Tag Archives: arthritis

At 25 Years, NIAMS Celebrates Progress, But Has a Long Way to Go

It’s been 25 years since the establishment of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and great strides have been made in diagnosis, treatment, and management of numerous conditions, “but you ain’t seen nothing yet,” said Dr. Francis Collins, director of the National Institutes of Health.

Opportunities for medical research have never been as great as they are today, said Dr. Collins, who gave the welcome address for NIAMS’ 25th anniversary at the NIH campus in Bethesda, Md.

Although prominent researchers in the field agreed that research has come a long way in the past 25 years, they stressed that there is still a long way to go. Currently, the molecular basis for 4,000 diseases is known, said Dr. Collins. “But we have effective treatment for only 200.”

In broad strokes, the day-long event touched on the past, present, and future of major diseases of bones, joints, muscles, and skin – including muscular dystrophies, osteoporosis, rheumatoid arthritis, and lupus – through panels and discussion involving prominent researchers, physicians, and patient advocates.

“These diseases are chronic, crippling, and common,” said Dr. Stephen Katz, director of NIAMS, in his opening address. “They affect every family in the United States.”

Among the attendees were many researchers and clinicians who said they felt loyalty and appreciation for receiving funding from NIAMS at some point in their career. For some, the progress in the past 2 decades was quite tangible.

“Public investment in osteoporosis research has really changed how we take care of the patients,” said Dr. Sundeep Khosla, president of the American Society for Bone and Mineral Research. Dr. Khosla, professor at the Mayo Medical School, Rochester, Minn., recalled a time more than 2 decades ago when calcium, vitamin D, and estrogen were the only options he could offer to patients with osteoporosis.

A few years later, bisphosphonates became available, then came anabolic drugs, and now more drugs are in the pipeline. Patient diagnosis also has advanced, he said. Although he agreed that the field still has a long way to go, he was optimistic about more progress. “Who knows what will happen in the next 25 years?” he asked.

There was talk of individualized therapy, balancing research and treatment, and a closer collaboration among scientists, all in the spirit of bringing better diagnosis and treatment to patients.

“We’re in a different world from when all we had was aspirin,” said Dr. Daniel Kastner, a scientific director at the National Human Genome Research Institute. “But what we really want is a cure. And we’re not there yet.”

Naseem S. Miller (@ReportingBack)

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Now tell me where ELSE it hurts…

When it comes to managing chronic pain, have physicians been looking in the wrong places? Physical findings in peripheral tissues rarely match up with patients’ reports of pain, or vice versa. Yet, clinicians typically examine only the area where the patient reports the pain, rather than looking at the whole body and considering that the patient’s perception of persistent pain may have a more central origin, according to pain expert Dr. Daniel J. Clauw.

Image by Kira.Belle via Flickr Creative Commons

“There is no chronic pain state where degree of damage or inflammation in the periphery correlates well with level of pain. Yet, the diagnostic algorithms or paradigms that everyone uses for treating chronic pain still assume that all pain is nociceptive. What we see in the peripheral tissues is not necessarily what our patients are experiencing,” Dr. Clauw said at last week at a 2-day scientific workshop on pain and musculoskeletal disorders, sponsored by the University of Michigan and held on the Bethesda, Md., campus of the National Institutes of Health.

That narrow focus has led many medical professionals to assume that when there is a disparity between peripheral findings and pain, the pain must be caused primarily by psychological factors. A prime example is fibromyalgia, still a somewhat controversial diagnosis. But as the first chronic pain syndrome identified as NOT being caused by peripheral inflammation or damage, fibromyalgia is “a metaphor for the centrality of chronic pain,” Dr. Clauw said.

So what should clinicians do differently? First, look beyond the immediate area the patient is complaining about. Has the patient had pain in other parts of the body? Experience frequent headaches? Have irritable bowel? Previous chronic neck pain, and now pain in the hip? “To me as a pain researcher, this is a blinking neon light that the person has a problem with pain processing. It may be that the particular symptom they’re coming in with is due to increased volume control setting rather than a pathologic problem in that part of the body,” Dr. Clauw told me.

