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02/08/2012 03:34 PM

Disparities in RHEUMATOID ARTHRITIS Drug Therapy(page 4)

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Making Inroads in Treating RA, a Clinical Context Report

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This report is part of a 12-month Clinical Context series.

By Nancy Walsh, Staff Writer, MedPage Today

Published: February 07, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

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NANCY WALSH: From MedPage Today, I'm Nancy Walsh, here in New York City where I'm speaking with Dr. Chaim Putterman, who is the Chief of Rheumatology at Albert Einstein College of Medicine and Montefiore Medical Center. Good morning.

CHAIM PUTTERMAN, MD: Good morning.

WALSH: When a patient first comes to you with possible rheumatoid arthritis, what sort of workup do you do?

PUTTERMAN: We have a pretty set workup for patients who come to us with suspected rheumatoid arthritis.

Unfortunately, we don't usually get to do that workup. By the time the patients come to us, they have an established diagnosis.

One of the things perhaps we want to emphasize in today's conversation is the fact that we would like to see our patients earlier and only see them when they have possible rheumatoid arthritis.

WALSH: Mm-hmm.

PUTTERMAN: Very rapidly, in the clinical history, we can establish whether we're thinking about rheumatoid arthritis.

If the patient has a symmetrical synovitis involving the small joints of the hand, of relatively recent onset, and there's no concurrent history or recent history of viral infection, rheumatoid arthritis clearly comes to the fore for the diagnosis.

That's most of the diagnosis, meaning there aren't a lot of confirmatory tests that need to be done if you have a firm clinical diagnosis. But there are some supplementary tests that we do.

We will look at serological activity; [b]rheumatoid factor and anti-CCP [anti-cyclic citrullinated peptide antibody] are very important.

We would like to confirm our clinical suspicion of systemic inflammation with an ESR and/or a CRP level, and finally, there are other supplementary blood tests that we will take, mostly to stage the patient from the point of view of thinking what other therapies we would like to give that patient at this time.

Finally, even if the patient has disease of relatively short short duration, we take x-rays that will both help us confirm the diagnosis, as well as guide us when we're thinking how aggressive to be with this patient, as well as for the purposes of a baseline for future studies.


WALSH: And, in general, what would your initial treatment approach involve?

PUTTERMAN: That is a very individualized decision, but if based upon our initial assessment, we believe that the patient does have rheumatoid arthritis, we very quickly would like to put that patient on effective treatment.

Methotrexate is our first DMARD [disease-modifying antirheumatic drug] of choice for the treatment of rheumatoid arthritis. Methotrexate does, however, take time to begin working.

While the methotrexate is working, while we started the methotrexate, the patient needs some temporary relief, we use NON-steroidal anti-inflammatory agents.

Many times, even though we would prefer not to use this, many times we also use corticosteroids short-term, either systemically, at relatively moderate doses of up to 10, 15, or 20 milligrams of prednisone equivalent per day, or sometimes, when there's a lot of local inflammation, we will use local injections of steroids as well.

Again, trying to give the patient some relief until our DMARD kicks in.

WALSH: What about biologics?

PUTTERMAN: Using biologics as a first line medication is still being debated.

I believe that the current recommendation of the American College of Rheumatology is not to begin anti-TNFs or other biologics as a first-line agent, but rather the first-line agent, as a DMARD, should be methotrexate.

Patients that fail methotrexate, have an incomplete response, or have a contraindication to methotrexate, those are the patients we will move on to our second-line medication, which are the potent biologic agents.

What has changed with the advent of biologics is that, as we know, they're very efficacious and many patients will have a good response.

We will move relatively quickly from methotrexate if the patient is not responding to that first line of therapy.

WALSH: What sort of window of opportunity do you use?

PUTTERMAN: I think the expression "window of opportunity" was a very good one; that's what rheumatologists have when we see a patient.

A lot of the damage takes place during the first two years of disease, and we view it as a clock that's ticking, and that we need to get the patient on effective treatment and their disease under control as soon as possible.

Unfortunately, as I mentioned before, we don't usually see the patients as quickly as we would like to, so they already have disease activity for several months, until they see a rheumatologist.

Once the diagnosis is made, which is relatively quickly, we bring them back, start methotrexate, and if there isn't a significant clinical response within something like two to three months, they are ready to move to biologic agents.

WALSH: How do you choose which biologic agent to use?

PUTTERMAN: A good question, a difficult question. Those are questions that we don't have excellent clinical studies to answer or evidence-based medicine.

Most U.S. rheumatologists will choose, as their first-line biologic, an anti-TNF. The reason is just because we have the largest amount of experience.

These were the first medications which are approved for the treatment of rheumatoid arthritis; they're FDA approved for that indication.

All of us have a tremendous amount of experience with the different anti-TNFs, and it's a very effective medication with a relatively tolerable side effect profile.

A more difficult question, which I can't answer, and that is really individual, based upon the patient and the physician, insurance also plays a role, is which of the anti-TNFs?

There are at the present time five different anti-TNF agents that are approved for the treatment of rheumatoid arthritis, and what one a given physician will choose for a given patient is not yet ... there isn't data to support, or isn't good data to support that decision at this time.

That is something that perhaps will change with the advent of personalized medicine and its introduction in rheumatology, where we might be able to predict, first of all, what sort of biologic a patient will respond to, as in which anti-TNF agent, the first agent that the patient is most likely to respond to.

And if we're choosing an anti-TNF agent, as many of us do at the current time, which is most likely for the patient to respond to.

WALSH: When you mentioned personalized medicine, what sort of markers would you be looking for?

PUTTERMAN: Well, at a scientific research level, perhaps the most accurate or predictive marker would be the histology in the joint, looking at the synovial membrane, at the area of inflammation, analyzing it for gene expression, for protein expression, for cytokine levels.

All that can potentially be helpful in predicting what is the driving cytokine which underlies the given inflammatory process in a given patient.

However, that is not practical to use on a routine basis. We're looking for serum markers that would help us and perhaps more careful analysis of systemic gene expression levels.

WALSH: And that sort of thing would help you if you were going to try using other agents, like the IL-6 inhibitors or rituximab.

PUTTERMAN: If we would know in advance, as an example, that IL-6 is driving inflammation in a given patient, rather than TNF, clearly it would make most sense to try an anti-IL-6 approach, rather than a TNF approach.

Similarly, you talked about rituximab. If we knew that B-cells are particularly important in the pathogenesis of our given patient, that perhaps would be the approach to use. We don't have that data.

We don't know whether there are given patients where we can predict, indeed, which biologic is the proper approach at the given time, but that is something I predict will change over the next few years.

It is important to note that the fact that not all of our patients respond to a given approach also supports the fact that different mechanisms are driving rheumatoid arthritis in a given patient.

Physicians by nature are lumpers.

Patients who present with symmetrical synovitis, with a positive CCP and rheumatoid factor, we will define them as rheumatoid arthritis.

From a pathophysiology point of view, from a mechanistic point of view, it is much more likely that different cytokines and different mediators, different cell types, different pathways, are driving disease in several ways, such that they all reached a common clinical phenotype.

But if we want to treat the patient optimally, we should treat according to the pathogenesis, rather than the clinical phenotype that we're seeing.

WALSH: What about switching between the drugs, if you know you're trying biologics and one isn't working. How long do you pursue one drug before you try another?

PUTTERMAN: One of the advantages of all of the biologics is their relatively quick onset of action. So our DMARDs, our disease modifying agents, actually used to be known as slow-acting anti-rheumatic drugs.

Thankfully, that's no longer the case, and we could expect in the majority of patients that begin receiving a biologic, a relatively quick response, so that within a month or two, we can comfortably say whether that patient will continue to respond or is responding to a given medication.

The problem is again where we don't have the data to address at this time or don't have the studies to address, is what do we do after a patient fails the first medication.

Again, most of the rheumatologists in the United States and worldwide, I believe, will reach for an anti-TNF agent as the first-line biologic, but what do you do if a patient fails the first-line anti-TNF?

As I mentioned, there are five anti-TNFs approved for use in the United States. We do know that sometimes switching to another anti-TNF, for reasons we don't totally understand, the patient will respond, even though they didn't respond to the first anti-TNF.

We need to decide whether, with the other biologic approaches that are out there and are approved, should the second-line medication be a second anti-TNF, or instead should we be switching to an anti-IL-6 approach, blocking co-stimulation, anti-CD-20 or the like?

Once again, these studies are important to us. They are being done at this time, and hopefully we'll have data and evidence to address what is the proper approach.

At this time, it sort of depends on the patient. If the patient has really no response to anti-TNF or perhaps has a significant side effect to a medication from this class, perhaps the more prudent approach to take is to switch the medication totally and pick a biologic from a second group.

WALSH: What sort of role do you see for some of the newer, the small molecules, you know, like tofacitinib, some of those new agents?

PUTTERMAN: It's exciting to be a rheumatologist nowadays. From no biologic a few years ago, we have now a plethora of approaches to choose from. There's a lot of interest, a lot of excitement in the field, and a lot of medications in development.

One of the approaches that appears to be very promising, with significant data supporting it, is indeed small molecules. As you mentioned, the JAK inhibitors and tofacitinib, which we heard a lot about in our recent ACR meeting.

