PSORIATIC ARTHRITIS NEWS AND VIEWS
VOLUME 1 ISSUE 1 SEPTEMBER
2001

PSORIATIC ARTHRITIS MEDICAL NEWS

Hello to all our members around the world. You have been reading my name, Jack Nicholas (Cornishpro@a...) for several weeks now in the daily summaries and I am finally sending out my first newsletter based on researching the web for interesting topics to share with our group. My goal is to publish twice a month.

I have lived in Michigan all my life and have had Psoriasis for over 35 years, plus Psoriatic Arthritis for 30+ years. My hope and dream is to see a cure for both diseases in my lifetime. The delay in getting this first issue completed was partially because of a virus that ate my old computer (I really wanted a new one anyway), causing me to buy a new one, and a visit to my local hospital for surgery.

There will be times when I will provide a complete article and other times I will attempt to paraphrase the information. The source of the information will be shown. I will include articles
on general health issues too, since so many of us deal with multiple conditions and medications. Please feel free to contact me directly with any comments or suggestions regarding ways to improve the newsletter and better serve all our members.

Please remember that by providing this information, we are not dispensing medical advice. Always discuss any new information with your Doctor.

First, let's go back to last year for our first article on Psoriasis research, and then a related article from last month follows with an update.

Effective Treatment May Finally Be Near for Psoriasis Sufferers
Boston, Aug.

10 (Bloomberg) -- Leslie Holsinger says most people think psoriasis
is just a rash.'' The red, scaly lesions that sometimes cover 15% of her body
cause more than a burning itch, though. Her psoriatic arthritis makes it
hard for her to climb stairs. Her toxic medications keep her from having
children. And often the drugs don't work. "I would pay a lot of money for something
to cure this,'' she says. A safe, effective treatment for psoriasis can't be
bought now at any price. Biotechnology companies including Biogen Inc.,
Genentech Inc., Immunex Corp., Idec Pharmaceuticals Inc., Medimmune Inc. and
Abgenix Inc., have psoriasis drugs in development, though. Some could reach
the market as early as 2002. "If one of these products shows strong efficacy, it could be a half-billion-dollar drug,'' said Peter Ginsberg, an analyst with US Bancorp Piper Jaffray. ``We're at a golden age of biotechnology where there are a lot of new treatments in Phase III,'' the final stage of testing generally required for U.S. regulatory approval.

Few Treatment Options

An estimated 2 percent of the U.S.population has psoriasis, representing a
market that could generate more than $500 million in annual drug sales. Psoriasis patients spend an average $800 per person annually on treatments that offer mostly temporary relief and dangerous side effects. Current treatments for severe psoriasis include methotrexate, a toxic cancer drug, cyclosporin, an immune-system suppressant that can cause cancer, and topical steroids, which can cause skin atrophy. ``It's like burning down the house to kill the cockroaches.'' Holsinger says Patients and their doctors are frustrated with the treatment alternatives, says Dr. Burt Adelman, vice president of medical research for Biogen, whose psoriasis treatment Amevive has a shot at being first to market. It is moving through the last of three stages of human testing. ``We have seen in Phase II as many as one-quarter of patients have clear skin. Forty percent achieve a 50 percent clearing,''

Adelman says. ``We're treated 1,500 patients with Amevive and not seen any pattern of serious adverse effects.'' Phase II tests, involving small numbers of patients, are used to determine effective doses and decide what
results to look for in large-scale Phase III trials. Another 1,000 patients are
now enrolled in Amevive Phase III tests. Biogen says it will release results in 2001.


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Psoriasis Drug May Bode Relief from Other Immune Ailments
July 26,2001 BOSTON

(AP) - An exquisitely targeted drug has been found to kill renegade
immune cells and clear up stubborn psoriasis, suggesting a promising new
approach to other diseases that occur when the body's defenses run amok. Those diseases include arthritis, multiple sclerosis and inflammatory bowel
disease." It's really exciting," said Cornell University dermatologist Dr. Richard
D. Granstein. He said it is one of several psoriasis drugs in testing
that are "opening up a whole new approach to treatment" of autoimmune
diseases.

