Slide Kit with Audio
This activity is based on a 45-minute slide lecture presented by Dr. John Goldman. This program is available as read only and with accompanying audio.
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Slide 1: Welcome to the Coalition of Rheumatology Educators program entitled “Managing Comorbidities in Rheumatoid Arthritis (RA).”
This activity is jointly sponsored by the American Academy of CME, Inc and Princeton CME. It is supported by educational grants from Amgen Inc, Wyeth Pharmaceuticals, Bristol-Myers Squibb Company, Genentech Inc, Biogen IDEC Inc, and Abbott Laboratories.
I am John Goldman, a practicing rheumatologist from Atlanta, and I will be your presenter for today’s activity.
Slide 2: What we are going to be doing with our session today is to recognize the connection between uncontrolled RA and the development of comorbid conditions.
We are also going to incorporate evidence-based approaches for the prevention and management of treatment adverse effects, as well as comorbidities of RA.
Slide 3: Think about these 2 questions as you listen to the presentation.
Should the expanding knowledge of RA-associated comorbidities change the way patients with RA are managed? And also, is the rheumatologist responsible for the global care of the RA patient?
Slide 4: Unfortunately, despite major enhancements in RA therapy during the past decade, the disease remains uncontrolled in many patients. The best outcome in RA patients is not just improvement of their RA, but also improvement of their total health.
We have to consider proper management of the disease to help stop the development of some of these serious and costly complications and comorbidities. The best way to treat comorbidities is to avoid them or manage them early in the disease process.
Slide 5: Comorbidities are inherently associated with RA. Uncontrolled RA is associated with various complications and comorbidities, including increased risk of mortality, inflammation and its consequences, cardiovascular disease, and RA and its effect on therapy. Smoking and RA have combined risks, both of causing rheumatoid and making it worse. Corticosteroid use in RA treatment has benefits, but we are learning more and more that there are risks. Diabetes and obesity in RA actually have their effect on the disease. Also, there are extraarticular manifestations of disease and its impact on RA outcomes.
These RA-related comorbidities may be associated with disease progression, or they may manifest as adverse events of current therapy. So we need to consider both the disease itself and the therapy. And these are the ones we will discuss today.
Slide 6: Complications of uncontrolled disease include nodules and extraarticular disease, as there is a link between nodules, extraarticular RA, and cardiovascular disease. There are increased risks of infection, increased risk of lymphoma, cardiovascular disease, and osteoporosis—both localized, juxtaarticular osteoporosis and systemic—and amyloidosis.
Slide 7: As you listen to the presentation, think about this question, “Should rheumatologists provide health prevention services?”
Slide 8: These health prevention services could include Papanicolaou smears, cholesterol testing, mammography, clinical breast examination, blood pressure management, influenza and pneumococcal vaccinations, colonoscopy, prostate exams and PSA levels, and advice on tobacco use, diet, and weight loss.
Keep in mind how common comorbidities are and how often they affect outcome. Through early and aggressive assessment and treatment, clinicians should strive to ensure that patients with RA avoid comorbidities and can coordinate this care with the patient’s primary healthcare team.
Slide 9: This cartoon by Kirwan notes that as we assess RA progression, we see inflammation, disability, and radiographic damage, and these are areas of immense concern.
Inflammation tends to be more common early in the disease, abating with time. Conversely, radiographic damage can occur early in the disease process, but also becomes more visible with time. Generally, disability occurring early corresponds to the inflammation, and with time, follows a similar pattern to radiographic change, as we see in this graphic—beginning early and worsening with time.
Slide 10: But consider the Titanic being sunk by the iceberg. Under this burden of the curve of inflammatory arthritis, inflammatory damage, and cumulative damage with years of RA, this begets tissue damage, early mortality, premature arteriosclerosis, amyloidosis, osteoporosis, and lymphoma.
Slide 11: The presence of RA-related comorbidities appears to be a predictive factor for negative patient outcomes. Rheumatoid is aggressive and knows no boundaries, and collateral damage can occur.