If the data pans out and this approach indeed turns out to be valid and approved for the treatment of RA, that would absolutely extend the number of patients who would respond to our current treatment approaches, and would give us another valuable way of treating a sometimes difficult disease.

WALSH: And especially where they're oral.

PUTTERMAN: Yes, especially when they're oral. Something has changed in our field as opposed to before approval of the biologics; then, when we told the patient we want to give you something by injection, either by infusion or subcutaneous injection, our patients were very reluctant.

This is not what they heard from their friends or from their relatives or from other patients currently being treated for rheumatoid arthritis.

Now, our waiting rooms are much more similar to that of perhaps a physician treating diabetes, where many of the patients are getting injections.

So that has definitely changed the concept, and the patients are now realizing the fact that many patients are receiving medication by injections for their disease, with good efficacy.

However, it is clearly a problem for some patients, and I think it would be unreasonable to expect patients to be given a choice between an injection and a pill of similar efficacy, and to choose an injection. I think most of us, physicians included, would go first for an oral medication.

WALSH: Do you ever find that you can withdraw the biologic? You know, there was some discussion about that at the ACR meeting.

PUTTERMAN: So, withdrawing of biologics. These are the sort of questions that we're grappling with on a daily basis in clinic.

A patient who we started on a biologic maybe improved very nicely on their first, into the second, and is doing very well and is basically in clinical remission, however we define that. Could we ever think about taking the patient off that medication? Again, the data is not yet available to address that question.

I'm familiar with a study that you referred to, that came out in the meeting, which I heard it understood in two ways.

You could understand that some patients were successfully titrated off their biologic. On the other hand, you could also see the other half, and many patients actually begin to have disease activity once they were tapered off the biologic in this study. So again, the answer is that we don't know yet.

After a period of disease quiescence, which I will define as complete remission for two years, together with the patient, the patient is agreeable, we will try to withdraw the biologic.

We will start by minimizing the steroids that the patient was getting, perhaps decreasing the dose of concurrent methotrexate that they're getting, and then even going down on the dose of biologic.

And if we do that successfully, as we're doing that sometimes, we will then try to totally take the patient off, understanding that there is a risk that the disease might return.

WALSH: What about long-term concerns, like malignancy, serious infections?

PUTTERMAN: I think those long-term concerns remain significant, both for patients and physicians. It sort of goes with the territory.

We're using very potent immunomodulators. We are affecting the immune system not only as it pertains to abnormal activation that leads to disease, but also the normal immune processes that are responsible for our immune surveillance, for our protection against infection and against malignancy. We don't have sufficient long-term data.

We know of many medications whose complications only became evident after many, many years of use. This is clearly something which we're very interested in. We're closely monitoring the studies that are coming out and do want to see the long-term follow-up.

That's not to say that the presence of a complication -- infectious complication or even of a malignancy -- is something that will prevent us from using this class of medication.

We know that patients with RA probably, just because of the disease and not because of medication, have an increased risk of malignancy. We do believe that aggressively treating patients does clearly increase their quality of life and probably will also improve their lifespan.

So it is a question more of knowing what the risks are and carefully addressing them with the patient and weighing them, and deciding together, whether the balance of evidence will still support using this class of medication, or perhaps there's certain patients where we need to be particularly careful in using a particular biologic approach.

WALSH: What about cardiovascular risks in the long term?

PUTTERMAN: When we think today, about causes of morbidity and mortality in patients with rheumatoid arthritis, rheumatologists are increasingly recognizing that cardiovascular mortality is the major cause underlying the fact that patients with rheumatoid arthritis have a shortened lifespan.

This is an area of great concern to us.

The reasons for this accelerated cardiovascular disease are not totally clear. There are many studies that are currently being done to try and understand this.

Is it the steroids, is it other medications, is it the systemic long-term inflammation that these patients have?

We do think that better treatment of rheumatoid arthritis will decrease the cardiovascular risk, but clearly this is something that is affecting the way we practice.

We are very aware of this, trying to modify other conventional risk factors, addressing smoking in these patients, hypertension, tighter control of diabetes, tighter control of lipids, hoping that we will be able to make a dent in the significant cardiovascular complications that these patients have.

WALSH: You mentioned smoking. There's some interest in smoking as possibly playing a role in the pathogenesis of RA.

PUTTERMAN: That is true. So especially together with anti-CCP, we do know that patients who smoke tend to have more severe disease.

Even without any relationship to the pathogenesis of RA, clearly the last thing a patient with RA needs is additional causes of any morbidity.

We want to address that with our patients, and the cardiovascular link is yet another reason for us to do it and to do it carefully and aggressively.

WALSH: How do you explain to a patient with rheumatoid arthritis what their disease is?

PUTTERMAN: Well, I think it's very important for the patient to understand.

If a patient doesn't understand the disease, clearly we are not going to have that patient as a partner in treating the disease and in getting the tests that they need to and in following up with their primary care physician and their rheumatologist, and undergoing the difficult smoking cessation, et cetera, et cetera. We need the patient as a partner, in how we diagnose, how we treat and how we follow the disease.

There is excellent information out there. We want to start by explaining to the patient ourselves.

If we don't think that the patient understands, we'll try to involve family members, other members of our professional healthcare team, in helping the patient understand the disease, what has been going on, what can they expect, what is the prognosis, complications, what is the treatment, benefits and potential risks of associated treatments.

Again, to enlist the patient as an advocate for themselves and for their care definitely improves the long-term prognosis of the patients.

WALSH: Do you have any final thoughts about the outlook for rheumatoid arthritis in the coming years?

PUTTERMAN: The outlook, we could actually tie it into what I tell my patients. I've been a rheumatologist for some time, and I think the field has really transformed during my professional lifetime. It is, as I mentioned, very exciting to be a rheumatologist, it's very encouraging.

We're very enthusiastic about the therapeutic successes over the last couple of years, and the many medications, many effective medications, that we have to treat our patients.

When we talk to our patients, I emphasize the excellent chances that we can get their disease under control. It might not be easy, it might not be the first medication that we use, but the chance that they will have a meaningful benefit from therapy is definitely much, much better than it was not that long ago.

From a physician perspective and as a rheumatologist, I think that what we're seeing now is only the beginning, and with our improved understanding of disease pathways and additional translational studies, we will continue to make major inroads into the treatment and hopefully the prognosis of patients with RA.

WALSH: Thank you very much, Dr. Putterman.

PUTTERMAN: Thank you.

WALSH: For MedPage Today, I'm Nancy Walsh.

Chaim Putterman, MD, has disclosed that he has no relevant financial relationships or conflicts of interest to report.

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Post edited by: Bettyg, at: 02/08/2012 03:48 PM


02/20/2012 03:46 PM
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Fewer Children for Women With RA, Lupus

By Nancy Walsh, Staff Writer, MedPage Today

Published: February 16, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Action Points

Note that women with rheumatoid arthritis and systemic lupus erythematosus typically have fewer children than they would like, with increased rates of infertility in RA patients and miscarriage in SLE patients playing a role.

Note that personal choice and concerns about the ability to care for a child while living with a disabling disease also contribute.

Women with rheumatoid arthritis (RA) and systemic lupus erythematosus typically have fewer children than they would like, a survey found.

Infertility and miscarriage were among the contributing factors. The infertility rate among women with RA who had fewer children than planned was 1.5 times the rate of women who said they had the same number of children as planned, according to Megan E.B. Clowse, MD, of the University of Nebraska in Omaha, and colleagues.

And women with lupus who had fewer children than planned had three times the rate of miscarriage as those who had the same number of children as planned, they wrote online in Arthritis Care & Research.

Personal choice and concerns about the ability to care for a child while living with a disabling disease also contribute, the researchers wrote.

Previous work has suggested that women with these autoimmune diseases have fewer children, but the precise reasons for this have been unclear.

To explore this, Clowse and colleagues sent a questionnaire about reproductive history to more than 1,000 women enrolled in the National Data Bank for Rheumatic Diseases, and got replies from 114 who had lupus and 578 with RA.

At the time of the survey, participants' average age was about 55. Disease onset had occurred around age 38 among those with RA and at 36 among those with lupus.

More than 60% of women with both diseases said they had no further plans for childbearing at the time of diagnosis but said they had 21% to 25% fewer children than they had expected.

Pregnancy loss was the predominant factor influencing the number of children among women with lupus.

A total of 22% of pregnancies among women with lupus ended in miscarriage.

Pregnancy loss was most pronounced for women who reported having fewer children than they had expected.

Women who had fewer children than they wished were younger at the time of their lupus diagnosis (25 versus 41, P<0.01).

The rate of stillbirth also was increased and has been reported to be five to 10 times higher in women with lupus than in healthy controls.

"Further investigation into the biologic causes of pregnancy loss in women with systemic lupus erythematosus may lead to advances in their care during this period and improve the pregnancy success rate," Clowse's group wrote.

Infertility was less of a concern among women with lupus than among those with RA, which was somewhat surprising, the researchers noted.

"On the surface, the two patient populations share primary vulnerabilities, as both diseases are characterized by systemic inflammation, affect women during their reproductive years, and require similar medications," they wrote.

Possible influences on fertility include cytokine abnormalities in RA and the use of nonsteroidal anti-inflammatory drugs.

