The Latest News in Rheumatology
11/8/2002
ACR: Infliximab (Remicade®) and Etanercept (Enbrel®)
Both Effective in Treating Ankylosing Spondylitis
ACR:
Remicade® Benefits Patients with Symptoms of Psoriatic Arthritis
ACR:
Enbrel®
is First Therapy Shown to Inhibit Bone/Joint Damage in Psoriatic Arthritis
Patients
Histoplasmosis: A Rare But
Potentially Serious Side Effect of Remicade® and Etanercept® Use
Serious
Hypersensitivity Reactions with Valdecoxib (Betra®)
FDA
Issues Caution Regarding Use of Bone Cement in Spinal Surgery Procedures
Can
Spouses That Help Too Much Actually Cause More Pain?
New
Results: Mild Aerobic Exercise Is No Protection From Osteoporosis
New Orleans, LA -- According to the findings of two new trials,
Remicade® and Enbrel® both appear to be effective in treating AS. The results were
presented at the American College of Rheumatology Annual Scientific Meeting by
Dr. Jan Brandt (Benjamin Franklin Hospital, Free University, Berlin, Germany)
and colleagues.
Results of Remicade® trial: After studying 69 patients over a 54-week
period, over half of those taking Remicade® experienced a 50% regression
of disease activity compared to only 9% of placebo.
The researchers conclude that these results are "a major
breakthrough" in the treatment of AS, although they point out that Remicade®
may cause "uncommon but potentially untoward side effects."
Therefore, they recommend that treatment be performed at experienced
rheumatologic centers.
Results of Enbrel® trial: Eight out of fourteen patients (57%) treated
with Enbrel® achieved a 50% regression of disease activity at week 6,
compared to only one of sixteen patients (6%) taking a placebo.
"In comparison to Remicade®, improvement starts more slowly and is
maintained for a shorter period of time upon treatment with Enbrel®,"
the researchers note. However, they found that Enbrel® caused fewer side
effects than did Remicade®.
Thus, the researchers conclude that Enbrel® seems to be another promising
treatment option for patients with active AS.
New Orleans, LA -- Remicade® appears to improve both synovitis and skin
lesion is psoriatic arthritis, as reported from a new trial at the American College of Rheumatology
Annual Scientific Meeting. The study was conducted by
Dr. Christian Antoni (Department of Medicine, Friedrich-Alexander-University,
Erlangen, Germany) and colleagues.
Results: 102 patients with active psoriatic arthritis took part in the study,
and 68% were also currently taking additional disease-modifying anti-rheumatic
drugs (DMARDs), primarily methotrexate. 69% achieved a greater than 75%
improvement, as opposed to less than 10% of the placebo group who claimed to
achieve a greater than 75% improvement.
One joint infection was observed at week 16 of treatment, but treatment was
overall well tolerated.
Dr. Antoni said that Remicade® resulted in a big, "impressive"
improvement in the skin and joints. "No other DMARD has been approved for
this disease besides Enbrel® in the U.S., so it is good to see that this
anti-TNF-alpha treatment works."
The researchers are currently undertaking another trial for Remicade® in psoriatic
arthritis.
New Orleans, LA -- Results from a recent study of Enbrel® show
significant inhibition in the progression of structural damage in people with
psoriatic arthritis, as reported at the American College of Rheumatology Annual
Scientific Meeting. Enbrel® is approved to reduce the signs and symptoms
associated with active psoriatic arthritis.
The study evaluated 205 patients with active psoriatic arthritis who also had
stable psoriasis. Patients first completed a 6-month portion in which they
either received Enbrel® or a placebo. Results of this section are described
online at SAA's Press Release section of the News page.
Then the patients were eligible to enter a 48-week open-label study in which
they received 25 mg twice-weekly Enbrel® injections. At one year, there
was inhibition of progression in the Enbrel® group, as shown by x-ray evidence.
There was no increase in the number of serious adverse events occurring in
patients treated with Enbrel® compared to those receiving placebo. Yet the rate
of injection site reactions in patients receiving Enbrel® was statistically
different compared to placebo (9% with placebo versus 36% with Enbrel®).