And treatment? Ensuring adequate exercise and sleep and reducing stress are important yet underemphasized. Cognitive behavior therapy also has been shown to help. Pharmacologic therapy that acts centrally, rather than peripherally, may also be effective. The antidepressant duloxetine (Cymbalta), for example, is a serotonin/norepinephrine reuptake inhibitor that has been recently approved to treat osteoarthritis of the hip and low back pain, in addition to fibromyalgia and diabetic peripheral nerve pain.

A major challenge, Dr. Clauw believes, might be in getting clinicians to change their approach to pain. “It takes a long time for people trained in one way of thinking to think differently. This isn’t just a new drug or a new device. It’s a major paradigm shift.”

-Miriam E. Tucker (@MiriamETucker on Twitter)

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Got Gout? Put Down that Coffee and Cola

As if suffering from gout isn’t bad enough, new research presented this week at American College of Rheumatology’s annual scientific meeting in Atlanta adds insult to injury.

Researchers led by Dr. Tuhina Neogi of Boston University reviewed data from their study of more than 600 adults with gout. Although previous studies have suggested that long-term caffeine use might relieve gout pain, short-term caffeine used might bring it on.

courtesy of flickr user doug88888 (creative commons)

 In this study, people who drank more coffee, tea, or soda, were significantly more likely to have a gout attack, even after controlling for all the other drinks they had. More specifically, 3-4 caffeinated drinks within the 24 hours prior to a gout attack was associated with a 40 to 80 percent risk of recurrent gout.

And there’s more bad news for gout patients, but this is just for women. Another Boston University research team led by Dr. Hyon Choi presented 22 years’ worth of data from the Nurses’ Health Study showing that women who drank more than two fructose-rich beverages daily (such as orange juice and Atlanta’s lifeblood, Coke) were more than twice as likely to develop gout as those who drank less than one of these beverages per month.

The good news? Diet soda was not associated with any increased risk for gout. Phew! But what about the caffeine? Ok, here’s the deal: Women with gout should stock up on caffeine-free diet soda, at least until the next study comes out. And if I look hard enough, there might be a study about the benefits of chocolate for people with arthritis around here somewhere . . .

–Heidi Splete (@hsplete on twitter)

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Osteoarthritis Pain Assessment Poses Challenges

  What is pain, and how much is too much?

Patients with painful hip or knee osteoarthritis say they know how much pain they should have to make joint replacement surgery necessary, and that their physicians are largely in the dark about their pain. Patients use the Supreme Court’s famous approach to identifying pain that warrants knee surgery: I know it when I feel it.

courtesy Flickr user GlobinMedChiro

To get the perspective of osteoarthritis patients, Dr. Gillian Hawker, a Toronto rheumatologist, and her associates put 58 local patients with moderately severe hip or knee osteoarthritis in focus groups, including 36 veterans of total joint replacement surgery. They discussed joint surgery appropriateness, and the point when appropriateness and their willingness to have the surgery intersect. The major determinant was their pain: their ability to cope with it, and its impact on their quality of life.

Patients “evaluated their pain against some invisible marker,” and despite having what they called high levels of pain they often said it was not bad enough to justify surgery, Dr. Hawker reported last month at the World Congress on Osteoarthritis. As one focus-group patient put it, “I don’t feel I’m ready.” But when their pain became bad enough, they said it trumped all other considerations of whether or not to have joint surgery. Most patients in the focus groups also said their pain had been “inadequately evaluated” by their physicians.

Other study results reported at the Congress also highlighted the highly subjective and variable nature of knee pain. Dr. Tuhina Neogi from Boston University measured central sensitization in knee osteoarthritis patients, and saw that both increased disease severity and duration significantly boosted the incidence of central sensitization, a neurologic process that alters the nervous system and potentially increases pain sensitivity.

Dr. Neogi and her associates found the only way to reliably measure central sensitization was by comparing pain in a patient’s knee affected by osteoarthritis and in the patient’s second, unaffected knee. Comparisons between different patients involved too much variable noise to show a significant link between osteoarthritis and central sensitization. Comparing knees within individual patients cut away the effects of genetics, and psychosocial and cultural factors, allowing each patient to apply their own unique, personal criteria for judging pain severity. 

