Yes, Dr. Deane says many studies have pointed to the positive results of treating rheumatoid arthritis (RA) with glucocorticoids. No, Dr. Goldman says corticosteroids have a significantly reduced role in the treatment of RA.

Yes, Dr. Deane adds that these agents may have utility in early RA and low-dose regimens could help prevent adverse effects associated with glucocorticoids.

When Philip Hench, MD first gave Compound E (cortisone) to patients with rheumatoid arthritis (RA) in 1948, the compound appeared to be a miracle cure for this debilitating disease.¹ Hench was awarded the Nobel Prize for his work. Unfortunately, it was soon apparent that significant side effects were associated with long-term glucocorticoid therapy and enthusiasm for using steroids in RA waned. Early glucocorticoid use for RA was difficult as there was little available data regarding optimal dose, timing, duration and efficacy of these agents. Largely based on anecdotal experience, many clinicians came to the conclusion that glucocorticoids only worked for temporary symptomatic relief, lacked disease modifying capability and had far too many adverse side effects. This prevailing opinion led to multiple guidelines that considered glucocorticoids as a treatment of last resort in RA.

In spite of the negative press and a lack of data regarding the possible disease modifying actions of glucocorticoids, it was difficult to ignore the symptomatic benefits. By the mid-1990s, a large percentage of patients with RA were using some form of glucocorticoid therapy.²

However, over the past decade, studies have made it clear that glucocorticoids can improve RA symptoms as well as reduce erosive disease. Accordingly, adverse effects notwithstanding, glucocorticoids should play a prominent role in RA management.

What The Literature Reveals
Let us take a closer look at a few examples of studies that support the use of glucocorticoids in RA. In a randomized, placebo-controlled study, Kirwan, et al., showed that prednisolone 7.5 mg daily over two years, along with other disease modifying antirheumatic drugs (DMARDs) in patients with early RA, led to improved symptoms and decreased erosions.³

In another randomized trial, van Everdingen, et al., showed that in patients with DMARD-naïve early RA (those having symptoms for less than one year), 10 mg of prednisone daily for two years led to greater improvement in symptoms as well as decreased use of nonsteroidal aniinflammatory drugs (NSAIDs) and intra-articular injections.4 Most importantly, while symptoms and other DMARD use were similar between groups at one year, researchers reported significantly less radiographic damage in the prednisone-treated arm approximately three years after the completion of the study.⁵

Other studies have found similar results. Wassenberg et al., showed that the addition of prednisone 5 mg daily to either gold or methotrexate led to decreased erosive disease in the prednisone-treated arm.⁶ Svensson et al., showed that in patients with early RA (those having symptoms for less than one year), adding prednisolone 7.5 mg daily to a DMARD regimen (methotrexate or sulfasalazine) led to delayed progression of erosions at two years in comparison to placebo.⁷

In the COBRA trial, researchers compared sulfasalazine alone to combination therapy with methotrexate, sulfasalazine and prednisolone. The prednilisone was dosed initially at 60 mg daily and tapered stepwise to 7.5 mg daily over seven weeks with cessation after 28 weeks. At five-year follow-up, there was significantly less erosive disease in the glucocorticoid-treated arm even though symptoms were similar in each arm.⁸

Are Glucocorticoids Effective In Treating Early RA?
In 1999, Green et al., treated 63 patients with mild, untreated early arthritis (symptoms less than 12 months) with a one-time dose of corticosteroids. Intra-articular methylprednisolone was administered if patients had less than five swollen joints. If more than five swollen joints were present, a one-time dose of intra-muscular methylprednisolone was administered. This dose was 120 mg if the patient weighed more than 55 kg or 80 mg if the patient wieghed less than 55 kg.¹⁰

The use of intramuscular methylprednisolone induced remission of arthritis at six months in 50 percent of patients who met the American College of Rheumatology (ACR) criteria for RA and had less than 12 weeks of symptoms at the time of steroid dosing. While this study lacked a control arm, these results suggest that if clinicians use steroids in very early disease, they can be a potent inducer of disease remission.10 Regimens with glucocorticoids may also work as well as regimens that utilize biologic therapy. Data from the BeST trial suggests that in early RA the use of combination therapy with methotrexate, sulfasalazine and step-down corticosteroid dosing (COBRA regimen) compares favorably to combination therapy with methotrexate and infliximab in terms of symptom control and prevention of progressing erosive disease.¹¹

This is an important finding considering the high cost of biologics and multiple adverse events associated with glucocorticoids. The results from these studies lead to the conclusion that glucocorticoids contribute to the control of symptoms and erosions, and are powerful agents for the management of RA, especially when one compares them to other costly agents available today.

