Posts Tagged ‘Arthritis Treatment’

What is Elderly-onset Rheumatoid Arthritis and How Should it be Treated?

Elderly onset rheumatoid arthritis (EORA) is a misnomer since it refers to rheumatoid arthritis affecting people 60 years of age or older. Since this author recently reached the age of 60 and certainly doesn’t consider himself elderly, the definition should be changed.
Rheumatoid arthritis (RA) affects 2% of those 60 years old and older and is generally more common among women. When RA presents in patients past the age of 60, it may present with an acute onset, with significant inflammatory symptoms, and predominant upper extremity involvement, eg. shoulders. Inflammatory markers in the blood such as the erythrocyte sedimentation rate (ESR) may be greatly elevated.
Diagnostic testing is similar to that for diagnosing RA in younger individuals. Acute phase reactants for inflammation such as the ESR and CRP will invariably be abnormal. Serologic testing for rheumatoid factor and anti-cyclic citrullinated protein (anti-CCP) are helpful.
The diagnostic imaging procedure of choice is probably magnetic resonance imaging (MRI), although diagnostic ultrasound may be useful.
Other disease processes that need to be excluded include: calcium pyrophosphate deposition disease (CPPD), osteoarthritis, gout, polymyalgia rheumatica (PMR), arthritis associated with infections such as hepatitis B,C , and immunodeficiency virus. Tuberculosis and fungal infections such as histoplasmosis, coccidiomycosis, and blastomycosis can also present with inflammation of many joints.
Endocrine disorders such as diabetes and Cushing’s disease may also present with diagnostic challenges.
Malignancy is another consideration. An inflammatory arthritis affecting many joints in a patient over the age of 60 should lead the physician to working up the patient for an underlying malignancy. Also, certain malignancies such as lymphoma are increased in incidence in patients with rheumatoid arthritis.
The treatment of EORA presents special challenges. First, a patient with RA past the age of 60 probably has other medical conditions. Second, they are probably on multiple medications. The diagnosis may be confounded by the fact the both ESR and rheumatoid factor can be elevated in older patients who don’t have RA. Finally, treatment with medications needs to be tempered with the knowledge that potential side-effects may be increased in this population where drug metabolism is less certain than that of younger patients.
Nonetheless, the approach to therapy for patients with EORA is not substantially different from the treatment strategies employed for younger patients.
Non-steroidal anti-inflammatory drugs (NSAIDS) are often used early on in younger patients. However, in older patients who may develop kidney and liver toxicity with these agents, the use of NSAIDS is probably a strategy that has to be watched closely.
Low dose prednisone (5-10mgs) given as a single morning dose provides symptomatic relief and can serve as a “bridge” until the effects of second line agents begin. The potential complications of long-term prednisone therapy such as osteoporosis and cataracts, among others, will be more of a concern than for younger patients.
Second line agents consist of two groups. They are the disease-modifying anti-rheumatic drugs (DMARDS) and the biologic drugs.
Disease-modifying drugs such as methotrexate, hydroxychloroquine (Plaquenil), sulfasalazine (Azulfidine), and leflunomide (Arava) are all potentially useful. Obviously, with older patients, potential toxicities and drug interactions need to be monitored for carefully.
Biologic therapies can also be used for patients with EORA. TNF inhibitors such as etanercept (Enbrel), adalimumab (Humira), infliximab (Remicade, and the two newer agents golimumab (Simponi), and certolizumab (Cimzia) are all effective and well tolerated in the older population of patients with rheumatoid arthritis.
Second line biologics such as rituximab (Rituxan) and abatacept (Orencia) have also been used in patients with EORA with results comparable to that for younger patients.
Advancing age should not, by itself, be a contraindication to the use of biologic therapies. The aim for older patients, as it is with younger patients, is to establish remission. This may be even more important in older patients since independence is cherished more. Finally, since cardiovascular events are an established complication of rheumatoid arthritis and are also more common in older adults, every effort should be instituted to establish and maintain remission.

