and the simplified disease activity index, require laboratory values that may not be available at the point of care. Others require either swollen or tender joint counts, or both. And still others are patient-centered and require no physician input. Once the preferred DAM is chosen, it is important to integrate it into the EHR in a seamless way.

Dr. King also said it is important for physicians to build patient buy-in and engagement by reviewing the flowsheet with them to keep them informed about clinical decision making.

Salahuddin Kazi, MD, Associate Professor of Internal Medicine at UT Southwestern Medical Center, agreed that establishing goals that are visible to both the patient and provider enables a better likelihood of achieving those goals, especially if there is a very structured process involved. Dr. Kazi will present “Using the ACR Rheumatology Clinical Registry to Document Rheumatoid Arthritis Disease Activity.”

“The underlying principle is that if you have a particular target and you treat it to the target, you will find improving outcomes for all patients,” Dr. Kazi said. “We’ve seen this in other conditions like high blood pressure and diabetes.”

Dr. Kazi suggested using the Rheumatology Clinical Registry, which has a tool to identify the target and record patient progress, which can then be shared with the patient. The tool provides a snapshot of an individual patient that allows the provider to monitor the patient over time, making it obvious if they are approaching or receding from their target. Furthermore, if enough patients are in the database, population management tools will identify outliers.

The RCR provides individual patient control, longitudinal patient control, population control, and benchmarking. “You would think that every EHR would have this, and they have it for diabetes and high blood pressure, but because rheumatology is in essence a less prevalent specialty and RA affects just about one percent of the population, it has become necessary for the ACR to build these tools for their membership,” Dr. Kazi said.

 

Distinguished Lecturer urges rheumatologists to help patients discover their ‘go-gene’

We are caught in an epidemic of sitting and the only way to combat it is with increased activity, according to Basia Belza, PhD, RN, FAAN, this year’s Distinguished Lecturer.

“Sitting is killing us,” said Dr. Belza, Professor at the School of Nursing and Adjunct Professor in the School of Public Health at the University of Washington. “We have engineered physical activity out of our daily lives. The devices that make our lives easier have eliminated physical activity and endanger us.”

Dr. Belza discussed the sitting epidemic and strategies to combat inactivity Monday during her lecture, “Unraveling the ‘Go-Gene.’” Simply sitting down cuts off electrical activity in the leg muscles, reduces energy expenditures to one calorie per minute, and reduces fat reductase enzyme product by 90 percent, she said.

After two hours of sitting, HDL cholesterol levels drop by 20 percent. After 24 hours, insulin drops 24 percent and the risk of diabetes rises. People with sitting jobs have twice the rate of cardiovascular disease compared to people with standing jobs, Dr. Belza said.

Sitting on the job is inevitable for many, she admitted. But she said 30 minutes of daily physical activity is not enough to counteract the negative impact of sitting for several hours at a stretch. She advised breaking up sitting with standing and walking at more frequent intervals. One simple strategy: stand up when talking on the telephone. Another easy step: drink more water during the day to stimulate more frequent walks to the restroom.

The need for increased activity is even more important for those with rheumatic diseases, she said. One of the most effective ways to reduce both pain and fatigue is to increase physical activity. One hour of physical activity three times a week reduces the pain and disability of arthritis by 47 percent, reduces the progression of diabetes by 58 percent, reduces hip fracture by 41 percent, and reduces the symptoms of depression by 30 percent, Dr. Belza said.

In older adults, regular physical activity reduces the risk of falls, reduces the risk of Alzheimer’s, and improves quality of life and well-being, she said. The challenge is ending sedentary habits to get people moving.

Dr. Belza started her personal journey to physical activity by way of fatigue. She began working with RA patients in the 1980s and discovered that there was no uniform tool that allowed clinicians to measure and evaluate fatigue. There were standard measures for pain, stiffness, and function, but not for fatigue.

“There was a gap between what our patients were reporting and our measurement instruments,” she said.

Dr. Belza created the Multidimensional Assessment of Fatigue, or MAF. The self-administered tool includes 16 items across four dimensions: severity, distress, degree of interference, and timing. The tool has been validated in RA, AS, lupus, and fibromyalgia, as well as cancer, HIV, post-partum women, Parkinson’s, and multiple sclerosis. The instrument has been translated into 25 languages and is used around the globe to assess the subjective effect and impact of fatigue.

Working with the MAF led to the realization that people with greater levels of physical activity tend to have less pain and fatigue compared to others with similar conditions who move less, Dr. Belza said. That led to her exploration of activity to combat fatigue.

“We all have what I call our ‘go-gene,’ those characteristics that motivate us to get up and go,” she explained. “As providers, we have to help our patients understand their go-gene, the things that motivate them and keep them moving.”

But getting people to increase their physical activity takes more than just motivation, she continued. People do not live or act in a vacuum. They are part of a larger social ecology that influences their beliefs and behaviors.

One way to boost physical activity is to provide opportunity and support. Evidence suggests that providers should focus on a single goal – physical activity – rather than dissipate their efforts across multiple targets such as activity, medication adherence, diet, and other goals at the same time, Dr. Belza said.

Behavioral strategies are the most effective, using tools such as contracts, rewards, feedback, goal-setting, and monitoring. And self-monitoring brings greater success than outside monitoring, she said.

Making activity easy and accessible is also important. A pilot project with 100 YMCA facilities offering the EnhancedFitness program for seniors has been wildly successful, Dr. Belza said. Seniors in the program showed improved social and physical function and their healthcare costs increased 50 percent less compared to nonparticipants. YMCA is rolling the program out to all of its 2,600 facilities nationally.

“Activity maintains our ability to live independently,” Dr. Belza said. “It is never too late to become physically active.”

Session will update attendees on current and pending compliance risks

ACR Clinical Symposium

Top 10 Compliance Risks Facing Physicians

11:00 am – 12:30 pm Tuesday

Room 202 B, WCC

A major part of any physician’s practice is the area of compliance. With a list of new regulations and initiatives by the Department of Health & Human Services, Office of Inspector General, and the Centers for Medicare and Medicaid Services, compliance is no longer an option. The birth and expansion of the Recovery Audit Contactor program and the proliferation of audits by Zone Program Integrity Contractors mandate an urgency and awareness among health care providers that regulatory compliance is essential.

To offer attendees the latest updates on the most significant issues facing physicians, nationally recognized compliance expert Robert W. Liles, JD, from Liles Parker, Attorneys & Counselors at Law, will present Top 10 Compliance Risks Facing Physicians from 11:00 am – 12:30 pm Tuesday in Room 202 B of the convention center. Here’s a summary of Liles’ Top 10 risks:

 Risk 1: ZPIC Administrative Actions are Expanding

“Over the last year, we have seen a proliferation of aggressive ZPIC enforcement actions, many of which represent a greater threat to providers than a mere overpayment demand,” Liles said. These actions have included unannounced site visits leading to probe sample and larger, statistically relevant sample audits, as well as an increase in prepayment reviews and the imposition of extrapolated damages.

Risk 2: Increased Risk of Criminal Referral, Suspension and Revocation

Among the most common infractions that Liles has seen prosecuted include the falsification of patient records, receiving and/or giving referral kickbacks, and employing clinical staff with “phony” credentials and licenses. “The number of revocation actions recommended by contractors, for example, has significantly increased over the past 12 months,” Liles said. “Particular issues of concern include failure to properly notify CMS and/or the appropriate Medicare contractor of changes in address and failure to cooperate during a site visit.”

 Risk 3: New Risks Facing Providers: Cloud Computing/Social Media

When it comes to both personal and professional use of the Internet and web-based tools, Liles reminds physicians to be cautious as to the amount and type of information they share. Cloud computing, for example, offers attractive benefits, such as convenience and cost savings. However, Liles warns that operating in a “cloud environment” could potentially jeopardize the security of protected health information.

 Risk 4: Recent HIPAA Breach Targets of the Office of Civil Rights

“Physician practices are under considerable scrutiny for HIPAA and HITECH privacy violations, and the number of criminal cases resulting from a privacy breach is increasing each year,” Liles said. “Millions of individuals’ information has been wrongfully disclosed, and approximately three-quarters of those breaches involved electronic records.”

The major areas of concern include information that is stored or exchanged as part of overseas outsourcing or through the use of unencrypted laptops, flash drives, cell phones, or breaches in cloud computing environments, he added.

 Risk 5: Increased Collection and Investigative Actions by Private Payor SIUs

It’s rare to find a case where only Medicare was adversely affected by a provider’s improper billing practices,” Liles said. “When the government files a case, the information becomes public and can readily be shared with the private payors’ special investigation units. The private payors are riding in the wake of the government’s case so to speak.”

 Risk 6: Significant Penalties for Failure to Screen

With the expansion of the permissive exclusion authorities, more and more individuals will ultimately be excluded from Medicare, said Liles, who advises physicians to screen all employees against the Office of the Inspector General and General Services Administration databases, both at hire and regularly thereafter.

Risk 7: Expansion of Medicaid Investigations and Audits

“Under the Affordable Care Act, every state was required to establish a new Medicaid Recovery Audit Contractor program,” Liles said. “While these programs are still in various stages of moving forward, Medicaid providers should take care to ensure that all Medicaid billings are appropriately handled.”

 Risk 8: Use and Compensation of Marketing Personnel

With regard to marketing staff, Liles said to be cautious in how they are compensated, making certain that they are not improperly incentivized to bring in patients and/or referrals for business covered by Medicare or another federal health benefits program. “Keep in mind that marketing practices which may be perfectly legal in any other industry may be illegal in healthcare,” he said.

 Risk 9: Gifts and other Forms of Remuneration

A continuing area of concern, according to Liles, is the giving of gifts and other items of value to referral sources. “Improper inducements can take many forms, and physicians and other providers must avoid even the appearance of giving anything of value to a referral source,” he said.

 Risk 10: Expansion of False Claims Act Cases Around the Country

Both the federal and state governments are recovering enormous funds as a result of whistleblower cases and government-initiated cases filed under the federal or state False Claims Act, Liles said. “Now more than ever before, it’s very important that you carefully review your compliance plan and make sure that any and all risks are carefully assessed as part of your ongoing efforts to remain compliant with all applicable laws and regulations,” he said.

FDA panel will describe abbreviated licensure pathway for biosimilars

During an ACR Clinical Symposium on Wednesday, a group of speakers from the Food and Drug Administration will describe an abbreviated licensure pathway for biological products that are demonstrated to be biosimilar to, or interchangeable with, an FDA-licensed biologic drug.