Among women with RA, those who had fewer children than they had planned reported rates of infertility 1.5 times higher than those whose families were the size they wanted or who were no longer childbearing at the time of diagnosis.

The infertility rate was 18% for women who had completed their families before being diagnosed, rising to 42% in women who had fewer children than expected.

Ovulatory dysfunction was the main cause for infertility in these women.

But infertility did not account for all of the lower rate of childbearing in women with RA, according to the researchers.


53% feared that they would be unable to care for children properly

37% worried that the disease or its treatment would have adverse effects on their offspring

17% thought they could pass on the arthritis to their children

Although some of these concerns are valid -- that their chronic pain and fatigue could interfere with maternal activities, for example -- improvements in medications should make this less of an obstacle in the near future, according to the researchers.

And although it may be true that certain medications commonly used for autoimmune diseases are teratogenic, such as methotrexate and cyclophosphamide, safer options such as hydroxychloroquine and azathioprine are available.

Educating patients will be the key to optimizing medical therapy during pregnancy, they said.

As to children inheriting the disease, the researchers explained that a child whose mother has RA does have a threefold increased risk of developing the disease, but that actually means that only 3% of children are likely to be affected.

However, these children also are at increased risk for other autoimmune diseases such as lupus and scleroderma.

A limitation of the study was its over-representation of educated and white women, which may limit its generalizability to the larger RA and lupus populations.

"To help women fulfill their childbearing goals, therefore, we must address patient education as well as the underlying causes of infertility and pregnancy loss," the researchers concluded.

Clowse is supported by the Arthritis Foundation.

Primary source: Arthritis Care & Research

Source reference:

Clowse M, et al "The effects of infertility, pregnancy loss, and patient concerns on family size of women with rheumatoid arthritis and systemic lupus erythematosus" Arthritis Care Res 2012; DOI: 10.1002/acr.21593. utm_content=&utm_medium=email&utm_campaign=DailyHeadlines& utm_source=

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03/04/2012 05:26 AM
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Steroid in RA Has Safe Effect on Glucose

By Nancy Walsh, Staff Writer, MedPage Today

Published: March 01, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.

Action Points

Explain that short-term treatment of early, active rheumatoid arthritis with high-dose prednisone did not lead to worsening of glucose tolerance

Note that increases were seen on the insulinogenic index, which measures early insulin secretion, for both the 30 mg and 60 mg doses.

Short-term treatment of early, active rheumatoid arthritis with high-dose prednisone did not lead to worsening of glucose tolerance, a Dutch study found.

On an oral glucose tolerance test, the mean area under the curve for glucose did not change significantly for patients receiving either 30 mg per day or 60 mg per day for a week, according to Michael T. Nurmohamed, MD, PhD, of VU University Medical Center in Amsterdam, and colleagues.

Moreover, increases were seen on the insulinogenic index, which measures early insulin secretion, for both the 30 mg (P=0.04) and 60 mg (P=0.02) doses, the researchers reported in Arthritis & Rheumatism.

The increased risk for cardiovascular disease seen in patients with rheumatoid arthritis may derive, at least in part, from abnormal glucose metabolism.

Although glucocorticoids are often used for the treatment of rheumatoid arthritis, the metabolic effects of these agents are unclear in these patients. For instance, in some studies, the use of glucocorticoids was associated with impairments in fasting insulin sensitivity and the development of diabetes.

But this treatment also could have metabolic benefits through lowering levels of inflammation, according to the study investigators.

To explore these potential effects, they enrolled 41 patients with untreated rheumatoid arthritis. Patients' mean age was 55, most were white women, and median duration of disease was 21 weeks.

At baseline and after one week of treatment, all participants underwent an oral glucose tolerance test.

At the screening test, 56% were found to have impairments in glucose metabolism and 7% were diagnosed as having previously unrecognized type 2 diabetes.

Inflammation, as reflected in erythrocyte sedimentation rate and C-reactive protein levels, correlated positively with the glucose AUC (P=0.04 and P=0.03, respectively).

Plasma C-reactive protein levels fell by a median of 84% with 60 mg per day of prednisone and by 75% with 30 mg (P<0.001 for both).

There was a substantial variation in individual response to the glucose tolerance test.

Seven of the patients whose glucose metabolism was impaired at baseline qualified as having type 2 diabetes after treatment with prednisone, increasing the percentage of diabetics from 7% to 24% (P<0.001).

However, four patients receiving 30 mg per day and five receiving 60 mg per day had impairments at baseline but had normal glucose after treatment.

Because of this variability in response, the researchers recommended that patients being treated with high-dose glucocorticoids have regular glucose monitoring.

Patients with longer disease duration were significantly more likely to have progression in their glucose impairments than were those whose glucose improved or remained the same (OR 1.068, 95% CI 1.017 to 1.122, P=0.009).

Disease duration also correlated with the changes in glucose AUC following prednisone treatment (P=0.007), the researchers found.

Insulin sensitivity was not altered during the oral glucose tolerance test for either prednisone dose.

Fasting insulin increased only with the 30 mg dose, but fasting C-peptide levels, which tend to be less variable than fasting insulin levels, increased with both doses.

The finding that inflammatory markers correlated with glucose levels confirmed that impaired glucose tolerance in patients with rheumatoid arthritis can be largely attributed to inflammation and the negative effects of inflammation on beta cell function.

"Several proinflammatory cytokines, including interleukin-6 and tumor necrosis factor-alpha, are known to interfere with the insulin receptor signaling cascade, resulting in impaired glucose uptake in insulin-sensitive tissues," the researchers explained.

A limitation of the study was its short duration, but the authors pointed out that in real-world practice, doses of prednisone are tapered rapidly, reaching low doses within two months.

Other limitations included use of surrogate measures to assess insulin sensitivity and beta cell function.

"Our data suggest that there is a balance in the diabetogenic and the anti-inflammatory effects of glucocorticoid therapy in patients with early [rheumatoid arthritis], making short-term exposure to high-dose prednisone a safe treatment option for most patients, from a metabolic standpoint," they concluded.

The study was supported by the Dutch Top Institute Pharma and Pfizer.

The lead author has received honoraria and fees from Pfizer, Abbott, Roche, MSD, and UCB.

Primary source: Arthritis & Rheumatism

Source reference:

den Uyl D, et al "Metabolic effects of high-dose prednisolone treatment in early rheumatoid arthritis: balance between diabetogenic effects and inflammation reduction" Arthritis Rheum 2012; 64: 639-646. utm_content=&utm_medium=email&utm_campaign=DailyHeadlines& utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

bettyg note: NO STEROIDS FOR LYME/CO-INFECTION PATIENTS; steroids SUPPRESS your immune system making you much worse!

04/03/2012 03:32 PM
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New Guidelines Focus on Early RA Treatment

By Nancy Walsh, Staff Writer, MedPage Today

Published: April 02, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, Nurse Planner

Action Points

The American College of Rheumatology has issued an update to its recommendations for rheumatoid arthritis, including guidelines for use of biologic agents, assessment of disease activity, and screening for tuberculosis.

Note that that most of the recommendations are based on level C evidence, combining data from the literature and expert opinion.

As a response to the rapidly changing world of rheumatoid arthritis treatment, the American College of Rheumatology (ACR) has issued an update to its recommendations, focusing on early treatment, screening for tuberculosis, and special considerations for high-risk patients.

Writing in the May Arthritis Care & Research, the guideline authors, led by Jasvinder A. Singh, MBBS, of the University of Alabama at Birmingham, re-emphasized the importance of more aggressive treatment in early disease per the 2008 guidelines.

They summarized their reasoning for this shift in approach as follows:

Better outcomes can be expected with earlier intervention

Joint damage is permanent once it occurs, so prevention is crucial

Intensive treatment can help patients maintain physical function and quality of life

However, they pointed out that most of the recommendations are based on level C evidence, combining data from the literature and expert opinion.

Disease Activity

A main point of the recommendations is that the goal of early treatment today is remission or at least low disease activity.

For patients who have been symptomatic for 6 months or less, the usual approach is monotherapy with a disease-modifying anti-rheumatic drug (DMARD), such as methotrexate.

Monotherapy is recommended whether disease activity is low, moderate, or high if no poor prognostic factors, such as extra-articular disease or bony erosions, are present.

However, if disease activity is moderate or high and poor prognostic factors are present, combination DMARD therapy can be tried, adding a drug such as hydroxychloroquine.

And if disease activity is high in early disease and the prognosis is poor, an anti-tumor necrosis factor (TNF) biologic agent can be tried in combination with methotrexate or alone.

When Patients Fail to Respond

The recommendations next addressed treatment strategies for established disease of 6 months or more duration, when patients fail to respond, deteriorate, or are unable to tolerate treatment.

Patients who have been on anti-TNF therapy for 3 months and have shown no response or a loss of benefit can be switched either to another anti-TNF agent or to a non-TNF biologic drug.

Those who have been on a non-TNF biologic for 6 months and have had inadequate response, or loss of effect, can be switched to a TNF or non-TNF biologic.

The reason for waiting 6 months with a non-TNF agent is that efficacy may take longer with these drugs, the authors explained.

Patients with high disease activity considered to have failed TNF treatment because of serious adverse events should be switched to a non-TNF biologic, but if the adverse event was not considered to be serious, either another anti-TNF agent or a non-TNF biologic can be used.

