Category Archives: Disease modifying anti-rheumatic drugs

These drugs are the first-line agents used in treating conditions like rheumatoid arthritis

Bitter Kola boosts libido and beats osteoarthritis

Results of a study published in African Journal of Pharmacy and Pharmacology have confirmed that bitter kola possesses sexual enhancing effects on male rats as evidenced by the increased mounting (MF) and intromission (IF) frequencies with increased number of subsequent ejaculations over the 20 min observation period.bitter-kola

The study is titled “Effects of ethanolic extract of Garcinia kola on sexual behaviour and sperm parameters in male Wistar rats.”

Another study published in Journal of Orthopaedic Surgery and Research by medical doctors, pharmacists and nurses at Obafemi Awolowo University Teaching Hospital (OAUTH) concluded: “Garcinia kola appeared to have clinically significant analgesic/anti-inflammatory effects in knee osteoarthritis patients. Garcinia kola is a potential osteoarthritis disease activity modifier with good mid term outcome. Further studies are required for standardization of dosages and to determine long-term effects.”

The study is titled “Clinical effects of Garcinia kola in knee osteoarthritis.”

Comment: Whoa…, I think I need this.

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Can rheumatoid arthritis kill you?

Here is an email question I received recently…

“I have been in search of a very important question, can you die from RA?  It is listed on a death certificate of a person I know that did not have an autopsy and there were no doctors present when this person died. The person had RA but I am not convinced that this is true and heard you can NOT die from RA alone.  I would appreciate any information you could offer.”

Actually, this is a very interesting question because it brings up an important issue.

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis, affecting more than 2 million Americans.  It is a systemic autoimmune disease that can affect virtually any organ system.

What is not appreciated by many people, including physicians, is that RA has been associated with a significant mortality risk.

It has been estimated from a number of studies that uncontrolled or poorly controlled RA can shorten life span by ten to fifteen years. Despite the many treatment advances made in recent years, early mortality from rheumatoid arthritis remains a significant concern.

So why is that?

The answer lies in the chronic inflammation caused by the RA. The inflammation sets up an autoimmune situation that is perpetually turned on.  Essentially there is no “off-switch.”

Elegant studies done by Dr. Gerald Weissman and colleagues at the New York University School of Medicine implicate chronic gingival inflammation as the underlying trigger.

In any event, this chronic inflammation leads to early atherosclerotic cardiovascular disease. Heart attacks and strokes are the end result.  While this affects all patients, the effect seems to be most pronounced in women.

Some investigations have provided evidence that aggressive intervention with disease modifying anti-rheumatic drugs (DMARDS) and biologic agents may reverse the tendency to early heart attack and stroke.

Another cause of early death can be lung involvement leading to fibrosis and destruction of lung tissue.

Early crippling and disability is rarely seen nowadays.  However, in the past, this too was a significant cause of early death.

Rheumatoid vasculitis is a devastating complication of RA.  This problem occurs as a result of inflammation of blood vessel walls.  The inflammation causes closure of blood vessels to major organs and that obviously can cause major problems.  Immunosuppressive therapy has had mixed results as far as resolution of the problem.  Occasionally, high dose steroids and biologics have been used with some modicum of success.

This discussion would not be complete without a mention of early death related to treatment.  Non-steroidal anti-inflammatory drugs (NSAIDS) used to treat pain and inflammation can cause stomach ulcers, gastrointestinal bleeding, as well as liver and kidney damage.

Disease-modifying drugs such as methotrexate used to slow disease progression may also present problems.  And biologic therapies, even though they have revolutionized our approach to RA, because of their profound effects on the immune system, can also cause complications leading to death.

Nonetheless, when RA is treated appropriately, the benefits of therapy, I think, outweigh the negatives.

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Rheumatoid arthritis drugs… which ones are friendly to the heart and which ones aren’t!

Rheumatoid arthritis (RA) is a chronic, autoimmune systemic disease which affects approximately two million Americans. While the symptoms that bring the patient to the doctor are the joint swelling and pain, the area of most concern may not be the joints.  It is well established that cardiovascular risk is markedly increased in RA and in fact it is this complication that shortens lifespan by between ten to fifteen years.

