PSORIATIC ARTHRITIS NEWS AND VIEWS VOLUME 1 ISSUE 2
SEPTEMBER
2001

PSORIATIC ARTHRITIS MEDICAL NEWS

We reported in our first newsletter about the new psoriasis drug
under test
called "Alefacept." This issue begins with additional information as
reported
in the New England Journal of Medicine.

Alefacept Reduces Severity of Chronic Plaque Psoriasis

WESTPORT, CT (Reuters Health) Jul 26 - Alefacept (Amevive; Biogen)
appears to
be an effective and well-tolerated immunomodulatory treatment for
chronic
plaque psoriasis, according to results of the multicenter Alefacept
Clinical
Study, which appear in the July 26th issue of the New England Journal
of
Medicine.

"Alefacept was designed to interfere with the co-stimulatory pathways
that
occur when an antigen-presenting cell meets a memory T cell," co-
investigator
Dr. Gerald G. Krueger, of the University of Utah Health Sciences
Center in
Salt Lake City, told Reuters Health. "We were hoping it would also
hook onto
a natural killer cell and therewith eliminate the memory effector
cell that
causes psoriasis." "As we demonstrate in our paper, there is a direct
correlation between memory effector T cells and improvement in
disease," he
said.

Dr. Krueger and associates randomly assigned subjects to alefacept
(170
patients) or placebo (59 patients). The treatment group received
alefacept in
doses of 0.025, 0.075, or 0.150 mg/kg, administered IV once a week
for 12
weeks. Five placebo group patients and three alefacept patients
discontinued
treatment because of worsening of psoriasis.
Two weeks after completion of alefacept treatment, mean scores on the
psoriasis area-and-severity index were lower than baseline by 38%,
53%, and
53% in patients receiving 0.025, 0.075 and 0.150 mg/kg, respectively.
These
scores were significantly lower than the 21% decline observed in the
placebo
group (p < 0.001).
Twelve weeks after treatment, between 42% and 63% of patients treated
with
alefacept had at least a 50% reduction in baseline score, compared
with 32%
of those given placebo (p = 0.02). Between 19% and 33% of patients
who
received alefacept exhibited at least a 75% reduction versus 11% in
the
control group (p = 0.02).
These results were mirrored in the group's recently completed phase
III
trial, Dr. Krueger told Reuters Health. In this trial, more than 1000
patients were treated with alefacept 0.075 mg/kg, either IM or IV.
"Again, we saw a delayed response," he said. "If someone achieved 50%
or 75%
improvement immediately post-treatment, they either stayed there or
got
better during the next 12 weeks. At the end of 12 weeks, they were
offered
another course." Twenty-three percent of the psoriasis cases cleared
after
the first course of treatment and 32% cleared after the second
course.

The study group also looked for evidence of infections that would be
anticipated if T-cell counts declined in a generally
immunosuppressive mode,
especially fungal infections, Pneumocystis, herpes simplex, and
herpes zoster.

*************************************

Editors note: The following article from the Southern Medical Journal
makes
reference to the possible connection
between cigarette smoking and psoriasis. I have chosen to include
only a very
small portion of the information because
of the length of the study. The following is the web site address
should you
desire to read the entire publication.
http://www.medscape.com/SMA/SMJ/2001/v94.n06/smj9406.14.stra/smj9406.1
4.stra-0

1.html

Tobacco Use and Skin Disease

Melody Vander Straten, MD, Daniel Carrasco, MD, Martha S. Paterson,
MD,
Monica L. Mccrary, MD, Diane J. Meyer, MD, Stephen K. Tyring, MD,
PhD,
Galveston, Tex [South Med J 94(6):621-634, 2001. © 2001 Southern
Medical
Association]

Abstract

Background The primary objective of this review is to evaluate the
mucocutaneous manifestations of tobacco use.
Methods. Computerized literature searches were conducted for English
language
articles related to skin/mucous membrane disease and use of tobacco.
The
primary criterion for assessing data quality and validity was the
demonstration of a causal relationship between tobacco use and
skin/mucous
membrane disease.
Results. This review of the literature shows that a number of
disorders and
diseases of the skin and mucous
membranes are related to tobacco use.