Disease Assessment

Recommendations on how to assess disease activity were published in a separate paper, also in the May Arthritis Care & Research and led by Salahuddin Kazi, MD, of Dallas VA Medical Center.

Kazi and colleagues recommended six tools for disease assessment.

Three of these rely exclusively on patient input and are easily used in clinical practice.

The Patient Activity Scale (PAS) I and II vary slightly in how function is assessed, while the Routine Assessment of Patient Index Data 3 (RAPID3) tool uses a multidimensional health assessment questionnaire.

The other three tools incorporate provider input, such as joint counts in the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), which incorporates measurement of an acute-phase reactant, and the Disease Activity Score in 28 joints (DAS28), which combines numbers of swollen and tender joints with either erythrocyte sedimentation rate or C-reactive protein measurements.

High-Risk Patients

The next section of the revised treatment recommendations addressed the use of biologics for patients with rheumatoid arthritis at higher risk because of comorbid conditions.

For those with hepatitis C, etanercept (Enbrel) might be tried, but biologics should be avoided for chronic hepatitis B that has not been successfully treated because of adverse events or contraindications.

Patients with solid tumors or nonmelanoma skin cancers treated more than 5 years ago can be treated with a biologic if their arthritis warrants it.

Rituximab (Rituxan) can be used for patients who were treated for a solid tumor or nonmelanoma skin cancer within the previous 5 years.

Rituximab also can be used when the patient has had melanoma or a lymphoproliferative malignancy, although the authors cautioned that little is known about biologic therapy in patients with recent cancers because these patients have routinely been excluded from clinical trials.

Anti-TNF biologics should not be used in patients with congestive heart failure class III or IV and whose ejection fraction is below 50%.

Tuberculosis Infection

The third section of the revised guidelines focuses on screening for latent tuberculosis infection, which should be done for all patients before initiating biologic therapy.

Either the tuberculin skin test or an interferon-gamma-release assay can be used, except for patients who have previously been given a Bacillus Calmette Guerin (BCG) vaccination and, therefore, have high rates of false positives with tuberculin skin testing.

A positive result on either of the screening tests should be followed by a chest x-ray and a sputum sample analysis if needed.

Patients found to have latent or active tuberculosis should receive treatment for the condition before initiating biologic therapy.

Finally, the authors recommended that vaccinations for influenza, pneumococcal disease, hepatitis B, human papillomavirus, and herpes zoster be done before patients receive treatment with either a DMARD or a biologic.

"These recommendations, which focus on common clinical scenarios, should be used as a guide for clinicians treating [rheumatoid arthritis] patients, with the clear understanding that the best treatment decision can only be made by the clinician in discussions with patients, taking into account their risk/benefit assessment, including consideration of comorbidities and concomitant medications, patient preferences, and practical economic considerations," Singh and colleagues concluded.

Evolving Therapies

In an editorial accompanying the recommendations, David I. Daikh, MD, PhD, of the University of California San Francisco, and E. William St. Clair, MD, of Duke University in Durham, N.C., observed that much has changed in the four years since the last recommendations, with the availability of new drugs and increased experience with the older agents.

They called on the ACR to continue refining treatment recommendations as therapeutic strategies evolve.

"The ACR has embarked on a major and important road to provide rheumatologists with sound, evidenced-based guidance for the management of rheumatic disease. The 2012 [rheumatoid arthritis] treatment recommendations represent another step down this road," wrote Daikh and St. Clair.

The authors of the treatment guidelines have disclosed receiving fees, grants, and honoraria from multiple companies, including Allergan, Novartis, Takeda, Abbott, Actelion, Centocor, Pfizer, Genentech, UCB, Merck, and Lilly.

The authors of the disease activity measures recommendations disclosed receiving fees and honoraria from various companies such as Amgen, AstraZeneca, Lilly, Merck, Novartis, and Pfizer. One is now an employee of Abbott Laboratories and owns stock in the company.

Editorialist St. Clair has received grants from Genentech and Biogen Idec.

Primary source: Arthritis Care & Research

Source reference:

Singh J, et al "2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis" Arthritis Care Res 2012; 64: 625-639; DOI: 10.1002/acr.21641.

Additional source: Arthritis Care & Research

Source reference:

Anderson J, et al "Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice" Arthritis Care Res 2012; 64: 640-647; DOI: 10.1002/acr.21649.

Additional source: Arthritis Care & Research

Source reference:

Daikh D, St. Clair E "Updated recommendations for the treatment of rheumatoid arthritis: another step on a long road" Arthritis Care Res 2012;64:648-651; DOI: 10.1002/acr.21659. utm_content=&utm_medium=email&utm_campaign=DailyHeadlines& utm_source=

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04/12/2012 04:10 AM
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RA TODAY; The Outlook Improves, A Clinical Context Report

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This report is part of a 12-month Clinical Context series.

By Nancy Walsh, Staff Writer, MedPage Today

Published: April 11, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

Patients suspected of having rheumatoid arthritis (RA) need to have a careful history and physical examination to exclude diseases that mimic RA such as infectious arthritis and systemic lupus erythematosus.

Numerous treatment options for RA exist, including non-steroidal anti-inflammatory drugs, methotrexate, plaquenil, sulfasalazine, STEROIDS, tumor necrosis factor inhibitors, and rituximab.

NANCY WALSH: From MedPage Today, I'm Nancy Walsh.

We're speaking with Dr. Diane Horowitz from Hofstra North Shore Long Island Jewish School of Medicine, and the Department of Rheumatology at North Shore University Hospital in Manhasset, the Long Island Jewish Medical Center in New Hyde Park, New York. Good morning, Dr. Horowitz.

DIANE HOROWITZ, MD: Good morning.

WALSH: What would you say are the most important aspects of the diagnosis of RA (rheumatoid arthritis) today?

HOROWITZ: First and foremost, you need to speak with your patient. You need to get a good history. You need to do a thorough physical exam.

Once you have that information, you can use that to guide your decisions regarding lab tests and imaging, either x-rays or more detailed imaging like ultrasound or MRI.

The history and the physical are the most important, and after that all the rest is supporting evidence.

WALSH: What sort of laboratory tests do you usually do?

HOROWITZ: I do laboratory tests for two purposes.

Number one is to help diagnose rheumatoid arthritis, so for that I would get the rheumatoid factor and the CCP. I also looked at inflammatory markers.

I also need to check their baseline kidney function, liver function, and blood counts; those are going to be important.

Depending upon what the patient tells me in their history and what I see in the physical, I may just have to do additional lab testing to rule out other causes, things that can mimic rheumatoid arthritis.

WALSH: What would some of those possible mimics be?

HOROWITZ: Sometimes infectious arthritis can mimic rheumatoid arthritis. It depends upon the duration of symptoms.

Sometimes you'll see a patient with parvovirus might have symptoms that could look like rheumatoid arthritis, and you need to make sure you eliminate that.

You want to look sometimes for lupus. Although the physical exam will most likely be somewhat different, depending upon what other symptoms the patient has, you would look for that.

There's a whole host of different things that cause arthritis and you need to make sure that you're treating the right thing.

WALSH: And do you always screen for tuberculosis?

HOROWITZ: You must screen for tuberculosis; it's the appropriate thing to do.

The medications that we use for rheumatoid arthritis -- not all of them, but most of them -- can increase the risk of reactivation of latent tuberculosis. And you need to make sure you're not putting the patient at any additional risk by treating them for rheumatoid arthritis.

WALSH: Once you've made the diagnosis, how do you proceed?

HOROWITZ: Well, the first thing you do is explain it to the patient, and explain to them their options. Tell them that there's different types of medications that you can use.

It depends upon what type of rheumatoid arthritis the patient has. Do they have a lot of erosive disease on x-rays? Do they have mainly symptoms?

What's the duration of their symptoms? And those are the questions that you need to ask initially, and that's how you decide to start treatment.

There are ACR guidelines on how to decide what treatment to start with first, but first you have to gather your information.

WALSH: And what would the first treatment usually be?

HOROWITZ: Well, it depends upon disease activity. For a patient who has mild disease activity and does not have evidence of erosive disease, you can think of a drug such as non-steroidal anti-inflammatories.

For patients who have moderate or more disease activity, you need to start thinking about disease-modifying agents.

WALSH: And what would your usual choice be among those disease-modifying agents?

HOROWITZ: In a patient who does not have erosive disease on imaging but does have moderate disease activity, I would probably start with methotrexate.

WALSH: And if the patient doesn't respond to methotrexate, what would you do?

HOROWITZ: Well, it depends why they didn't respond to methotrexate.

You need to make sure that you brought the methotrexate up to an appropriate level, and you need to make sure that the patient was taking the drug and didn't have any adverse effects that would make them stop taking the drug.

If the patient has erosive disease or develops erosive disease, either seen on x-rays or sometimes you can see contractures on physical exam, if that were to develop, you need to start thinking of a biologic agent.

If the methotrexate, or methotrexate plus plaquenil, or sulfasalazine, which is another combination you can use, don't work, then you also would escalate to a biologic.

There's a lot of debate in the rheumatology community whether or not you should have biologics used as a first-line treatment, but it's not the currently accepted paradigm unless the patient has erosive disease.

WALSH: What role is there for steroids in the early treatment?