Assessing The Role Of Glucocorticoids
How should clinicians use glucocorticoids for RA? While information is still limited, the studies to date can help answer this question.

Given their wide clinical availability and known behavior, prednisone and prednisolone are the glucocorticoids of choice in RA. Additional forms of glucocorticoids may be available soon. These may include forms that avoid many of the adverse side effects. While optimal dosing regimens are yet to be determined and may vary widely in individual patients, it is reasonable to use a higher initial dose (30 to 60 mg daily) to obtain control of inflammation in early, active RA with rapid tapering to doses below 7.5 mg to minimize adverse effects.

The work presented by Green et al., makes the use of one-time, high-dose glucocorticoids intriguing.¹⁰ This needs further study before the emergence of more wide-reaching recommendations.

Based on available data, the optimal duration of glucocorticoid therapy may range from six to 24 months during early disease. Also, it is reasonable to use short courses of glucocorticoids in patients with long-term disease who are experiencing a flare. The role of chronic glucocorticoid use is less clear in established RA, for which other DMARD and biologic therapies are known to work well to reduce symptoms and prevent progressive erosions. However, if it is proven that longer-term use of glucocorticoids does lead to protection against erosions above and beyond that provided by other agents, glucocorticoids may provide significant benefit in late disease, especially in settings where ongoing inflammation is present.

Also, in certain states such as pregnancy, renal failure or other organ disfunction, corticosteroids may be the preferred agent for the treatment of RA. In addition, clinicians should also use intraarticular steroids in RA and this may be the preferred method for administration in patients with few swollen or tender joints.

Can Low-Dose Regimens Reduce The Risk Of Adverse Effects?
One cannot easily ignore concerns about the toxicities of glucocorticoids, especially in the setting of long-term use of high-dose glucocorticoids. However, as outlined in a recent review, clinicians can avoid many of the known adverse effects of glucocorticoids by using low doses.¹¹

In particular, several RA studies have shown that prednisone use of less than 7.5 to 10 mg daily is not associated with significantly increased risk for infection over two years of follow-up.^4,12 Also, cardiovascular disease does not seem to be substantially increased in patients taking a prednisone equivalent of 7.5 mg a day or less although risks do appear to increase with higher doses.¹³ Other side effects such as hypertension, fluid retention and psychological disturbances seem to be uncommon in RA patients on low-dose glucocorticoids.¹¹ Any dose of glucocorticoids likely leads to abnormal bone loss. However, clinicians can minimize this common adverse effect with proper preventive therapy, including calcium and vitamin D supplementation, and bisphosphonate use.

As our knowledge increases regarding the adverse effects of unchecked inflammation on cardiovascular disease, bone loss, malignancy and infection risk, we may recognize that the rapid control of inflammation offered by glucocorticoids may lead to a reduction of long-term adverse outcomes in RA.

Improved lipid levels have been seen in RA patients whose inflammation was controlled with regimens containing glucocorticoids.¹⁴ Researchers have also discovered that periarticular osteoporosis in the hand was less pronounced in RA patients receiving glucocorticoids in comparison to controls.¹⁵

Final Notes
Some may argue that early use of anti-TNF drugs or other biologic therapies to rapidly control inflammation in early RA may offer the same benefits as those with glucocorticoids. This may be true. However, biologic therapies have substantial health risks (some of which may still be unknown) and are expensive. Corticosteroids are inexpensive and have well known adverse effects. When one compares the risks and costs of these agents to each other, corticosteroids may be a less costly and safer choice than biologic therapy.