The session, titled Biosimilars Development: Food and Drug Administration Perspective, will take place from 9:00 – 10:30 am in Ballroom C at the Washington Convention Center.

This issue of biosimilars is important to the rheumatology community because of the increasing use of biologics in the therapy of rheumatic diseases, especially rheumatoid arthritis. The abbreviated licensure pathway for biosimilars was established by the Biologics Price Competition and Innovation Act of 2009.

“Although conceptually similar to the abbreviated approval pathways established for drug products under the Federal Food, Drug, and Cosmetic Act — that is, the generic drug pathway — the implementation of the biosimilars pathway will likely entail novel challenges due to the larger and typically more complex structure of biological products,” said Nikolay P. Nikolov, MD, Clinical Reviewer in the Division of Pulmonary Allergy and Rheumatology Products at the FDA’s Center for Drug Evaluation and Research.

Dr. Nikolov will discuss clinical considerations in the development of biosimilars during Wednesday’s symposium. Leah Christl, PhD, Associate Director for Biosimilars in the FDA’s Office of New Drugs, will describe the regulatory framework of biosimilars development, and Marjorie Shapiro, PhD, Chief of the FDA’s Laboratory of Molecular and Developmental Immunology in the Division of Monoclonal Antibodies, will discuss the role of analytics in biosimilars development.

A panel discussion with questions from the audience will follow the speaker presentations. The speakers and the panel will also discuss the use of a step-wise approach for biosimilar product development programs.

“Each step is designed to evaluate the extent to which there is residual uncertainty regarding the demonstration of biosimilarity between the proposed biosimilar drug and the reference product, and to identify the next steps to address that uncertainty,” Dr. Nikolov said.

Biologics have revolutionized the treatment of RA, although access to these drugs may be limited due to their relatively high cost. The abbreviated licensure pathway established by the BPCI Act is expected to facilitate the development of biosimilar biologic drugs and provide additional treatment options.

According to the act, biosimilarity means that “the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components,” and that “there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.”

“It is important for rheumatologists to understand the scientific considerations that underpin the development of biosimilars so they can make informed decisions on the potential use of biosimilars in their clinical practice,” Dr. Nikolov said.

Biosimilar development involves extensive structural and functional characterization (that is, analytics) that demonstrates the biological product is highly similar to its reference product. The FDA uses animal data and human clinical data to address residual uncertainty about the impact of any observed analytical differences.

In addition to Drs. Christl and Shapiro, the panel discussion will include Badrul Chowdhury, MD, PhD, Director of the Division of Pulmonary Allergy and Rheumatology Products at the FDA Center for Drug Evaluation and Research, and Sarah K. Yim, MD, Associate Director of the Division of Pulmonary Allergy and Rheumatology Products at the same facility.

Microchimerism alters the concept of ‘self’

Recent advances delineating immunologic changes that occur during normal pregnancy, as well as observations indicating the impact of pregnancy on disease activity and/or risk of some autoimmune diseases, have created an opportunity to examine the potential for a number of new therapeutic approaches for autoimmune disease.

Wednesday’s ACR Basic Science Symposium, Immunology of Pregnancy and Impact on Autoimmune Pathogenesis, will examine the immediate effects and the long-term consequences of pregnancy on the immune system. The symposium begins at 7:30 am in Ballroom A of the convention center.

“Conceptually, it would be useful for us to reconsider what is defined as ‘self’ because pregnancy normally creates a legacy of immigrants that isn’t limited just to circulating cells, but also includes differentiated specific cell types in tissues,” said J. Lee Nelson, MD, Professor of Medicine at the University of Washington and editor of the bioscience journal Chimerism.

Initial microchimerism studies evaluated diseases where an adverse role was hypothesized; however, the potential for benefit has also been apparent, even in autoimmunity. Microchimerism refers to the harboring of a small number of cells, or DNA, that originated in a different individual, a phenomenon that occurs naturally between mother and child.

“A number of factors are thought to contribute to maternal-fetal tolerance during pregnancy,” Dr. Nelson said. “The placenta does not express classical HLA-A, -B, or -DR molecules. Instead, it expresses HLA molecules with limited polymorphism, especially HLA-G.”

Fetus-to-mother transfer is detectable as early as four weeks of gestation, and the amount of fetal material in the maternal circulation increases as gestation progresses, Dr. Nelson explained. While most of the fetal material in the maternal circulation is cell-free DNA, some fetal cells also reach the mother.

“A small number of cells of fetal origin persist in the mother many years later,” she said. “Similarly, some maternal cells are transferred to the fetus and create long-term maternal microchimerism that can be found decades later.”

For women who have an autoimmune disease and become pregnant, disease activity can be affected. Most women with rheumatoid arthritis experience pregnancy-induced amelioration of their arthritis. Similarly, multiple sclerosis usually improves during pregnancy. However, this beneficial effect of pregnancy does not occur with most other autoimmune diseases, such as myasthenia gravis, idiopathic thrombocytopenic purpura, or autoimmune hemolytic anemia.

“In earlier studies we found that fetal-maternal HLA disparity was associated with RA improvement during pregnancy,” Dr. Nelson said. “In subsequent studies we found that higher levels of fetal microchimerism correlated with improvement during pregnancy and decreased levels with relapse postpartum.”

The health of the fetus can also be affected by immunologic events during pregnancy. Neonatal lupus is an example of passively acquired autoimmunity. While the mother sometimes has systemic lupus, often the mother is asymptomatic but has autoantibodies to SSA and SSB antigens. However, the fetus can develop a number of disease manifestations, the most serious of which is congenital heart block, Dr. Nelson said.

An increasingly researched area is the long-term consequences of pregnancy and maternal-fetal cellular exchange. The risk of developing RA, for example, is reduced in women who have given birth. “Interestingly, the benefit attenuates with elapsing time after delivery and is no longer significant 15 years after the birth,” Dr. Nelson said.

Conversely, it is also possible that microchimerism could be acquired with RA-risk associated HLA alleles. Studies of women who lack HLA alleles that are RA risk-associated have shown a significant increase of microchimerism with RA risk-associated HLA alleles compared to healthy women.

“Because maternal-fetal exchange is bidirectional, maternal microchimerism could similarly be acquired during fetal life,” Dr. Nelson said. “Thus the legacy of maternal-fetal exchange could result in a kind of ‘mini gene transfer.’”

Systemic sclerosis has striking clinical similarities to graft-versus-host disease that occurs as a complication of hematopoietic cell transplantation, and thus is a known condition of chimerism. A number of studies, although not all, have found increased levels of microchimerism of fetal origin in SSc patients.

“Although there are also differences, similarities include the hallmark feature of indurated skin, sicca syndrome, gastrointestinal and pulmonary involvement, and sometimes myositis,” Dr. Nelson said. “SSc can also overlap with primary biliary cirrhosis, which appears similar to graft-versus-host disease of the liver.”

Management of back pain becomes more complex with age

The Institute of Medicine, along with several key publications, recently highlighted the critical importance of assessing and treating back pain in older adults. It’s a common, costly, disabling, yet under-addressed condition in this population.

“Most of what we know about back pain is based on research on younger individuals, and I would argue that it is not appropriate to assume that what works for younger individuals will be equally effective or safe in older individuals,” said Una E. Makris, MD, Assistant Professor of Internal Medicine, Division of Rheumatic Diseases at UT Southwestern Medical Center.

Dr. Makris and a panel of experts will address the diagnostic and treatment challenges in this population during an ACR Clinical Symposium on Tuesday titled Approach and Management of Back Pain in Older Adults, which will be held from 2:30 – 4:00 pm in Hall E of the convention center.

Dr. Makris’ research focuses on back pain in older patients, yet she said that despite the high prevalence, cost, and morbidity attributed to back pain, it remains both under-assessed and under-treated in older adults.

“We have limited evidence to support our decisions on older persons, mostly because older persons with multiple comorbidities and polypharmacy are often excluded from randomized clinical trials,” she said.

David G. Borenstein, MD, Clinical Professor of Medicine at George Washington University Medical Center and a partner at Arthritis & Rheumatism Associates in Washington, D.C., will discuss the fundamental differences between younger and older adults and how the clinician’s management approach should differ. “This problem is truly a continuum dealing with different components of the musculoskeletal system,” Dr. Borenstein said.

In younger individuals, the most common problems are associated with muscular strains and disc problems, such as disc protrusions or herniations – conditions often resolved spontaneously without the need for surgery, Dr. Borenstein noted.

“As one grows older, we start to have changes which don’t necessarily fully go away,” he said. “When older individuals start having osteoarthritis in the lumbar spine, they can have episodes that last longer and longer, and at some point they may have difficulties that cause them to have joint pain in the back that is quite persistent, which will require ongoing therapy.”

Therapy for older individuals, though similar to treatment for younger patients, has more potential side effects, said Dr. Borenstein, noting that older individuals may be more prone to some of the toxicities in the medications.

More difficulties arise in people aged 60 and older who have lumbar spinal stenosis where the problem may be more leg than back pain. When oral drug therapy and injection therapy are ineffective in controlling leg pain, surgery may ultimately be required.

“As individuals age, clinical judgment becomes an increasingly important quality to the interaction,” Dr. Borenstein said. “It is not only the doctor who needs to participate in that, but you need to have the patient understand the pluses and minuses of what is being done so that they truly participate in the decision process.”

A. Jay Khanna, MD, Associate Professor of Orthopaedic Surgery at Johns Hopkins University, will discuss surgical options in his presentation, “Where Does the Pain Come From? A Surgeon’s Perspective on Back Pain in Older Adults.”

“As with patients of any age who have axial low back pain, we like to do whatever we can to avoid surgical intervention,” Dr. Khanna said. “Many studies show that fusion for low back pain only produces good or excellent results in about 60 percent of patients. However, for older patients who may have medical comorbidities and/or osteoporosis, we almost always avoid surgery for the treatment of low back pain only.”

Older patients are more likely than younger patients to show significant stenosis on their MRI or other imaging studies, and are also more likely to have symptoms of neurogenic claudication or radiculopathy with pain or weakness. When these patients fail aggressive, nonoperative management, or if they have a progressive neurological deficit, they can be good candidates for decompression or stabilization procedures, Dr. Khanna said.

“We try our best to avoid large and complex surgical procedures in older patients to avoid the higher rates of morbidity associated with large surgeries,” he said. “If patients have relatively focal symptoms and focal findings on their imaging studies, they may be candidates for minimally invasive spine surgical procedures. These procedures allow us to change the risk profile of a surgical procedure and decrease the overall risk of the surgery, especially those risks related to post-operative medical complications.”