HOROWITZ: Steroids are very important in early treatment.

I see them as a bridge. They're a bridge when a patient comes to you and they're feeling very uncomfortable.

You want to make them feel comfortable and you want to decrease their pain while you're trying to either choose an agent or have chosen an agent and you want to wait for that agent to take effect.

And when I say "agent," I mean either a disease-modifying agent or a biologic agent.

WALSH: What about the TNF (tumor necrosis factor) inhibitors? What role do they have now?

HOROWITZ: They have a very important role in rheumatoid arthritis, and since the late '90s they have had an expanding role. They are very helpful for many of our patients in decreasing symptoms and also halting the progression of erosions.

WALSH: Do you generally have a preference for which you would start with?

HOROWITZ: That's a really hard question to answer because there are a lot of different TNF agents on the market now; there's one IV and four sub-Q formulations that you can use for the TNFs.

Everyone may have a preference based upon what they've used most frequently, but the data is not so different between the agents. So sometimes we're affected by health plan decisions; certain health insurances only cover one agent or another. It really is very individualized.

WALSH: And of course now there are a number of other choices with more coming, even oral agents.

HOROWITZ: True. It's very exciting, the oral agents.

WALSH: What role do you see for drugs such as tofacitinib?

HOROWITZ: I think oral agents will be very interesting. First of all, there're some patients who really resist the idea of having to do injections at home, and for them an oral agent might be a gateway to them to be able to use a biologic without having to have either a sub-Q injection or an IV infusion. For some patients, that's very exciting.

I think it will also be helpful because they may be able to help us in patients who are TNF inadequate responders. It's a whole other treatment option, and it's a very interesting -- the basic science behind it -- so I look forward to the JAK kinase inhibitors and the Syk kinase inhibitors coming to market.

WALSH: Have you ever used a drug like rituximab?

HOROWITZ: I do. Rituximab is for someone who has failed a TNF or two. Rituximab is not a first-line therapy, but it is very effective.

WALSH: Of course, not all the drugs that have been investigated have turned out successful.

I know a couple months ago two studies were published on ocrelizumab and so they're not going to go forward with approval on that because of safety concerns.

HOROWITZ: Very true. And that drug is quite similar, actually, to Rituxan. There is a phase III and two phase II trials that showed that the ocrelizumab had an increased risk of opportunistic infections and serious infections, and that's why the development program for rheumatoid arthritis was not continued.

I'm under the impression they're still being developed actually for multiple sclerosis, but not for rheumatoid arthritis. We have Rituxan, so that is not a large loss in the treatment paradigm for rheumatoid arthritis.

WALSH: Well, in general, how much of a potential problem are infections, and also malignancies, with biologic treatments?

HOROWITZ: That's another interesting question. So infections are an issue. There is an increased risk of infection; not so much to stop us from using these drugs, but it is something that clinicians need to be aware of and they need to discuss it with their patients.

Malignancy also -- and it's discussed quite frequently. But the data is kind of -- contrasts itself, some show more of a problem than others.

I think the most important thing to do in terms of infection and malignancy is educate your patients so that they can make an informed decision, and also to do the appropriate surveillance.

WALSH: What's known about the pathogenesis of RA?

HOROWITZ: The pathogenesis of RA is a combination of environment and genetics. We know -- for the past 20 years or more we've known about the shared epitope, and that is one of the strongest genetic factors for rheumatoid arthritis.

Over the past few years, there's been a flurry of candidate genes and single nucleotide polymorphisms that have been discussed in the genetics of rheumatoid arthritis.

But it's not just genetics, because you can have identical twins where one of them has rheumatoid arthritis and the other does not. The concordance rate in monozygotic twins is 15 to 30%, so it's clearly not all genetics.

There is definitely an environmental factor. The three hot areas in the environmental cues for rheumatoid arthritis are the gut flora, periodontal disease, and smoking.

So there, the idea is that someone may have a genetic predisposition, but there's an environmental factor that sets that genetic predisposition rolling to create disease.

WALSH: Well, what would you say is the outlook for patients with RA today and tomorrow?

HOROWITZ: I think the outlook is very good. If you look at what's gone on in the past 10 to 15 years, we've revolutionized the treatment of rheumatoid arthritis.

When TNFs came into the market, patients saw a great decrease in disability, and that's very important. And down the pipeline, there're many new drugs coming.

I think that patients should be hopeful and look forward to the future because there will be many options available.

WALSH: And can they expect to reach lasting clinical remission?

HOROWITZ: That's another interesting question. That is, the goal is to have what we call a DAS-28 remission.

Right now, currently, it does not happen for the majority of patients with our current treatments, or at least with their first- or second-line treatments, but it is the goal for the future.

WALSH: Do you have any final thoughts for our listeners?

HOROWITZ: I think that our listeners need to be careful when they initiate treatment for arthritis, to make sure that they've taken a careful history and physical, because that's so critical and you just don't want to miss something that could be mimicking rheumatoid arthritis.

WALSH: Okay. Thank you very much, Dr. Horowitz.

HOROWITZ: Thank you.

WALSH: MedPage Today, I'm Nancy Walsh.

Diane Horowitz, MD has disclosed that she has no relevant financial relationships or conflicts of interest to report. RheumatoidArthritis/32113?utm_content=&utm_medium=email& utm_campaign=DailyHeadlines&utm_source=

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Post edited by: Bettyg, at: 04/12/2012 04:18 AM

04/13/2012 01:27 AM
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The Road to Remission in RA WITH rheumatologist Dr. Vivian Bykerk , a Clinical Context Report

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This report is part of a 12-month Clinical Context series.

By Nancy Walsh, Staff Writer, MedPage Today

Published: April 11, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner


WALSH: I'm Nancy Walsh from MedPage Today, here in New York at the Hospital for Special Surgery with rheumatologist Dr. Vivian Bykerk. Good morning.

BYKERK, MD: Good morning, Nancy.

WALSH: So, when you first see a patient with undifferentiated arthritis, what is your approach?

BYKERK: We go back to basic medical school principles:

Take a really good history and physical.

By history, we're really already in our minds trying to figure out what bucket the patient fits into.

For instance, seropositive rheumatoid arthritis, lupus, Sjogren's, anything that has an antibody associated with it.

Might they be somebody who fits in the spondyloarthropathy bucket?

Will they have psoriatic arthritis, ankylosing spondylitis, a variant of any of these?

Will they have some kind of reactive arthritis?

Was there a preceding infection?

And then we think is this going to be something chronic or self-limited.

Is this seropositive disease versus seronegative disease?

Is there a potential infectious origin that we should be thinking about?

And, particularly in the Northeast, we would think of Lyme disease, but I think if you lived in South America, you would think of a different infection. So that is what's going through our head.

Tagging on to the other side of that is the physical:

What's the pattern of joint involvement?

Did it start with a few joints; i.e., oligoarticular, and then become polyarticular?

What time course has occurred since the onset?

Did it start out palindromic and then become persistent?

Is it predominantly large joint, or small joint, or mixed?

Is it involving DIPs, which puts it more in the seronegative bucket? Is the joint pattern involving the neck or spine, which would put it more in the seronegative bucket?

Are there prominent extra-articular features, and then are there systemic features?

So if there are a lot of fevers, rashes, sweats, it's more likely to be a connective tissue disease, such as lupus maybe, even vasculitis.[/b]

So those are the kinds of things we're thinking from the beginning.

The next would be to think how are we going to confirm our findings. And depending on how long symptoms have been going on, we'll want to do some sort of laboratory investigation.

So we'll want to know are there signs of inflammation in the lab,[b] is the CRP high, is the ESR high, is the hemoglobin low?

You know, what degree of signs of inflammation is there?

If we think about the new ACR criteria for rheumatoid arthritis, if you already have an erosion, by definition, you have rheumatoid arthritis; then you don't need to do anything else beyond history and physical.

If you don't have an erosion, then you need to count joints, look at serology, look at acute phase reactants, and use all of that to make a diagnosis, or a classification, anyway.

WALSH: Do you ever do any more elaborate imaging, such as MRI?

BYKERK: I do, particularly in young men or women who have back pain in some large joints.

And those people sound like they're going to have spondyloarthropathy, but, very commonly, their SI joints, by plain radiography, are negative, and MRIs of the SI joints would be indicated.

Another example would be somebody from whom I'm getting a lot of complaints of joint pain, and I can't find that much on physical examination.

I might ultrasound the wrist or MCP joints or even MTP joints to see if I can confirm what I think is synovitis.

So atypical presentations, subtle presentations where there's nothing else to confirm what's going on.

Or somebody I'm very worried about, somebody who might not want to go on a certain course of therapy. I know they have rheumatoid arthritis.

I can tell they have joint pain, joint swelling; it's pretty subtle.

Patient doesn't feel too bad. They don't want to start therapy.

And then if they see on an ultrasound, hey, you know, there's rip-roaring red spots all over these joints, which is, what, power Doppler, they may be more convinced that there is a problem.

And with ultrasound, we can see erosions early. As early as four months. Similarly, with MRI. So sometimes if we wanted to get a sense of joint disease severity early on, high resolution imaging can be very, very helpful.

WALSH: And so what is your first therapeutic strategy?

BYKERK: If it's RA, the first therapeutic strategy, most often, is methotrexate. And I escalate quickly, and if need be, I go to sub-Q fast.