In conclusion, glucocorticoids should play an important role in the treatment of RA. While more studies are needed providing greater detail regarding their optimal use, we know they improve symptoms and, more importantly, act as DMARDs, especially when clinicians use them in early disease stages. One can minimize the adverse effects of glucocorticoids by using low doses, limiting the duration of therapy and ensuring appropriate preventative measures in regard to osteoporosis, cardiovasular disease and infections. Hopefully, there may even be improved versions of glucocorticoids in the future with less adverse effects.

With these approaches, we can maximize the benefits and minimize the toxicities of glucocorticoids in RA, and move closer to realizing Dr. Hench’s dream for mastery over this disabling disease.

References
1. Hench P, et al. The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone: Compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis. Proc Staff Meet Mayo Clinic 24: 181-97, 1949.
2. Bijlsma JW, et al. Glucocorticoids in the treatment of early and late RA. Ann Rheum Dis 62(11): 1033-7, 2003.
3. Kirwan JR. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. N Engl J Med 333(3): 142-6, 1995.
4. van Everdingen AA, et al. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med 136(1): 1-12, 2002.
5. Jacobs JW, et al. Followup radiographic data on patients with rheumatoid arthritis who participated in a two-year trial of prednisone therapy or placebo. Arthritis Rheum 54(5): 1422-8, 2006.
6. Wassenberg S, et al. Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 52(11): 3371-80, 2005.
7. Svensson B, et al. Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: a two-year randomized trial. Arthritis Rheum 52(11): 3360-70, 2005.
8. Landewe RB, et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum 46(2): 347-56, 2002.
9. Green M, et al. Persistence of mild, early inflammatory arthritis: the importance of disease duration, rheumatoid factor, and the shared epitope. Arthritis Rheum 42(10): 2184-8, 1999.
10. Goekoop-Ruiterman YP, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 52(11): 3381-90, 2005.
11. Da Silva JA, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann Rheum Dis 65(3): 285-93, 2006.
12. Capell HA, et al. Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial. Ann Rheum Dis 63(7): 797-803, 2004.
13. Wei L, MacDonald TM, Walker BR. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med 141(10): 764-70, 2004.
14. Boers M, et al. Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis. Ann Rheum Dis 62(9): 842-5, 2003.
15. Haugeberg G, et al. Reduced loss of hand bone density with prednisolone in early rheumatoid arthritis: results from a randomized placebo-controlled trial. Arch Intern Med 165(11): 1293-7, 2005.


No, says Dr. Goldman, citing a lack of convincing evidence on the efficacy and dosing of corticosteroids, the risk profile of these agents and the rise of other treatment alternatives such as biologics.

Few clinical discoveries in the history of medicine have had such a profound influence on research in the medical sciences and on the treatment of so many different diseases as the work by Hench, Kendall, Slocumb and Polley in 1949.^1,2

However, when it comes to treating rheumatoid arthritis (RA), the advent of the biologic age may compel us to reevaluate the popularity of corticosteroids, which are currently used to treat between 44 to 75 percent of patients with RA.³

Anecdotally, low-dose corticosteroids may have some efficacy as our patients with RA tend to feel better initially. However, this can be a misleading feeling of wellness. There is no consensus in the literature on the efficacy, safety and adverse effects of low dose corticosteroids nor is there agreement on the proper dosing of low-dose corticosteroids for RA.^4-7,8

Some studies have shown that low-dose corticosteroids can help patients with RA feel better and allow patients with RA to function and work.^8,9 However, other studies show that corticosteroids do not improve long-term function even if the patients have low disease activity scales (DAS 28).^10,11 Research has shown short-term effectiveness of corticosteroids for RA but there are currently no results showing long-term efficacy.6 Pre-biologic data shows similar short-term efficacy to disease modifying antirheumatic drugs (DMARDs) such as chloroquine, penicillamine and gold.^6,12

A Closer Look At The Cited Benefits Of Corticosteroids
Crucial to this debate is the fact that corticosteroids do decrease the risk of joint damage one would see on X-rays.