Patients with RA are twice as likely to have a myocardial infarction, 70% more likely to have a stroke, and 70% more likely to develop an infection. Patients with RA can have up to 25 times increased risk of non-Hodgkin’s lymphoma. Studies have shown that this seems to relate to the amount of inflammation. Life expectancy in patients with RA is reduced by up to 18 years. Osteoporosis is common in patients with RA, and the new World Health Organization fracture risk assessment criteria, which we are now told will come out in 2008, will include RA as a highlighted fracture risk in the assessment profile. Women with RA have a 41% higher mortality rate compared with men.
Slide 12: How common are these comorbidities? The British Society of Rheumatology Biologic Register noted that there were 58% with more than 1 and 25% with more than 2 comorbidities. This looked at hypertension, depression, peptic ulcer disease, and respiratory disease.
The study by Kroot had data on 186 patients with early RA, who were followed up for 4.3 years. 27% had more than 1 comorbid condition, including cardiovascular disease (29%), respiratory (18%), and dermatologic (11%). Also, two thirds of patients had comorbidity present before RA.
A study presented at the 2007 American College of Rheumatology (ACR) meeting in Boston was a population-based study that looked at the National Health Interview Survey results in over 31,000 patients. They looked at the respondents who might answer yes to, “Have you ever been told by a doctor or other health professional that you have had some form of arthritis, RA, gout, lupus, or fibromyalgia?”
While the respondents reported the diagnosis of a variety of comorbidities, they focused on 11. They found that the respondents who said they had been told they had arthritis were 2.6, 6.3, 11.8, and 33.1 times more likely to have 1 to 2, 3 to 4, 5 to 6, or 7 or more comorbidities. There was a moderate odds ratio of 1.5 to 3.1 for diabetes, vision problems, thyroid problems, gastrointestinal, and neck and back pain. And a modest odds ratio increase of 1.2 to 1.4 for neurologic, respiratory, cardiovascular, anxiety and depression, cancer, and stroke.
Slide 13: Due to the varied comorbidity profile, patients with RA have an increased risk of mortality, and life expectancy is reduced by 18 years. In this graphic, which shows patients with RA who have an increased risk of mortality, the orange bars are a cohort analysis of Mayo Clinic data when a patient was diagnosed with RA, between 1955 and 1994. They found that patients with RA had a significantly higher risk of death with a standard mortality ratio of 1.27. It was higher in women at 1.41 compared to men at 1.08.
The blue bars are an analysis of data on patients with RA treated at 4 centers over 35 years. And again, the findings show the standard mortality ratio to be higher, 2.26. Again, it was more elevated in women, 2.36, as compared to men at 2.14.
Slide 14: Mortality is influenced by inflammation, disability, and prednisone use. This slide shows the all-cause mortality in early and established RA, looking at cardiovascular disease, cancer, and infection. For each additional damaged joint, the risk increase was 15%. For each increase in SED rate of 10 mm, the increased risk was 30%. Each 1-point increase in the Stanford Health Assessment Questionnaire (SHAQ), showed a 55% increase. And for each milligram of prednisone, there was a 15% increase in all-cause mortality. In prednisone use itself, there was an 81% increase. The all-cause mortality is increased in RA and cardiovascular events lead the way.
Slide 15: Now, at the ACR meeting in November 2007, a study from the Mayo Clinic looked at the 10-year cardiovascular risk in newly diagnosed patients with RA. As we can see, the bars compare non-RA with RA patients. They look at cardiovascular increase, a risk of greater than 50%, 20% to 50%, 10% to 20%, 6% to 10%, and less than 6%. The absolute risk assessment shows that more than half of the patients, aged 50 to 59—and these are newly diagnosed subjects who were put in this study, excluding the history of cardiovascular disease—and all of those over the age of 60 had a 10% or greater risk of cardiovascular disease within 10 years. These data are impressive, because if you look at the 50 to 59 age range, it was 85% compared to 27%. And when you look at the 60 to 69 age range, it was 100% compared to 79%.