There are data to show that combination therapy is more effective than monotherapy.

There are also data to show that monotherapy is just effective on its own, so that literature is confusing.

And that literature -- the confusion of that literature is reflected in the various practice recommendations across various countries.

I believe Europeans do not advocate for a combination therapy because they're not convinced the literature is strong enough to say that combination therapy is any better than monotherapy.

The U.S. practice recommendations are positive on combination therapy, so it's not clear; there are studies for and against.

Now, I think the reason that monotherapy, methotrexate monotherapy, may not be as effective as combination therapy is because people use too little, too slowly; in other words, they start their dosing too low, they take too long to escalate.

And I think when you escalate quickly or even start right at your therapeutic dose and even start at your therapeutic dose by sub-Q, you may see a faster result on methotrexate.

Again, conjectural, experience-based, based on some data we've seen from the Canadian early arthritis cohort data, but it remains to be proven whether that is more effective than combination therapy.

In any event, methotrexate is sort of the anchor and the mainstay and the first stay of therapy.

Whether or not we add hydroxychloroquine and/or sulfasalazine remains to be determined; we know that 30% of people will fail that.

And even methotrexate responders, where they remain in low disease activity, 30% of them will go on to have radiographic damage, so it's not the be-all and end-all.

We know that people who delay methotrexate, particularly if they have the poor prognostic factors, they will not do well.

WALSH: What are the poor prognostic factors?

BYKERK: People who have high joint counts, high serology, prolonged disease, smoking.

WALSH: Okay. And then what do you do after the DMARDs?

BYKERK: I think it's reasonable to give people an 8- to 12-week trial of DMARDs minimum. If you're starting to see a good response, you continue.

If you've only used methotrexate, you're starting to see a good response, you could consider adding in another DMARD.

bettyg note:

LYME/CO-INFECTION PATIENTS SHOULD NOT USE STEROIDS; they suppress our immune system and make us much worse!!

Then there's the use of steroids in that early interval. So again, I think it's controversial.

I'm not sure that steroids are necessarily the be-all and end-all, but there's good data that you know if you use steroids early that you get as good a response as if you were to use a TNF inhibitor early, or almost as good.

And so judicious early use of steroids, where you taper rapidly and taper off, I would say, in my view, you don't want to continue steroids.

But there will be colleagues that say No, we should keep using 2 and 3 mg of prednisone with methotrexate; it's the cheapest, most effective way, and it may be. You know, there is some truth to that.

But we also know that people on prednisone have higher cardiovascular morbidity for whatever reason.

We know that there's more cataracts.

There may be more bone issues if the drug isn't tapered down.

And we know patients tend to use that medication to self-manage their flares.

So even though we think they might only be on 2 or 3 mg, they may be bumping that prednisone up all the time.

WALSH: So when do you decide to go to a biologic?

BYKERK: If my patient can't get into low disease activity state by 3 to 4 months, and I've used full-dose methotrexate and I've probably injected some joints or used a short course of prednisone. And I may or may not have added additional DMARDs depending on the patient preference, because patients have a hard time, by the way, suddenly taking, you know, a whole pile of medications for just arthritis. If you told them it was cancer, no problem, but for rheumatoid arthritis, you can't always get them to take all the meds. So if you can only get them to take one med, go for methotrexate. But anyway, having said all of that, if they're not getting into a low disease activity state pretty quickly, that's when I decide to [go with a biologic].

WALSH: And what would you start with first?

BYKERK: The first thing we decide is, are they better off using IV or sub-Q. I think most docs would make that decision, IV or sub-Q. And then if they choose the subcutaneous route there are lots of options now. I mean there are the traditionals, the etanercept, adalimumab. And then we now have certolizumab, we have Simponi, and we've got sub-Q abatacept coming out. And pretty soon we're going to have sub-Q tocilizumab.

So, which one should we really use first? Traditionally we've used one of the TNFs first, and it works, you know. Having done that, I think another substantial proportion of people do very well with TNFs. And I mean in the literature we quote somewhere around 30% are TNF nonresponders. I think it's lower than that in early RA, but time will tell.

WALSH: And for the patients who don't respond to a TNF inhibitor?

BYKERK: So for patients who don't respond, again, you need to give them a 3-month trial. You usually have a good sense at 8 weeks, but you should give them at least a 3-month trial.

If there's zero response, which is rare, I'd say less than 10%, we would move to a new mechanism of action. And then we go through whether it should be abatacept, rituximab, tocilizumab; each has its pros and cons.

I think the new kid on the block is tocilizumab, but with that medication, studies have shown very high remission rates and good results on monotherapy. But a new kid on the block, people are still somewhat concerned about adverse events.

Abatacept, people are very comfortable with it for its safety profile, its reputation as it takes a little longer; again, that's pretty variable in patients. Some people would try a second TNF. I think that if there's zero response, that's probably not a great strategy.

Then the other question is whether they're seropositive or not. I think the data are pretty good that if you're seropositive you've got a great chance of responding to rituximab, and it's every six months.

What scares a few people off is that there have been a couple of deaths from PML, and so that might concern some people going with that drug early. And the other thing I think we still don't know with rituximab is how many years can we use it safely. So we know we can use it 3 or 4 years safely. The safety data suggest maybe a lot longer from the clinical trials data, but we don't have great registry data yet to say we can go out 6, 8, 10 years with that medication.

WALSH: And do you have that kind of data for the TNF inhibitors?

BYKERK: We do. There's a lot of mostly European registries, also Corona, that have data on the TNFs out 8, 9 years now, probably coming up on 10, and there's also the clinical trial data that has gone out 10 years, so we have good long-term data on TNFs.

WALSH: So, today, how do you define remission?

BYKERK: Great question. You know, there are new remission criteria. They have been proposed by ACR and EULAR; I'm sure you're familiar with them. They use two ways: One is what we call an index-based definition, where we use a simple disease activity index. You add up the CRP, the patient global, the physician global, the 28 joint count tender and the 28 joint count swollen, and it has to be less than 3.3, and that's remission.

Then the other is what we call a Boolean-based definition from the same paper, where you use four variables: Patient global, swollen joint count, tender joint count, and CRP, and each one of them has to be 1 or less, which is even tougher.

When we look in the Canadian early arthritis registry and we look at a year and we say, okay, how many people can meet these criteria for remission, compared to the most commonly used remission, which was the DAS28, less than 2.6. So to get to a DAS28 of less than 2.6, about 50% of people can do that at a year, starting with methotrexate alone or in combination, plus or minus prednisone, and then escalating to biologics if you're not and not doing well.

And that's a Canadian system where there's a little bit of delay to biologic therapy compared to the American system. The proportion of people that meet the index-based definition, about 22%, and the proportion of people that meet the Boolean definitions, about 20%, so one could look at that as a glass half full, half empty. You know, if only 20% are getting a remission, that's not so great. But if we look at zero swollen joints, almost 50% of people make zero swollen joints.

Why would that matter or not? That's a very physician- and provider-based definition. Well, one way to look at zero swollen joints is if you aren't swelling in your joints, you're probably not damaging your joints. Now, they may still hurt because there's been some damage. They may still hurt because there is subclinical synovitis that the physician is not picking up, or there may be back pain, and so the physician global -- or patient global -- is high because their back hurts and their RA is really in remission. We don't know; there are many factors playing in here. But I would say we want to stamp out synovitis, and by stamping out synovitis, you're stamping out the risk for damage, you're hopefully improving function back to normal, and you're hopefully not seeing any further radiographic damage.

WALSH: What do you recommend as far as preventing cardiovascular disease?

BYKERK: There are all the things that one does anyway to try and prevent cardiovascular disease. But, you know, you're coming from the perspective of patients with RA have higher cardiovascular disease, and it's probably linked to disease activity and persistence of higher disease activity.

So the more inflammation burden you have, the higher risk you have for cardiovascular disease, and that can mean anything from atherosclerosis to poor myocardial function for whatever reason, not fully understood.

And so I think the main recommendation is get your patients into remission soon. Then the other is, of course, to adhere to modifying all the possible modifiable risk factors for cardiovascular disease.

WALSH: Do you routinely recommend things like lipids?

BYKERK: That's controversial, depending where you go and who you ask. Some physicians are adamant that "That's not my job as a rheumatologist, I don't measure lipids, I'm not comfortable treating them," to "Yes, I'm a general care provider and I'm going to measure lipids and treat that and I'm going to measure, make sure the CRP -- high sensitivity CRP is down to normal, and I'm going to use a statin if that isn't happening, and particularly if there's a family history and if there's diabetes or there are other risk factors."

You know, the way of identifying cardiovascular risk is not well understood, fully understood, in RA yet. The question becomes should we be doing ECGs on people? Should we be doing echos? What will we find? Who do we do it for, and do we do it in over 50, over 40, over 60? Those kinds of things, in day-to-day practice, I don't think have been fully worked out.

WALSH: What role do you see for the new oral agents?

BYKERK: They look good, and certainly tofacitinib looks very good; all the data look excellent. We've certainly seen medications come and go that looked great at that stage.

The other issue will be what they do price-wise. You know, if they price it competitively, I think we'd probably use them before TNF inhibitors. You know, if over time they outdo methotrexate, that pill will take over from methotrexate. It's really hard to say. I'm optimistic about them.