In data from the COBRA trial, patients who initially received high doses of corticosteroids and subsequently tapered dosing had lower Total Sharp Scores (TSS) than those who did not get high-dose corticosteroids. According to the study, there was an average TSS increase of 5.6 per year among the aforementioned patients treated with corticosteroids. However, that increase in TSS is too high in comparison to DMARDs such as methotrexate or biologics.¹³

There is data on curtailing TSS with low-dose corticosteroids in a small number of patients. However, this data does not show good disease modification since there is also a high TSS in both groups.¹⁴ The annual TSS increases were 7 (+/-5) in the prednisone group and 13 (+/-11) in the placebo group. At best, this translates into the loss of almost two joints per year, 10 joints in five years or 20 joints in 10 years.^9,14 This is not acceptable.

There is a study that suggests low-dose corticosteroids are more cost-effective than nonsteroidal antiinflammatory drugs (NSAIDs) and COX-II inhibitors.15 However, the differences are small and we should be cautious about extrapolating too much from this study’s overall conclusions.

COX-II inhibitors are associated with higher cost but better health outcomes than corticosteroids.15 The sensitivity analysis varying cost showed that COX-II inhibitors were superior when the cost was less. There was more cost when using omeprazole or misoprostil to prevent gastrointestinal toxicity. Omeprazole use lead to better outcomes but misoprostol use did not.

A Guide To Potential Side Effects With Corticosteroids

Another study suggests that corticosteroid use may decrease the risk of lymphoma in patients with RA.¹⁶ The decreased risk appears to be associated with long-term use (more than two years) of corticosteroid therapy. This may be related to the lymphocyte depleting effects of corticosteroids.

Understanding The Risk Profile Of Corticosteroids
Why shouldn’t health care providers use long-term, low-dose corticosteroids in the management of RA? Unfortunately, even low doses of corticosteroids carry a cumulative toxicity.^12,17 For a list of potential side effects, see “A Guide To Potential Side Effects With Corticosteroids.”

There is also a lack of physician input, patient monitoring and patient compliance regarding the prevention of glucocorticoid-induced osteoporosis.⁶ The ACR recommends advising patients of calcium and vitamin D therapy but patients need more preventative therapy like bisphosphonates or teriparatide. We need to consider this with every prescription of corticosteroids. The use of bisphosphonates and teriparatide can prevent corticosteroid-induced osteoporosis.6 Unfortunately, adjunctive use of these agents increases the cost of low-dose corticosteroids along with co-pays.

Those agents are also unsuitable for younger women who may consider pregnancy since bisphosphonates are teratogenic. Yet there are increased risks of osteoporosis and osteoporotic fractures among patients with RA who are treated with corticosteroids.18 This patient population has an increased risk of infection from use of corticosteroids as well.¹⁹ Increased infections also occur with the combined use of corticosteroids and anti-tumor necrosis factor (anti-TNF) medications.^20-22

Rheumatoid arthritis reportedly decreases a patient’s life expectancy by 10 years. Others have said that progressive mortality with RA is akin to what one might expect with coronary artery disease and stage IV Hodgkin’s disease. However, this data comes from an era when therapeutic regimens for RA routinely included corticosteroids.²³

The advent of biologics has improved the prognosis of patients with RA in terms of reducing the risk of associated cardiovascular events such as stroke and coronary artery disease.^24,25

Keep in mind that RA itself is associated with an increased risk of cardiovascular disease — although one study has shown a decreased risk — and there are increased risks of cardiovascular disease with corticosteroid use.^26-30 Yet new biologics like anti-TNF drugs appear to be associated with lower cardiovascular risk and the ability to taper corticosteroid dosages.^31-33 New biologics and those under development can also lead to decreased dosing of corticosteroids.³⁴ Recent data suggests that anti-TNF drugs can prevent stroke and, in combination with methotrexate, can decrease the risk of myocardial infarction.^24,25 This may be due to decreased insulin resistance and improvement in cardiovascular risk factors from anti-TNF medications.^35,36

A significant aspect of toxicity in corticosteroids, corticosteroid dose creep occurs over time with long-term therapy. If we define low-dose prednisone as less than 10 mg/day (and this may be way too much), one may see an increasing dosage up to 12 mg/day.¹⁷ Other authors have said only 10 to 20 percent of patients with RA need corticosteroid doses over 10 mg/day.⁸