Geneticists gaining new insights into biology of aging

Aging is inseparable from living. And like life itself, aging can be altered, influenced, and possibly slowed.

“There is a basic biologic process of aging,” said Jan Vijg, PhD, Professor and Chair of Genetics at the Albert Einstein College of Medicine. “We know we can intervene in the process. But if we intervene, will we see a significant increase in lifespan? That’s a question we cannot answer. Yet.”

Twenty years ago, aging research was a scientific backwater, Dr. Vijg said Sunday morning during an ACR State-of-the-Art Lecture on Advances in the Biology of Aging. Today, barely a week goes by without at least one aging-related paper in a major medical journal. This increasing interest is due in part to a change in the concept of aging.

Aging was long seen as a complex of inevitable deteriorative changes that predispose to disease and death, Dr. Vijg said. The current concept views aging as the sum of all the changes an organism undergoes from conception to death. This new way of thinking opens the door to examine the processes and pathways that can bring change to an organism, starting at the genetic level.

Aging can be considered a phenotype, Dr. Vijg continued. It can be seen as accumulating genetic instability, growing macromolecular aggregations, increasing cellular apoptosis and senescence, decreasing immune system function, decreasing internal temperature control, degenerating skin, slowing memory and learning function, decreasing vision and hearing, and escalating degenerative diseases.

The phenotypic view treats aging as a disease, which implies the possibility of a cure. This allows medical research to focus on interventions aimed at specific steps in one or more of those pathways. But historically there has been relatively little work into the basic biology of aging.

That changed the in 1980s following the discovery that a pair of mutations to the daf-2 gene that controls part of the insulin-IFG-1 receptor pathway can nearly double lifespan of nematodes, fruit flies, mice, and other organisms. Individual organisms with the altered allele were physically smaller than their wild-type counterparts, but lived considerably longer.

More recently, a genome wide association study of centenarians found similar mutations in the IGF-1 receptor that acts to downregulate IGF signaling. In humans, reduced IGF-1 activity increases cancer and oxidative stress but lowers cardiovascular disease, neural diseases, diabetes, and osteoporosis.

Biologic research reveals life as a stochastic process – a balance of forces and counterforces that is subject to random internal and external influences, Dr. Vijg said. Change happens and natural selection favors change that enhances early survival and reproduction.

The degenerative processes that we call aging are a byproduct of the evolutionary process. There are few evolutionary benefits to long life, particularly long life after the age of reproduction. “Natural selection is only interested in advantages through reproductive age,” Dr. Vijg said. “Anything that happens in old age has no reproductive advantage, so there is no selective pressure against aging.”

Decreasing telomere length and genetic drift appear to be two important contributors to aging, he continued. Human cell cultures proliferate indefinitely until they suddenly begin to slow and cellular senescence sets in. The apparent culprit is telomere length, which decreases slightly with each new generation of daughter cells.

Older cells and cells from older individuals show increasing genetic drift, apparently because DNA repair-mechanisms break down over time, Dr. Vijg explained. Both telomere shortening and DNA repair-breakdown can be altered experimentally in vitro, but the potential side effects are unknown. And because cellular activity represents a balance of positive and negative feedback, there will be side effects.

Balance-counterbalance can be seen in the daf-2 gene mutations that downregulate IGF-1 receptor signaling. The mutation leads to longer life but smaller body size. In the wild, larger individuals tend to survive and reproduce more effectively than smaller competitors, so the mutation would have no competitive advantage.

The same interplay can be seen in TOR signaling. Rapamycin can downregulate TOR signaling in mice at midlife, thereby increasing their lifespan significantly. But mice treated with rapamycin to increase lifespan also have an increased incidence of tetes malformation and cataracts, Dr. Vijg noted.

“When you are looking at aging, you need a rational basis for intervention,” he said. “But you also need watch for side effects from your intervention.”

FDA officials, ACR leaders to provide update on drug safety issues

Timely communication of evolving safety information is a critical element in the ability of practitioners to provide the best care for their patients with rheumatic diseases. Members of the ACR Drug Safety Subcommittee will be joined by representatives from the Food and Drug Administration for a symposium to update attendees on late-breaking and ongoing issues in patient safety, including changes at the FDA that will affect drug safety monitoring and reporting. The symposium will be held from 9:00 – 10:30 am today in Room 207 A of the convention center.

“Safety is dynamic and always changing. It’s extremely important for all of us to keep abreast of developments that may affect the safety of our patients,” said Arthur Kavanaugh, MD, of the University of California, San Diego. Dr. Kavanaugh and Michael Weisman, MD, of Cedars Sinai Medical Center, will serve as co-moderators and will open the symposium with an update on issues and initiatives from the ACR Drug Safety Subcommittee, including a review of the inaugural ACR Drug Safety Summit, held last April.

Fellow subcommittee member John Cush, MD, of Baylor Research Institute, will then discuss the current scientific understanding of cancer risk from biologic therapy and RA. “Cancer is an area of great concern for us, but also an area where there’s a perception that not much is known yet,” Dr. Cush said. “In reality, much is known. We’ve been working with biologics for almost 20 years and they’ve been used in upwards of 4 million people worldwide.”

Dr. Cush said there have been many studies looking at cancer risk, including a large number of clinical trials for RA and other autoimmune conditions. “There have been large, population-based studies, large captured cohorts from insurance claims databases, and large registries that have tracked patients on these drugs and looked at the issue of cancer,” Dr. Cush said. “The bottom line is that much of the cancer risk is that which is imposed by the disease, with rheumatoid arthritis being among the most studied. The idea that there is added risk imposed by the drug is scant; there’s little support for that.”

 

FDA Update

Larissa Lapteva, MD, MHS, and Sally Seymour, MD, of the FDA Division of Pulmonary, Allergy, and Rheumatology Products, will provide an update on current safety issues from the FDA’s perspective. Dr. Lapteva will discuss the clinical development programs for new anti-rheumatic products, focusing on the main findings and issues pertaining to safety and efficacy of these products.

“This will be an opportunity for practicing rheumatologists to hear about the benefits and potential risks of new drugs to aid in choosing treatment options most suitable for their patients,” Dr. Lapteva said. “Presenting information about new drugs improves transparency of drug development and the review process.”

Dr. Seymour will focus her presentation on recent post-marketing safety issues with medications approved for rheumatology indications.

“The purpose of my presentation is to provide practitioners with information on recent safety updates to product labeling for approved products,” Dr. Seymour said. “This is important because product labeling is frequently updated and practitioners may not be aware of new safety information.”

Two teams advance to Knowledge Bowl finals

The games have begun! Two teams emerged from Sunday’s qualifying rounds and advanced to today’s championship round in the 2012 ACR Knowledge Bowl.

The University of Minnesota’s “Growing Rheum” team racked up 1,700 points in the first qualifying round to top the University of Michigan’s “GoBlueAnnArborRheum,” which tallied 900 points. A string of incorrect answers left the University of Vermont’s “Green Mountain Rheum” team a distant third with -900 points.

Results from the second qualifying round were even more lopsided. The University of Colorado’s “Know Bones About It” bounced back from a 900-point deficit to win with a score of 3,100 points. The University of Pittsburgh’s “Steel City Joints” finished second with 1,400 points and Duke University’s “Blue Devils” trailed with 700 points.

The ACR Knowledge Bowl is loosely based on the hit television game show Jeopardy!, with six categories of rheumatology-related trivia. Each category has five answers, ranging in value from 100 to 500 points. Contestants get the answers and must come up with the right question.

First-round categories included Lupus, Antiphospholipid Syndrome, Scleroderma, Systemic JIA, Do You Know Your Antibodies, and ID in Rheum. The second round focused on Enzymes and Myopathy, GIO, Cancer and Rheumatology, Connective Tissue, Rheum for Treatment, and Lupus and Pregnancy.

Some clues were strictly clinical: “THIS is the only class of medications demonstrated in clinical trials to prevent new digital ulcers in scleroderma” brought the correct response, “What are endothelial receptor antagonists?”

And some clues stumped the contestants: “Belimumab is an antibody against this factor” got no answers at all. The correct response would have been “What is BLyS (or BAFF)?”

Yesterday’s winners meet the 2011 Knowledge Bowl champion, “New Orleans Mardi Gras” from Ochsner Medical Center, in today’s final round, which will be held from 11:00 am – 12:30 pm in Hall D. Come early, as seats are expected to fill up fast!

Clinician Scholar Educators to discuss their award-winning projects today

During a special session today, recipients of the Rheumatology Research Foundation’s Clinician Scholar Educator Awards will describe the projects they developed with the support of their awards, which recognize and fund rheumatologists dedicated to providing high-quality educational experiences to trainees. Recipients receive $50,000 annually from the REF for three years and must be ACR or ARHP members with experience in training medical students, graduate students, residents, and fellows.

Abby Abelson, MD, Department Chair and Education Program Director of the Department of Rheumatologic and Immunologic Disease at the Cleveland Clinic, will lead off the session, which will be held from 9:00 – 10:30 am in Room 145 A at the Washington Convention Center. Dr. Abelson will describe her project, “A Web-Based, Problem-Based Learning Rheumatology Curriculum for Medical Students.”

“I developed an interactive format designed to expose students, residents, and fellows to a variety of rheumatologic conditions, emphasizing the basic science and pathogenesis of each condition,” Dr. Abelson said. “For example, one problem- based learning module in the curriculum focuses on the pathogenesis of rheumatoid arthritis and leads the student to the rationale for targeted therapy.”

Dr. Abelson’s curriculum includes case studies dealing with psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, osteoarthritis, and RA. She has used the curriculum in the Cleveland Clinic’s Lerner College of Medicine for the last four years.

“I also used the grant to attend the Harvard Macy Institute program for clinical educators to learn curriculum development, learner-centered education, group learning, and evaluation and assessment of learning,” she said. “It would not have been possible for me to develop as a clinical educator or develop the curriculum without the support of this award.”

The other Clinician Scholar Educator Award recipients who will discuss their projects this morning are:

  • Jessica Berman, MD, from the Hospital for Special Surgery, who will discuss “Focusing on Basics: Musculoskeletal Modules”
  • Christopher E. Collins, MD, from Washington Hospital Center, who will describe his “Web-Based Interactive Rheumatology Experience (WIRE)”
  • Deana M. Lazaro, MD, from the Brooklyn VA Medical Center, who will highlight her project in a presentation titled “Development of Multimodal Rheumatology Elective: A Controlled Study”
  • Amy L. Woodward, MD, MPH, from Vanderbilt University School of Medicine, who will discuss “A Modular Curriculum in Pediatric Rheumatology for Residents, Pediatricians, and Adult Specialists.”