Slide 16: Now, cardiovascular disease may be linked to medicines commonly prescribed to manage signs and symptoms of RA. This slide shows the risk of hospitalization for cardiovascular event. It is a case-controlled study using the Pennsylvania Medicare-Medicaid database which showed 946 hospitalizations for stroke or M.I. in 3,501 patients. This study showed that patients receiving methotrexate, compared with patients using glucocorticoids and cytotoxic, immune suppressive drugs were more likely to experience a cardiovascular event, such as stroke or myocardial infarction, 50% and 80%, respectively.
There was no increase in risk in cardiovascular events in this study with TNF therapy, but as you will see later in this presentation, there are data that show that. The increased risk of stroke and composite end point was especially seen with corticosteroids.
Slide 17: There is an interplay of factors that seem to cause premature death in patients with RA. Patients with RA not only die earlier, they die with cardiovascular disease and there is a relationship to aging. The prevalence of RA in older patients has increased over the younger population. Research has shown the possibility that the immune system is senescent in patients with RA. The question is, Is this premature senescence due to aging, which causes RA? Or does RA cause this aging of the immune system? So, an older immune system makes one at greater risk for developing RA.
Slide 18: Now, the potential mechanisms of increased risk for cardiovascular disease and RA include increased prevalence of cardiovascular risk factors, increased thrombotic tendency, decreased physical activity, and drug toxicity—we talked about corticosteroids and NSAIDs—and both COX-1 and COX-2 have cardiovascular risk factors. Methotrexate and TNF may have effects both ways, but actually may help improve or decrease cardiovascular risk. Methotrexate may have a cardiovascular risk on the relationship of hyperhomocysteinemia, which is 1 of the things that is combated with concomitant folic acid therapy.
There also may be increased risk because of endothelial dysfunction, dyslipidemia, insulin resistance, and congestive heart failure. And patients with RA have increased hypertension and hyperthyroidism, as well as inflammation.
Slide 19: Now some of you may perform lipid profiles a large percentage of the time. But those of you who do not, let me show you some data about lipids in RA that could prove interesting for you to consider whether to do lipid profiles. Consider the perspective, the way I look at it and when I talk to audiences, RA should be considered an elevated LDL.
The cardiovascular rate of mortality in patients with RA may result from chronic inflammation. This graphic shows the similarities between arteriosclerosis and RA. Inflammation plays a role which may lead to cardiovascular disease. As you can see, the difference between the arteriosclerotic plaque and the normal arterial wall is similar to the rheumatoid joint, which also shows the normal schematic on one side as the other side shows inflammatory cells.
Slide 20: Now, look at the carotid plaques. We see them diagramed on this slide; common, external, and internal carotid arteries. This is a case-controlled study involving 394 patients. The carotid plaque was more prevalent among patients with RA, 44%, in systemic lupus, 37%, compared to healthy controls, 15%.
Slide 21: Now, as the study progressed, we see here 2 sides of this slide. The prevalence of carotid plaque increased in RA and lupus with up to 80% in the rheumatoid population and 73% in the lupus population compared with 45% in the healthy controls.
But furthermore, regardless of age, the plaque prevalence in RA and lupus is comparable to patients with diabetes, which itself is a cardiovascular risk factor. Again, think of RA as an elevated LDL.
Slide 22: Now, if you look at extraarticular disease and how it is associated with cardiovascular events, as you can see in this diagram, those with nonextraarticular RA have a greater percent of survival compared to those with severe extraarticular disease.
This is a medical record review that demonstrates the risk of a first-ever cardiovascular event, which is greater in 81 patients with RA and extraarticular disease, compared to 184 controls. The hazard ratio (HR), after adjusting for age, sex, smoking, rheumatoid factor, and erosive disease, is up to 3.25.