I Have Rheumatoid Arthritis. What Are My Chances For Becoming Disabled And Can I Do Anything About It?

Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune, inflammatory disease that affects more than 2 million Americans. It is a condition that is associated with increased mortality (rate of death) as a result of malignancy (lymphoma), cardiovascular events (heart attack and stroke), and significant disability.
The purpose of this article is to discuss the state of the art as it relates to disability.
It is clear that persistent disease activity leads to joint damage which leads to disability. While a patient has active disease- disease that is not well controlled- they will experience some degree of functional impairment. With the onset of permanent joint damage though, disability becomes a significant issue.
How severe is the risk of disability from RA? A number of epidemiologic studies have demonstrated that roughly 20 per cent of patients with RA are disabled within one year, between 32 and 50 per cent of patients by 10 years, and up to 90 per cent after 30 years.
The most sobering statistic is the extent of potential disability in the first year. Disability of this magnitude has an enormous physical, social, psychological, and economic impact.
Basic research has demonstrated that tumor necrosis factor (TNF) is a major contributor to the joint damage that results from RA. TNF stimulates cells called osteoclasts to “chew away” at cartilage and bone. This chewing away process ultimately causes irreversible joint damage.
While current therapies such as the combination of methotrexate with TNF-inhibitors (Examples include Enbrel, Humira, and Remicade) are very effective for controlling early RA, there has been scant proof of their ultimate impact on work outcomes.
Recent studies though have demonstrated that early intervention with methotrexate and TNF-inhibitors is effective in reducing work disability. The best current study (presented at the European League Against Rheumatism meeting in 2007), is the PROWD study evaluating the effects of a combination of methotrexate with adalimumab (Humira). The study showed that patients treated with the combination of methotrexate and adalimumab fared better as far as job loss and work time lost compared with patients taking methotrexate alone.
All studies evaluating the newer therapies seem to agree on one issue: Because of the consequences that result from irreversible joint damage, only early aggressive intervention prevents irreversible disability.
Therefore, prevention of disability and restoration of function should be an important goal of therapy. Both persistent disease activity and joint damage contribute to disability. The use of a combination of methotrexate and TNF inhibition early reduces inflammation and controls joint damage. It is this control of joint damage that helps preserve physical function and reduce work disability.

I Have Rheumatoid Arthritis And Have Heard About Cimzia… What Is It?

Biologic therapy has revolutionized our approach to the treatment of rheumatoid arthritis (RA). Less than 10 years ago, the best we could hope for was to “modify disease” or slow it down and also help with symptoms. Now the goal is to not only control symptoms, it is to get RA into complete remission. Biologics are protein-based medicines that are synthesized in a laboratory. They act like laser beams to target the immune abnormalities that are felt to cause RA.
First generation biologics such as etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira) are known as TNF-inhibitors and have done wonders for many patients. Second generation biologic such as rituximab (Rituxan) which acts against B cells and abatacept (Orencia) which works on T cells are both welcome additions to the arsenal of weapons available to combat RA.
Cimzia (certolizumab) is an investigational TNF-inhibitor. It differs from the current crop of TNF-inhibitors since it is “pegylated.” This means that a substance called polyethylene glycol has been attached to the molecule. This pegylation lengthens the half-life of the drug- meaning the drug stays in the system longer. Cimzia also has had a piece of protein removed from the molecule. The piece of protein that has been removed contained a small amount of mouse protein (yes… these drugs are often created using mouse proteins). By removing the piece of mouse protein, it is hoped that Cimzia will cause fewer adverse reactions.
A recent presentation on June 14, 2007 at the annual meeting of the European Congress of Rheumatology (EULAR) described data on Cimzia.
The team studied 2 dose regimens, which patients received subcutaneously as add-on therapy to methotrexate.
In a phase 3, multicenter, double-blind, placebo-controlled, parallel-group study, the investigators recruited 992 patients with RA who received either the study drug or placebo. The investigators wanted to know the rate at which people had a 20% improvement, as defined by the American College of Rheumatology criteria (ACR 20).
The patients, who had previously been treated for at least 6 months with methotrexate, were randomized to treatment with either pegylated certolizumab or placebo. Those on treatment received 3 400-mg doses every 2 weeks, followed by 200 or 400 mg doses of certolizumab pegol every 2 weeks. The patients continued methotrexate as usual. The investigators assessed the efficacy and safety parameters at 2-week intervals.
In an early analysis at 24 weeks, the investigators found that 581 patients completed the study: 259 of the 397 on 200 mg of the drug, 278 of the 394 on 400 mg, and 44 of the 201 on placebo. The ACR20 response rate was 59.2% in the 200 mg group, 61.2% in the 400 mg group, and 13.5% of those who received methotrexate and placebo. The proportion of patients who experienced a significant side effect was 74.0% in the 200 mg group, 76.1% in the 400 mg group, and 57.7% in the placebo group. The majority of adverse events were mild to moderate.
“Pegylated certolizumab adds significant benefit in reducing the signs and symptoms of RA in combination with methotrexate, compared to using methotrexate alone,” said lead investigator Edward C. Keystone, MD, professor of medicine at the University in Toronto, and director of the Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, in Ontario.
Bottom line: Pegylated certolizumab works like a TNF blocker and appears to treat the signs and symptoms of RA. Whether it’s better than the TNF blockers that are currently available is still no known. It is better than placebo.