Conclusions. Since millions of persons use tobacco despite its well
publicized relationship to increased mortality, knowledge of the
mucocutaneous morbidity associated with tobacco use may help
physicians in
counseling their patients.

Psoriasis (A paragraph taken from a section of the study)

Many researchers have shown a relationship between smoking and
psoriasis,
especially palmopustular psoriasis. O'Doherty et al[21] showed that
palmopustular psoriasis was associated with a high prevalence of
smoking. In
addition, Mills et al[22] showed that in plaque psoriasis, there was
a
significantly higher prevalence of current smoking (46%) as compared
with
matched controls (24%), and more patients with psoriasis had smoked
before
the onset of psoriasis (55%) as compared with controls (32%).
Finally, the
daily consumption of cigarettes correlated with the risk of
developing
psoriasis, with the higher number of cigarettes smoked (more than 20
cigarettes per day) being associated with greater risk. This was
confirmed by
Poikolainen et al,[23] who found that among psoriatic women the mean
number
of cigarettes smoked was 8.6 compared with 4.7 for controls. It
should be
noted that some treatments for psoriasis are flammable and therefore
may pose
a danger to smokers.

Key Points

Dermatologic effects of cigarette smoking include facial wrinkling,
facial
gauntness, complexion color changes, decreased skin moisture,
yellowed nails,
harlequin nails, halitosis, nicotine stomatitis, and skin burns.
Indirect
effects of cigarette smoking include poor wound healing; psoriasis;
atherosclerotic peripheral vascular disease; Buerger's disease;
Raynaud's
disease; diabetic foot disease; oral yeast infections; condyloma
acuminatum;
and cutaneous findings in HIV and AIDS, Crohn's disease, and
malignancies.
Recognition of dermatologic signs of tobacco use can be a clue to
many of the
serious underlying systemic diseases associated with smoking and also
with
use of smokeless tobacco.

************************************

TB Test Required For Arthritis Patients Wishing To Take Remicade

August 16, 2001 WASHINGTON (AP) - Rheumatoid arthritis patients must
be
tested for tuberculosis before they begin taking a treatment called
Remicade,
the drug maker and the government announced.
Patients using Remicade are at least four times more likely than
average
Americans to get active tuberculosis, the Food and Drug
Administration
estimates. The problem: Apparently the drug suppresses users' immune
systems
enough that if they unknowingly carry the TB germ, the respiratory
illness
can suddenly flare up. The warning is serious because untreated, TB
can kill
- and it's also an airborne illness that these patients could spread
to
family and friends.
Worldwide, 88 cases of tuberculosis have been reported among the
estimated
170,000 people who have tried Remicade, FDA's Dr. Bill Schwieterman
said
Wednesday. Fifteen of those people died.
Some 2 billion people worldwide are infected with TB and risk
developing an
active case of the disease. In the United States, TB cases dropped to
a
record low of 16,377 last year. But the illness is a continuing
threat here,
with increased foreign travel and immigration from countries where TB
is
common.
Rheumatoid arthritis afflicts more than 2 million Americans when
their immune
systems go awry and attack their joints, causing severe swelling,
pain and
stiffness.
Remicade is a bioengineered drug that roams patients' blood to sop up
an
immune system protein called tumor necrosis, a factor responsible for
much of
the swelling.
But that immune suppression, so important in fighting rheumatoid
arthritis,
can leave users at a higher risk for serious infections. Remicade's
label has
long carried warnings about various infections, but it now will carry
a boxed
warning in bold type about the TB risk - the strongest warning
possible for a
prescription drug.
The warning doesn't say people should stop using Remicade. The risk
of
activating latent TB appears highest in the first three to six months
of use,
so doctors should carefully evaluate those patients, Schwieterman
said.
But before prescribing Remicade to a first-time user, doctors should
test for
TB - it's a simple skin test - and treat TB carriers, the FDA
concluded.
Manufacturer Centocor Inc. will send letters to thousands of doctors
who
prescribe Remicade, both for rheumatoid arthritis and the bowel
ailment
ailment Crohn's disease, alerting them to the warning.
A similar rheumatoid arthritis treatment called Enbrel also
suppresses the
immune system and carries warnings that users face the risk of
serious
infections. But so far, Enbrel users don't seem to face a special TB
risk,
Schwieterman said. Copyright 2001 The Associated Press. All rights
reserved.