Slide 23: Now, extraarticular disease is also associated with noncardiac vascular disease. In this retrospective chart review of 609 patients in the Mayo Clinic database, adjusted for age, sex, body mass index, smoking, and rheumatoid factor, there is severe extraarticular disease associated with peripheral arterial events (HR 2.3), venous thromboembolism (HR 3.7), and all noncardiac events (HR 2.1). Extraarticular disease was not associated with cerebrovascular events alone.
Slide 24: Which of the following statements regarding cardiovascular disease in RA is true? Arterial sclerosis may be mediated through conventional cardiovascular risk factors; Strategies for controlling traditional cardiovascular risk factors may be less beneficial in RA; Methotrexate and TNF inhibitors may decrease cardiovascular mortality; or all of the above.
Slide 25: Strategies to prevent cardiovascular disease and mortality in RA patients that focus solely on controlling traditional cardiovascular risk factors may be relatively less beneficial in RA. Physicians must balance RA risk versus traditional factors versus nonsteroidal anti-inflammatory drugs. Arterial sclerosis and RA may be mediated through the conventional cardiovascular risk factors, prednisone risk, and unfavorable body composition. Of note, methotrexate use has been shown to decrease cardiovascular disease. And the data for TNF inhibitors have been mixed, but I am going to show you today how there is decreased cardiovascular morbidity in patients with TNF therapy.
Slide 26: Methotrexate has been shown to decrease cardiovascular mortality, but in this study, TNFs also appear to lower mortality risk. In these 7 studies that examine the effect of TNF inhibitors on mortality risk and patients with RA, a majority found that the standardized mortality ratio fell below 1, indicating a favorable impact on mortality in this patient population.
Slide 27: Now, researchers hypothesize that TNF inhibitors may reduce cardiovascular mortality. This graphic from an article by Dixon and his colleagues looks at traditional risk factors of dyslipidemia and insulin resistance. TNF inhibitors may alter lipid balance and improve insulin resistance.
If we look at the spectrum of arterial sclerosis to hemostasis, TNF inhibitors may interfere with fatty streak formation by limiting it or by slowing plaque progression, and may improve the endothelial cell dysfunction and lessen the prothrombotic state. They may inhibit plaque rupture, and they may even be involved in the repair, reducing the ischemic damage in post-event modeling.
Slide 28: Let us look at smoking. There is a strong relationship between smoking and RA. Smoking is a known environmental risk factor for the development of RA. It has been shown to have the following associations: increased risk of disease; increased risk of CCP positivity when there is shared epitope; increased disease severity; increased extraarticular manifestations; increased death; increased pulmonary disease; and increased cardiovascular complications.
I would like to talk a little bit about some of the data and support these associations on the next slide.
Slide 29: We talk about citrullination, which plays an integral role in autoimmune diseases. In this graphic, peptidylarginine is converted by peptidylarginine deiminase to peptidylcitrulline. This happens in the body and allows the citrulline sites within the protein to be a target for cleavage during apoptosis.
Studies have validated the association of CCP as a diagnostic test in RA. Third-generation CCPs detect citrulline sensitivity similar to rheumatoid factor about 80%, but with increased specificity up to 98%.
Slide 30: If we look at this model of the etiology of RA with CCP, from an article by Klareskog and associates, research into citrullination is leading to a clear understanding of smoking’s impact on rheumatoid disease activity.
This was a population-based, case-control study, in which the researchers evaluated the presence of citrulline in bronchoalveolar cells. They stained the cells with an amino chemical stain using rabbit anti-modified citrulline antibody on chemically modified cells from healthy smokers.
Now, panel A and B are from smokers, and you can see the citrulline staining. Panel D is actually a nonsmoker. And panel C is the control, in which they did not modify the cells.
Slide 31: As you can see here, smokers with pulmonary inflammation had an average of 28.5 citrulline cells, compared to an average of 13.75 citrulline cells found in smokers who were healthy. Nonsmokers were found to have no bronchoalveolar lavage cells stained positively with antibodies for citrullinated protein.