How Does My Rheumatologist Know When I Need A Treatment Change For My Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is a systemic, progressive, autoimmune inflammatory disease that has as its main targets, the joints. It affects more than 2 million Americans.
In recent years, tremendous strides in understanding how RA develops has led to the development of targeted therapies.
The aggressive use of disease-modifying anti-rheumatic drugs (DMARDS) such as methotrexate, in combination with biologic therapies has resulted in sustained effectiveness, improved tolerability, and better response levels. The result has been a significant reduction in joint damage and work-related disability.
Remission is now the norm rather than the exception in patients who are seen early. The concept of a narrow window of opportunity- usually the first 3 to 6 months of disease- where aggressive therapy can prevent deformity and disability has also been recognized as a major reason for the improved prognosis.
Despite these advances, several problems still remain. A large number of patients stop treatment for a variety of reasons including lack of response and side effects. It is unclear whether the new drugs being used can actually help joint damage to heal. Long-term side effects also remain a concern.
So how do rheumatologists make the decision to change therapy?
The first question that needs to be resolved is “what is an inadequate response?” The definition is not an easy one.
There are actually three answers. The first is what is called primary failure where the drug doesn’t lead to any kind of improvement right from the outset. Secondary failure occurs when the drug works initially but then over time, the beneficial effects fade. Finally there are side effects and other toxicity issues to consider.
Another very important factor is the patient’s own feelings as to how they are doing. What are considered are both pain relief as well as ability to function with activities of daily living.
Added to this mix is the result of different imaging modalities such as magnetic resonance imaging, ultrasound, and plain x-ray. Of these three, plain x-ray is the least sensitive and least useful method.
Laboratory parameters that measure systemic inflammation such as the erythrocyte sedimentation rate (ESR) and C-reactive protein are also used in decision-making.
Some rheumatologists advocate the use of measuring devices of disease activity. They have the following names: Disease Activity Score (DAS), Disease Activity Index (DAI), and Global Arthritis Score(GAS). These measuring devices all involve analyzing different disease parameters, scoring them, then coming up with a number. The higher the number or score, the worse the patient is doing. These different scoring methodologies have a few things in common. They usually incorporate some count of swollen and tender joints. They also usually require adding in one of the laboratory measures of inflammation. Some also add in the results of a patient’s Health Assessment Questionnaire. This latter item tallies the patient’s ability to perform routine daily activities. Finally some methods also incorporate a patient self-assessment.
There is no consensus as far as which tool is the best to use. There is growing interest though in using the tools more often than they are being used now. Stay tuned.