Dr. Abelson said this morning’s session is an important way to disseminate information about the kinds of projects supported by the Clinician Scholar Educator Award, and she hopes other rheumatologists are inspired to apply for the award. “I also think it’s important for the presenters to get feedback from others on how to continue to improve their projects,” she added.

The individuals selected to receive Clinician Scholar Educator Awards serve as role models for future rheumatologists and rheumatology health professionals. Applicants need to demonstrate a desire to develop a career in medical education and training, with the aim of enhancing education in the musculoskeletal and rheumatic diseases and attracting the best-possible trainees to careers in rheumatology.

Candidates for the award also must be affiliated with an accredited graduate school, medical school, or training program in internal medicine, pediatrics, or rheumatology. A faculty appointment is not necessary, and clinicians in private practice affiliated with an academic institution are encouraged to apply. Past recipients are not eligible to apply again.

Experts debate use of cyclophosphamide versus rituximab in ANCA-associated vasculitis

In Sunday’s Great Debate session, two experts gave their opinions on the current roles of cyclophosphamide versus rituximab when treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis. The general consensus was that cyclophosphamide continues to have a role while rituximab may be considered a valid option to cyclophosphamide for remission induction in newly diagnosed patients with severe ANCA-associated vasculitis.

In 2011, the Food and Drug Administration approved rituximab in combination with glucocorticosteroids for the treatment of granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis, two forms of ANCA-associated vasculitis. The FDA’s approval raised the question of the proper role of rituximab versus cyclophosphamide in patients with these diseases.

In 2010, two randomized controlled trials reported that remission induction therapy with rituximab achieved similar remission rates to a remission induction therapy with cyclophosphamide, said Ulrich Specks, MD, Professor of Medicine in the Division of Pulmonary and Critical Care Medicine at the Mayo Clinic College of Medicine.

The rituximab in ANCA-associated vasculitis (RAVE) study compared the use of rituximab versus cyclophosphamide for remission induction in 197 newly diagnosed ANCA-positive patients with active severe GPA or MPA, said Dr. Specks, who was a co-principal investigator of the trial. At six months, 64 percent of those who received rituximab were in remission without receiving steroids versus 53 percent who received cyclophosphamide.

In the rituximab or cyclophosphamide in ANCA-associated renal vasculitis (RITUXVAS) study, which included 44 newly diagnosed ANCA-positive patients with severe renal vasculitis, complete remission was achieved in 82 percent of patients who received rituximab and 91 percent of patients who received cyclophosphamide. The trial’s authors concluded that over 12 months, one course of rituximab achieves the same results as six months of cyclophosphamide followed by azathioprine.

Results of the RAVE trial suggest that “rituximab represents the first proven alternative to cyclophosphamide for remission induction in severe ANCA-associated vasculitis. This is of particular importance for patients who present with severe disease flare and those who want to preserve their fertility,” Dr. Specks said.

“Rituximab can replace cyclophosphamide for remission induction in ANCA-associated vasculitis,” he said. “It is not inferior to cyclophosphamide for newly diagnosed disease and it is superior for relapsing disease. One course of rituximab (375 mg/m2 x 4) is as effective as 18 months of cyclophosphamide and azathioprine.”

Furthermore, rituximab does not need to be combined with other agents, such as cyclophosphamide, methotrexate, or azathioprine in the management of ANCA-associated vasculitis, Dr. Specks noted. He cautioned, however, that rituximab is an immunosuppressive agent associated with infection risk. The risk “seems similar to that of carefully monitored cyclophosphamide followed by azathioprine,” he said.

 Role of Cyclophosphamide

Cyclophosphamide continues to have a role in the treatment of GPA/MPA in patients with rapidly progressive glomerulonephritis with creatinine levels > 4.0mg/dL, alveolar hemorrhage requiring mechanical ventilation, past adverse events specific to rituximab, and active disease despite rituximab therapy, said Carol A. Langford, MD, MHS.

Dr. Langford, Chair of Rheumatic and Immunologic Diseases and Director of the Center for Vasculitis Care and Research at the Cleveland Clinic, said she would discuss cyclophosphamide and rituximab as equally valid options in newly diagnosed patients with severe disease.

“The introduction of cyclophosphamide changed the face of vasculitis,” she said, by providing an opportunity for long-term survival and follow-up of patients, and exploration of the immunologic mechanisms of ANCA-associated vasculitis. And for many forms of severe vasculitis – such as severe polyarteritis nodosa, Churg-Strauss syndrome, granulomatous angiitis of the central nervous system, and other vasculitides in which life-threatening disease is present – cyclophosphamide remains essential, she said.

“For the first time, we have an alternative to cyclophosphamide for GPA/MPA. There remain important questions about rituximab that are being answered, and many of these questions have been guided by our experience with cyclophosphamide. As studies continue, the use of cyclophosphamide versus rituximab must be weighed individually,” Dr. Langford concluded.

Serum autoantibodies help diagnose, predict outcome of systemic sclerosis

Among the connective tissue diseases, systemic sclerosis – or scleroderma – has the highest proportion of patients with disease-specific, nearly mutually exclusive serum autoantibodies. Rheumatologists should be familiar with their detection, clinical and laboratory associations, and implications for patient follow-up, according to Thomas. A. Medsger, Jr., MD, Co-director of the Scleroderma Center at the University of Pittsburgh.

Dr. Medsger will present this year’s REF Paul Klemperer, MD Memorial Lectureship, Serum Autoantibodies in Systemic Sclerosis: Usefulness in Diagnosis, Clinical Subsetting and Predicting Outcomes, at 7:30 am Tuesday in Ballroom C of the convention center.

“There is a standard clinical classification for the disease systemic sclerosis,” Dr. Medsger said. “That classification includes diffuse cutaneous, which is widespread skin thickening; limited cutaneous, which is minimal skin thickening; and either one of those in overlap with another connective tissue disease, such as myositis or lupus.”

Detection of antinuclear antibodies is an important screening tool when evaluating a patient for possible scleroderma, he added, noting that approximately 98 percent of patients with scleroderma will have a positive ANA test by indirect immunofluorescence.

“The ANA test doesn’t specifically tell you that the patient has scleroderma,” Dr. Medsger said. “The disease must be diagnosed on the basis of history and a physical examination. Basically, if a patient has skin thickening affecting the fingers, the diagnosis is scleroderma.”

The value of a positive ANA test lies in the subsequent identification of the systemic sclerosis patient’s specific antibody. A positive ANA test can be subclassified into one of nine systemic scleroderma-associated autoantibodies, eight of which can be identified by commercially available testing.

Dr. Medsger noted that it is rare for a patient to have more than one of the autoantibodies, and that antibody status typically does not change over time. Approximately 85 percent of scleroderma patients who test positive for ANA will have one or the other of those eight antibodies, he said.

“Knowing which antibody the patient has is key because specific clinical manifestations are associated with each one,” Dr. Medsger said. “If you know the antibody, you can get an idea of what the patient is up against, and what might happen in the future.”

Dr. Medsger said that knowledge of the scleroderma patient’s autoantibody helps the physician design clinically relevant and cost-effective follow-up plans for individual patients and should be incorporated into standard clinical practice and management.

“If at all possible, all new systemic sclerosis patients should undergo ANA testing by IIF and have their scleroderma-related antibody identified,” Dr. Medsger said. “It helps the managing physician better inform the patient and guide ongoing monitoring and follow-up.”

ARHP sessions highlight infusion room management issues

The management and operation of infusion rooms, from both a clinical and administrative standpoint, will be the topic of two special sessions Monday morning. In the first session, a veteran infusion nurse will review some of the most important infusion room operational logistics, including reimbursement processes, scheduling considerations, and the skills required for infusion registered nurses. A second session will focus on clinical aspects, offering attendees an update on the management and prevention of infusion room reactions. Both sessions will be held in Room 204 A of the convention center.

Infusion Room Information

At 7:30 am, Sharon Manson, RN, MS, NP, from Rush University Medical Center, will present Infusion Room Information for Medical Professionals. Manson will focus on the role of the infusion room nurse and give attendees an overview of some of the clinical and operational issues involved in managing infusion rooms.

“An infusion room nurse must have an understanding of the processes required to ensure reimbursement of infusion therapies,” Manson said. “On the clinical side, the nurse needs to have a strong knowledge of management and complications of disease, along with experience in the handling of therapeutic or cytotoxic agents.”

The infusion room nurse must also have strong venous access skills, including up-to-date knowledge of venous access devices, and be well trained in the management of acute infusion reactions, Manson said.

Infusion Reactions

From 9:00 – 10:00 am, Christine Elliott, RN, of Virginia Mason Medical Center, will update attendees on the use of infusible medications during a session titled Infusion Reactions: Management and Prevention. Elliott, who has 13 years of experience managing rheumatologic patients on infusible medications, will focus on some of the inherent risks and recommended responses for adverse infusion reactions.

“There are a number of exciting new therapies that have been developed in the past 10 years to treat rheumatic disease,” Elliott said. “While IV biologics are now a part of mainstream clinical management, there are inherent risks for infusion reactions that clinicians need to be aware of and prepared for.”

Common infusion reactions, which are generally mild to moderate, include uriticaria, flushing, itching, throat irritation, and shortness of breath. Less common are more severe reactions, which can include chest pain and anaphylaxis.

“To lessen the risk of adverse reactions, premedication with an antihistamine, acetaminophen, or corticosteroid is recommended prior to administering some infusion medications, including rituximab and pegloticase,” Elliott said. She is quick to point out, though, that reactions can occur even in patients who have been premedicated, and that clinicians must be vigilant in monitoring their patients once the infusion is started and know what to do in the event of a reaction.

“Sometimes, in the case of mild or moderate reactions, if you just stop the infusion, give normal saline, and monitor, the symptoms will go away and you can simply restart the infusion,” Elliott said. “If the symptoms don’t go away by stopping the infusion, then some medication may be required, such as diphenhydramine, hydrocortisone, or acetaminophen.”

Perception and treatment of OA is changing

Attitudes about osteoarthritis are changing. Once thought of simply as wear and tear on the joints, OA is now recognized as a disease with specific risk factors, pathophysiology, and management.

“Important new evidence has changed our views on the evaluation and treatment of OA,” said Carla Scanzello, MD, PhD, Assistant Professor of Medicine at Rush University Medical Center. “Many primary care physicians and patients themselves have not caught up with the new paradigm.”