Slide 32: Furthermore, the researchers found that patients who had ever smoked and tested positive for the HLA-DR shared epitope gene, which is a major genetic risk factor, had a 21% relative risk increase in developing RA when a double epitope was detected. Those positive patients with a single shared epitope showed 6.5%, and 1.5% with those that had no shared epitope. But even more so, if you had the shared epitope, but did not have the CCP—and notice that the relative risk scale here is much lower in the second panel—the risk was about the same for those who smoked and those who never smoked.
Slides 33 and 34: Smoking is associated with disease activity in RA. In a study of 287 patients with early RA, followed over 10 years, 29% were current smokers, 7% were former smokers, and 64% were never smokers. Smokers presented with disease at an earlier age, along with more tender and swollen joints, a higher DAS28, a higher frequency of rheumatoid factor, and more radiographic damage. At completion of this study, despite treatment, smokers still had higher disease activity and more radiographic joint damage. And this was independent of age, sex, education level, alcohol, or duration of follow-up.
Slide 35: Now we’ll transition from smoking into the topic of corticosteroids.
Based on your knowledge in this area, which of the following statements would you consider to be true as it relates to corticosteroid use in RA? Initial use of corticosteroids causes a decrease in a patient’s feeling of well-being; Sharp scores with corticosteroid use show greater improvement compared with methotrexate use; use of corticosteroids can affect a possible decrease in lymphoma; or none of the above.
Slide 36: If we look at the corticosteroid risk and benefits, we know that corticosteroids have been used in the management of RA for many years. There is some efficacy of low-dose corticosteroids, and the degree to which patients feel better initially, but this can be a seductive feeling of wellness. There is no agreement on efficacy, safety, or adverse events of low-dose corticosteroids. Of interest, there is no agreement on what the dose definition is of low-dose corticosteroids. Is it less than 15, less than 10, less than 5, 1 to 2? There is no agreement. Now, Sharp scores show improvement, but I am going to show you the type of improvement they have, and it is less than we see with methotrexate and with biologics. And there is a decrease in lymphoma after 2 years of using corticosteroids.
Slide 37: If we look at this graphic on Sharp scores in which patients are followed for 5 years, these patients received 10 mg per day, which, in some circles is not low-dose. They had less radiographic joint damage at 2 years.
Now, if you consider that an untreated patient with RA has a risk of increased Sharp score of 5 to 10 a year, if we look at these graphics—the top line being placebo; the bottom line being prednisone—they begin with 10 to 15 and increase above 40 at 2 years and above 80 at 5 years for the placebo group. And in the prednisone group, they go to 20 within 2 years and up to 40 in 5 years. This is still a tremendous increase.
Slide 38: Furthermore, if you look at another study, COBRA, treating patients with a combination therapy of prednisolone, methotrexate, and sulfasalazine was superior to monotherapy with sulfasalazine for suppressing disease activity in radiographic progression.
The bars show the results in 1 year. We show the Sharp score increased by 17% in the sulfasalazine group, and 6.5 in the COBRA group. However, even with this improvement over 5 years, the radiographic improvement is vastly more limited. And that is what we achieve with methotrexate or with biologics.
Slide 39: The use of corticosteroids may decrease the risk of lymphoma. This study from Baecklund, presented at EULAR 2007 in Barcelona, showed that there appeared to be an association with more than 2 years of corticosteroids, but this decrease was not dose related. It may be related to the lymphocyte depleting effects of corticosteroids. However, this information has not been reproduced by other investigators.
Slide 40: Corticosteroids and TNF inhibitors are associated with cardiovascular disease. Let us look at the differences. Cardiovascular disease appears to increase with corticosteroid therapy. Myocardial infarction is increased, because corticosteroids increase insulin resistance. Also, there is accelerated arterial sclerosis, which is associated with corticosteroid therapy and they can increase hypertension.
New data suggest TNF inhibitors can prevent against stroke, and TNF inhibitors plus methotrexate may decrease MI and cardiovascular disease. They also decrease insulin resistance and cardiovascular risk factors.