What Every Rheumatoid Arthritis Patient Should Know About Anti-TNF Drugs

Patients with severe rheumatoid arthritis (RA) who have poor prognostic factors or rapidly progressive disease are considered to be candidates for early treatment with biologic drugs such as TNF-inhibitors.
These drugs are targeted therapies that act on tumor necrosis factor, a cytokine, to block its action in the immune response that is out of whack in patients with RA. Cytokines are chemical messengers that are produced by cells to permit signaling among each other.
TNF-inhibitors may be used in conjunction with disease modifying anti-rheumatic drugs (DMARDS) such as methotrexate, although they may also be used alone.
Since their first use approximately fifteen years ago, much information has become gleaned from clinical experience as well as clinical research trials.
About one-third of patients with RA treated with anti-TNF drugs fail to respond. This failure of response is called primary treatment failure.
And another significant percentage of patients lose response over time. This phenomenon is termed secondary treatment failure.
Patients with primary treatment failure are generally switched to another anti-TNF drug with a different mechanism of action.
Patients who experience secondary failure can have their dose of drug increased either by increasing the amount of drug given or by decreasing the interval between doses of drug.
Anti-TNF drugs do come with potential serious side effects that must be monitored for.
These include an increased risk of infection as well as a possible increase in risk of cancer reoccurrence (although this is highly speculative). TNF-inhibitors can also increase the risk of tuberculosis.In addition, an increased incidence of other fungal infections such as histoplasmosis and coccidiodomycosis has also been noted.
Other potential side effects include a risk of neurological syndromes that mimic multiple sclerosis and injection site reactions.
Options for patients who have developed failure to TNF-inhibitor treatment include switching to either abatacept (Orencia) or rituximab (Rituxan).
Abatacept acts to block the activation of T-cells which are felt to play a significant role in the immune response.
Rituximab acts by depleting B-cells, which are also felt to be a significant contributor to the role of RA progression.
Another drug that is waiting in the wings is tocilizumab (Actemra). This drug inhibits the action of interleukin-6, another cytokine that has multiple effects on the immune system. Actemra has many desirable effects but because interleukin-6 is so ubiquitous, it also has some undesirable effects as well. These include elevation of liver enzymes as well as elevation of lipids.
Other drugs that have even different mechanisms of action include the various protein kinase inhibitors such as the Syk and JAK inhibitors that are currently being studied. These drugs have multiple effects on the immune system and are attractive because unlike anti-TNF drugs, protein kinase drugs are taken orally. However, they too have potentially undesirable side effects that must be accounted for.
The current buzz is the development of biomarker profiles that will potentially allow customized therapies for RA patients. By biopsying the synovium (lining of the joint)and identifying the biomarkers that are present within the synovium, it may be possible to “customize” the correct drug or combination of drugs that will get a patient into remission.
This will provide a much more targeted approach to treatment and may potentially lead to a cure for this devastating disease.

Can Rheumatoid Arthritis Treatments Reduce The Chance Of Heart Attack?

