The Latest News in Rheumatology
1/3/2003
Gut Inflammation and Spondyloarthropathies
Hip Fracture Patients and Osteoporosis
Ankylosing Spondylitis -- Cardiac Manifestations
Commentary: Be Strong and Resolute -- Continue to Use
COX-2 Selective Inhibitors at Recommended Dosages in Appropriate Patients
Celebrex's
Ulcer Link Questioned
The Spondyloarthropathies (SpA) are a group of related diseases with common
clinical and genetic characteristics, of which the prototype disease in this
group is ankylosing spondylitis. Other spondyloarthropathies include reactive
arthritis, psoriatic arthritis, undifferentiated spondyloarthropathy, and
arthritis associated with inflammatory bowel disease.
Over recent years, there has been special interest in the relation between
spondylitis and gut inflammation. Two-thirds of patients with undifferentiated
SpA have gut inflammation, and a fraction of these patients go on to develop
Crohn's disease.
Authors Filip De Keyser, MD, and colleagues focus on growing evidence that
gut inflammation in SpA is related to Crohn's disease, and on therapeutic
implications resulting from this concept. They discuss how the relatively new
anti-TNF alpha therapies (such as Remicade and Enbrel) in patients with SpA is
in large part based on this concept. Their article is published in the December
2002 issue of Current Science.
A person with a hip fracture is at an increased risk for another fracture.
In fact, 5% of hip fracture patients are likely to have another hip fracture
within a year, and about one in five will break another bone in the following
two years. Researchers from the University of Winsconsin Medical School in
Madison conducted a study to determine if hip fracture patients are being
evaluated and treated for osteoporosis, which is also a potential complication
associated with spondylitis. Results were published in a recent issue of Arthritis Care &
Research.
Results: Investigators reviewed records of hip fracture patients at
four Midwestern U.S. health systems, specifically looking at the frequency of
DXA use (an x-ray that measures bone density), calcium, and vitamin D
supplementation and antiresorptive drug treatment.
- DXA was only used on 12-24% of the patients depending on which facility
was being reviewed.
- Calcium and vitamin D supplements were prescribed to as few as 1% of the
patients at one of the centers, and up to just 27% of the patients at
another center.
- Drug treatment was offered to only 7% of the patients at one center, and
up to 37% of the patients at another center.
Since hip fracture patients are at very high risk for additional fragility
fractures, these researchers feel that more effective approaches in managing
these patients are needed by the medical community.
According to researchers D. Lautermann and J. Braun from Herne, Germany,
there is a definite association of heart disease with ankylosing spondylitis
(AS) and other spondyloarthropathies (especially in Reactive Arthritis). But the
magnitude of this relationship is less clear. They review cardiac manifestations
in AS in a
recent issue of Clinical Experimental Rheumatology.
Lautermann and Braun mention three types of inflammatory cardiac problems that can be
associated with AS:
- aortitis and aortic insufficiency, possibly resulting in the need for
cardiac surgery
- conduction problems of the atrioventricular node, possibly resulting in
the need for a pacemaker
- myocardial involvement, possibly compromising left ventricular function
There seems to be an HLA-B27-associated cardiac syndrome, meaning that
certain heart problems seem to occur more frequently in HLA-B27 positive people,
regardless of whether they have a rheumatic disease or not. HLA-B27 is a
perfectly normal gene that is found in approximately 8% of the population, but
since the majority of people with spondylitis test positive for HLA-B27, this is
a potentially important area of research. They point out that although
prospective studies have not been performed, HLA-B27 related heart disease does
not seem to be associated with increased mortality.
Perhaps most importantly, Dr. Lautermann and Dr. Braun say that previous
studies show how patients can
be recognized at pre-clinical stages, meaning that early features of cardiac
problems can be detected by echocardiography in patients without symptoms. Echocardiography is a diagnostic test which uses ultrasound waves to
make images of the heart chambers, valves and surrounding structures.
As reported in the Spondylitis Association of America's "Straight Talk
on Spondylitis" publication:
"A small number of people with spondylitis will display signs of chronic
inflammation in the base of the heart - around the aortic valve and origin of
the aorta (i.e. that vessel which takes all blood from the heart to be
distributed throughout the body). Years of chronic and silent inflammation at
these sites can eventually lead to heart block and valve leakage, sometimes
requiring surgical treatment. Although well-recognized, these cardiac lesions
are probably seen in fewer than 2% of all patients with spondylitis, and nearly
always in males. The lesions are readily detectable by the physician's
examination and when necessary, cardiac testing. Routine physical examination by
a physician can detect this complication before it becomes very serious."