The research was paid for in part by the drug's manufacturer, Biogen,
which expects to seek federal approval for the medication later this year.
Findings on the new drug, a fusion of two proteins known as alefacept, were
published Thursday in The New England Journal of Medicine. Later testing, which
is still unpublished, reinforces evidence that the drug is generally
safe and effective for some patients, said New York University dermatologist
Dr. Mark Lebwohl, who took part in those experiments. About 2 percent of
people suffer from red patches, silvery scales or other symptoms of psoriasis.

It is usually mild but persists for a long time. In severe cases, it can
cover large expanses of skin and lead to a form of arthritis. There is no
outright cure but there are many treatments, including ointments, sunlight or
ultraviolet treatments, and stronger drugs that can damage the liver
or kidneys. The disease is suspected to stem from an immune reaction to
an unknown irritant made by the body. Immune fighters known as memory
effector T cells marshal an attack and prompt inflammation of skin tissue. The
new drug targets the overactive T cells while leaving the rest of the immune
system largely intact.

Existing treatments launch more broad-based attacks
on immune cells, which can weaken the body's defenses against disease and cause other side effects. "We're just going after the specific cells that we're
most interested in stopping," said Dr. Charles Ellis, a University of Michigan
dermatologist who co-wrote the New England Journal report on the
drug. His team tested it on 229 psoriasis patients, at 22 health centers, who
had failed to respond to standard drugs. Those given the biggest
injections improved an average of about 50 percent in their symptoms.

The psoriasis vanished or nearly did so in a quarter of the patients. People did
not need more treatment for an average of 10 months, a longer time than with
other therapies. The researchers found no serious side effects. The later
tests on more than 1,000 patients arrived at similar findings, Lebwohl said.
Almost three quarters of the patients improved by 50 percent or more, and
many were left with little or no psoriasis, he said. He predicted that the drug
will replace other treatment for some patients.


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For those of you involved with either Vioxx or Celebrex, this is a
worthwhile
article from Great Britain.

NICE Says COX-2 Inhibitors Should Be Reserved for High-Risk Patients
LONDON

(Reuters Health) Jul 26 - Britain's National Institute for Clinical
Excellence - (NICE) said on Thursday that Merck and Pharmacia's
blockbuster cyclooxygenase 2 inhibitors, Vioxx (rofecoxib) and Celebrex
(celecoxib), should not be used routinely. In guidance to the National Health
Service, NICE said that selective inhibitors of COX-2 should be used instead
of standard non steroidal anti-inflammatory drugs (NSAIDs) only by people with
rheumatoid arthritis, or osteoarthritis who are at high risk of developing
serious gastrointestinal adverse events. NICE defined high-risk
patients to include those over 65 years, those already using medications known to increase the likelihood of upper gastrointestinal adverse events,
those with serious co-morbidity, and those requiring prolonged use of maximum
recommended doses of standard NSAIDs. NICE also announced that its
appeals' committee has rejected all appeals by Pharmacia and Merck.

Both companies had complained that the Institute's guidance was perverse in the light of the evidence submitted. Pharmacia also claimed that the Institute had failed to act fairly and Merck complained that it had exceeded its powers. NICE
chief executive Andrew Dillon told a news conference in London that although COX-2 inhibitors offer some benefit in terms of reducing adverse events,
there was still uncertainty about the absolute value of the drugs. "Where the
COX-2 drugs have been introduced elsewhere in western-style countries, they
have literally exploded into the system. There has been very widespread
use. That has generated very significant financial pressures." He said NICE
estimated that switching high-risk patients to COX-2 inhibitors would cost the
NHS an extra £25 million per year. Broader use of the drugs could have cost
an extra £100 million per year. A Merck spokeswoman told Reuters Health that
the firm estimates that the NICE guidance would allow COX-2 inhibitors to be
given to 80% of osteoarthritis patients in the UK. "We don't see the guidance
as being particularly restrictive. We are just disappointed that it does not
distinguish between the different products," she said. Dillon said NICE had
advised manufacturers that more robust cost-effectiveness studies
should be carried out before it reviews its guidance in 2004. The guidance says
that all NSAIDs, including the COX-2 selective agents, can cause
gastrointestinal adverse events, including life-threatening perforations, ulcers or
bleeds. "The risk of NSAID-induced complications is particularly increased in
patients with a previous clinical history of gastro duodenal ulcer, gastrointestinal bleeding or gastro duodenal perforation. The use of even a COX-2 selective agent should therefore be considered especially carefully in his situation." The guidance adds that concerns have been raised over the cardiovascular effects of COX-2 drugs. One study comparing Vioxx and naproxen detected an increase in the rate of myocardial infarction in the Vioxx group.