—Mitchel Zoler (on Twitter @mitchelzoler)

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Filed under Anesthesia and Analgesia, Family Medicine, IMNG, Internal Medicine, Neurology and Neurological Surgery, Orthopedic Surgery, Primary care, Psychiatry, Rheumatology, Surgery

Video of the Week: Despite CV Risks, Meridia Offers Help to the Right Patient

Researchers  involved in the Sibutramine and the Role of Obesity Management in Relation to Cardiovascular Disease in Overweight and Obese Patients (SCOUT) trial have concluded that long-term use of the weight loss drug sibutramine (Meridia) was not associated with an increased risk of death; however, the drug was associated with a significantly increased risk of nonfatal myocardial infarctions and strokes among overweight and obese people with preexisting cardiovascular conditions. The findings were presented at the International Congress on Obesity in Stockholm, and then published in the September 1 issue of the New England Journal of Medicine. Read our story by Elizabeth Mechcatie here.

Mitchel Zoler spoke with Dr. Stephan Rössner of the obesity unit at the Karolinska Institute in Stockholm, who was an invited discussant for the SCOUT presentation. The drug is still a good option for patients without cardiovascular problems, he said.  Sibutramine can be considered for patients with eating disorders, sleep apnea or arthritis, who need additional help losing  or maintaining weight, provided that cardiovascular risk factors are monitored, he added.

Check back here or at Internal Medicine News next week, when Elizabeth Mechcatie will be covering the FDA Advisory Committee meeting on sibutramine September 15-16. You can follow Elizabeth’s coverage on Twitter, @ElizMech.

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Filed under Cardiovascular Medicine, Drug And Device Safety, Endocrinology, Diabetes, and Metabolism, Family Medicine, IMNG, Internal Medicine, Video

When RA Gets in the Way, and When It Doesn’t

There are people who don’t want to exercise, even though they are physically capable of doing so. Ironically, many people with rheumatoid arthritis want to exercise, but they are unable to do so because of chronic pain.

from flickr user dglider (creative commons)

The physical and psychological benefits of exercise are no secret, but in a study by Dr. Vibeke Strand of Stanford (Calif.) University, 49% of women reported that RA pain prevented them from participating in sports and exercising. Dr. Strand’s study, presented at the annual European Congress of Rheumatology (EULAR) in Rome  included nearly 2,000 women with RA.

Of these women, approximately two-thirds said that they experienced pain on a daily basis, including a majority of those who reported taking pain medication regularly. The study participants also reported that RA interfered with leisure activities and personal relationships, and even contributed to the deterioration of friendships and the end of marriages, Dr. Strand said in an interview.

The complete study data highlight the challenges of assessing and treating pain in patients with RA. The study results were limited by the use of self-reports of RA, but approximately 67% of the women said that they were constantly searching for new forms of pain relief.

Another event at the meeting highlighted how exercise empowers RA patients, including some who are severely disabled. An organization called Biking Against Rheumatism in Europe (BARIE) sponsored a multiday event in which a group of bikers, including individuals with severe RA riding on customized bikes, rode from Brussels to Rome, arriving on the first day of the meeting. Dr Strand’s data suggest that most of them were battling chronic pain. The goal of BARIE is to raise awareness of rheumatism. Ideally, more awareness will lead to more support for research, so more patients can live pain free for better physical and psychological health.

–Heidi Splete (on twitter @hsplete)

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Tocilizumab Approval Causes Buzz

One year after asking the Roche group to submit additional data for its monoclonal antibody tocilizumab, the FDA has approved the biologic agent for the treatment of moderate to severe rheumatoid arthritis (see story).

Although the drug, to be marketed under the name Actemra, is entering a somewhat crowded biologics market—it is joining abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab —it is the first and so far only interleukin-6 (IL-6) receptor inhibitor to be approved for the indication, and clinicians are cautiously optimistic that it will improve the lives of patients who have not responded to therapy with methotrexate alone or in combination with other disease modifying antirheumatic drugs (DMARDS).

 In fact, tocilizumab has been approved specifically for those adult patients who have failed methotrexate and one or more tumor necrosis factor antagonist, according to an announcement released today by the drug’s manufacturer, Roche Holding AG. 

The FDA approval is a much-anticipated development, according to Dr. Larry Greenbaum, a rheumatologist in private practice in Indianapolis. “It’s very exciting. Actually, one of the drug representatives has been stopping by my office for the last year or two, dropping hints about this product, although the company has not been allowed to “detail” the drug before release. And of course, there have been many drug company ads creating a crescendo of drum beats before the official release date,” he said in an interview.