Lastly, RA patients on corticosteroids have more glucocosteroid adverse events (GAE) including: fractures (pelvis, vertebral and hip), hypertension, diabetes, gastrointestinal complications, pneumonia, urinary tract infection, cataract, myocardial infarction and stroke.3 These complications lead to increased costs of care for patients.⁴

Emphasizing The Unresolved Questions On Corticosteroids
What are the ACR 20, ACR 50 and ACR 70 responses with corticosteroids? Also bear in mind there are currently no published clinical studies that compare corticosteroids with DMARDs or with DMARDs and biologic therapy.

Intermittent (alternate day) dosing of corticosteroids is better than daily dosages but what is the long-term effect of periodic dose packs and injections? In practice, dosing of corticosteroids does not seem to stay as low as one might see during studies of dose creep. Why does this occur? There is a need to continue to negotiate corticosteroid dosage and lower it as much as possible.^1,17

In the event that biologics are effective for RA, how far could we taper or could we stop corticosteroid therapy? Due to the risk of corticosteroids and biologics, it would be wise to use a purified protein derivative (PPD) with all RA patients who are able to be tested. However, clinicians put many patients on corticosteroids without considering PPD. Why? An excellent clinical response within the BeSt study shows that providers can consistently ease patients off infliximab with tapered dosing.^32,33,37 Can we do this with other biologics? We certainly cannot do this with corticosteroid tapering.

In Conclusion
“For the clinician, the need for careful observation and sound judgment with glucocorticoid use remains critically important.”³⁸

While we may consider short-term corticosteroid use for patients with RA, clinicians should use biologics and a DMARD immediately. Long-term safety and efficacy are better with biologics.

The Cochrane Database System Review suggests that “since prednisolone is highly effective, short–term placebo controlled trials studying the clinical effect of low-dose prednisolone or other oral corticosteroids are no longer necessary.”³⁹ However, we do not have data on the ACR 20 response of low-dose corticosteroids nor do we have data on the use of biologics and corticosteroid sparing and overall benefit.

Although corticosteroids may decrease TSS, they are not nearly as effective in this regard as biologics and/or methotrexate or leflunomide. As researchers noted in the CIMESTRA study, intraarticular corticosteroids can decrease joint erosion among RA patients.⁴⁰ However, since intermittent dosing with corticosteroids may be safer, we need to know more about this option.

New studies indicate oral corticosteroids do not stop the delay of neutrophil apoptosis one may see among patients with RA but methotrexate does.41 This may help to explain some of the effects and lack of effect of corticosteroids.

All health care providers should exercise prudent caution when considering corticosteroid use for patients with RA. Corticosteroids appear to be used rapidly by many in clinical scenarios in which other types of therapy may suffice and be safer options. We need to be aware of corticosteroid efficacy and safety before using these medications. We should emphasize a thorough diagnostic evaluation and review a safety checklist before initiating corticosteroids. In short, clinicians should ensure a complete patient history and physical, complete blood count and differential, urinalysis, metabolic panel, chest film, PPD, sedimentation rate/CRP, an osteoporosis risk profile, assessment of active infection and a cardiovascular evaluation.¹

There are proponents of common use of low-dose corticosteroids for the management of RA and there are those of us who do not advocate low-dose corticosteroids as a common option in treating this disease.^6,7,42 In my opinion, we should only consider low-dose corticosteroids when it is the best choice for the individual patient and when we have exhausted other treatment options.