Further research is needed to resolve this issue but in the meantime
the potential increased risk should be taken into account when prescribing COX-2agents for patients with cardiovascular disease, according to the guidance. The drugs are not being prescribed routinely in preference to standard NSAIDs in this group of patients. "Furthermore, many patients with cardiovascular disease receive low-dose aspirin and this carries an increased risk of gastrointestinal events," the guidance states. "In patients who are taking low-dose aspirin, the benefit of using COX-2 selective agents is reduced. Prescribing COX-2 selective agents preferentially over standard NSAIDs in this situation is therefore not justified on current evidence."

Finally, the guidance says there is no evidence to justify simultaneous prescription of gastro-protective agents and COX-2 agents in an attempt to further reduce the risk of adverse events. On the subject of cost-effectiveness, the NICE report notes that an as yet unpublished study, commissioned by the Canadian Coordinating Office for Health Technology Assessment, estimated that the cost of COX-2 agents per quality-adjusted life year became favorable only in the case of high-risk patients.

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FDA Strengthens Warning That Painkiller Oxycontin Can Be Addictive
and Deadly
WASHINGTON (AP) -
Doctors were urged Wednesday to restrict the prescription painkiller Oxycontin to patients with serious pain, as the government strengthened warnings thatimproper use of the pills can cause addiction and kill. The actions by the Food and Drug Administration and Oxycontin maker
Purdue Pharma
are an attempt to stem illegal use of the painkiller. Oxycontin is a
long-lasting version of oxycodone, a narcotic considered important
therapy
for many patients suffering
long-term, moderate to severe pain from cancer or other illnesses,
FDA
stressed. When swallowed whole, the tablet provides 12 hours of pain
relief.
But if chewed, snorted or injected, Oxycontin produces a quick, and
potentially lethal, high. It has been linked to more than 100 deaths.
Drug
abusers don't read warning labels. But the hope is that if doctors
give
Oxycontin just to patients with serious, chronic pain, it will become
harder
for abusers to get leftover tablets. "We're hoping ... people will
consider
this a serious drug for serious pain," said Dr. Cynthia McCormick,
FDA's
chief of addictive products. Oxycontin will bear the FDA's strongest
type of
warning - a black box calling Oxycontin as potentially addictive as
morphine
and explaining that chewing, snorting or injecting it can kill, she
said. It
is not for mild pain or for temporary pain, such as after dental or
surgical
procedures. Purdue wrote 800,000 doctors about the warnings. Also,
the FDA
posted a patient-information Web site urging that Oxycontin be kept
in a
secure location and that unneeded tablets be flushed down the toilet.
Copyright2001 The Associated Press. All rights reserved.

