January/February 2009

Top 10 Arthritis-Related Events of 2008

Each year the Arthritis Foundation highlights the top 10 most significant events affecting the arthritis community. From achievements in public policy to new research findings, 2008 was a year marked by groundbreaking developments on both scientific and social fronts.
News that made the Arthritis Foundation’s Top 10 include reports on the ongoing severity of and risk for arthritis; the proof and promise of biologic medications in treating several forms of arthritis; clues to better understanding arthritis' origins; and the growth of governmental support for programs designed to help people with arthritis.

1. House Passes Landmark Arthritis Legislation
2. Early Aggressive Therapy Best for RA
3. Kinase Inhibitors Promising Treatment for RA
4. Arthritis Hampers Activity in Adults With Diabetes
5. Biologic Therapies Benefit Children With JA
6. Cardiovascular Risk High in Arthritis
7. State Arthritis Programs Enhanced
8. Immune System Ages Early in Arthritis
9. Gingivitis and RA Linked
10. Nearly Half of Americans Will Develop OA

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 1) HOUSE PASSES LANDMARK ARTHRITIS LEGISLATION

The U.S. House of Representatives passed the Arthritis Prevention, Control and Cure Act (APCCA), the first comprehensive arthritis legislation in more than 30 years. The legislation seeks to expand and strengthen research and public health initiatives proven to combat the burden of arthritis and improve access to pediatric rheumatologists to address the country’s severe shortage of these critical health professionals.

Although the bill never came to a vote in the Senate, the momentum behind the bill is strong and optimism for congressional passage in 2009 is high.

The APCCA encompasses several initiatives that have the potential to greatly improve the lives of people with arthritis. It’s written to:

Enhance public health activities related to arthritis. By fully implementing the Center for Disease Control and Prevention (CDC) National Arthritis Action Plan (NAAP), several public health activities can be enacted.

Proposed endeavors include collecting prevalence/incidence data; conducting public health surveillance; identifying best practices for prevention, diagnosis, management and care of arthritis; promoting community-based and patient self-management programs and activities; developing public information and education programs; expanding physical activity programs; and informing the public about nutrition education opportunities.

Expand and intensify research and public health activities related to juvenile arthritis. Grants and cooperative agreements will be made available to collect data on the prevalence, incidence and outcomes associated with juvenile arthritis at the CDC, including the development of a National Juvenile Arthritis Patient Registry.

Invest in tomorrow’s pediatric rheumatologists. To overcome the desperate shortage of physicians who specialize in the treatment of children with arthritis and related diseases, the Act provides for grants to institutions supporting pediatric rheumatology and expands public-private partnerships to encourage pediatric rheumatology education and training. A loan repayment program would provide funds for professionals entering the field of pediatric rheumatology.

To receive updates on the Arthritis Foundation's advocacy efforts, visit www.arthritis.org/advocacy and sign up to become an Arthritis Advocate.

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2) EARLY, AGGRESSIVE THERAPY BEST FOR RA

Twenty years ago, doctors believed the best protocol for treating rheumatoid arthritis (RA) was to start slow and build gradually until an adequate level of pain and inflammation control was reached. This way of thinking has changed over the years, and physicians now treat RA much more aggressively from the time of diagnosis. With the advent of new biologic medications, the treatment possibilities for people with RA are many and their appropriate use is still being established.

Several key studies released data in 2008 provide physicians with more information on which to base their treatment decisions. Two of note showed that traditional disease-modifying antirheumatic drugs (DMARDs) can be used with excellent effect. Three others showed effective uses of adalimumab (Humira) in the treatment of RA.

One study used traditional DMARDs, comparing a step-up approach to therapy (sulfasalazine alone; then after 3 months, methotrexate was added; and when the maximum tolerated dosage of methotrexate was reached, hydroxychloroquine was added) against parallel triple therapy (giving the three drugs at the same time from the beginning). The research team found that highly effective control of disease activity can be achieved using conventional DMARDs as part of an intensive disease management strategy. In this study, step-up therapy was as effective as parallel triple therapy.

Another study found that people with RA who respond well to methotrexate therapy – achieving a low disease activity score within four months – continue to have very good clinical responses throughout the first year. An initial good response to methotrexate defines a sub-population of people with early RA who can expect excellent one-year clinical prognoses.