Slide 41: Osteoporosis and osteoporotic fractures are elevated in patients with RA who are treated with corticosteroids. And a steroid, as you know, can decrease bone density rapidly. A study presented at the ACR meeting in 2007 showed that even low-dose corticosteroids may increase bone loss.
The ACR has recommendations that are available to advise patients on corticosteroids, to take calcium and vitamin D. But as we all know, these patients are going to need more to prevent osteoporosis and bone loss, such as bisphosphonates or teriparatide. However, of concern, there is a lack of physician attention in preventing corticosteroid-induced osteoporosis, the monitoring of it, and in improving patient compliance.
Studies have begun to examine the role of TNF inhibitors in this area. And a recent study found that TNF inhibitors do not appear to alter the 1-year change in bone mineral density in the hand, hip, or spine. There is another study from Sweden, in which they used lunar-adapted software to look at bone density in the hand in patients with RA, and this seemed to help improve bone density by using this model.
Slide 42: A clear link between diabetes and RA has not been established. Current evidence shows that systemic inflammation predisposes patients to insulin resistance and type 2 diabetes mellitus. C-reactive protein (CRP), leukocytosis, low serum albumin, and IL-6 are associated with the development of diabetes.
An analysis looking at the National Health and Nutrition Examination Survey III—the NHANESIII—from 1988 to 1994, did not show a strong association between RA and diabetes. But you cannot definitely exclude a modest non-null association.
Slide 43: Metabolic syndrome, which is insulin resistance, is associated possibly with diabetes, hypertension, and obesity. In fact, different groups have different criteria for the metabolic syndrome: abdominal obesity; elevated triglycerides, 150 mg/dL or under treatment; elevated serum HDL cholesterol, less than 40 mg/dL in men or less than 50 mg/dL in women, or under treatment; blood pressure greater than 130/85 mm Hg, or on treatment; or fasting blood glucose 110 mg/dL or on treatment.
In a study of 200 patients with RA, in 400 age and sex matched controls, it found that the metabolic syndrome was correlated with disease activity. Unfortunately, the risk of having moderate to high disease activity was 9 times higher in patients with metabolic syndrome compared to the healthy controls.
Slide 44: There are studies that indicate that TNF inhibitor therapy may have beneficial effects on insulin resistance, and therefore, may contribute to the reduction of cardiovascular disease in patients with RA.
Slide 45: Consider the relationship of RA to obesity. Which of the following would you anticipate occurring when obesity occurs concomitantly in patients with RA? Disease severity is improved when a patient is obese; leptin may modulate the immune response and inflammation; disease severity increases when the patient is mildly obese; or all of the above.
Slide 46: Obesity is a risk factor for rheumatoid disease, in both onset and severity. It may result from steroid use, from TNF inhibitor use, or from immobility and deconditioning. It is associated with increased mortality and it has an independent association with impaired quality of life in RA. Obese patients are less likely to respond to DMARDs, and the contribution of the adipokines, such as leptin and resistin, may be playing a role.
Slide 47: I have often wondered why my obese patients had elevated SED rates. This study from the ACR 2006 meeting showed that increased body fat was found to be an important predictor of elevated CRP in women with RA. And again, this could possibly be related to the adipokines.
The level of body fat remains 1 of the most potent factors associated with elevated CRP levels. And rheumatologists need to consider the level of obesity in patients when interpreting the CRP values, as this is an indicator of disease activity and treatment and response.
Slide 48: This is another study on this issue, which came out at the ACR meeting in November 2007. Note that the increased body mass is associated with reduced rate of remission. These patients were on a combination therapy with or without infliximab and they were on methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone. They noted the role of body mass index (BMI)—the higher it was without infliximab, there was a decreased probability of remission. Remember that normal BMI is about 20 to 25, above 25 is overweight, and above 30 is obese. We can see that with combination therapy without infliximab, the percentage of remission continues to drop. So, patients with increasing BMIs were less responsive to this systemic inflation related to these perhaps adipokines.