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Institute Warns of Confusing Drug Names WESTPORT, CT (Reuters Health)
Jul 27
- A nonprofit outfit dedicated to preventing medication errors is
warning
healthcare professionals about three pairs of confusing drug names
that could
cause harm if a drug mix-up were to occur. The alert deals with
confusion
over the diabetes drug Lantus (insulinglargine) and Lente insulin;
the
antidepressant drug Serzone (nefazodone) and the antipsychotic
Seroquel
(quetiapine); and the oral diabetes drug Avandia (rosiglitazone
maleate) and
the anticoagulant Coumadin (warfarin). This week's warnings are the
latest in
a series of alerts about the drugs issued by the Institute for Safe
Medication Practices (ISMP), a Huntingdon Valley, Pennsylvania
organization
that independently reviews errors reported through the US
Pharmacopeia's
Medication Errors Reporting System. ISMP is repeating the warnings in
an
effort to draw attention to the problem. Often it takes time for
healthcare
systems and regulators to act on problems that could lead to
potentially
dangerous medical errors, explained Rebecca Wilfinger, an ISMP
spokeswoman.
"When we see it happen again, it's time to say it again," she told
Reuters
Health. ISMP issued its initial warning about the potential for
confusion
between the written and oral orders for Lantus and those for Lente
insulin
last May. Lente insulin has a more rapid effect and shorter duration
of
activity that Lantus, it said. Just one error has been reported with
this
pair of drugs, but ISMP warns that the potential for confusion is
high.
Seventeen errors have been reported involving the drugs Serzone and
Seroquel
since ISMP issued its initial alert in November 1997. The similarity
of the
drug names may lead to prescribing errors because of poor handwriting
or
confusion between the names, it said. And because both their names
start
with"ser," the products could be stored near each other, leading to
dispensing errors. Finally, ISMP repeated its warning over Avandia
and
Coumadin. It initially alerted health professionals about the two
names in
July 1999 and followed up with a second warning a year later. "While
is it
difficult to imagine that these very different names could be
confused, they
actually look very similar if the prescriber has poor handwriting,"
ISMP
said. The Institute recommends that healthcare professionals take
appropriate
steps to prevent these serious mix-ups. "It's incumbent upon all of
us
involved in the healthcare system to create fail-safe systems, with
multiple
checks," Wilfinger said.

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Maker Of OxyContin Hit With Lawsuits July 26, 2001 The Associated
Press The
maker of OxyContin has been hit
with at least 13 lawsuits from patients who have become addicted to
the
painkiller and others who want to hold the company responsible for an
alarming wave of overdoses and deaths among abusers.``This drug has
been like
a cancer attacking the very fabric of our little corner of the
world,'' said
Ira Branham, a lawyer and state legislator from Pikeville, Ky., who
is suing
on behalf of three people and the estate of a dead woman. He said the
responsibility should ``fall on
the shoulders of the company that was the genesis of this problem.''
OxyContin, America's best-selling narcotic painkiller is made by
Purdue
Pharma LP of Stamford, Conn. Many of the plaintiffs say they received
OxyContin legitimately and became addicted by taking the prescribed
dose.
Other lawsuits seek to hold the company responsible for illegal use
of the
drug, which has become a deadly scourge in some parts of the country,
especially Appalachia. Among those suing is the state of West
Virginia, which
alleges Purdue Pharma violated state consumer law. ``They
were telling doctors that OxyContin was far less addictive than other
painkillers in this class of drugs,'' said Doug Davis, an assistant
attorney
general in West Virginia. ``Now, we have a lot of people addicted to
OxyContin in West Virginia.
So was that a misleading statement? Yeah.'' Purdue Pharma spokesman
James
Heins disputed the allegations, saying victims were using the drug
illegally
or improperly. Dr. J. David Haddox, senior medical director, said the
chances
of someone becoming addicted when taking OxyContin as directed are
extremely
small. ``A lot of these people say, `Well, I was taking the medicine
like my
doctor told me to,' and then they start taking more and more and
more,''
Haddox said.
``I don't see where that's my problem.'' Already, the billions of
dollars in
claims represent more than what Purdue Pharma has made on OxyContin.
OxyContin is a slow-release narcotic that is prescribed for victims
of
moderate to severe chronic pain from such ailments as arthritis, back
trouble
and cancer. One pill is designed to last 12 hours, but those who
abuse
OxyContin usually crush it and then snort or inject it, producing a
quick,
heroin-like high. OxyContin abuse first became widespread in
mountainous
areas of Kentucky, West Virginia, Virginia, Tennessee and Maine. It
has since
spread to urban centers, including Boston, Philadelphia and South
Florida.
OxyContin abuse has been blamed for more than 100 deaths nationwide.
Purdue Pharma said that those estimates are unreliable and that in the vast
majority of those cases, the victims were abusing other drugs at the same
time. To try to curb illegal use, Purdue Pharma and the Food and Drug
Administration announced an agreement this week to place the strongest warning
possible on the painkiller, stressing to doctors that the pills are only for
patients with serious pain and that improper use can cause addiction and
death.