A number of clinical studies have retrospectively examined the relationship between certain medications and the risk of cardiovascular events.  The report card has provided some real surprises.heart-attack_0

For example, methotrexate, the workhorse disease modifying anti-rheumatic drug (DMARD) of choice reduces cardiovascular mortality by almost 70 per cent. The mechanism is felt to be due to a reduction of atherosclerotic plaque formation as well as increased clearance of foam cells (Solomon DH, et al. Circulation 2003; 11: 1303-1307).

The other major player in the treatment of RA is the TNF inhibitor group.  These are used in more than 50 per cent of RA patients in the US. These drugs apparently reduce the risk of cardiovascular events by almost 50 per cent (Gonzalaz A, et al. Ann Rheum Dis. 2008; 67: 64-69). Why this occurs is still not clearly understood.

Steroids have been used to treat RA since the early 1950’s.  Steroids have been shown to worsen cardiovascular risk because of their effects on both blood pressure as well as blood glucose.  Steroid use in RA has been associated with increased carotid plaque formation as well as increased arterial stiffness.  So what dose is a safe dose?  The answer is still unknown.

Non-steroidal anti-inflammatory drugs (NSAIDS) raise blood pressure.  Randomized clinical trials have shown that cardiovascular risk is associated with COX-2 inhibitors but also with non-selective COX drugs also.  The upshot? All NSAIDS regardless of class, are associated with increased cardiovascular risk.

Hydroxychloroquine, a drug often used to treat mild RA, is associated with a decrease in diabetes and may also improve lipid status.  Actemra increases lipid profile but the long term effects are still unknown.  Leflunomide (Arava) increases blood pressure.  The eventual effects are still a subject of conjecture.

So what about aspirin?  This medication is used for cardiovascular prophylaxis.  In higher doses it also has anti-inflammatory effects although these are limited by the potential gastrointestinal side effects known to be caused by high dose aspirin. It is well known that other NSAIDS should not be used in patients taking aspirin for cardiovascular prophylaxis since they blunt that effect.

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Conventional Medication Combo May Be As Effective As Anti-TNF Agents In RA

Nancy Walsh writing in Medpage Today reported, “Among patients with established rheumatoid arthritis, a combination of conventional disease-modifying drugs was as effective as early use of anti-tumor necrosis factor (TNF) agents,” according to a study presented at the annual meeting of the British Society for Rheumatology. Investigators found that individuals “who received disease-modifying anti-rheumatic drugs (DMARDs) had a change over 12 months on the Health Assessment Questionnaire (HAQ) of 0.45 points compared with 0.30 points for those given anti-TNF therapy.

I disagree with the findings of this study.  Conventional combination DMARDS are touted as being as effective as anti-TNFs by a few rheumatologists.  Personally, I don’t think they work as well and have their own share of potential side effects.

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Methotrexate reduces risk of death from rheumatoid arthritis by 70%!

Methotrexate may reduce the risk of death in rheumatoid arthritis patients, according to study results published Arthritis and Rheumatism. Researchers assessed the association of mortality and treatment with methotrexate in 5,000 rheumatoid arthritis patients at 10 rheumatology practices in the U.S. The data methotrexate-tabletsused in the study was collected from 1981 to 2005.

Among patients taking methotrexate, there was up to a 70% lower risk of death compared to patients not taking methotrexate. This effect appeared to occur after patients took methotrexate for more than one year. The effect did not continue to increase with longer duration of use. According to researchers, it appears that methotrexate must be taken continuously on its prescribed schedule to maintain therapeutic effects.

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Treat To Target for Rheumatoid Arthritis

Dr. Steve Paget summarized the “treat to target” approach for rheumatoid arthritis (RA) elegantly in a recent article.  He laid out ten principles that make sense.

rheumatoid-arthritisThey are:

1. The primary target for RA treatment should be clinical remission.

2. Clinical remission is defined as the absence of signs and symptoms of significant inflammation.

3. While remission is the target, low disease activity is an acceptable alternative.

4. Until the treatment target is reached, drug therapy should be adjusted every three months.

5. Measures of disease activity need to be obtained and documented every month for patients with high disease activity and every three months for patients with low disease activity.

6. Validated measures of disease activity should guide treatment decisions.

7. Structural changes and functional impairment shoulkd be considered when making clinical decisions.

8. The treatment target should be maintained indefinitely.

9. The choice of the disease measuring and the level of target should take patient factors, co-morbidities, and drug-related risk into consideration.