Slide 49: Now, despite the negative implications of obesity, many physicians do not advise their overweight and obese patients to lose weight. A recent study at the Mayo Clinic found that only one third of patients with a BMI greater than 30 actually had it listed on the chart diagnosis. The study further found that less than 50% of the obese patients were advised by their physician to lose weight. There was a similar population base survey in the 2005 Behavioral Risk Factors Surveillance Survey, and it found that less than half, about 45.7%, of overweight or obese patients had been told by a clinician that weight loss would help alleviate their arthritis symptoms. Emerging evidence does suggest that physicians’ advice has the most impact in getting patients to lose weight.
Slide 50: Rheumatologists can assess obesity with BMI measurements, waist size measurement—which is part of the metabolic syndrome criteria, calipers looking at skin fold, digital scales using bioelectric impedance analysis, and the old dunk tanks—which replace volume—the hydrostatic measurement. Or you can use the DXA method. Now, that does not mean that you will necessarily have agreement from third-party payers, but you can measure fat mass, lean mass, and bone mass, and show the patient a graphic of where they are to give them incentive.
In this study, which came out in “Rheumatology News” in May 2007, DXA imaging showed weight and fat loss in a 105-kg woman after aggressive diet and exercise. She went from 53.2% total body fat to 57 kg, or 17.7% total body fat.
Slide 51: Now, let us look at extraarticular disease. Which of the following are considered extraarticular disease manifestations of RA: amyloidosis; pleurisy; rheumatoid nodules; or all of the above?
Slide 52: Extraarticular manifestations of disease are many, including nodules; Felty’s syndrome; lung diseases such as interstitial lung disease, nodules, and Caplan’s disease and others; pleurisy; vasculitis; and amyloidosis.
Slide 53: In a paper reported at the ACR 2006 meeting, investigators looked at the CORRONA database, at the association between subcutaneous nodules and the association with cardiovascular disease in patients with RA. The analysis concluded that the presence of a subcutaneous nodule on examination identifies a patient who has significantly greater risk for developing cardiovascular disease. We have always known that this is an indicator of more severe disease and it suggests that there is a possible association between subcutaneous nodules and cardiovascular disease.
Slide 54: There is another study presented at the 2006 ACR meeting, looking at extraarticular disease. This study examined a national database for declining rates of serious extraarticular manifestations of RA in a large cohort of US veteran inpatients. There was a decline in extraarticular manifestations of Felty’s disease, of carditis, and a leveling off of vasculitis, then a sudden drop. There was, however, some increasing interstitial lung disease and pleuritis. These findings temporally corresponded with more aggressive RA therapy and the use of TNF inhibitors.
Slide 55: The clustering of chronic conditions associated with RA increases medical costs and complexity of cases being managed by healthcare providers. The impact of comorbidity in RA worsens all adverse outcomes, including inflammation, infection, quality of life, morbidity, and mortality.
Slide 56: To reiterate the need for discussion on this topic, let us revisit what I mentioned at the beginning of my talk.
To achieve the best outcomes in RA, we all need to remember that the best outcome in an RA patient is just not improvement of their RA, but improvement of their total health. The best way to treat comorbidities is to avoid them or manage them early in the disease process. Healthcare providers should be alert to a range of potential comorbidities in patients with arthritis and should be able to indicate better integration of clinical and public health strategies in the areas of chronic disease management, shared risk reduction like obesity, counseling weight loss, immobility, and counseling in physical activities.
Rheumatologists need to work with the patient’s healthcare team. Physicians must perform vigilance over comorbidities, including cardiovascular disease, smoking, corticosteroid use, diabetes, and extraarticular disease, as we discussed today.
Slide 57: In closing, I ask again for you to consider what your answers would be to these 2 questions.
Should the expanding knowledge of RA-associated comorbidities change the way patients with RA are managed? And is the rheumatologist responsible for the global care of the RA patients?