Florida, Maine, West Virginia, Ohio and South Carolina have put
restrictions on the drug's distribution to Medicaid recipients. Some pharmacies in
Virginia are considering fingerprinting everyone who fills a prescription for
painkillers. At Purdue Pharma, a family-owned company that has been media-shy
throughout most of its 109-year history, Heins said he knows of at least 13
lawsuits since May. OxyContin, introduced in December 1995, has been a
breakthrough drug for Purdue Pharma, accounting for 83 percent of its revenue
this year. Doctors wrote 6.9 million prescriptions for OxyContin from May
2000 to May 2001, producing $1.27 billion in sales, according to IMS Health,
a health information company. To get the word out about the new drug,
Purdue Pharma invited hundreds of doctors to pain management meetings.

Some doctors were recruited to instruct their peers at seminars, which stressed
the importance of aggressively treating pain. ``Aggressive marketing of
pharmaceuticals has been on the rise for the past few years,'' said Steven
Findlay, director of research at the National Institute for Health Care
Management. ``What we're seeing is a marketing campaign that has gotten a
little too assertive and had the unfortunate result of increasing the prescriptions of the drug that were clearly inappropriate.'' John Craig, a pharmacist in Scottburg, Ind., said OxyContin salesmen from Purdue Pharma were
``in your face.'' ``It was as if OxyContin was the best drug out there,''
Craig said. ``They said it had a low potential for abuse. That's what
we were told at the beginning. I think everyone was surprised - and they were
probably, too - when we started seeing all the overdoses.'' Dr. Jerry A. Menikoff, an expert in public health law at the University of Kansas Medical School, said if
plaintiffs can show that Purdue Pharma downplayed the risks, the OxyContin
lawsuits could stick. ``The question is, did the manufacturer properly notify the
consumer of all the risks?'' Menikoff said. ``If you're pushing inappropriate
uses of medication, then you can be responsible for the consequences.'' Dr. Claire V. Wolfe, an expert in chronic pain at Ohio State University, said if the
lawsuits succeed in discouraging Purdue Pharma from selling OxyContin, her
patients will suffer. ``You would take away a drug that is a really big
help,'' Wolfe said.``Frankly, I think (prescription drug abuse) is the doctors' responsibility. It's the physician who's writing the prescription.'

Copyright 2001 the Associated Press. All rights reserved.

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(Psoriatic Arthritis is very similar to Rheumatoid Arthritis, so I have included the following article to help those of you who may not be familiar with some of the treatment options. )

Treatment Options for Patients with Severe Rheumatoid Arthritis Are
Gradually Increasing
[Drug &Ther Perspect 17(12):4-8, 2001. © 2001 Adis International
Limited]

Introduction

Rheumatoid arthritis is a chronic inflammatory autoimmune disease
which affects approximately 0.5 to 1% of the population. Inflammation of
synovial tissue in peripheral joints leads to joint erosion and eventual
destruction resulting in significant pain, fatigue, functional disability and
early mortality in affected patients. Non steroidal anti-inflammatory drugs
(NSAIDs) are commonly used as initial treatment but they offer symptomatic
relief only and most patients require alternative or additional therapy.
Disease modifying anti rheumatic drugs (DMARDs) are now being given
earlier in the course of the disease with the aim of reducing joint damage.
However, few are fully effective when administered as monotherapy. Although
the efficacy/toxicity ratio of some of the older DMARDs (e.g. methotrexate, sulfasalazine) is favorable, their tolerability is not ideal and frequent
monitoring for adverse events is required. Two agents which inhibit
the production of the cytokines have recently been introduced. Infliximab
and Etanercept both inhibit tumor necrosis factor- (TNF) and have shown
promising reductions in disease activity either alone or in combination with
methotrexate. For patients unresponsive to monotherapy, combination
regimens of DMARDs may improve responses.