Now that the biologic adalimumab has been on the market for several years, long-term study results are being released. Five-year results of the ongoing PREMIER study were released at the American College of Rheumatology Annual Scientific Meeting in October. This study compared the effectiveness of adalimumab in people with early RA (less than 3 years’ duration) by comparing initial adalimumab plus methotrexate therapy, adalimumab alone, or methotrexate alone for two years. After the first two years, participants were able to continue taking adlimumab either with methotrexate or not. After a total of five years, combination therapy led to the best long-term inhibition of radiographic progression, best clinical remission rates, and best reduction of inflammation as measured by C-reactive protein.

For more information on medications used to treat RA and other forms of arthritis, visit www.arthritistoday.org.

To order your free copy of the Arthritis Today Drug Guide or the Arthritis Foundation’s DMARDs brochure, call 800-283-7800.

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3) KINASE INHIBITORS PROMISING TREATMENT FOR RA

The treatment of rheumatoid arthritis (RA) has improved tremendously over the past decade since the introduction of biologic agents. These agents, however, are expensive to produce and must be administered via injection or intravenous infusion. In 2008, great strides have been made toward the development of a new type of RA medication that can be taken by mouth. These drugs are called kinase inhibitors and they interrupt the transfer of chemical signals involved in inflammation.

Spleen tyrosine kinase (Syk) is an important mediator of immune signaling in a variety of cells, including mast cells, macrophages, neutrophils, and B cells. Results of a clinical trial testing a Syk kinase inhibitor were released in November in which researchers studied people with active RA who were already taking methotrexate. Participants received either the new drug at difference dosage amounts or placebo. After 12 weeks of treatment, researchers found the two higher dosages tested were both effective; however, there were more adverse events with the highest dosage. The participants noted symptom relief in as little as one week. There was also a significant decrease from baseline in biomarkers of disease activity. The research team concluded, “The rapid onset of effect, the improvement in arthritis parameters and serum biomarkers show that inhibition of Syk kinase is a viable new target for the treatment of rheumatoid arthritis.”

Jak-3 is a kinase involved in chemical signal transfer in B cells, T cells and natural killer cells – all of which are implicated in RA pathology. Early results of a clinical trial of a Jak-3 inhibitor were released in 2008. In this study, people with active RA who were receiving stable dosages of methotrexate but who did not get adequate relief from that drug were recruited. The participants received one of six dose levels of an oral Jak-3 inhibitor or placebo. The research team determined that doses of the Jak-3 inhibitor at 3-mg twice daily and higher were significantly more effective than placebo. Of participants in the 15-mg group, and nearly 38 percent reached clinical remission, whereas only 9 percent in placebo group got that result. Adverse events were dependent on the dosage taken. The research team concluded that the oral Jak-3 inhibitor in combination with methotrexate is efficacious, safe and well tolerated in patients with active rheumatoid arthritis and is suitable for further evaluation in and expanded clinical trial.

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4) ARTHRITIS HAMPERS ACTIVITY IN ADULTS WITH DIABETES

An important study released by the Centers for Disease Control and Prevention (CDC) in 2008 found more than half of adults with diagnosed diabetes also have arthritis, a painful condition that can be a barrier to physical activity. Physical activity is an important health strategy for managing both diabetes and arthritis, and lack of activity hinders successful management of these diseases.

The CDC analyzed data from the 2005 and 2007 Behavioral Risk Factor Surveillance System (BRFSS), which is a state-based, telephone survey. The data found the prevalence of arthritis among adults with diabetes to be 52 percent, compared with about 27 percent for all adults.

The prevalence of physical inactivity was significantly higher among adults with both diabetes and arthritis (30 percent) compared with those with diabetes alone (21 percent), arthritis alone (17 percent) and among adults without arthritis or diabetes (11 percent). A person with both arthritis and diabetes is 1.3 times more likely to be physically inactive than a person with neither condition, even after adjusting for age, sex and body mass index (BMI).

The study suggests adults with diabetes and arthritis have additional barriers to physical activity, such as concerns about pain, or aggravating and worsening arthritis condition, thereby limiting the ability to manage both conditions.
“Arthritis is a frequent comorbid condition for adults with diabetes,” said John H. Klippel, M.D., president and CEO, Arthritis Foundation. “But for both diseases, physical activity is key to effective management. A lack of physical activity actually results in undesirable consequences including increased pain, stiffness, inflammation, physical limitation and potential disability.