References
1. Hess EV, Goldman JA. Corticosteroids and Corticotropin in Therapy of Rheumatoid Arthritis in Arthritis and Allied Conditions: A Textbook of Rheumatology 1972 Lea and Febiger: Philadelphia, Pa., 495–516.
2. Hench PS, et al. The effect of a hormone of the adrenal cortex (17 hydroxy-11-dehydrocorticosterone: compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis Proc Staff Meet Mayo Clin. (24)4: 181-197, 1949.
3. Townsend HB, Saag KG. Glucocorticoid use in rheumatoid arthritis: benefits, mechanisms, and risk Clin Exp Rheumatol (22) Suppl 35: S77-82, 2004.
4. Pisu M, et al. The cost of glucocorticoid-associated adverse events in rheumatoid arthritis Rheumatology (44)6: 781-788, 2005.
5. Da Silva JA, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data Ann Rheum Dis (55)5: 285-293, 1996.
6. Saag KG. Low-dose glucocorticoids are neither safe nor effective for the long-term treatment of rheumatoid arthritis Arthritis Care Res (45)5: 468-471, 2001.
7. Conn DL. Resolved: Low-dose prednisone is indicated as a standard treatment in patients with rheumatoid arthritis Arthritis Care Res (45)5: 462-467, 2001.
8. Pincus T, Sokka T and Stein M. Are Long-Term Very Low Doses of Prednisone for Patients with Rheumatoid Arthritis as Helpful as High Doses Are Harmful? Ann Intern Medicine (136)1: 76-78, 2002.
9. van Everdingen AA, et al. Low dose Prednisone therapy for Patients with Early Active Rheumatoid Arthritis: Clinical Efficacy, Disease-Modifying Properties, and Side Effects: A randomized, Double-Blind, Placebo-Controlled Clincial Trial Annal Internal Medicine (136)1: 1-12, 2002.
10. E. Tanaka, et al. Long-term Corticosteroid Use Does Not Reduce Functional Disability In Patients With RA Regardless Of Control Of Disease Activity FRIO194 European League Against Rheumatism (EULAR) 2007.
11. N. Iikuni, et al. Does Corticosteroid Suppress The Progression Of Disability In RA Patients In Low Activity State? Studies In A Prospective Cohort Study FRIO164 EULAR 2007.
12. Saag KG, et al. Low dose corticosteroids in Rheumatoid Arthritis: A Meta-analysis of their Moderate-Term Effectiveness Arthritis Rheum (39)11: 1818-1825, 1996.
13. Robert, BM, et al. COBRA combination therapy in patients with early rheumatoid arthritis: Long-term structural benefits of a brief intervention Arthritis Rheum (46)2: 347-356, 2002.
14. Johannes WG, et al. Follow-up radiographic data on patients with rheumatoid arthritis who participated in a two-year trial of prednisone therapy or placebo Arthritis Rheum (54)5: 1422-1428, 2006.
15. Bae SC, et al. Cost-effectiveness of low dose corticosteroids versus non-steroidal antiinflammatory drugs and COX-2 specific inhibitors in the long-term treatment of rheumatoid arthritis. Rheumatology (42)1: 46-33, 2003.
16. E. Baecklund, et al. Long-term Steroid Treatment May Decrease Lymphoma Risk In Rheumatoid Arthritis. Results From a Swedish Case Control Study of 400 RA-Lymphomas OP0047 EULAR 2007.
17. Curtis JR, et al. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Care Res (55)3: 420-426, 2006.
18. Vicente EF, Emecar G. Incidence Of Osteoporosis And Osteoporotic Fractures In A Spanish Cohort Of Patients With Rheumatoid Arthritis FRI0303 EULAR 2007.
19. Greenberg JD, et al. Association Of Methotrexate (MTX), TNF-Inhibitors (TNF-I) And Prednisone (PRED) With Risk Of Infection Among RA Patients THU0151 EULAR 2007.
20. Napalkov P, et al. Risk Of Serious Infection In A Large US Cohort Of Patients With Rheumatoid Arthritis (RA) Treated With Common RA Therapies FRI0174 EULAR 2007.
21. C. Salliot, et al. Infections during tumor necrosis factor- blocker therapy for rheumatic diseases in daily practice: a systematic retrospective study of 709 patients Rheumatology (46)2: 327–334.