OA is currently seen as a disease of the diarthrodial joint, which includes bone, synovium, capsule, periarticular muscles, sensory nerve endings, and meniscus, Dr. Scanzello said during Saturday’s ARHP Clinical Focus Course, Treating the Patient with Osteoarthritis: Interventions, Innovations and Clinical Insights.

Cartilage cells called chondrocytes become activated and proliferate in OA, and they become more responsive to inflammatory mediators. The collagen matrix is disrupted, resulting in surface softening and roughening, fibrillation, fissuring, ulceration, and exposure of bone.

Subchondral bone turnover increases, leading first to reduced bone density, then to increased bone density. Osteophytes, or bone spurs, form. And the synovial membrane thickens, increases in vascularity, and is subject to low-grade inflammation and fibrosis, Dr. Scanzello explained.

Changes to the surrounding musculature can lead to atrophy and changes in gait that can increase joint loads. All of these changes affect both the peripheral and the central nervous system, leading to localized and widespread pain.

However, OA is not an inevitable consequence of aging, Dr. Scanzello said. The prevalence of OA increases with age into the 70s, then falls off, she said. Female gender is a risk factor, as are race and ethnicity.

Genetics accounts for 50 percent to 60 percent of OA, and obesity is another strong risk factor. Joint injury carries a five-fold increase in risk. Farming, jobs that requiring kneeling or squatting, and competitive athletics also increase risk. So do joint alignment, joint shape, joint laxity or hypermobility, endocrine diseases, and hemochromatosis, Dr. Scanzello said.

The biomechanical forces that affect a joint are often situated outside the joint itself, said Charles Ratzlaff, PT, PhD, FCAMT, a research fellow at Brigham and Women’s Hospital and Harvard Medical School. “The joint is an organ that gets increased load and tries to adapt. Sometimes it can stabilize and sometimes it can’t.”

A physical exam is still the cornerstone of OA management, Dr. Ratzlaff said, and half of patients with symptomatic OA have normal imaging. If the patient has joint pain that increases or decreases in frequency with either effusion, flexion contracture, or altered gait, it is most likely OA.

Early diagnosis and early management are key, he said. Neuromuscular training – exercise designed to strengthen and increase joint stability and function – can delay progression and dramatically improve a patient’s ability to perform normal activities of daily life.

Core muscle weakness is a common problem among OA patients. The transverse abdominus and interlinked muscles stabilize the back and create the appropriate biomechanics for movement of the extremities, Dr. Ratzlaff explained. Generalized strengthening may further degrade joint support, but core muscle training can be a potent nonpharmacologic intervention.

The ACR issued new guidelines on pharmacologic management of OA earlier this year based on new therapies and new safety data on existing agents. While there is no cure for OA, the ACR currently recommends acetaminophen for pain relief followed by topical analgesics, oral NSAIDs, intra-articular therapies, duloxetine, tramadol, and opioid analgesics.

Current data show that acetaminophen is marginally more effective than placebo but less effective than NSAIDs, reported Marc Hochberg, MD, MPH, Professor of Medicine and Epidemiology and Public Health, and Head of Rheumatology and Clinical Immunology at the University of Maryland School of Medicine. There is also good evidence that acetaminophen is associated with increased risk of renal dysfunction and liver failure, he said.

“There is a small margin of safety for acetaminophen when used at high doses,” Dr. Hochberg cautioned. “I think rheumatologists should consider not using acetaminophen.”

The ACR found no evidence supporting the use of neutraceuticals and does not recommend the use of glucosamine or chondroitin. Data on biologics used to reduce inflammation, primarily anti-TNF agents, has been uniformly negative in OA, Dr. Hochberg added.

Rheumatic Disease Update sessions highlight latest science

Over the next three days, the ARHP is sponsoring a series of five Rheumatic Disease Update sessions that will offer the latest news on vasculitis, inflammatory eye disease, gout, low back pain, and lupus.

Philip Seo, MD, MHS, Assistant Professor of Rheumatology at Johns Hopkins University School of Medicine, will present the first of two update sessions today. Dr. Seo will provide an update on the evaluation and management of vasculitic conditions, which are relatively uncommon but carry some of the highest morbidity and mortality rates among rheumatic conditions. Dr. Seo’s one-hour session will begin at 11:00 am in Room 204 A at the Washington Convention Center.

Also today, Gary N. Holland, MD, will provide an update on inflammatory eye disease from 2:30 – 4:00 pm in Room 206. Dr. Holland, who is the Jack H. Skirball Professor of Ocular Inflammatory Diseases at the David Geffen School of Medicine at the University of California, Los Angeles, is particularly interested in chronic anterior uveitis in children, which is often associated with rheumatic conditions. “We have had two consensus conferences that included pediatric rheumatologists, uveitis specialists, and pediatric ophthalmologists to address some of the problems that have come to light in the management of kids with uveitis, and especially those with JIA,” Dr. Holland said.

“We have formulated recommendations for a more uniform approach to the evaluation and management of children with uveitis. This lecture will be one of the first public presentations of our findings. Eventually, our recommendations will be published in a set of whitepapers.”

A key concern, Dr. Holland explained, is the significant variation in care that children with uveitis receive. Under treatment is common, he said, because many clinicians fail to appreciate the severity of pediatric uveitis, which can to lead vision-limiting complications that could be avoided with more aggressive treatment. Furthermore, clinicians may not realize the speed with which uveitis can progress in children — complications can develop between scheduled visits.

There are also special concerns when dealing with pediatric patients. “Children with uveitis are probably more prone than adults to developing glaucoma as a complication of the disease, yet glaucoma is a difficult problem to diagnose and manage in a small child,” Dr. Holland said. “It can get out of control even before it is recognized.”

The drugs used to manage uveitis and its complications in adults may not be appropriate for children. Brimonidine, which is commonly used for glaucoma in adults, can cause somnolence or respiratory suppression in children.

There are also misconceptions about the disease itself. Uveitis in children with JIA is a chronic condition that requires long-term therapy. Discontinuation of treatment when inflammation is controlled is almost always associated with recurrent inflammation, Dr. Holland explained. Clinicians must make a commitment to ongoing treatment that often includes chronic immunosuppression.

Children with chronic anterior uveitis are best managed through a team approach, Dr. Holland said. Pediatric rheumatologists are not able to monitor the effects of immunosuppression on the eye, and may not be familiar with issues like amblyopia, or lazy eye, which can cause a child with uveitic complications to lose vision permanently, even if the complication is eventually addressed. On the other hand, pediatric ophthalmologists may not have extensive experience with uveitis issues, while not all uveitis specialists are familiar with the special needs kids have in medication selection or followup.

“And not everyone with inflammatory eye disease can be managed by a uveitis specialist — there just aren’t enough of us to go around,” Dr. Holland said. “We want to disseminate these recommendations to everyone who may be involved in the management of a child, whether it is a pediatric rheumatologist, a uveitis specialist, a pediatric ophthalmologist, a general ophthalmologist, or an adult rheumatologist.”

Gout
Gout is saddled with centuries of misconceptions. Often viewed as a disease of elderly men, gout also affects elderly women. In fact, gout is the most common inflammatory arthritis of humans. Some 8.3 million Americans have gout, or about 4 percent of the population.

Naomi Schlesinger, MD, Professor of Medicine and Chief of Rheumatology at the University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, will address the most common myths and misconceptions about gout tomorrow during another ARHP update session. Dr. Schlesinger’s one-hour session will begin at 9:00 am in Room 206.

Another misconception: Gout is typically seen as a lifestyle disease, the result of inactivity and a rich diet. If patients simply ate a more balanced diet, the thought goes, their gout would disappear. Neither the cause nor the treatment of gout are that simple, Dr. Schlesinger said.

“Diet is only helpful to a very small degree because most of the uric acid in gout is not the result of diet but from the breakdown of cells,” she explained. “If you have gout, you need to be on medication.”

X-rays are essentially useless in the diagnosis of gout because it takes years to produce joint changes that are visible on an X-ray. And serum urate levels may not be diagnostic because about half of patients with acute gout have normal serum urate levels.

To make a definitive diagnosis of gout, monosodium crystals need to be found in synovial tissue and/or tophi.

Topical ice also may be helpful in diagnosing gout because patients with acute gout typically present with hot joints and the ice often relieves their joint pain, Dr. Schlesinger explained. Therefore, application of topical ice should be part of the history taking and physical examination when one suspects acute gout, or if the nature of the inflammatory arthritis is unclear.

There are different treatment approaches for acute and chronic gout. Pain relief and anti-inflammatory action are essential for acute treatment. Nonsteroidal drugs, colchicine, and corticosteroids are the most commonly used drugs for acute gout. Recent trials with an interleukin-1 inhibitor have also shown promise.

Urate-lowering therapies, as well as chronic anti-inflammatory therapy, are used for chronic treatment. Xanthine oxidase inhibitors such as allopurinol and febuxostat are the standard of care. Pegloticase, a uricase, is new to the market and may be important for the induction of urate-lowering therapy. A variety of new agents, mostly uricosuric drugs, are currently in development.

“Clinicians and patients will say, ‘It’s just gout,’” Dr. Schlesinger said. “It’s not just gout, it’s a serious disease. Gout is under diagnosed and at times over diagnosed. People get adverse events and may even die from treatment. Education regarding the diagnosis and treatment of gout are key.”

Gout needs to be accurately diagnosed and treatment needs to be improved, Dr. Schlesinger added. “One needs to terminate the acute attacks, control hyperuricemia and tissue deposition using the target serum urate level of <6.0 mg/dL, as well as using prophylactic medications to prevent acute attacks,” she said.

Low Back Pain
Fully 80 percent of the population will have at least one episode of low back pain in their lifetime. But many rheumatologists are unsure about how to deal with this common problem.

“Low back pain is one of the most common complaints in the rheumatology practice,” said Jeffrey N. Katz, MD, MSc, Professor of Medicine and Orthopedic Surgery at Harvard Medical School and Director of the Orthopedic and Arthritis Center for Outcomes Research at Brigham and Women’s Hospital. “There is a wealth of clinical trial data on back pain treatments, some of which is not well appreciated by rheumatologists.”

Dr. Katz will explore treatment approaches to low back pain from 9:00 – 10:00 am Tuesday in Room 143 A.

Back pain tends to be episodic, he explained. About 80 percent of patients who present with low back pain will have another episode within 12 months. The good news is that the natural history of low back pain is good. Most patients recover regardless of treatment or lack of treatment. “

A lot of attention is paid to how you treat an episode of low back pain,” Dr. Katz said. “It turns out that is not so important. How a particular episode is treated should not be the focus. Our effort should be focused on preventing future episodes because they are very costly and disabling. It is a chronic, episodic disease and we would like to figure out how to reduce the number of episodes.”