A recent study has shown that the use of a combination of a tumor necrosis factor (TNF) inhibitor along with methotrexate therapy in people with rheumatoid arthritis (RA) was associated with a reduction in heart attack risk of 80 percent compared with patients using methotrexate alone, according to research presented recently at the American College of Rheumatology Annual Scientific Meeting in Boston, Mass.
Rheumatoid arthritis is a chronic, systemic, autoimmune disease that not only causes pain, stiffness, swelling, and limitation of function in joints, but also damages internal organs as well.
Approximately, 2.1 million Americans are afflicted with RA, most of them women. As mentioned above, while joints are the principal areas affected by RA, inflammation can develop in other organs as well. Heart attacks, resulting from inflammation of the coronary vessels, are more common in RA sufferers.
Researchers recently studied the risk of heart attack in patients using a TNF-inhibitor (a drug that blocks cytokines and can turn off the chronic inflammation that causes destruction in RA), methotrexate (a drug used to treat RA by blocking the metabolism of cells) and other disease modifying anti-rheumatic drugs (DMARDs), which are a category of drugs used in RA to slow down the disease progression, in a large population of patients with RA-many of whom were also taking aspirin.
Using information obtained from MediCal, California’s Medicaid program, researchers studied patients over the age of 18, suffering from RA, who were treated with TNF-inhibitors, methotrexate, or other DMARDs, over a six-and-a-half year period.
A total of 19,233 patients with RA were identified. The patients’ mean age was 55 years.
Approximately 79 percent were women. Of these patients, 13,383 took methotrexate; 14,958 took other DMARDS; and 4,943 took TNF-inhibitors. Exposure of one group of patients to TNF-inhibitors (taken alone or in combination with methotrexate) was compared to that of the other group taking methotrexate alone.
During the study period, 441 patients suffered heart attacks, of which eight percent were fatal.
Researchers found that patients on a combination of TNF-inhibitors with methotrexate treatment had a heart attack risk of only 20 percent of the risk compared to patients taking methotrexate alone.
However, there was no statistical difference seen among patients who were taking TNF-inhibitors alone, TNF-inhibitors with other DMARDs, other DMARD therapies without methotrexate, or a combination of DMARDs and methotrexate. Therefore, this reduction in cardiovascular events appears to be a function of the combination of methotrexate and TNF-inhibitors.
“TNF-inhibitor therapy, in combination with methotrexate, dramatically reduces the risk of heart attacks in patients with RA and should be seriously considered- especially in high-risk patients,” said Gurkirpal Singh, MD, clinical professor of medicine in the division of gastroenterology at Stanford University School of Medicine, and an investigator in the study.
The notion that RA is a potentially crippling disorder is widely accepted. However, what is not generally known is that it is a potentially lethal disease leading to an increased risk of heart attack and stroke.
It is imperative that patients with RA understand the systemic nature of this condition and the need for aggressive intervention. This study lends more ammunition to the argument that patients with RA need to be treated with a combination of methotrexate and biologic therapy to not only reduce the chances for crippling deformity but also to reduce the likelihood of cardiovascular death.

Hidden Danger…Who Else With Rheumatoid Arthritis Has Anemia?

Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic, autoimmune disease for which there is no known cure. It is a common disorder and affects more than 2.1 million Americans.
Because it is a systemic condition, it affects more than joints. Like other inflammatory conditions, RA causes anemia. The anemia is not the result of bleeding (although some patients treated with non-steroidal anti-inflammatory drugs can develop gastrointestinal bleeding), or deficiency of vitamin B12, folate, or iron.
This type of anemia is called the anemia of chronic disease (ACD).
Patients with RA who develop anemia are more likely to have more severe joint disease, worse quality of life indicators, and more severe disease.
As mentioned earlier, while m some patients with RA can develop an iron deficiency anemia as a result of non-steroidal anti-inflammatory drug therapy and subsequent gastrointestinal blood loss, most anemia (60%) associated with RA is due to ACD.
While it is difficult sometimes to differentiate iron deficiency anemia from ACD, there are laboratory characteristics that separate them. The key differentiating feature is that iron deficiency anemia is due to an absolute lack of iron. ACD is not due to iron deficiency- there’s plenty of iron available; ACD is due to an inability to unlock the iron that is available.
Another complicating problem is that some patients with RA have both types of anemia.
ACD is due to systemic inflammation. The severity of ACD can be predicted by the amount of elevation of laboratory markers of inflammation such as the erythrocyte sedimentation rate (”sed rate”) and the C- reactive protein (CRP).
In RA, many chemical mediators of inflammations, called cytokines, are overproduced. These cytokines inhibit the ability of iron stores to be used.
These inflammatory cytokines affect the production of red blood cells at different levels.
One inflammatory cytokine, interleukin-6 (IL-6) adversely affects iron utilization by causing increased production of hepcidin. Hepcidin is an inflammatory protein that prevents release of iron from cells called macrophages. It also reduces absorption of iron from the small intestine.
Other cytokines such as interferon-y and tumor necrosis factor (TNF) block the production of erythropoietin, a hormone that is critically needed for the production of red blood cells. In addition, TNF and interleukin-1 (IL-1) prevent the maturation of red blood cells.
The net effect is a marked reduction of iron available to make red cells.
Studies on anemia in rheumatoid arthritis have produced interesting data. Patients with ACD have more severe disease. If patients have a good response to RA treatment, the anemia improves at the same time. Some data exists that treatment of the ACD will also help improve the symptoms of RA.
The association of inflammatory mediators with the development of ACD indicates that anemia should be monitored during the course of therapy in patients with RA.
Newer biologic agents such as tocilizumab which block the effects of interleukin-6 may help with the resolution of ACD. Preliminary pilot data has shown that blockade of IL-6 in RA patients helps improve quality of life and improves fatigue coincident with the resolution of anemia.