10. The patient needs to be informed about the treatment target and how it will be achieved.

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New Osteoarthritis Drug Slows Cartilage Wear?

The Holy Grail for osteoarthritis treatment is a disease modifying osteoarthritis drug.  This article talks about one possibility.

Kevin Deane writing in MedScape reported on a study from Belgium published in the Annals of Rheumatic Diseases. In this randomized, double-blind, placebo-controlled trial, called SEKOIA, Yves Reginster and colleagues used strontiumstrontium ranelate at either 1 or 2 g daily compared with placebo in 1371 patients with grade 2 or 3 knee osteoarthritis, as defined by Kellgren and Lawrence, with a joint space width of 2.5-5 mm. Patients were followed for 3 years, and outcomes included x-ray changes in joint space width, overall health related to osteoarthritis as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and pain as measured on a visual analog scale.

Treatment with strontium ranelate at a daily dose of 1 or 2 g was associated with a statistically smaller reduction in joint space width on plain x-rays. Treatment with the 2-g/day dose was also associated with improved health status related to osteoarthritis, as measured by the overall WOMAC score (P = .045) and a WOMAC subscore of pain (P = .028). The WOMAC subscore for physical function and knee pain as measured by the visual analog scale trended toward improvement in patients treated with the 2-g/day dose but did not reach statistical significance.

Reginster and colleagues concluded that treatment with strontium ranelate at daily doses of 1 or 2 g is associated with a significant reduction in progression of radiographic joint space width, and at 2 g/day with an effect on overall health associated with osteoarthritis.

Comment: Strontium may be effective.  It is already used to treat osteoporosis in Europe.  However, it has potential side effects including: deep vein thrombosis and a potentially fatal skin condition called Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome)

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New strategy prevents rheumatoid arthritis in mice

Eureka Alert reported the results of a striking finding. Dana-Farber Cancer Institute scientists have demonstrated a new strategy for treating autoimmune disease that successfully blocked the development of rheumatoid arthritis in a mouse model. They say it holds promise for improved treatment of arthritis and other autoimmune disorders in people.

The scientists report in the Journal of Clinical Investigation that infusing a highly specific type of cell that regulates immune responses into arthritis-prone mice shut down the cascade of inflammation that damages tissues and joints.

The method worked best when the infusions of CD8+ Treg cells were given at the same time that the animals were injected with a protein that triggered the arthritis-causing autoimmune reaction. “We found we could almost completely inhibit the disease in this setting,” said Harvey Cantor, MD, chair of the Department of Cancer Immunology and AIDS at Dana-Farber and the study’s senior author.

Too bad we couldn’t predict wrheumatoid-arthritishen people were going to be exposed to whatever triggers RA and give them this preventative at that moment.

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Some RA Patients May Be Able to Taper Biologics

Slide 1.From the American College of Rheumatology meeting 2012

Tapering or even stopping tumor necrosis factor (TNF)-inhibitor therapy is feasible for a sizable number of patients with RA who are stabilized and in remission, according to a randomized trial. “This study is relevant for the burden of treatment for RA patients and the economic burden to society. These drugs are expensive. If we can taper the intervals and use less drug, we can reduce the cost and possibly reduce the risk of infection and lymphoma,” said study leader Bruno Fautrel, MD, PhD, from University of Paris Medical Center in France.

This is good news since these drugs cost approximately $2,000 a month.

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New rheumatoid arthritis drug… the inside scoop!

The first oral biologic drug has finally hit the runway.

Here’s the “skinny” on it from the American College of Rheumatology…

Xeljanz (tofacitinib) is a first-in-class oral JAK inhibitor which has shown clinical effectoveness in patients with moderate to severe rheumatoid arthritis. xeljanz

Tofacitinib is approved for patients with an inadequate response to both biologic and non-biologic disease-modifying anti-rheumatic drugs (DMARDS) .

It should not be used in combination with other biologic agents. Current labeling for tofacitinib does not include an indication for inhibition of structural damage.

Data on safety suggests that infections, including severe “traditional” infections, as well as opportunistic infections and Herpes zoster, have occurred. Long-term safety studies and post-marketing safety data is being collected. Monitoring for blood abnormalities, liver enzyme abnormalities, lipid abnormalities and kidney damage is appropriate prior to initiation of therapy and throughout treatment.

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