Diet and exercise are among the most effective preventive steps, he said. Increasing flexibility and core muscle strength are key steps in preventing future episodes.

Sciatic pain due to a herniated disk is more difficult to treat because the natural history of disk protrusions is less positive than for garden variety back pain, Dr. Katz said.

“The question of whether to think about surgery or injections should be a preference-based decision,” he said. “There are no strict indications for these more invasive procedures. We need to understand the risks and benefits to help patients make choices based on their own preferences.”

Spinal stenosis is a growing problem for older patients. Fortunately, stenosis is highly responsive to surgery, Dr. Katz said, and rheumatologists should be more familiar with the common indications for spinal stenosis surgery.

“Garden variety back pain gets better and sciatica gets better, but more slowly. Spinal stenosis often doesn’t get better,” he said. “For many patients, surgery becomes the wiser decision even though they are older and the risks of surgery are higher. The more back pain you see, the more surgical decision-making you can engage in with your patients before referring them to a surgeon.”

Lupus
The final ARHP Rheumatic Disease Update session will be held from 2:30 – 4:00 pm Tuesday in Room 145 A. Michelle Petri, MD, MPH, Professor of Medicine and Director of the Lupus Center at Johns Hopkins University School of Medicine, will provide an update on systemic lupus erythematosus

Metabolic abnormalities in autoimmunity to be reviewed

Recent research suggests that metabolic abnormalities in T-cell differentiation and activation play a key role in autoimmunity and systemic lupus erythematosus.

An ACR Basic Science Symposium this afternoon will address the interplay between metabolic responses and T-cell function in systemic autoimmunity. The session, Metabolic Abnormalities in Autoimmunity, takes place from 4:30 – 6:00 pm in Room 143 A at the Washington Convention Center.

Andras Perl, MD, PhD, who planned the session, will discuss metabolic control of systemic autoimmunity. Dr. Perl, who is Chief of Rheumatology and Professor of Medicine, of Microbiology and Immunology, Biochemistry and of Molecular Biology at the Upstate Medical University of the State University of New York at Syracuse, has done extensive research into new treatment for lupus that avoid the significant side effects of current therapies.

“I will discuss the molecular basis and consequences of mitochondrial dysfunction in lupus T cells, which my colleagues and I discovered in 2002 to be a key mechanism of abnormal T-cell activation and cell death in SLE,” Dr. Perl said.

“When activated, mitochondrial dysfunction produces less energy in the form of ATP and predisposes lupus T cells to death by necrosis,” he explained. “The increased production of necrotic materials from T cells is an important activator of B cells, dendritic cells, and inflammation in SLE. The activation of the mammalian target of rapamycin, which serves as a sensor of mitochondrial dysfunction, is a biomarker and a target for treatment in lupus patients.”

In the September issue of Arthritis and Rheumatism, Dr. Perl and his colleagues published the results of a randomized clinical trial that suggests that treatment with the amino acid N-acetylcysteine improves lupus disease activity by blocking mTOR in T lymphocytes. N-acetylcysteine is a precursor of glutathione, a natural antioxidant lost in lupus autoimmunity and another biomarker of T-cell dysfunction. Highdose N-acetylcysteine helps the body replenish glutathione and boost T-cell function.

Another speaker, James C. Oates, MD, Associate Professor of Rheumatology at the Medical University of South Carolina, will describe the biology of reactive nitrogen intermediates, a key part of the innate immune response in lupus patients.

“Reactive nitrogen intermediates play antithetical roles in lupus by possibly accelerating disease and inducing the production of autoantibodies at high levels, but low levels of these compounds can actually be protective,” Dr. Oates said.

Animal research has shown that mice with lupus express an enzyme that produces very high levels of nitric oxide through inducible nitric oxide synthase.

“However, the endothelial form of nitric oxide synthase (eNOS) makes very low levels of nitric oxide, much lower than the inducible form,” Dr. Oates said. “It plays a protective role in preventing inflammatory cells from causing inflammation in tissues. Patients with lupus glomerular kidney disease under express this protective form of nitric oxide.”

Dr. Oates and his colleagues are currently investigating the protective effects of eNOS, showing that eNOS is downregulated in lupus. They are also studying the functional consequences of eNOS downregulation.

“We have knocked out endothelial nitric oxide synthase in a mouse model of lupus and found a very profound acceleration of kidney disease in these knockout mice. The mice die younger, they get protein in their urine, and they have much more aggressive glomerular lesions,” Dr. Oates said.

“We are following the protective effects of eNOS by looking at the effect of lupus serum on cultured endothelial cells,” he continued. “We found that expression of the endothelial form of nitric oxide synthase is reduced with lupus serum. When you add back a natural form of a nitric oxide donor that emulates eNOS activity, you can improve endothelial cell function. That is, you can downregulate chemokines that are upregulated as a result of the reduction in eNOS.”

Dr. Oates’ long-term interest is to determine how to emulate or augment the function of eNOS to improve outcomes.

The symposium’s third speaker, Jonathan D. Powell, MD, PhD, Associate Professor of Oncology and of Pharmacology and Molecular Sciences at Johns Hopkins University, will address the metabolic control of T-cell differentiation.

Foundation Memorial Lectureship to explore early pathogenesis of rheumatoid arthritis

In Monday’s Foundation Memorial Lectureship, Gary S. Firestein, MD, will present ideas that challenge the conventional understanding of the early stages of rheumatoid arthritis and argue that autoimmunity might not be a part of the disease in its preclinical stages.

Dr. Firestein, Professor of Medicine and Dean and Associate Vice Chancellor of Translational Medicine at the University of California San Diego School of Medicine, will present his lecture, Pathogenesis of Rheumatoid Arthritis: The Voyage from Pre-Rheumatoid Arthritis to Joint Destruction, from 9:00 – 10:00 am in Hall E of the convention center.

“I plan to present some interesting ideas that reframe how we think about the earliest stages of rheumatoid arthritis. While it’s clear that autoimmunity plays a role in RA, it is not so clear that autoimmunity occurs in its very earliest moments,” he said.

Dr. Firestein will discuss how the initiating antigens that are present in early RA bind to major histocompatibility genes, how the antigens are presented to the cells of the adaptive immune system, and how that presentation can lead to a normal response against altered antigens rather than an autoimmune response against self-antigens.

“There are two main influences in RA susceptibility — the genes we are born with and random environmental influences like smoking, infections, and toxic exposures that cause inflammation. We have learned that environmental exposures alter some antigens through citrullination, which converts arginine into citrulline,” Dr. Firestein said.

“If an individual has a gene associated with how antigens are presented to immune cells, altered antigens might be presented to T cells. However, the altered antigens — such as citrullinated peptides — don’t bind to all the major histocompatibility genes very well, but they do bind well to the MHC genes associated with RA,” he added.

Together with William P. Arend, MD, from the University of Colorado, Denver, Dr. Firestein published a commentary in Nature Reviews Rheumatology this year concluding that proven risk factors for the development of RA, including circulating anti-citrullinated protein antibodies that are generated from a normal immune response, can appear more than 10 years prior to the onset of clinical disease.

In the development of RA, major histocompatibility genes for RA bind with the altered antigens and present them to T cells as a “new” protein that the immune system does not recognize. This process can lead to the production of anti-citrullinated protein antibodies.

“These antibodies can be produced long in advance of clinical disease. As the amount of antibodies increases and immune complexes form, the antibodies are able to penetrate the synovium, fix complement, and activate local synovial inflammation,” Dr. Firestein explained. Later, true autoimmunity can occur through a process known as epitope spreading.

For a number of years, Dr. Firestein and his colleagues at UCSD have been doing research on cytokines, signal transduction pathways, and aggressive synoviocyte behaviors in RA as mechanisms of joint destruction. His laboratory is focused on studying aspects of rheumatoid arthritis that implicate pathways other than autoimmunity.

“We need to understand how RA gets started if we are going to intervene before there is actually clinical disease. Someone with the correct histocompatibility genes and abundant citrullinated proteins might have a very high risk of developing rheumatoid arthritis in the not-too-distant future,” Dr. Firestein said.

“Once we can identify patients with a very high risk of RA, we can begin thinking about therapeutic interventions, not to treat RA but to prevent RA,” he continued. “For example, we might be able to interfere with the production of antibodies to the altered antigens or block the further citrullination of peptides by inhibiting the enzymes responsible for citrullination.”

Symposium will address what rheumatologists should know about dermatology

Some of the biologics widely used in rheumatology, especially tumor necrosis factor inhibitors, can cause rare and sometimes paradoxical adverse side effects in the skin of patients taking them.

Monday’s ACR Clinical Symposium, Dermatology Topics for Rheumatologists: What You Need to Know, will feature information on cutaneous reactions to biologic agents by Jan P. Dutz, MD, a physician who is both a dermatologist and a rheumatologist at the Vancouver General Hospital Skin Care Centre and Professor of Dermatology and Skin Science at the University of British Columbia in Vancouver. The session will be held in Hall D of the Washington Convention Center from 4:30 – 6:00 pm.

“We have a pretty good handle on the overall safety record of biologic agents used in rheumatology, but some of these agents have either unique or paradoxical effects on the skin. These are rare side effects,” he said.

What is paradoxical about one adverse side effect is that TNF inhibitors, which may be used to treat psoriasis, can also cause worsening or de novo development of psoriasis, Dr. Dutz said.

“TNF inhibitors are one of the mainstays of treatment for severe psoriasis and yet we know that a small proportion of patients, either having psoriasis or having other connective tissue diseases and never having had psoriasis, develop psoriasis after they have been put on TNF inhibitors,” he explained. “This is an uncommon occurrence, but it needs to be in the back of a treating rheumatologist’s mind.”

In his talk, Dr. Dutz will discuss the frequency of this and other skin reactions to biologics, the pathophysiology of the reactions, and strategies for treating skin reactions to biologics with topical or systemic agents.

Other potential side effects to TNF inhibitors include hair loss in the form of alopecia areata and loss of pigment in the form of vitiligo.

“Another side effect of biologic therapy is a slight increase in the risk of infection, and the infection is often seen in the form of cutaneous infections, the most common of which are staphylococcal or streptococcal infections. There are also occasional case reports of dermatophyte fungal infections. In addition, there have been isolated observations of worsening of atopic dermatitis,” Dr. Dutz said.

Less is known about the cutaneous side effects of other biologics than about effects associated with TNF inhibitors, but Dr. Dutz will cover what’s known about other agents as well.