Rheumatoid Arthritis… Is Gene Therapy the Answer?

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis affecting approximately 2.1 million Americans. It is a chronic, progressive, systemic, autoimmune disease for which there is no cure.
However, within the last 10-15 years, biologic therapies aimed at the immune dysfunction that occurs in RA have enabled physicians to treat patients with much more success… in fact, often allowing the achievement of remission.
Gene therapy approaches have been employed recently in the hopes that patients who do not achieve remission may still yet get needed relief.
The first gene therapy approach was developed by Targeted Genetics in Seattle, Washington. Their compound, tgAAC94 was developed as a potential supplement to systemic anti-TNF-alpha (anti-tumor necrosis factors drugs such as Enbrel, Humira, and Remicade have become the standard of care for rheumatoid arthritis) therapy for use in patients with inflammatory arthritis who had one or more joints that did not respond to systemic therapy.
The product used a recombinant adeno-associated virus to deliver a DNA sequence that coded for a form of the TNF-alpha receptor (TNFR). TNFR blocks the immune stimulating activity of TNF-alpha. Direct injection of tgAAC94 into affected joints leads to the localized production of soluble TNFR within joint cells, reducing the activity of TNF-alpha within the joint and, potentially, leading to a decrease in the signs and symptoms of disease and stopping joint destruction.
The adeno-associated virus is a naturally occurring virus that has not been associated with any disease in humans.
Data from an initial Phase I trial demonstrated that injecting tgAAC94 into joints was safe and well-tolerated in patients taking conventional disease modifying anti-rheumatic drugs (DMARDS).
No drug-related serious adverse events were reported. Beneficial results as far as signs and symptoms were also demonstrated.
While this first study demonstrated both the safety and efficacy of gene therapy, a more recent study confirmed it.
Dr. Christopher H. Evans and co-investigators reported their findings using a viral vector that carried the gene that blocks interleukin-1, another protein that promotes inflammation and causes cartilage breakdown, in the February issue of Human Gene Therapy.
“Arthritis is a good target for (gene therapy) because the joint is a closed space into which we can inject genes,” was a statement issued by Evans.
Unlike the tgAAC94 study, tissue was removed from the knuckle joints of two patients with severe RA and a harmless virus was inserted into the tissue cells, in order to serve as a vector to carry a gene that blocks action of the interleukin-1 protein to the joint. After being placed in culture to grow and multiply, the cells were injected back into the afflicted joints.
One patient who received gene therapy in two joints experienced an 85 percent reduction in pain in one joint within 1 day, and both joints were pain-free from 1 week onward. Remarkably, the researchers report, joints receiving the therapy were protected from flares that occurred during the study period.
The second patient also responded to gene therapy, with a 70 percent reduction in pain between weeks 2 and 3.
This paper, therefore, also showed that painful symptoms can be lessened through gene therapy.
Both of these studies have demonstrated that gene therapy is feasible in humans. More importantly, it has been shown that this approach may be helpful for delivering biologic agents into stubborn joints that do not respond to systemic therapies.

I Have Rheumatoid Arthritis And Have Heard About Golimumab… What Is It?

Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease for which there is no current cure. However, the advent of biologic therapy has made it possible to induce remission in the majority of patients.
However, in order to effect remission, research suggests that a critical therapeutic window may exist within the first two years of disease onset when the rate of x-ray progression of the disease- which correlates directly with potential disability- can be slowed. X-ray changes occur within two years of disease onset in 50-70 percent of RA patients.
Many experts have suggested control of disease progression should start early to limit joint damage in RA. RA is associated with substantial disability and economic losses.
Most studies have shown that a combination of methotrexate and TNF-inhibitors work effectively to slow x-ray progression and improve daily functioning. TNF-inhibors include drugs such as etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira). A second generation of biologics has become available for use in patients who fail first line treatment. These include drugs such as abatacept (Orencia) and rituximab (Rituxan).
Newer biologic drugs are currently under study. One such drug is golimumab. Golimumab (Centocor, Schering-Plough) is a fully-human TNF-inhibitor monoclonal antibody that targets and neutralizes both the soluble and the membrane-bound form of TNF-alpha. Golimumab is being investigated for administration by subcutaneous (SC) injection and intravenous (IV) infusion.
In RA clinical trials in the U.S., patient responses to treatment are measured using the American College of Rheumatology (ACR) response of 20% (ACR 20), 40% (ACR 50), and 70% (ACR 70). In other words, if a patient has a 20 percent response to treatment, they have an ACR 20 response. If they have a 50 percent response to treatment they have reached ACR 50… and so on. The greater the number of patients reaching a higher ACR level the more effective the treatment.
The greater the number of patients responding at a given ACR level, the better the drug.
For instance, a drug that gives an ACR 70 response of 40 percent is much better than a drug that gives an ACR 70 response of 20 percent.
According to new findings presented from a double-blind, placebo-controlled, dose-ranging Phase 2 study, nearly 75 percent of patients with moderately to severely active rheumatoid arthritis (RA) receiving golimumab (CNTO 148) and methotrexate experienced at least 20 percent improvement in arthritis symptoms (ACR 20) at one year.
Investigators also reported that more than one-third of patients treated with golimumab and methotrexate achieved remission at one year.
In this preliminary study of the effects of golimumab in RA, 172 adults with active RA for at least three months’ duration despite methotrexate therapy were randomized to one of five treatment groups: placebo every two weeks or golimumab 50 or 100 mg every two weeks or every four weeks.
All patients received stable doses of methotrexate of at least 10 mg/week. At week 16, 62 percent, 31 percent and 12 percent of all patients receiving golimumab (combined golimumab treatment groups) plus methotrexate experienced ACR 20, ACR 50 and ACR 70 improvements, respectively, compared with 37 percent, 6 percent and zero percent of patients receiving placebo plus methotrexate, respectively.
At week 52 of the study, ACR 20, ACR 50 and ACR 70 scores improved to 74 percent, 45 percent and 22 percent respectively, among patients receiving golimumab plus methotrexate (combined golimumab treatment groups). Moreover, patients receiving 50 mg every two weeks and 100 mg every two weeks maintained efficacy through week 52, even after converting to every four weeks administration at week 20.
Patients receiving golimumab plus methotrexate also achieved remission, as assessed by the abbreviated disease activity scale (DAS 28), which measures tender and swollen joints, inflammation and overall disease activity including measurement of erythrocyte sedimentation rate (ESR). A DAS 28 of less than 2.6 indicates remission.
After 16 weeks of treatment, 27 percent of patients in the golimumab (combined golimumab treatment groups) plus methotrexate group achieved remission as assessed by DAS28 (DAS

Golimumab was generally well tolerated in the study through week 52. Serious adverse events (AEs) reported were eight percent for the combined golimumab groups compared with six percent for the placebo group. No deaths, cases of tuberculosis or other opportunistic infections were reported through 52 weeks, and serious infections were uncommon. The most common clinically relevant serious AEs through week 52 were pneumonia (three patients), lung cancer (one patient), cardiac tamponade (one patient), and cardiac failure (one patient). One patient died from coronary artery disease approximately four months after completing 52 weeks of the study.
While these adverse events appear serious (and they are), they are not worse than what is usually seen in clinical trials involving RA. RA is not a benign disease and patients will develop medical problems that are not necessarily related to the medication being studied. However, all adverse events have to be reported.
The results from this early (phase 2) study shows promise. Through the development of new drugs and through the further investigation of mechanisms of disease, a cure for RA will be found, hopefully, in the now too distant future.