The good news is that safe and effective self-management programs are available. People living with arthritis and diabetes can benefit from participating in one of the Arthritis Foundation’s exercise or self-management programs, such as the Arthritis Foundation Aquatic Program, the Arthritis Foundation Exercise Program and the Arthritis Foundation Self-Help Program,” said Dr. Klippel.

To learn about the Arthritis Foundation exercise and self-management programs available in your community, call 800-283-7800 or visit www.arthritis.org.

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5) BIOLOGIC THERAPIES BENEFIT CHILDREN WITH JA

Up until 2008, the only biologic agent approved by the Food and Drug Administration for use in children with juvenile idiopathic arthritis (JIA; sometimes called juvenile rheumatoid arthritis) was etanercept (Enbrel), which gained the OK for use in children in 1999. But 2008 was a banner year for kids living with arthritis because two new biologic agents were approved for use in children.

On February 21, 2008, adalimumab (Humira) was approved by the FDA for reducing signs and symptoms of moderately to severely active polyarticular JIA in patients four years of age and older. Then on April 8, 2008, abatacept (Orencia) was approved for use in patients six years and older.

Results of additional studies showing the safety and efficacy of biologic drugs in children were released in 2008 as well. Two studies of particular relevance and importance involved the two newly approved medications: adalimumab and abatacept. Both studies represent coordinated efforts by pediatric rheumatologists worldwide and highlight the importance of professional cooperation when conducting clinical trials in relatively rare diseases.

One study assessed the safety and efficacy of abatacept, a biologic drug that acts on T cell activity, in children with active JIA who didn’t find relief from other treatments. Of the participants who responded well to abatacept, half continued to receive the biologic and half were unknowingly switched to placebo. The researchers then waited to see if the children would experience a disease flare. Flares occurred in 53 percent of participants getting placebo and 20 percent of those getting abatacept. On average, it took 6 months for those given placebo to have a flare.

Another study was conducted to evaluate the efficacy and safety of adalimumab in children with active JIA who had not responded adequately to treatment with nonsteroidal anti-inflammatory drugs. The participants either had never been treated with methotrexate or had been treated but experienced adverse events or inadequate response. All patients received adalimumab for 16 weeks and half also received methotrexate. After this portion of the study, half of the participants continued to receive adalimumab, and half were unknowingly switched to a placebo. The researchers then waited to see if the children would experience a disease flare, and how long it would take for that to occur.

After the initial phase of treatment, 94 percent of those children receiving both adalimumab and methotrexate showed a significant improvement in disease signs and symptoms. During the second phase of the study, disease flares occurred in 71 percent of those receiving just placebo, 65 percent of those receiving just methotrexate, 43 percent of those receiving just adalimumab, and 37 percent of those receiving adalimumab plus methotrexate. Because disease flare was defined as a relatively small degree of worsening, many patients met the criteria for a disease flare while still showing substantial improvement compared with study entry.

After the double-blind phase of the trial was complete, some participants continued to receive adalimumab. Of those, after two years of treatment, 40 percent had achieved 100 percent improvement in symptoms compared with when they first entered the study.

For more information on juvenile arthritis, call 800-283-7800 to buy the Raising a Child With Arthritis: A Parent’s Guide book or request a free copy of the Arthritis in Children brochure.

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6) CARDIOVASCULAR RISK HIGH IN ARTHRITIS

Over recent years, evidence has shown that people with rheumatoid arthritis (RA) are more likely to have cardiovas­cular disease (CVD) than the general population, even after adjusting for traditional CVD risk factors, such as diabetes, high cholesterol, smoking, high blood pressure and being overweight. An important study released in 2008 has now found that people with RA have as high or an even greater risk of CVD than people with type 2 diabetes, a recognized risk factor.

In this study, the research team found the prevalence of CVD was 5 percent in individuals without diabetes, 12.4 percent in people with type 2 diabetes, and 12.9 percent in those with RA. After adjusting for age, sex and conventional cardiovascular risk factors, the study found that a person with type 2 diabetes is twice as likely to have CVD as a healthy individual, and the likelihood for a person with RA to have CVD is 2.7 times that of a person without RA.