The novelty of tocilizumab lends to the excitement. “There are multiple anti-TNF medications currently, and the reps for those drugs are trying very hard to convince clinicians to choose one medication over another, even though they are probably more similar than different,” Dr. Greenbaum commented. As an IL-6 blocker, tocilizumab IS different, which is why the industry is buzzing, he noted.

The new-drug hype notwithstanding, there are still a number of questions to be answered before clinicians can consider the potential clinical impact of tocilizumab, according to Dr. Greenbaum. “The main questions for me are: Is this medication any safer or more dangerous than the current biologic drugs? Is this medication more or less affordable (or accessible) than the current biologics? Where does this medication belong in the treatment algorithm?

“Undoubtedly, the company is going to try and convince doctors to use this medication immediately after methotrexate failure, but they will first have to convince doctors (and insurers) that this strategy is warranted,” Dr. Greenbaum said.

Of particular concern are the side effects. Biologic agents are powerhouse drugs, and powerhouse drugs often have the potential for causing serious adverse effects. Among the serious tocilizumab-related adverse events that have been reported in pivotal clinical trials include infections that lead to hospitalization or death, including tuberculosis, bacterial, invasive fungal, viral and other infections; gastrointestinal perforations; hypersensitivity reactions; and cellulitis. In March 2009, Roche’s Chugai Pharmaceuticals reported that among nearly 5,000 rheumatoid arthritis patients in Japan who had been treated with tocilizumab between April 2008 and February 2009, 15 deaths occurred and the possibility of a link to the drug could not be denied, although the exact causes of the deaths were unknown, according to a press release issued by the company.

Some of the common side effects associated with tocilizumab include upper respiratory infections, including pneumonia, inflammation of the nose and throat, headache, high blood pressure, increased liver enzymes, increased cholesterol levels, neutrophil decreases, and platelet decreases, according to the company.

The drug’s approval comes with a Risk Evaluation and Mitigation Strategy (REMS), which includes a medication guide, communication plan, and timetable for submission of assessments. The drug itself will be available the week of January 18, 2010.

—Diana Mahoney (on Twitter @dmpm1)


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Rheumatoid Arthritis 5.0

From the annual scientific sessions of the American College of Rheumatology in Philadelphia

Rheumatologists have remade rheumatoid arthritis, a pretty big deal for them if only because it’s “the major systemic rheumatic disease that we as a specialty treat,” said Dr. Michael E. Weinblatt, a Harvard rheumatologist, at the end of a 90-minute session on Sunday afternoon that unveiled a new definition of rheumatoid arthritis to the world.

The culmination of a 3-year collaboration between the American College of Rheumatology and the European League Against Rheumatism (EULAR), the new RA definition, the first in more than 20 years, is a consensus agreement from a large panel of experts on which patients with a new inflammatory arthritis have enough risk of progressing to erosive arthrtis that all rheumatologists would immediately start treatment with a disease modifying drug.

“We need to change the way we think about arthritis,” because today “the aim is to prevent development of the disease that satisfied the 1987 ACR  criteria,” said Dr. Alan J. Silman, a rheumatologist at Manchester University, UK. “Satisfying the 1987 criteria is bad news. No one now waits till the disease becomes erosive to start disease modifying therapy.”

the new RA diagnostic criteria/photo by Mitchel Zoler

the new RA diagnostic criteria/photo by Mitchel Zoler

The  new criteria use four basic categories of signs and symptoms, and a point system in which a score of 6 or more means definite rheumatoid arthritis, with no need for radiographic change. The score table and the steps that created it were reported by Dr. Gillian A. Hawker, a rheumatologist at Women’s College Hospital in Toronto. This is actually the fifth definition of rheumatoid arthritis, a lineage that began just over 50 years ago with the first definition from the American Rheumatism Association.

A new definition that breaks so dramatically from the old is bound to trigger issues that will take months to sort out, such as  insurance coverage, research designs, and a need to apply the new definition carefully to avoid misdiagnoses. But the main message at Sunday’s session on what this means was that “this sets the stage for us to treat patients earlier,” Dr. Weinblatt said. “It will allow more rapid institution of disease-modifying therapy.”

An article with my full coverage of the new RA diagnostic criteria is here.

—Mitchel Zoler, 1 AM Oct 19 in Wynnewood, PA (on Twitter @mitchelzoler)

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