Is There Any Evidence That Meditation Helps Rheumatoid Arthritis?

Today, arthritis patients are not only more receptive to complementary therapies- what has been called alternative therapy- but actually prefer it to conventional medicines.
There are many reasons for this. These reasons include the adverse publicity surrounding the side effects of medicines such as Vioxx and Bextra, cost of pharmaceutical agents, insurance restrictions that make it difficult for patients to get the types of medicines they need, and the widely held concept that “natural” implies safe.
As has been demonstrated on multiple occasions, a natural remedy is not necessarily safe, nor is it necessarily even effective.
However, there are natural therapies for which there is little evidence supporting their usefulness in conditions like arthritis, but also a paucity of data showing they are harmful.
Such is the case with meditation. Meditation not only is safe but has had beneficial applications in other rheumatic conditions such as fibromyalgia.
A recent study has demonstrated that meditation may also be useful as an adjunctive treatment for rheumatoid arthritis (RA).
A meditation training program, called Mindfulness-Based Stress Reduction (MBSR) was developed by Dr. Kabat-Zinn and other researchers at the University of Massachusetts Medical School. MBSR teaches participants to focus the mind in a special way. This technique is supposed to increase clarity and calmness.
Researchers at the University of Maryland School of Medicine assessed the effect of this meditation therapy on depressive symptoms, psychological distress, general well-being, and disease activity among RA patients. The results of the study indicates that there are potential benefits of MBSR and that it can be used with a conventional course of physical and pharmacological therapy.
Sixty-three adult RA patients were selected to participate in this novel pilot study. The subjects averaged 54 years in age and predominately women. All patients remained under their rheumatologist’s care and continued to take their routine medications throughout the study.
Thirty-one of the participants were randomized to receive MBSR therapy, starting with an 8-week training course followed by a 4-month maintenance program. The remaining 32 participants were assigned to a waiting list, agreeing to attend assessment sessions in exchange for free MBSR training at the study’s conclusion.
Both groups of participants underwent psychological and rheumatological examinations at baseline, and again at 2 months and 6 months into the study. Researchers used the Symptom Checklist-90-Revised, a self-report questionnaire, to evaluate depressive symptoms and psychological distress. Overall well-being was measured by the Psychological Well-Being Scales, made up of questions designed to evaluate positive outlook and approach to coping with difficulties. RA clinical factors were assessed by the Disease Activity Score in 28 joints (DAS-28).
Researchers compared scores of psychological and physical disease symptoms among MBSR participants with those of the control group. Patients receiving MBSR found the program to be enjoyable and continued throughout the follow-up period.
After 2 months, both groups showed improvements in depressive, psychological, and emotional symptoms, with no significant difference between the MBSR group and the control group. By 6 months, however, gains in the control group had largely disappeared, while MBSR participants maintained or improved further in psychological outcomes. By the end of the study, the MBSR group achieved a significant 35 percent reduction in psychological distress.
The meditation program had no impact on RA disease activity, measured by the DAS-28, which is a composite score derived from swollen joints, tender joints, and the erythrocyte sedimentation rate (ESR).
The studies flaws include its small sample size and the relative homogeneity of the control group.
The study showed that patients with RA may benefit from a meditation program such as MBSR class. MBSR is also safe and appealing to participants. The lead investigator, Dr. Elizabeth Pradhan, also states, “For doctors wishing to offer patients a complement to medical management, mindfulness meditation may offer hope for improving psychological distress and strengthening well-being in patients with RA.”
(Pradhan EK, et al. Effect of Mindfulness-Based Stress Reduction in Rheumatoid Arthritis Patients. Arthritis Care & Research. October 2007).