*************************************

FDA Advisers Endorse Arthritis Drug

August 17, 2001 WASHINGTON (AP) - An experimental treatment for
rheumatoid
arthritis moved a step closer to the market, although studies show it
promises just modest effectiveness. Advisers to the Food and Drug
Administration recommended on a 6-2 vote that Amgen Inc.'s Kineret be
approved. Studies found that about 15 percent more patients who took
Kineret
than who received a dummy shot saw improvement in joint swelling and
pain.
Other treatments sold today come with higher effectiveness rates. But
experts
note that those drugs don't help everyone so additional options are
needed.

Kineret, known chemically as anakinra, works differently than other
therapies, by blocking a protein called interleukin-1 that is one
cause of
the swelling associated with arthritis.
Side effects included irritation at the drug's injection site and a
small
risk of serious infection.
The FDA is not bound by its advisers' recommendations but typically
follows
them.
Copyright 2001 The Associated Press. All rights reserved.

************************************

Editors Note: Because some of our members also fight the battle of
coronary
artery disease, (besides psoriasis and psoriatic arthritis), I have
included
the following article about antioxidants and lipid lowering
medications. My
own
intimate involvement with the subject began in 1989. I had a heart
attack,
discovered I have CAD which runs in the family, had my last cigarette
after
35 years, experienced 7 angioplasties and 4 stents over 8 years,
lost 25
pounds through diet and exercise, started daily vitamin therapy and
lipid
lowering medications, and made some other lifestyle changes too. So
this
subject is very near and dear to my heart. No pun intended of course.

Antioxidant Supplements Reduce Benefits of Lipid-Lowering Drugs

MedscapeWire August 10, 2001 By Hong Mautz New York - Taking
antioxidant
vitamin supplements with 2 substances commonly prescribed to lower
cholesterol can sharply diminish a key beneficial effect of the
therapy,
warns a new study. Some experts say these latest negative findings
about the
popular supplements strongly suggest that the vitamins should not be
used to
treat or prevent heart disease.
Researchers examined nearly 150 people who had both coronary artery
disease
(CAD) and low levels of high-density lipoprotein (HDL) cholesterol.
They were
given niacin (vitamin B3) and simvastatin.
Close to half of the subjects also were given a cocktail of
antioxidant
supplements that included vitamins E and C, beta-carotene, and
selenium.
Rather than helping patients with CAD, however, the antioxidants
limited the
effectiveness of the niacin-simvastatin combination.
"We found that there was an adverse interaction between the
antioxidant
cocktail and the lipid-lowering therapy," says Greg Brown, MD, PhD,
co-author
of the study, which is published in the August issue of
Atherosclerosis,
Thrombosis, and Vascular Biology. "The adverse effect on HDL appeared
specific for the HDL2 component, which is responsible for most of the
risk-reducing benefits of HDL."
After a year of treatment, the combination of simvastatin and niacin
with the
antioxidant vitamin supplements increased HDL2 by 15% compared with
60% in
patients who did not receive the supplements.
"There is a substantial reduction in the rise of HDL2, the most
protective
component of HDL," says Brown, a professor of medicine in the
cardiology
division of the University of Washington in Seattle. "The effect is
detrimental when antioxidant vitamins are taken with the lipid-
lowering
drugs."
In an editorial accompanying the study, Lewis Kuller, MD, DrPH,
professor and
chairman of the Department of Epidemiology in the School of Public
Health at
the University Of Pittsburgh, Pennsylvania, says that physicians
should be
cautious about promoting antioxidant vitamins in patients with CAD.
"All the hype about antioxidant vitamins being a big winner in
preventing
heart disease is totally unproven," says Kuller. "For people who are
on
lipid-lowering drugs such as niacin, a combination with vitamin E is
not a
good choice." Only a diet rich in antioxidants has been proved to be
associated with a low risk of CAD, he says.
"People who take vitamins are a highly selected group of individuals
who are
interested in their health, so they often don't smoke, they exercise
and
weigh less, and they are often better educated," explains
Kuller. "That may
be one of the reasons they are healthier: It doesn't have anything to
do with
taking vitamins."
The American Heart Association does not recommend using antioxidant
vitamin
supplements to maintain or increase cardiovascular health; instead it
recommends eating a variety of foods daily from all of the basic food
groups.