Rockville, MD -- Officials from the FDA's Center for Biologics Evaluation and
Research suggest that doctors should be alert to the possibility of
histoplasmosis as a potentially life-threatening complication of treatment with
Remicade® and Enbrel®, as reported in October's Arthritis &
Rheumatism journal.
Histoplasmosis is a systemic fungal disease caused by inhalation of dust
contaminated by Histoplasma capsulatum (HC) that typically begins in
the lungs but may spread to other organs. Signs or symptoms of histoplasmosis
include fever, malaise (sense of fatigue and ill health), cough, dyspnea
(labored or difficult breathing), and interstitial pneumonia on chest
radiographs. It is particularly common in the rural Midwest, but is worldwide in
distribution and has been seen in most sections of the United States, including
urban areas.
Through May 31, 2002, there have been 22 cases (5 fatal) of histoplasmosis in
the U.S. associated with TNF-alpha therapies, 19 of which were linked to
Remicade® and 3 to Enbrel®. Lee and colleagues do not know whether RA or
Crohn's disease may be an independent risk factor for histoplasmosis, as the
original batch of recent histoplasmosis cases began in patients with either of
these two diseases.
Dr. Jong-Hoon Lee (FDA, Rockville, MD) and colleagues report that
histoplasmosis should be considered early in the evaluation of patients who
reside in HC-endemic areas in whom infectious complications develop during treatment of the
aforementioned drugs. In the U.S., the highest HC-endemic areas are the Ohio and Mississippi river
valleys.
Lee and colleagues are unsure why infection seems to be particularly
associated with Remicade®, but it could be for a variety of reasons, including
the way in which Remicade® effects the body, other medications that may be used
concurrently with Remicade® or Enbrel®, etc. They also caution that as with
any database used to collect information on drug-associated risks, results are
limited by underreporting, the possible presence of unrecognized confounding
factors, and the potential for inclusion of coincidental events.
The warning was added to the package insert of Remicade® in August 2001,
indicating that for patients who have resided in HC-endemic areas, "the
risks and benefits of Remicade® treatment should be carefully evaluated before
beginning treatment."
The European Medicines Evaluation Agency has issued a drug safety
announcement about serious hypersensitivity and skin reactions for patients
using Bextra® based on reported reactions from patients in the U.S.
Reported complications include anaphylaxis, angioedema, and serious skin
reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis,
erythema multiforme, and exfoliative dermatitis. Some of these have occurred in
patients with a history of allergic reactions to sulfonamides.
The agency is warning patients that if they have had an allergy to
sulfonamide antibiotics, they may be prone to sever side effects. Anyone who
experiences skin rash; swelling of the face, lips, or tongue; wheezing;
difficulty in breathing or swallowing; or swelling, blistering, or peeling of
the skin should seek immediate medical attention.
Washington (Reuters Health) -- The FDA has issued a caution on the use of a
particular type of bone cement used to treat osteoporosis-related fractures of
the spine during vertebroplasty and kyphoplasty procedures. Some people with AS
undergo such procedures.
Complaints about complications due to leakage of polymethylmethacrylate
cement (including soft-tissue damage and nerve-root pain and compression) have
been reported to the FDA and published in literature. Other reported problems
include blood clots in the lungs, respiratory and cardiac failure, and death.
In vertebroplasty, bone cement is injected into the fractured vertebrae in
order to stabilize it and prevent further collapse. In kyphoplasty, doctors use
a surgical instrument to expand the space between the vertebrae, and fill the
space with bone cement.
The FDA says that long-term safety and efficacy of the use of
polymethylmethacrylate bone cement in these two procedures had not been tested
in proper, controlled trails. The agency also noted that the procedures involve
modifications to the bone cement that have not been well studied, and for which
standardized formulations and safety guidelines do not exist.