As we saw with Top 10 item number 4, diabetes and arthri­tis are involved in a feedback loop that leads to worsening of both diseases. If you add in heart disease risk, the vicious cycle becomes even more serious. Arthritis pain prevents people from getting the exercise they need, which can contribute to weight gain and the development of type 2 diabetes. Both diabetes and rheumatoid arthritis increase a person’s risk of CVD, as does obesity. Physical activity can break this cycle because it lessens your risk of disability due to arthritis, helps control weight and reduces your risk of developing type 2 diabetes.

Another study released in 2008 looked at cardiac complica­tions that occur after total joint replacement. The research­ers matched people who had had a joint replacement and suffered a cardiac complication with an equal number of people who had had a joint replacement but no cardiac complication. Along with the typical factors associated with a higher risk of cardiac complications (a history of irregular heartbeat, coronary artery disease, heart attack, heart failure), the research team identified two new risk factors for cardiac complications following total joint replacement: having two joints replaced at the same time, and having surgery on a joint that had already been replaced once.

These studies emphasize the importance for people with arthritis to be particularly diligent when it comes to caring for their heart and preventing cardiovascular complications.

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7) STATE ARTHRITIS PROGRAMS ENHANCED

The Centers for Disease Control and Prevention (CDC), guided by recommendations in National Arthritis Action Plan: A Public Health Strategy, has been funding arthritis programs since 1999. In 2008, the state-based programs funded through the CDC entered into a new, enhanced phase.

In 2007, a panel of national experts reviewed the arthritis programs funded through state health departments and made several important recommendations that led to major changes in the program that took effect in 2008.

An important outcome was to strengthen programs by providing states with sufficient funds to extend effective, evidence-based interventions to reach more people with arthritis. States will now use CDC funding to dramatically increase the availability of interventions such as Arthritis Foundation exercise programs, strengthen partnerships with Arthritis Foundation chapters and others, increase public awareness, and improve their ability to monitor the burden of arthritis and coordinate activities. The central aim is to improve the quality of life of people affected by arthritis.

As a result of increased investment in funded states, the CDC has funded 12 states for the period of 2008-2011, with average funding levels of approximately $500,000. This funding level is now on par with other major chronic disease programs.
With this enhanced program, states will increase awareness that something can be done for arthritis and will help people strive toward a goal of a life free of arthritis pain.

To learn more about the services the Arthritis Foundation offers near you, visit www.arthritis.org and type in your zip code in the box provided.

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8) IMMUNE SYSTEM AGES EARLY IN ARTHRITIS

Patients with autoimmune diseases such as rheumatoid arthritis (RA) have immune system abnormalities that resemble characteristics of immune dysfunction typically seen in the elderly. Studies released in 2008 reinforce and expand upon evidence previously released that people with autoimmune arthritis perhaps are biologically older than their chronologic age would indicate.

With aging, the thymus gland shrinks and produces fewer and fewer new T cells – a cell type intimately involved in the RA disease process. To compensate for this reduction in new cells, existing T cells replicate and divide more frequently. Every time a cell replicates, a buffering segment at the end of each DNA strand called the telomere gets a bit shorter. Therefore, the biologic age of the immune system can be estimated by the length of the T-cells’ telomeres.

One study released in 2008 dug deeper into this phenomenon to determine the root of the premature aging. All immune cells ultimately come from bone marrow stem cells. Because stem cells have the ability to repair their telomeres, they have been considered to live forever; however, even in healthy individuals the stem cell reserve dwindles slowly as life progresses.

Researchers have now examined the biologic age and function of such bone marrow stem cells in RA. In people with RA, bone marrow stem cells lose their telomeres at a faster pace than in healthy individuals. Telomere sequences in 30-year-old people with RA were already as short as those in the 60-year-old healthy controls. This marked telomere shortening indicates the bone marrow cells were stressed in an attempt to keep up with high replication demands.

Thus, the researchers concluded that not only the immune cells but also the stem cells from which they originate are aging before their time. Defective function of bone marrow stem cells was independent of disease activity, suggesting bone marrow failure as a potential factor in the development of RA.

With data accumulating that the immune system in adults with RA ages prematurely, researchers released new data in 2008 showing similar premature aging in the immune system cells of children with juvenile idiopathic arthritis (JIA).
The research team measured three indicators of immune cell aging. The scientists found that children with JIA showed an accelerated loss of T cells with advancing age. An accelerated decrease in the number of T cells in JIA patients may reflect loss of the ability of the thymus to produce new cells or the inability of existing T cells to proliferate fast enough. Their findings indicate that the immune system of JIA patients is considerably older than their chronological age, as is seen in RA patients.