“There are isolated case reports of initiation or worsening of lupus-like reactions in the skin and case reports of vasculitis associated with other biologics. There are also case reports of worsening psoriasis associated with rituximab,” he noted.

Most of these adverse side effects are treatable, but some are severe enough that rheumatologists may need to discontinue or change the biologic therapy. Dr. Dutz will go over a treatment algorithm that rheumatologists can follow to manage such situations.

“I hope rheumatologists who attend this session will learn to be able to recognize and manage simple skin reactions to TNF inhibitors and understand when to refer to a dermatologist for further diagnosis and management,” he said. “We need to pay attention to the skin in our patients because the skin can tell us not only about the disease, but about the efficacy of treatment and can alert us to side effects of treatment.”

Also speaking during this symposium is Soon Bahrami, MD, a dermatopathologist at the University of Louisville, who will discuss how to interpret a dermatopathology report; and Richard K. Scher, MD, MS, Assistant Professor of Dermatology at Weill Cornell Medical College, who will describe nail signs of systemic disease.

 

Session to review latest treatment options for lupus

The role of new agents in the treatment of lupus, cutaneous manifestations seen in lupus patients, and the treatment of lupus nephritis will be the focus of Sunday’s session, Update on Treatment of Systemic Lupus Erythematosus, from 2:30 – 4:00 pm in Hall E of the convention center.

Bevra H. Hahn, MD, Professor Emerita in Rheumatology at the David Geffen School of Medicine, University of California, Los Angeles, will review new treatments for lupus, including belimumab, the only FDA-approved new treatment for lupus, and other agents currently under study.

“Now that belimumab has been available for more than a year, I can talk about its safety and effectiveness. I’ll discuss the appropriate candidates for this agent and its indications. The usual candidates for belimumab are seropositive patients with active disease in spite of standard treatment,” Dr. Hahn said.

Among the other new treatments currently under study, she will indicate which ones are likely to receive FDA approval in the next few years and which ones are not as far along in the drug research pipeline. Her discussion will include some drugs that are already available for off-label use in lupus patients — rituximab, tocilizumab, and abatacept. She will also discuss type 1-interferon inhibitors and laquinomod, which is under investigation in clinical trials for use in lupus and lupus nephritis, as well as Crohn’s disease and multiple sclerosis.

“Attendees will learn how each of these agents affects the pathogenesis of lupus and how they might be effective in treatment. New agents for lupus hold the promise of effective treatment for patients who are not doing well on their current therapy or have a lot of adverse side effects from their current therapy,” Dr. Hahn said.

Also during this session, David Fiorentino, MD, PhD, Associate Professor of Dermatology at Stanford University School of Medicine, will address cutaneous manifestations in lupus patients and how rheumatologists can treat them.

“I’ll be talking about both lupus non-specific and lupus-specific skin diseases, and the latter group includes acute cutaneous lupus, subacute cutaneous lupus, discoid lupus, lupus panniculitis, and tumid lupus,” Dr. Fiorentino said.

He will use images of the different types of skin disorders in lupus patients to help clinicians recognize the manifestations, as well as provide information on how to control the manifestations.

“The diagnosis of these disorders is not trivial. It can be very challenging to classify them. Clinicians need to be aware of how cutaneous manifestations might be a barometer for systemic disease and have significance beyond the skin,” he said. “For example, a patient who has vasculitis on the skin, which is a lupus non-specific finding, should cause the clinician to worry that systemic disease is at a high risk of worsening or may have already flared. Alternatively, if you see a patient with lupus who begins to get discoid lesions, these lesions have little implication regarding the systemic disease.”

Dr. Fiorentino will also offer some practical tips on how to use medications safely and effectively to manage skin manifestations in lupus, and how to identify the lupus patients most likely to respond to antimalarials.

The third speaker, James E. Balow, MD, Clinical Director of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, will provide an update on the treatment of lupus nephritis.

Clinical review to address preoperative assessment, perioperative management of rheumatology patients

Rheumatologists often have to work with orthopedic surgeons to manage patients with rheumatic disease. In Sunday’s clinical review lecture, Preoperative Assessment and Perioperative Management of the Patient with Rheumatic Disease: What Every Rheumatologist Should Know, rheumatologist Linda A. Russell, MD, will cover the key aspects of the assessment and management of patients in need of elective bone surgery.

The session will take place from 1:00 – 2:00 pm in Hall E of the convention center.

In addition to providing rheumatologists with insights into important components of the preoperative assessment of patients with rheumatic disease, Dr. Russell will discuss the preoperative and perioperative management of biologic and nonbiologic disease-modifying antirheumatic drug therapy and antiplatelet and anticoagulant therapy. She will also identify the possible perioperative complications of common orthopedic procedures.

Dr. Russell is an Assistant Attending Rheumatologist and Director of Perioperative Medicine at the Hospital for Special Surgery and an Assistant Professor of Clinical Medicine at Weill Cornell Medical Center in New York. She specializes in the treatment of osteoporosis, lupus, rheumatoid arthritis, and gout.

“At the Hospital for Special Surgery, rheumatologists and orthopedic surgeons have a very good working relationship. We have a co-management style for taking care of patients perioperatively, which has become a national trend. The medical doctor — often a rheumatologist — helps care for a patient undergoing an orthopedic procedure,” she said.

At HSS, rheumatologists take care of patients with rheumatic disease before surgery, while the patient is in the hospital, and after surgery. Dr. Russell will describe the rheumatologist’s role in treating patients with specific diseases who are undergoing surgery, including patients with rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.

She will discuss when to stop and restart medications for inflammatory arthritis pre- and postoperatively, noting that while many of these medications keep the disease process well controlled, some increase the risk of infection perioperatively and need to be stopped for surgery.

“However, some patients have certain conditions such as antiphospholipid syndrome, and if you stop a blood thinner, they are at great risk of clotting, so I will also discuss the risks and benefits of stopping medications that prevent bleeding. Often these patients cannot go to surgery on these medications because they will bleed too much,” Dr. Russell said.

In addition, she noted, rheumatologic patients with cervical spine disease should be considered for fiber optic intubation when needed, and patients with ankylosing spondylitis may be at risk for vertebral fractures if they are physically strained or stressed during surgery.

“Patients with inflammatory arthritis are at greater risk for cardiovascular disease, so when rheumatologists screen a patient preoperatively, they have to pay particular attention to the patient’s cardiovascular health and whether the patient needs an EKG, echo, or stress test,” she said.

Dr. Russell also cautions that patients with inflammatory rheumatic diseases, such as rheumatoid arthritis or ankylosing spondylitis, are at greater risk of osteoporosis, which may affect orthopedic outcomes. So, she noted, it is important for rheumatologists to assess the patient’s bone health preoperatively.

Also, some patients with inflammatory arthritis are at risk for lung disease and need to be screened before surgery with a pulmonary function test.

“Patients with rheumatic disease often consider their rheumatologist their primary care doctor, and so I think rheumatologists need to understand the risks of any procedure the patient requires and help prepare the patient for those risks,” Dr. Russell said.

Classification and treatment of Sjögren’s to come under scrutiny

Sjögren’s syndrome is a relatively understudied, multisystem autoimmune disease that involves multidisciplinary treatment in rheumatology, ophthalmology, and oral medicine. The ACR has developed new classification criteria for Sjögren’s, which will be discussed in Sunday’s symposium, Classification and Treatment of Sjögren’s Syndrome, from 4:30 – 6:00 pm in Ballroom C.

“Sjögren’s syndrome is a very important condition for which rheumatologists are expected to be experts in diagnosis and management. The under-attention it has received in terms of research has been a major problem for Sjögren’s patients,” said session co-moderator Lindsey A. Criswell, MD, MPH, Chief of Rheumatology and Professor of Medicine and Orofacial Sciences at the University of California, San Francisco.

Dr. Criswell noted, however, that tremendous progress, led by the Sjögren’s International Collaborative Clinical Alliance, has been made in the last few years with regard to efforts to refine classification criteria for this disease.

The ACR’s newly proposed classification criteria were published in the April issue of Arthritis Care & Research and are based on data from the SICCA Sjögren’s registry. The criteria will enable better research into the etiology, genetics, and therapy of Sjögren’s.

Stephen Shiboski, PhD, Professor of Biostatistics at the University of California, San Francisco, will discuss the new classification criteria during today’s session.

“Dr. Shiboski will highlight the fact that, over the past four decades, a variety of approaches to diagnosing or classifying Sjögren’s syndrome patients have been proposed and used in different studies, but there hasn’t been a uniformly agreed upon approach to classification, and that has hampered research,” Dr. Criswell said.

The criteria capture the three main components of Sjögren’s syndrome: dryness and other effects in the patient’s eyes, dryness and other effects in the patient’s mouth, and systemic manifestations. The proposed classification for Sjögren’s patients is based on objective test results, and patients must meet two out of three objective features of the disease to be classified with Sjögren’s.

“There is a distinction to be made between classification criteria and diagnostic criteria. Classification criteria are uniform criteria developed to ensure consistency in patients included in epidemiologic, treatment, or other studies of the condition,” Dr. Criswell said.

Two other speakers for the symposium, Steven E. Carsons, MD, and Ann L. Parke, MD, will discuss preliminary clinical practice guidelines for Sjögren’s syndrome and the rationale and procedures for guideline development.

Dr. Carsons, Chief of Rheumatology, Clinical Immunology, and Allergy at Winthrop-University Hospital, and Professor of Medicine at the State University of New York, Stony Brook, will discuss clinical guidelines being developed under the auspices of the Sjögren’s Syndrome Foundation and some of the challenges associated with developing clinical guidelines for Sjögren’s syndrome.

The guidelines development committee selected three main topics to first be addressed in the guidelines: which treatments are beneficial for the treatment of inflammatory joint disease associated with primary Sjögren’s syndrome; what is the appropriate management of fatigue in primary Sjögren’s syndrome; and what is the role of oral and biologic disease-modifying anti-rheumatic drugs for the SICCA syndrome components of Sjögren’s syndrome, Dr. Carsons said.

“The committee feels that guidance regarding the management of these key questions in Sjögren’s syndrome represents a significant unmet need,” he said.

Dr. Parke, a rheumatologist at St. Francis Hospital and Medical Center, will address the procedures used in developing the guidelines. The co-moderator for this session, Frederick B. Vivino, MD, is Chief of Rheumatology at the University of Pennsylvania’s Presbyterian Medical Center.

New links found among bone, inflammation, rheumatic diseases

If you graduated from medical school in 2007 or earlier, some of the concepts you learned regarding the relationship between bone, inflammation, and rheumatic diseases are changing.