While the FDA is working with professional organizations and manufacturers of
orthopedic devices to consider regulatory options to evaluate the long-term safety
and usefulness of the bone cement in the two procedures, the agency advises
surgeons to take extra considerations when considering these surgeries to treat
osteoporotic compression fractures of the spine.
A full copy of the FDA notice can be found online at www.fda.gov/cdrh/safety/bonecement.html.
New York (Reuters Health) -- According to a recent study in Germany,
spouses that attend to their partners' chronic back pain may unknowingly make
the pain feel worse. Doing simple acts of kindness (like giving a massage or a
glass of water) may backfire by increasing the amount of pain the partner is
feeling.
Dr. Herta Flor of the University of Heidelberg in Germany and her colleagues
studied thirty patients. Ten patients had chronic low back pain and a spouse
attending to them when they felt uncomfortable. Another ten had spouses who
tended not to focus on their pain and would instead distract them from it. A
final ten people in the study did not have any chronic pain.
They found that patients with chronic back pain showed 2.5 times more brain
activity in regions of the brain associated with pain when their attentive
spouses were in the same room than when they were alone. These patients also
showed more external signs of pain (i.e. moaning) when their spouse was
around.
In contrast, they noticed that the patients whose spouses did not appear to
attend to their pain (either they ignored it or suggested a distracting
activity) did not show a higher brain activity in response to back pain when
their spouses were present.
Patients with either type of spouse showed no differences in brain activity
in the presence of their spouse when they experienced pain in their finger,
which is a region unaffected by chronic pain.
Dr. Flor explains that attending to a spouse's problem is a good thing, and
that people with attentive spouses tend to have happier marriages. However, she
says that paying attention to every bout of a partner's chronic pain may only
worsen it over time.
"Once the pain lasts for a longer time, then this kind of behavior can
aggravate the problem," Flor says. She recommends that spouses of patients
with chronic pain receive counseling on how to respond to their partner's ills.
Day-to-day activities like walking, shopping, and housework may help the
heart, but they do not do much for the body's bones, according to a Johns
Hopkins study.
Previous studies suggested that aerobics could play a role in building bone
mineral density and protecting bones from osteoporosis, which is a complication
associated with spondylitis patients. This new study, published in the November
issue of the Journal of Internal Medicine, found that neither
light-intensity activities nor aerobic fitness level contributed to bone health.
Among a group of older adults studied, those with greater muscle strength and
higher body fat (especially in the abdomen) had higher bone mineral
densities.
The study's lead author, Kerry J. Stewart, Ed.D. and director of clinical
exercise physiology at Hopkins, and colleagues studied 84 adults (38 men and 46
women) ages 55 to 75 with higher than normal blood pressure but who were
otherwise healthy. They were not exercising regularly, meaning that they did not
partake in moderate or high intensity exercise for 30 minutes a day, three or
more time a week.
Researchers used x-rays to measure participants' bone mineral density in the
total skeleton, lower spine and hip, and MRI to calculate abdominal fat. In
addition to being tested while undergoing treadmill and weight-training
exercises, the participants completed a physical activity questionnaire.
Stewart and colleagues found that aerobic exercise was not associated with
bone mineral density, but abdominal fat was. Muscle strength was associated with
bone mineral density at some but not all sites.
"Carrying extra body weight increases the forces on bone, strengthening
it, though the largest forces come from more vigorous exercise rather than
routine low-intensity physical activity," claims Stewart. He says that
low-intensity exercises, like walking, do not appear to be effective in
preventing aging-related bone loss.
30% of the women were taking estrogen and progesterone supplements. In this
study, the hormone replacement therapy contributed only modestly to bone mineral
density and only in the lower spine. Other studies suggest that hormone
replacement therapies have a more positive influence on bone.
These researchers do not advocate gaining weight to fight osteoporosis.
"Paradoxically, a higher percentage of abdominal fat seems to increase bone
mineral density, but it also increases the risk of heart disease, high blood
pressure and diabetes, and worsens the symptoms of chronic conditions, such as
knee arthritis," says Stewart.
They conclude that further research needs to be done to define which methods
will reduce obesity while preserving or enhancing bone health.