These findings illustrate that premature aging of the immune system, and disturbed T cell numbers and functionality could be contributing to the immunologic abnormalities associated with autoimmunity and aging.

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9) GINGIVITIS AND RA LINKED

Results of several studies released in 2008 have linked periodontal disease (also called gingivitis or gum disease) and rheumatoid arthritis (RA), revealing that people with RA are much more likely to have gum disease than people without RA.

One possible explanation for this co-occurrence is that pain and inflammation in the hands makes brushing and flossing difficult, leading to poor oral hygiene. However, the studies found that although oral hygiene was a factor, it did not fully explain the association between the two diseases. The results of these studies suggest that other parameters – most likely factors related to chronic inflammation – are responsible for the increased prevalence of gum disease in people with RA.

One small study found that RA patients are nearly eight times more likely to have periodontal disease compared to the control subjects. These findings accounted for such demographic and lifestyle characteristics as age, sex, education and tobacco use.

Other studies delved deeper into the association to look for disease and biochemical factors that could link the two conditions.

In a group of U.S. veterans with RA, scientists found that periodontal disease was more common and more severe in people with RA compared to people with osteoarthritis (OA). The research team found no association between gum disease and RA disease activity.

In research funded in part by grants from the Arthritis Foundation, another research team did find an association between periodontal disease symptoms and RA disease activity. This team, who reported findings in 2007 that periodontal disease was frequent and severe in people with RA, evaluated oral health in a larger group of people with RA. The overall prevalence of gum symptoms was 82 percent. And after adjusting for confounding factors, RA disease activity was significantly associated with periodontal symptoms. This relationship was further amplified with oral dryness, a common problem in RA patients.

Three research groups indicated that anti-citric citrullinated protein (anti-CCP) antibodies may play a role in the overlap of these two diseases. Anti-CCP antibodies are specific for RA, and precede the onset of clinically detectable disease. Concentrations of these antibodies were higher in people with both RA and evidence of infection with the bacteria that causes gingivitis.
The finding of these various studies argue for greater attention to dental care in people with rheumatoid arthritis.

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10) NEARLY HALF OF AMERICANS WILL DEVELOP OA

A landmark government study released in 2008 suggests nearly one in two people (45 percent) will develop painful knee osteoarthritis (OA) over their lifetime, with the highest risk among those who are obese.

The study was conducted using data from the Johnston County Osteoarthritis Project, a long-term study of black and white women and men age 45 years or older living in rural North Carolina. It is one of the largest longitudinal studies to monitor the onset and progression of knee and hip OA in this country.

Symptoms were determined through a question about each knee: “On MOST days do you have pain, aching, or stiffness in your LEFT (or RIGHT) knee?” Radiographic knee OA was determined by taking X-ray views of both knees, which were read by a radiologist and scored using the Kellgren/Lawrence (K/L) scale. Symptomatic knee OA was defined as a K/L grade of ≥2 (at least mild radiographic OA) and symptoms in the same knee.

The study found that 60.5 percent of obese individuals – that is, those having a body mass index (BMI) greater than 30 – will develop symptomatic knee OA over their lifetime. The study also found that those with a prior knee injury were also at high risk, with a probability of developing the disease over their lifetime of 57 percent.

“Weight loss can lead to a decreased risk of symptomatic knee OA, and the association between the modifiable risk factor, BMI, and lifetime risk of OA in this study further underscores the need for public health weight loss and management interventions that would contribute to a decreased lifetime risk of OA,” conclude the study authors.

“While Americans are looking forward to longer life expectancies than ever before, the reality is that they will also be facing many more years of pain and disability,” said John H. Klippel, M.D., president and CEO of the Arthritis Foundation. “Obesity in this country is at an all-time high, putting millions at risk for disabling arthritis. Coupled with sedentary lifestyles and an aging baby boomer population, we are facing a public health crisis if Americans and Congress don’t take action.”

For more information on how you can make physical activity a part of your life, visit www.letsmovetogether.org or call 800-283-7800 to order a copy of the Arthritis and Walking brochure or Arthritis Today Walking Guide.

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