Category Archives: Anti-TNF drugs

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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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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TNF Inhibitors and the Placenta… Which Should You Worry About During Pregnancy?

Mary Ann Moon writing in Rheumatology News reported on the conclusions of two studies. One concern rheumatologists have had is what to do about pregnant patients who are on TNF inhibitors.  Two observational studies (one from University California San Francisco and the other from Erasmus Medical Center, pregnant-womanRotterdam) provide some information.

The upshot is that stopping Remicade and Humira at the end of the second trimester reduces the amount of antibody transferred to the infant and shortens the time for the infant to clear the antibody. Cimzia doesn’t need to be stopped since it doesn’t cross the placenta.

Comment: This is important since it reduces the likelihood of opportunistic infection in the infant.

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Long-Term Humira Use … Few Adverse Events

Nancy Walsh writing in MedPage Today reported, “Long-term immunosuppressive treatment with Humira,  a TNF inhibitor drug used in humiradiseases such as rheumatoid arthritis and psoriatic arthritis,  is associated with low rates of adverse events such as serious infections and malignancies, with differences being seen according to the underlying disease,” according to  a study published in the Annals of the Rheumatic Diseases.

Investigators found that “the most frequently reported serious adverse events across indications were infections.” The study indicated that “the most common infections among patients with rheumatoid arthritis were cellulitis – occurring at a rate of 0.3 per 100 patient-years – and pneumonia, seen at a rate of 0.7 per 100.”

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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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TB Hides In Bone Marrow

Michelle Fay Cortez writing in Bloomberg News reported on a study in “Science Translational Medicine.  Researchers said they have uncovered the first evidence of tuberculosis hiding in mesenchymal stem cells in the bone marrow of people treated for the disease.”

tb-bacteriaAccording to the article, “the bacteria’s hideout in the self-renewing cells, where they capitalize on protection from the body’s own immune system, may explain how the germs survive.”

This is disturbing news since these sequestered tuberculosis bacteria can be protected from drugs used to eradicate them.

This has important  implications for patients intending to go on biologic therapy for rheumatoid arthritis and other diseases.

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Brain Activity Changes In Rheumatoid Arthritis Patients Responding To Anti-TNF Therapy

Nancy Walsh writing in MedPage Today reported on a study which showed, patients with rheumatoid arthritis who responded to anti-tumor necrosis factor (TNF) treatment showed distinct differences in brain activity on functional MRI brain(fMRI) compared with nonresponders.

The study waspublished in Arthritis & Rheumatism. Researchers found that, “unlike nonresponders, TNF responders showed high signal intensity on fMRI in several areas of the brain at baseline, including the prefrontal cortex, the somatosensory cortex, and the insular cortex.” Also, “only patients who had this exaggerated brain activity at baseline had begun to show clinical responses one month later, with decreases in disease activity scores of 1.8 points compared with a decrease of only 0.2 points in nonresponders.”

Interesting how the brain works…

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Anti-TNF Medications Lead To Higher Shingles Risk In RA Patients

One of the most painful and debilitating conditions is shingles.  Find out what a recent study showed…shingles

Nancy Walsh writing in MedPage Today reported, “Patients with rheumatoid arthritis (RA) undergoing treatment with agents such as Enbrel (etanercept), Remicade (infliximab) or Humira (adalimumab) appear to have a significantly increased risk for developing shingles,” according to a study published in the Annals of the Rheumatic Diseases. Researchers found that “the incidence of shingles among patients on anti-tumor necrosis factor (TNF) treatment was 1.6 per 100 patient-years, compared with an incidence of 0.8 per 100 patient-years among those receiving traditional disease-modifying anti-rheumatic drugs (DMARDs).”

Comment: What can I say?  These are worrisome findings and indicate that people with RA on biologics should be vaccinated.

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Apremilast (Celgene) Effective in Psoriatic Arthritis

From the American College of Rheumatology…

Apremilast (Celgene), an investigational oral small-molecule inhibitor of phosphodiesterase 4 (PDE4), led to significant improvement in the signs and symptoms of psoriatic arthritis in patients who failed to respond to recommended drugs, including DMARDs and biologics, in the phase 3 PALACE-1 trial.

psoriasisLead investigator Arthur Kavanaugh, from University of California, San Diego, who reported the results, said the drug was “well tolerated and has a good side-effect profile.”

Psoriatic arthritis is a very common type of arthritis and unlike what many physicians think, is not the same as rheumatoid arthritis and must be treated differently.

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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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