************************************

Cholesterol Drug Warnings Urged

August 21, 2001 WASHINGTON (AP) - Nearly two weeks after a popular
cholesterol-lowering drug was pulled off the market for causing
deadly muscle
destruction, a consumer group charged Monday that five similar
medications
have killed an additional 81 people.
Public Citizen petitioned the government to force manufacturers to
give
special warning brochures to the millions of Americans who take those
medicines - statins - telling them to quit the pills at the first
sign of
muscle pain or weakness.
Statins dramatically lower cholesterol and reduce patients' risk of
heart
attacks.
"Most people taking these drugs aren't aware that they could sustain
serious
muscle damage and could even die," said Dr. Sidney Wolfe of Public
Citizen's
Health Research Group.
"Serious muscle and kidney damage, and potentially death, may be
averted only
if the patients taking statins stop the drugs at the first sign of
muscle
pain or weakness," Wolfe wrote the Food and Drug Administration
Monday.
The FDA disputed Wolfe's death count, saying its own investigation
last year
uncovered just 18 deaths that could be linked to the five statins on
the U.S.
market - Lipitor, Mevacor, Pravachol, Zocor and Lescol.
But the agency will consider Wolfe's request for stiffer warnings.
Pfizer Inc. already has asked the FDA to approve a brochure written
in
layman's language that would accompany every bottle of the top-
selling statin
Lipitor, explaining the risk.
Wolfe's petition comes almost two weeks after one statin, Baycol, was
pulled
off the market when the FDA linked it to 31 U.S. deaths from a side
effect
called rhabdomyolysis. That's a rare but life-threatening condition
in which
muscle cells are destroyed. In severe cases, it leads to kidney
failure.
Every statin has been linked to rare reports of a muscle side effect,
and
their labels carry that warning.
Wolfe analyzed FDA records to uncover 772 cases of rhabdomyolysis
since 1997
among the six statins sold in this country. Half - 387 cases - were
caused by
Baycol alone, explaining why Bayer pulled it off the market.
But Wolfe said he found another 385 rhabdomyolysis cases among users
of the
other five statins still sold, including 81 deaths dating back to
1987, when
the first of those drugs hit the market.
That's still a rare risk, considering 8 million Americans are
estimated to
use statins. But Wolfe argues that severe muscle destruction and
death are
preventable if patients are aware of the early warning signs.
He urged the FDA to put stronger warnings on the statins' labels, to
write
every U.S. physician telling them about the risk, and to mandate that
every
patient get a brochure with each bottle telling them to stop the
pills and
call a doctor if they suffer muscle symptoms.
A closer look at the FDA's reports shows duplicates and patients who
actually
died of other causes, leading federal health officials to link just
18
rhabdomyolysis deaths to statins during an investigation last year,
said
FDA's Dr. John Jenkins.
Merck & Co., maker of Zocor and Mevacor, says it provides Zocor users
a
layman's explanation of the muscle side effect on its Internet site.
Bristol-Myers Squibb is seeking to capitalize on Baycol's departure
with
full-page newspaper ads of Pravachol that mention the muscle risk,
but
company spokesmen didn't return calls seeking comment Monday.
Lescol-maker Novartis maintained the risk is small and that patients
are
appropriately warned. Copyright 2001 The Associated Press. All rights
reserved.