“Many investigators, including my own group, have focused on osteoclasts and bone resorption over the past 10 years,” said Ellen Gravallese, MD, Professor of Medicine at the University of Massachusetts Medical School. “What we are finding now is that the osteoblasts, which make bone, are also impacted significantly by inflammation in rheumatic disease. In addition, there is an interweaving of the pathways that regulate osteoclasts and osteoblasts, and important crosstalk between these pathways. Much important work has focused in the last five years on cells in the osteoblast lineage.”

It’s not just the importance of osteoblasts and osteoblastic regulatory pathways that is new, Dr. Gravallese noted. There’s a new focus on the osteocyte, a cell type that is embedded in bone and is emerging as a key regulator of the pathways that affect bone resorption and formation.

Dr. Gravallese will outline the basic biology of bone resorption and regeneration as it pertains to rheumatic disease during the annual Oscar S. Gluck, MD Memorial Lecture, which she has titled Bone Wasn’t Built in a Day: New Insights into Destruction and Repair in Rheumatic Disease. The one-hour session will begin at 10:00 am Sunday in Ballroom B at the Washington Convention Center.

The interaction between inflammation in rheumatic diseases and bone is far more complex than bone resorption mediated by osteoclasts and bone deposition mediated by osteoblasts, Dr. Gravallese said.

“We are understanding much more about the crosstalk between the two, specifically about the role of two pathways — the bone morphogenic protein, or BMP pathway, and the WNT signaling pathway. These two pathways play important roles in regulating bone,” she said. “We can’t just think about osteoclasts in a vacuum. We have to think about interactions between the osteoclasts and other cell types.”

Dr. Gravallese will review some of that biology and examine its relevance to rheumatic diseases during Sunday’s session. She will discuss how it is specifically relevant to the healing of bone erosions in RA and what it might tell rheumatologists about the impact of inflammation on bone in diseases such as lupus and spondylarthropathies.

Dr. Gravallese will also discuss a variety of new therapeutic agents that are moving through the research and development pipeline. A few of these new agents target the osteoclast. There are also several research programs looking at new agents that target anabolic bone pathways. Some of these new agents are already in clinical trials or are being tested in animal models.

“I want to show attendees what is coming down the pike and what it is about anabolic pathways that could be clinically very important,” Dr. Gravallese said. “This is all about how the latest discoveries in biology translate down the line into new clinical interventions.”

Turning patients into partners can mean better treatment outcomes, lower costs

Rheumatology practices, clinics, and health systems that don’t encourage patients to become partners in their healthcare are missing out on improved outcomes, improved patient satisfaction, improved operational efficiency, and lower costs.

The Dana Farber Cancer Institute in Boston realized all of those benefits with the creation of a pair of patient advisory councils following a highly publicized medication error that killed a prominent newspaper reporter in the 1990s and exposed significant operational problems. A decade later, outcomes are improved, costs are down, and patient satisfaction has never been higher.

“Making the patient a partner is really about appreciating the power of the patient voice,” said Janet Porter, PhD, former Executive Vice President and Chief Operating Officer for Dana Farber. “Figuring out an easy way to engage patients in decision making will, in the long run, give you better outcomes. This will make your life as a hospital administrator easier, not harder.”

Dr. Porter is a co-presenter at a special ARHP Concurrent Session titled Patients as Partners in Design and Delivery, which will be held from 4:30 – 6:00 pm Sunday in Room 204 A of the Washington Convention Center. Her co-presenter is Martie Carnie, patient advocate and former co-chair of the Patient and Family Advisory Council at Dana Farber.

“The patient is a partner in care,” Carnie said. “Treating your patient as your partner doesn’t increase your work volume. In reality, your work decreases. And treating your patient as your partner increases patient satisfaction. In a partnership, you can set realistic expectations and you can meet those expectations. Regardless of the actual outcome, the patient experience can be positive. And when it comes to outcome, we have been able to show that patient outcomes are much better when you integrate the patient experience into the practice.”

Some hospital administrators give lip service to treating patients as partners, but for Dr. Porter it started with her job interview at Dana Farber.

“There was a patient on my search and interview committee,” Dr. Porter said. “I was lucky because the patient didn’t like the other candidate. You could say I got my job because of patient involvement.”

When Dana Farber decided to construct a new building, patients were involved from the very first step, including selecting the architectural firm. Thanks in part to patient involvement, the Yawkey Center for Cancer Care was completed ahead of schedule, $10 million under budget, and with record patient satisfaction.

“If you ask the patients first, you get it right the first time and don’t have to redo things. We don’t do anything at Dana Farber without asking the patients first,” said Dr. Porter.

Working with patients as partners is a dramatic departure from the typical hospital culture, Carnie acknolwledged. With 10 years of experience as a patient advocate, she knows patients have firm views on everything from building design to information brochures. And because patients are so intimately involved in hospital processes and procedures, they tend to have very practical ideas about how to improve operations.

Not only did patients choose the architect for Dana Farber’s treatment center, they helped redesign the treatment workflow. A GPS-based location and navigation system for the center was designed with help from the patients. The result: The mean exam wait time fell from 39 minutes to 21 minutes.

Patient input can be equally important in seemingly simple areas such as patient information brochures. What seems perfectly clear to a hospital communication specialist can be impenetrable jargon to the patient. And when patients don’t understand, compliance falls and outcomes plummet.

A typical hospital brochure might say something like, “Your nurse and your provider will assist you in the emergency room.” That’s a perfectly clear sentence to anyone who works in a healthcare environment, Carnie said, but for patients, the first question will be ‘what’s a provider?’

“If you’re giving patients information they don’t understand, they aren’t going to be compliant with the medication or testing or whatever you need them to do,” Carnie said. “The end results are not going to be as positive as they could be if you were working with the patient as a partner to make sure everything is clear before they walk out the door.”

ARHP sessions will examine infection risk during immunosuppressive therapy

The growing use of immunomodulatory therapies for rheumatologic diseases has raised important concerns about infectious diseases. A series of three ARHP presentations on Tuesday will explore the risks of infection associated with immunomodulating agents and potential strategies to reduce infection.

“Rheumatologists are using a lot of modalities to treat rheumatoid arthritis, particularly antibodies and receptor inhibitors directed against cytokines such as tumor necrosis factor alpha,” said Neil Ampel, MD, Professor of Medicine at the University of Arizona College of Medicine and staff physician at the Southern Arizona Veterans Affairs Health Care System. “These drugs are very effective for treating rheumatologic diseases, but they cause significant immune suppression.”

Not surprisingly, patients who take immunosuppressive agents are at increased risk for infection. Frequent infectious diseases associated with anti-TNF treatment include tuberculosis, histoplasmosis, and coccidioidomycosis (Valley fever). Dr. Ampel will explore the risk, as well as risk reduction strategies, during a presentation on Fungal Infections and Tuberculosis in Patients with Rheumatoid Arthritis from 7:30 – 8:30 am Tuesday in Room 145 A of the Washington Convention Center.

The risk of infection during immunosuppressive therapy cannot be entirely avoided, Dr. Ampel said, but there are strategies to reduce risk. Treatment guidelines call for infectious disease screening before the use of agents such as infliximab and etanercept, although this basic safety precaution is not always taken. Skin tests for latent tuberculosis are available and a serum screen for minimally active Valley fever infection is also recommended.

Patients who test positive can be pretreated for the latent or minimally active infection to reduce the risk of a full-blown infection during anti-TNF treatment. And if one of these infections does break through during immunotherapy, immunosuppressive agents can be restarted once the infection has been successfully treated.

Hepatitis has emerged as another infection of concern in the setting of immunotherapy for rheumatologic disease. Rheumatologists recognize the risk for hepatitis, said Daniel Furst, MD, Professor of Medicine and Director of Therapeutic Research for the Department of Rheumatology at the University of California, Los Angeles. What clinicians may not recognize is that different forms of hepatitis require different management strategies.

“The effect of TNF on hepatitis B and hepatitis C are essentially the opposite,” Dr. Furst said. “TNF inhibition can be used pretty safely on background therapy with hepatitis C, but it has to be used very carefully with hepatitis B.”

Dr. Furst will explore the complexities of Hepatitis in Patients with Rheumatologic Disease from 9:00 – 10:00 am Tuesday. TNF increases dissemination in hepatitis C, he said, which suggests that anti-TNF treatment is appropriate. But TNF inhibits dissemination in hepatitis B, which suggests avoiding agents that suppress or inhibit TNF.

“This is a problem that we run into all the time,” Dr. Furst said. “Both hep B and hep C are pretty common once you start looking. Rheumatologists are supposed to do hep B and hep C screens before beginning therapy with biologics, but we know it doesn’t always happen. You have to screen your patients for both types of hepatitis and understand the differences between B and C to maximize the benefits of treatment while you minimize the risks.”

To vaccinate or not to vaccinate is another common conundrum for clinicians who use biologics as well as older immunosuppressive agents such as methotrexate and steroids. With few exceptions, the answer is to vaccinate.

“There is significant evidence that the uptake of immunization and preventive vaccines is suboptimal,” said Gil Melmed, MD, Director of Clinical Trials for the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center. “In rheumatoid arthritis, psoriasis, Crohn’s disease, or any condition for which immunosuppressives are prescribed and vaccinations are therefore indicated, the utilization of vaccines is significantly poorer than it should be.”

Dr. Melmed will discuss Immunization in Patients with Rheumatologic Disease from 10:30 – 11:30 am Tuesday. The basic message, he said, is that preventive immunizations should be considered in all patients, whether they are newly diagnosed, being evaluated for immunotherapy, or are already on immunotherapy.

“There is a fear of administering vaccines to individuals on immunosuppressive therapy because of the perceived risk of activation of the condition which the vaccine is intended to prevent,” he explained. “In fact, guidelines from the American College of Rheumatology and the Centers for Disease Control strongly advocate for vaccinations precisely because these patients are at increased risk for infection. Vaccines against influenza and pneumococcal pneumonia, for example, should basically be given to everybody. There is significant lack of utilization because there is a knowledge gap among practitioners who prescribe these agents, including biologics.”

The broad rule is that live vaccines should not be given to patients on immunosuppressive agents, Dr. Melmed added, but the broad rule is not universally applicable. For example, there may be a greater risk from shingles infection in unvaccinated patients on immunosuppressive therapy than from shingles in patients who receive the live herpes zoster vaccine while on low doses of immunotherapy.

“This information regarding infection prevention with prophylactic immunizations has direct clinical relevance to all providers who prescribe immunosuppressive and biologic therapies, and may impact daily clinical practice,” Dr. Melmed said.