WALSH: Do you ever find that you can actually take a patient off treatment?

BYKERK: Yes, yes. And so they did this out of the Leiden and early arthritis cohorts; there was a study out of Europe. And they saw basically 15% of people could become medication free; same with the BeSt study. But in the BeSt study, of the 15% who became medication free, another 8% had to go back on at some point down the line.

If you look at predictors of who cannot come off, it's people who've had longer symptom duration before they started treatment, people who had persistent synovitis, obviously, and people who were smokers.

WALSH: Do you have any final thoughts about rheumatoid arthritis, what patients can look forward to?

BYKERK: I think that having a diagnosis like rheumatoid arthritis is tough. Patients have to wrap their heads around the fact they have a chronic illness, and that there's a good possibility they're on medications for life. That's the downside, and that is a downside; it's tough. But the earlier they're seen and the earlier they're treated effectively, the less the impact the disease will have on their life. They can't deny it; yet, it doesn't need to be the catastrophe or the disaster that it was in years past.

WALSH: Thank you very much, Dr. Bykerk.

BYKERK: My pleasure.

Bykerk has disclosed the following relevant financial relationships:

Served as a Consultant or on an Advisory Board: Augurex, Boehringer Ingelheim Pharmaceuticals, Bristol-Meyers Squibb, Pfizer, Roche Laboratories - Genentech, and UCB Pharmaceuticals RheumatoidArthritis/32121?utm_content=&utm_medium=email& utm_campaign=DailyHeadlines&utm_source=

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Post edited by: Bettyg, at: 04/13/2012 01:37 AM

04/22/2012 03:06 AM
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IL-6 Blocker Stops RA Joint Damage

By Nancy Walsh, Staff Writer, MedPage Today

Published: April 13, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

Typically the extent and progression of joint damage in rheumatoid arthritis is primarily related to the degree of the inflammatory process.

In contrast, none of the variables of clinical activity showed significant correlation with x-ray changes in patients receiving tocilizumab and methotrexate, [b]suggesting that the effects of IL-6 inhibition on progression of joint damage in rheumatoid arthritis are independent of effects upon inflammation.

Treatment of rheumatoid arthritis with an anti-interleukin (IL)-6 receptor antibody significantly slows the progression of joint damage even in patients who continue to have active disease, a post-hoc analysis revealed.[/b]

After a year of treatment, patients receiving placebo plus methotrexate had a mean score of 21.7 on the clinical disease activity index, while those receiving tocilizumab (Actemra) plus methotrexate had similar mean scores of 20.2 (P=0.19), according to Josef S. Smolen, MD, of the Medical Unit of Vienna in Austria, and colleagues.

Yet there was a threefold difference between the two therapies in radiographic progression -- with a mean change of 1.2 points for the placebo group and only 0.4 points in the tocilizumab group (P=0.0009) -- on total Genant-modified Sharp scores, the researchers reported in the May issue of Arthritis & Rheumatism.

It has long been known that joint damage in rheumatoid arthritis is associated with ongoing inflammation in untreated patients and in those managed with conventional therapies.

However, recent publications have demonstrated that treatment with the tumor necrosis factor inhibitors can interfere with radiographic progression, even in patients who remain symptomatic or who have persistently high levels of acute phase reactants.

To determine whether a similar phenomenon occurs with inhibition of IL-6, Smolen and colleagues analyzed data from the LITHE trial, which randomized 531 patients to methotrexate plus either placebo or tocilizumab in doses of 4 mg/kg or 8 mg/kg every 4 weeks for a year.

Radiographs of the hand and feet were assessed at baseline and 1 year.

In a correlation analysis, patients randomized to receive placebo showed a significant association between progression in radiographic scores and disease activity indices at 1 year (r = 0.26 to 0.28, P=0.002 to 0.006).

But in patients receiving tocilizumab, x-ray progression did not correlate with any disease variables including C-reactive protein levels (r = 0.08), swollen joint counts (r = 0.007), or the simplified disease activity index (r = 0.005), with P values being nonsignificant for all comparisons, according to the researchers.

"Taken together, these data suggested that the link between surrogate markers of disease activity and progression of joint damage could be seen in placebo-treated patients also when the [total Genant-modified Sharp score] was employed, but that [tocilizumab] treatment abrogates this association between disease activity and destruction, similar to previous reports for TNF inhibitors," they wrote.

The researchers noted that total Genant-modified joint scores include measurements of both erosions and joint space narrowing.

Over the course of the study year, erosion scores changed by 0.65 points in the placebo group and 0.25 points in the tocilizumab group, while the corresponding changes on joint space narrowing were 0.53 and 0.14 points, respectively.

"This finding indicates that [tocilizumab] interferes independent of disease activity with both osteoclastogenic and cartilage-degrading pathways," the researchers observed.

The study was limited by being a post-hoc analysis, although the original data had been collected prospectively, and by focusing on patients who completed the study.

The authors noted that it remains to be seen if other biologics such as rituximab (Rituxan) and abatacept (Orencia) also have these dissociative effects on radiographic and clinical outcomes.

They also cautioned that patients who do not respond clinically to tocilizumab should have a change in treatment even if radiographic progression is halted because of persistent difficulties with physical function and quality of life.

The study was funded by grants from Roche and the European Community's Seventh Framework Program.

Smolen and one of his co-authors have received honoraria from Roche.

Primary source: Annals of the Rheumatic Diseases

Source reference:

Smolen J, et al "Tocilizumab inhibits progression of joint damage in rheumatoid arthritis irrespective of its anti-inflammatory effects: disassociation of the link between inflammation and destruction" Ann Rheum Dis 2012; 71: 687-693; DOI: 10.1136/annrheumdis-2011-200395. utm_content=&utm_medium=email&utm_campaign=DailyHeadlines& utm_source=

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05/07/2012 12:45 AM
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Biologic tocilizumab Works as Monotherapy in Early RA

By Nancy Walsh, Staff Writer, MedPage Today

Published: May 03, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

l comment(s)

Action Points

This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

This study found that treatment with tocilizumab – with or without methotrexate – leads to significant and very early suppression of rheumatoid arthritis (RA) disease activity and damage.

Note that decreases in these earliest inflammatory changes were already being seen on MRI after only 2 weeks of treatment, which is important because it shows that there was a real tissue effect in the synovium.

GLASGOW -- Treatment with tocilizumab (Actemra) – with or without methotrexate – leads to significant and very early suppression of rheumatoid arthritis disease activity and damage, a researcher reported here.

In a large cohort of patients with at least moderate disease activity, the relative risk of achieving remission at 6 months was 40.4% among those receiving tocilizumab plus methotrexate, and 34.8% for those receiving the monoclonal antibody alone (P=0.19), according to Philip G. Conaghan, MD, of the University of Leeds in England, and colleagues.

That finding suggested that this interleukin-6 receptor inhibitor can be given as monotherapy in patients who are unwilling or unable to take methotrexate, he said.

And after only 3 months, a substudy showed that pre-erosive changes detectable on MRI were being reversed, with a change in the synovitis score from baseline of &#8722;0.9 (95% CI &#8722;1.6 to &#8722;0.2, P&#8804;0.01) for the combination group and a change of &#8722;1.9 (95% CI &#8722;2.8 to &#8722;1, P&#8804;0.0001) for the monotherapy group, Conaghan reported at the annual meeting of the British Society for Rheumatology.

Furthermore, decreases in these earliest inflammatory changes were already being seen on MRI after only 2 weeks of treatment, which is important because it shows that there was a real tissue effect in the synovium.

"IL-6 blockade with tocilizumab doesn't just treat the C-reactive protein level, which has been a concern. It has actual tissue effects like the TNF blockers," he said.

The study included 556 patients whose mean baseline disease activity score was 6.33.

Most were women, who averaged 53 years of age.

Mean duration of disease was 8.2 years, and patients had a mean of 14 swollen joints and 25 tender joints.

They also had to have at least one radiographic erosion, indicating progressive disease.

"This was a real-world study, and these are the typical patients we are now treating with biologics," Conaghan said.

Improvements of 20%, 50%, and 70% on American College of Rheumatology criteria were similar among patients treated with the combination and those on monotherapy, respectively:

ACR20, 72% versus 71%

ACR50, 45% versus 41%

ACR70, 25% versus 26%

None of those differences were statistically significant, according to Conaghan.

Quality of life, as measured on the Health Assessment Questionnaire, improved to a similar degree in both groups (&#8722;0.56 versus &#8722;0.55, P=0.93).

Serious adverse events were seen at rates of 21 per 100 patient-years in the combination group and 18 per 100 patient-years in the monotherapy group.

As expected, elevations in liver enzymes were seen more commonly among patients also receiving methotrexate (16% versus 6%).

In the MRI substudy, which included 63 patients, the mean change in osteitis score from baseline to week 12 was &#8722;3.6 (95% CI &#8722;6.5 to &#8722;0.7, P&#8804;0.001) in the combination group and &#8722;5.1 (95% CI &#8722;8.6 to &#8722;1.6, P&#8804;0.01) in the monotherapy group.

Only one patient, who was in the combination group, had developed a new erosion at week 12.

In the past, joint damage was assessed radiographically, and on probability curves typically was driven by about 10% of patients with progressing disease.