22. L. Kalouche-Khalil, et al. Sinus CT-Scan: Is It Useful Before Anti-TNF Blocking THerapy? THU0178 EULAR 2007.
23. Pincus T, Callahan LF. Remodeling the pyramid or remodeling the paradigms concerning rheumatoid arthritis – lessons from Hodgkin’s Disease and coronary artery disease J Rheumatol (17)12: 1582-1585, 1990.
24. K. Michaud, Z. Nadareishvili, F Wolfe Effect On The Risk Of Stroke In Patients With Rheumatoid Arthritis THU0187 EULAR 2007.
25. Singh G, et al. Added Bonus: Combination TNF-Inhibitor/Methotrexate Therapy Is Superior To Methotrexate Monotherapy In Reducing The Risk Of Acute Myocardial Infraction In Patients With Rheumatoid Arthritis OP0106 EULAR 2007.
26. Sodergren A, et al. Increased incidence of and impaired prognosis after acute myocardial infarction among patients with seropositive rheumatoid arthritis. Ann Rheum Dis. (66)2: 263-266, 2007.
27. Maradit-Kremers H, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. (52)2: 402-411, 2005.
28. Krishnan E, Lingala VB, Singh G. Declines in mortality from acute myocardial infarction in successive incidence and birth cohorts of patients with rheumatoid arthritis. (110)13: 1774-1779, 2004.
29. Shepshelovich D, Sherer Y, Shoenfeld Y Accelerated atherosclerosis in rheumatoid arthritis Harefuah. (144)8: 561-563, 598, 2005. 30. del Rincon I, et al. Effect of glucocorticoids on the arteries in rheumatoid arthritis. Arthritis Rheum (50)12: 3813-3822, 2004.
31. Bathon J, et al. Rates of Cardiovascular Events in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis Treated with Etanercept or Placebo in Clinical Trials 344/344 ACR 2006
32. Van der Bijl, AE, et al. Persistent Good Clinical Response After Tapering And Discontinuation Of Initial Infliximab Therapy In Patients With Early Rheumatoid Arthritis: Three-Year Results From The BeST Trial OP0180 EULAR 2006.
33. van der Kooij S, et al. Remission Induction In Early Rheumatoid Arthritis With Initial Infliximab And Methotrexate Therapy: Four-Year Follow-Up Data Of The Disease Course After Infliximab Discontinuation In The BeST THU0215 EULAR 2007.
34. Nishimoto N, et al. Long Term Safety And Efficacy Of Tocilizumab (An Anti-IL-6 Receptor Monoclonal Antibody) In Monotherapy In Patients With Rheumatoid Arthritis OP0227 EULAR 2007.
35. Seriolo B, et al. Influence Of Anti-TNF Alpha Treatment On Insulin Resistance In Patients With Active Rheumatoid Arthritis OP0015 EULAR 2007.
36. Ancuta C, et al. Effects Of Anti-TNF-Alpha Therapy On Cardiovascular Risk Factors In Patients With Active Rheumatoid Arthritis AB0275 EULAR 2007.
37. Van Der Kooij, SM, et al. Remission Induction in Early Rheumatoid Arthritis (RA) with Initial Infliximab (IFX) and Methotrexate (MTX) Therapy: The Disease Course After IFX Discontinuation in The BeSt Trial 658 ACR 2006
38. Kimberly RP. Glucocorticoid therapy for rheumatic diseases Curr Opin Rheumatol (4)3: 325-331, 1992.
39. Gotzsche PC, Johansen HK Cochrane Database Syst Rev 2004 (3): CD000189.
40. Hetland ML, et al. Is it Possible To Stop Radiographic Progression With Conventional Treatment In Rheumatoid Arthritis? Two-Year Results From The Cimestra Study OP0127 EULAR 2007.
41. Weinmann P, et al. Delayed Neutrophil Aptosis In Very Early Rheumatoid Arthritis Patients Is Abrogated By Methotrexate Therapy AB0384 EULAR 2007.
42. Kirwan JR The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. NEJM (333)6: 142-146, 1995.

Editor’s note: For related articles, see “Issues And Answers In Diagnosing And Treating RA” in the September/October 2006 issue, “Emerging Agents For RA: Can They Have An Impact?” in the September/October 2006 issue or “Essential Keys To Diagnosing Early RA” in the May/June 2007 issue of Arthritis Practitioner. Also be sure to visit our archives.