According to Dr. Marc. C. Hochberg from the Division of Rheumatology and
Clinical Immunology Department at the University of Maryland School of Medicine,
Baltimore, Maryland, COX-2 selective inhibitors have shown to have comparable
efficacy to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in
patients with osteoarthritis (OA) and rheumatoid arthritis (RA).
Dr. Hochberg explains that large studies have shown that patients with OA and
RA not taking low-dose aspirin have fewer symptomatic and complicated upper
gastrointestinal problems when treated with COX-2 selective inhibitors than with
nonselective NSAIDs.
When used in recommended dosages, he claims that there is no convincing
evidence that patients treated with COX-2 selective inhibitors have an increased
incidence of cardiovascular thrombotic events (blood clot), including non-fatal
myocardial infarction (deprivation of circulating blood that affecting the heart
muscle and tissues around it), than patients treated with either placebo or
nonselective NSAIDs other than naproxen.
He recommends co-therapy with low-dose aspirin for patients with OA or RA at
increased risk for cardiovascular problems because "the need for
gastroprotective therapy in such patients is controversial."
Dr. Hochberg's commentary was published in the December 2002 issue of Arthritis
Research & Therapy.
(AP) -- Approximately 107,000
Americans per year are hospitalized with complications from taking older
anti-inflammatory drugs, and ulcer complications kill an estimated 16,500 a
year.
A new study suggests that the arthritis drug Celebrex does not
protect the stomach from dangerous bleeding ulcers as well as previously
thought. Celebrex and two similar new anti-inflammatory drugs are heavily
advertised as being more safe for arthritis patients based on research that
found that they caused fewer ulcers and other gastrointestinal complications
than older anti-inflammatory medicines. The three drugs have combined annual
sales exceeding $6 billion.
The new study focused on arthritis patients at high risk of recurrent ulcers,
and showed that nearly 10% each year would develop another bleeding ulcer. The
study found the same results for an older anti-inflammatory drug diclofenac, combined with
ulcer medication Prilosec, which doctors often prescribe for arthritis patients
to protect their stomachs. Researchers said that neither treatment protected as
many patients from kidney complications in the new study as past studies showed.
Results: 287 patients who had a previous bleeding ulcer and were at a
high risk of developing another potentially life-threatening ulcer took part in
the study. Half took the anti-inflammatory dicolfenac with Prilosec, and half
took Celebrex.
- 5% of the patients receiving Celebrex and 6.5% of the patients receiving
diclofenac and Prilosec had recurrent bleeding during the six months
- 25% of the patients receiving Celebrex and 31% of the diclofenac/Prilosec
group suffered kidney complications, including high blood pressure and
swollen ankles
- 6% in each group suffered life threatening kidney failure
This equates to annual ulcer rates of about 9% and 11% respectively, claims
Dr. David Y. Graham of the Veterans Affairs medical Center in Houston. "The
results were unexpected: neither regimen provided a good or even acceptable
level of protection from recurrent bleeding," says Dr. Graham.
Dr. Francis K.L. Chan explained that physicians should avoid prescribing
these drugs to patients with known kidney disease, poorly controlled
hypertension, and heart failure because "previous studies reported a very
low incidence of kidney side effects since they excluded patients with major
medical illnesses" from the study.
Yet the study still backs up the American College of
Rheumatology's current guidelines for treating arthritis. In fact, researchers
believe that both treatments did a
good job of reducing pain and enabling patients to perform daily activities over
the six-month period.
Dr. Todd Stitik, associate professor of physical medicine and rehabilitation
at University of Medicine and Dentistry of New Jersey in Newark says that for
patients whose prescription plan covers the expensive COX-2 inhibitors, one less
pill is more convenient and reduces changes of interactions with other
medications. For others, numerous genetic anti-inflammatory and ulcer drugs are
available.
The researchers say that these results indicate that more research is needed
to prevent bleeding stomach ulcers in people at risk who have been taking NSAIDs
for pain management over the years.