Today, however, MRI permits the detection and assessment of inflammation and disease activity before progression and damage have occurred.

"ACR is now considering including very early time points in clinical trials, with the current emphasis on early detection and treatment," Conaghan said.

"It's unethical now to do clinical trials with long lead times, so we need markers of early response that are surrogates for later outcomes, and MRI can provide that," he said.

The study was sponsored by Roche.

The authors reported no conflicts of interest.

Primary source: British Society for Rheumatology

Source reference:

Dougados M, et al "Double-blind study of tocilizumab plus methotrexate versus tocilizumab plus placebo in patients with active rheumatoid arthritis despite prior methotrexate: progression of structural damage, quality of life, and physical function at 24 weeks" BSR 2012; Abstract 016.

Additional source: British Society for Rheumatology

Source reference:

Conaghan P, et al "Tocilizumab as monotherapy or in combination with methotrexate associated with early reductions in tissue inflammation: 12 week results from a magnetic resonance imaging substudy of a randomized controlled trial" BSR 2012; Abstract 012. utm_content=&utm_medium=email&utm_campaign=DailyHeadlines& utm_source=

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05/09/2012 01:11 AM
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RA UK Registry Data Reassuring on Biologic Safety

By Nancy Walsh, Staff Writer, MedPage Today

Published: May 02, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

These studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

The increased risk from cardiovascular disease seen in rheumatoid arthritis was not further heightened by current aggressive therapies such as anti-tumor necrosis factor (TNF) drugs, according to a study from the U.K.

Note that a second study reported that treatment with anti-TNF agents in patients with a prior history of cervical intraepithelial neoplasia 3 did not result in genital cancer cases.

GLASGOW -- A registry sponsored by the British Society for Rheumatology (BSR) continues to provide reassuring safety data regarding the more aggressive treatment strategies now used for patients with rheumatoid arthritis, studies presented here confirmed.

It has been well recognized that patients with rheumatoid arthritis have twice the risk for cardiovascular mortality as the larger population (standardized mortality ratio 1.5), according to Audrey Low, MBBS, and colleagues from the University of Manchester in Manchester, England.

With the treatment approach of early escalation of conventional disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate and leflunomide, including dosage optimization, the excess risk has fallen to 20% for cardiovascular mortality (standardized mortality ratio [SMR] 1.2, 95% CI 1 to 1.5), Low said in a poster session at the BSR annual meeting.

In addition, among patients being treated with tumor necrosis factor (TNF) inhibitors, the standardized mortality ratio stands at 1.6 (95% CI 1.5 to 1.8), which is similar to the background risk, she said.

"That is reassuring, because patients receiving the anti-TNF agents typically have much more disease activity and higher burdens of inflammation, which can contribute to cardiovascular risk," Low told MedPage Today.

The analyses included all patients enrolled in the registry between 2001 and 2008.

A total of 3,367 patients were receiving escalated DMARD therapy, and 12,051 were being treated with anti-TNF agents.

Those receiving escalated DMARD treatment were older (60 versus 56 years), and had shorter disease duration (6 versus 11 years).

For ischemic heart disease, the risks were:

Escalated DMARD, SMR 1.4 (95% CI 1 to 1.8)

Anti-TNF, SMR 1.8 (95% CI 1.6 to 2.1)

For stroke, the risks were:

Escalated DMARD, SMR 1.1 (95% CI 0.6 to 1.8)

Anti-TNF, SMR 1.3 (95% CI 0.9 to 1.8)

"So even though the overall pattern is improving, we still need to do better in identifying risk factors for cardiovascular mortality in patients with rheumatoid arthritis," Low said in conclusion.

In a separate poster presentation, her University of Manchester colleague Louise Mercer, MBBS, reported that there were no new or recurrent genital cancers among women who had a previous history of carcinoma in situ of the cervix and were treated with anti-TNF agents.

"We at the BSR registry get lots of questions from around the country asking if these women can be safely treated with anti-TNF therapy," she told MedPage Today.

So her group looked at all women in the registry with a diagnosis of cervical intraepithelial neoplasia grade III with or without mention of severe dysplasia prior to receiving anti-TNF treatment.

A total of 48 were on nonbiologic DMARD therapy and 190 were receiving anti-TNF treatment. The patients' mean age was 50.

Median disease duration was 4.5 years among those on conventional therapy and 10 years among those on TNF inhibitors.

For the DMARD group, there were two incident genital cancers during 159 person-years of follow-up, for a rate of 13 per 1,000 person-years (95% CI 2 to 45).

One of these was a metastatic squamous cell cancer of the vulva, and the other was metastatic cancer of the cervix. In both cases, the carcinoma in situ had developed more than a decade earlier.

In the anti-TNF group, during 893 person-years of follow-up, there were no incident genital cancers, "and we concluded that the treatment appears safe for these women," Mercer said.

In most cases, it was only through the national cancer registry that the earlier cervical lesions were identified.

"In only about 10% to 15% of cases did the consultant ask about this history and report it," she added.

Neither of the poster presenters had any disclosures.

Two of their investigators reported receiving research grants from several companies, including Merck, Abbott, Pfizer, Roche, and UCB.

Primary source: British Society for Rheumatology

Source reference:

Low A, et al "Cardiovascular mortality rates are elevated in a national cohort of subjects with rheumatoid arthritis compared with the UK general population whether they were or were not treated with biologic drugs: results from the BSRBR" BSR 2012; Abstract 71.

Additional source: British Society for Rheumatology

Source reference:

Mercer L, et al "Outcome of women with previous carcinoma in situ of the cervix with respect to female genital cancer, following treatment with non-biologic DMARD or anti-TNF for rheumatoid arthritis: results from the BSRBR" BSR 2012; Abstract 70. utm_content=&utm_medium=email&utm_campaign=DailyHeadlines& utm_source=

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05/09/2012 01:17 AM
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RA Found Sooner Using Newest Disease Criteria

By Nancy Walsh, Staff Writer, MedPage Today

Published: May 04, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that this study shows that the new criteria classify at baseline similar numbers of patients as having RA, that the previous criteria would have taken up to 5 years to identify.

GLASGOW -- The recently revised 2010 classification criteria for rheumatoid arthritis successfully identified affected patients in the U.K. earlier than a previous set of criteria did, a researcher reported here.

Among a cohort of patients diagnosed in 1990, the rate of rheumatoid arthritis was 31.7 per 100,000 population when retrospectively applying the earlier 1987 criteria, according to Jennifer Humphreys, PhD, of the University of Manchester in England, and colleagues.

In contrast, the rate using the new criteria was 40.4 per 100,000 population, Humphreys reported at the annual meeting of the British Society for Rheumatology.

The 1987 case definition was formulated based on patients with longstanding rheumatoid arthritis, and thus had poor sensitivity for early disease.

The older criteria required four of these seven findings for the diagnosis:

Morning stiffness

Arthritis in three or more joints

Arthritis in the hand joints

Symmetric involvement

Rheumatoid nodules

Rheumatoid factor positivity

Radiographic changes

To provide criteria for research and clinical trial purposes in the era of much more effective therapy, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) jointly established these revised criteria, requiring a total score of at least 6 for the diagnosis:

Joint involvement -- scores of 0 to 5 depending on number of large and small joints affected

Serology -- rheumatoid factor and/or anti-cyclic citrullinated peptide, scores of 0 to 3 depending on whether low-positive or high-positive

Acute phase reactants -- elevated C-reactive protein and/or erythrocyte sedimentation rate, scores of 0 to 1

Duration of symptoms, less or more than 6 months, scores of 0 to 1

To examine the incidence using the new criteria, Humphreys and colleagues analyzed data from all adult patients in the Norfolk Arthritis Register, which is a primary care inception cohort established in 1990.

The register included 260 patients whose mean age was 54 and mean disease duration was 30 weeks.

More than two-thirds were women, and 57% had disease involvement in more than 10 joints.

Among women, the overall incidence rate according to the 1987 criteria was 44 per 100,000, and for men, the rate was 19 per 100,000.

Incidence rates varied according to age in both sets of criteria, ranging from 19 to 91 per 100,000 among women according to the new criteria and from 16 to 94 with the older criteria.

At 5 years, the cumulative age and sex-specific incidence rates were similar with the two sets of criteria.

"However, after 5 years, 3% of patients satisfied the older criteria but not the new criteria, and 10% satisfied the 2010 criteria and not the 1987 criteria," she said.

So although similar numbers of patients ultimately were identified using the two sets of criteria, it took up to 5 years for the older criteria to do so.

"This meant that if the older criteria were still being used to determine eligibility for treatment, those 10% of patients could have gone on to develop persistent, erosive, and disabling rheumatoid arthritis," Humphreys explained.

Furthermore, some patients met only one set of criteria over time, while others never met either, findings that require further exploration to ensure that neither undertreatment nor overtreatment occurs, she said.

The authors reported no conflicts of interest.

Primary source: British Society for Rheumatology

Source reference:

Humphreys J, et al "Incidence of rheumatoid arthritis in the UK using the 2010 ACR/EULAR classification criteria and comparison with estimates using the 1987 ACR criteria" BSR 2012; Abstract O39. utm_content=&utm_medium=email&utm_campaign=DailyHeadlines& utm_source=

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