************************************

Communication Needed to Prevent Statin and Other Drug Side Effects,
AHA Says

August 24, 2001 By Deborah Flapan - from Medscape News &
MedscapeWireNew York
-

The American Heart Association (AHA) said this week that more open
dialogue
between doctors and patients is needed to head off the appearance of
dangerous drug side effects, such as rhabdomyolysis from statin
therapy. The
statement came in response to a recent petition filed with the US
Food and
Drug Administration (FDA) to require "black box" warnings, the
strongest
warning the FDA can mandate, on all of the cholesterol-lowering
drugs. Public
Citizen, a consumer advocacy group, filed the petition earlier this
week,
soon after the statin Baycol (cerivastatin) was pulled from the
market
because of reports of rhabdomyolysis and deaths related to the muscle
disorder.
"We know that the FDA looks carefully at adverse drug reactions to
determine
if special warnings or labels are warranted," said Sidney Smith, MD,
Chief
Science Officer of the American Heart Association. "After careful
review of
the available information on the statin class of drugs, the FDA
should be in
the best position to determine whether special labeling will be
effective."
Smith encouraged open communication between physicians and their
patients.
"Doctors should warn their patients to be on the watch for potential
side
effects of any medication. And patients need to take the initiative
and call
their physician if they experience an unusual side effect.
Appropriate labels
can also be a valuable tool in patient education."
In the case of statins, patients should watch for muscle aches and
pains,
dark urine and other signs and symptoms as noted by the FDA and the
package
insert included with the medicine.
The AHA emphasizes that lifestyle decisions such as diet and exercise
should
be the foundation for strategies to lower cholesterol, although
statins and
other cholesterol-lowering drugs can play an important role in
overall
cholesterol management.
"In general, we don't think that patients should stop taking
medications
without talking to their physician. If a patient is experiencing side
effects, the physician can often switch the patient to a different
statin or
other medicine that will continue to manage their cholesterol without
the
side effects," said Smith.
Editors Note: In the last two weeks there have been an extraordinary
number
of medical articles on my web sites, about cholesterol lowering
medications
and possible side effects. I would personally encourage you to
discuss this
information with your own physician. I most certainly will be, at my
next
cardiologist and rheumatologist appointments.

************************************

Health News to Love: Chocolate Is Good for You

By Patricia Reaney-Reuters - GLASGOW, Scotland (Sept. 3)

Good news for chocoholics. The treat favored by millions not only
tastes
delicious but is healthy for you, American researchers said on
Monday.
Chocolate contains compounds called flavonoids that can help maintain
a
healthy heart
and good circulation and reduce blood clotting -- which can cause
heart
attacks and strokes. "More and more, we are finding evidence that
consumption
of chocolate that is rich in flavonoids can have positive
cardiovascular
effects," Carl Keen, a nutritionist at the University of California,
Davis,
told a science conference. "We not only have observed an increase in
antioxidant capacity after chocolate consumption, but also modulation
of
certain compounds which affect blood vessels."
Antioxidants are substances that help reduce the damage of cancer-
causing
charged particles in the body. Fruits, vegetables, nuts and whole
grains are
high in antioxidant vitamins such as C and E.
NOT ALL CHOCOLATE CREATED EQUAL
Flavonoids in chocolate are derived from cocoa, which is rich in the
compounds. Research has shown that a small bar of dark chocolate
contains as
many flavonoids as six apples, 4.5 cups of tea, 28 glasses of white
wine and
two glasses of red. But Dr. Harold Schmitz said there were variations
in the
levels of flavonoids in chocolate and cocoa products depending on the
production process, in which many flavonoids are destroyed. "All
chocolates
are not created equal in regards to flavonoid content," Schmitz, a
scientist
with confectionery maker Mars Inc., told a news conference.
Flavonoids are thought to reduce the risk of cardiovascular disease,
the
number one killer in many industrialized countries, by reducing
platelet
aggregation -- when blood platelets combine into a sticky mass and
form
clots.
Keen and his colleagues measured the impact of chocolate on platelets
in the
blood in 25 volunteers. They presented their findings to the British
Association for the Advancement of Science conference in Glasgow. The
researchers collected blood samples from volunteers who ate 25 grams
(0.9
ounces) of chocolate with a high flavonoid content and other
volunteers who
ate bread. They took blood samples from both groups two and six hours
after
they ate the chocolate and bread to measure their platelet
activation.
Volunteers who consumed the chocolate had lower levels of platelet
activity,
which would reduce the probability of having a blood clot. The
scientists
found no change in the group that ate the bread.
Keen said the results of the study support earlier research showing
that
cocoa acts like low-dose aspirin which helps to reduce blood
clotting. But he
warned that eating chocolate should not be substituted for taking low
dose
aspirin because they work through different mechanism in the
body. "These
results lead us to believe that chocolate may contribute to a
healthy,
well-balanced diet," Keen added.

**************************
Thanks again, and please send your comments and suggestions.

Jack Nicholas - Cornishpro@a... (A Big Fan of Chocolate)
Issue 2001 9/08-2