Cause Remains Uncertain Rheumatoid arthritis results from an inappropriate inflammatory response but the causative event remains elusive. Therapy Aims to Reduce Joint Damage The goal of treatment is to control inflammation sufficiently to prevent or retard joint damage with the ultimate goal being to induce complete
remission A number of criteria are used in clinical trials to measure response
to treatment and are often combined to form a composite measure of
treatment response, e.g. the American College of Rheumatology (ACR) criteria
Minimal clinical responses defined as a 20% improvement (ACR 20).
Try NSAIDs First NSAIDs reduce joint pain and swelling and may improve function; however, they do not alter disease progression. Nevertheless, because of the unpredictable course of rheumatoid arthritis at presentation they are usually used as initial treatment. If patients continue to experience persistent joint
symptoms, morning stiffness, and fatigue for 3 months, treatment with DMARDs
is indicated. Start DMARDTreatment Early Delaying treatment with DMARDs until joint damage is evident was found to be associated with poor long term outcomes. The current treatment strategy therefore involves the early use of DMARDs to limit joint damage and preserve function. The term DMARD applies to a diverse array of drugs such as penicillamine, oral or intramuscular gold, sulfasalazine, antimalarials (chloroquine and hydroxychloroquine) and immunosuppressants (methotrexate, azathioprine, cyclosporin, leflunomide).There is typically a delay in onset of clinical efficacy with these drugs which ranges from 4 weeks to 6 months depending on the DMARD being used. Adverse events are a major limitation of the use of DMARDs and monitoring of complete blood counts is recommended for all
DMARDs (excepthydroxy-chloroquine and leflunomide). Additional monitoring of
liver function tests, serum creatinine and urine proteins is required for
some DMARDs. The cost of adverse event monitoring adds significantly to
the cost of treatment with these agents. Nevertheless, the consequences of
rheumatoid arthritis are so severe that the efficacy/toxicity ratio of drugs
such as methotrexate, sulfasalazine and hydroxychloroquine appears to be
favorable. Such treatments are best administered by specialist rheumatologists.
Methotrexate Commonly Used Among the older DMARDs, methotrexate appears to have the best long term efficacy and is often selected as the initial DMARD. This observation conflicts with the registered indication which is for patients with
severe, acute disease who do not respond to a course of NSAIDs and at least
one other DMARD. This caution is a reflection of the potentially serious
adverse events associated with this drug including an increased risk of
lymphoma. Despite methotrexate's ability to reduce disease activity and joint
damage, it rarely leads to true remission and combination therapy is
frequently required. Leflunomide at Least as Effective? Leflunomide is a more recently introduced DMARD which was reviewed in Drugs& Therapeutic Perspectives Jul 2000; 16 (1): 1-5. Leflunomide appeared to beat least as effective as methotrexate and more effective than sulfasalazine. Leflunomide also delayed radiological progression, assessed after 12 or 24 months of treatment, at least as effectively as methotrexate or sulfasalazine and reduced functional
disability(assessed using a Health Assessment Questionnaire) to a greater extent than either methotrexate or sulfasalazine after treatment durations of
6 to 24months. The drug had a faster onset of action (4 weeks) than either methotrexate or sulfasalazine and was as well tolerated as both of these
drugs in clinical trials. TNF inhibitors show promise Infliximab and Etanercept have recently been approved for use in the treatment of rheumatoid arthritis. Both drugs have been shown to reduce disease activity and joint damage so can be
considered as DMARDs. However, unlike the more traditional DMARDs these drugs directly target TNF, a proinflammatory cytokine, which plays a key role in the pathological inflammatory process in rheumatoid arthritis. Both drugs
have a faster onset of action (1 to 2 weeks) compared with the DMARDs described in the previous sections. They have been associated with an increased
risk of upper respiratory tract infection and more rarely with cases of
serious infection. For this reason they should not be given to patients with
active infections and should be discontinued if a patient develops a serious
infection or sepsis. Approximately 10% of patients receiving infliximab have
developed antibodies to the drug but the clinical significance of this is not
yet known. In contrast, etanercept antibodies have only rarely been reported
in etanercept-treated patients. Increase Efficacy by Combining DMARDs
If residual inflammation remains after maximum doses of DMARD
monotherapy, combinations of DMARDs should be considered. Methotrexate is the drug most commonly used in combination. These studies generally indicate increased efficacy for combination therapy compared with monotherapy and
tolerability does not appear to be increased. The use of combination regimens is becoming more common for the treatment of patients with refractory rheumatoid arthritis but long term follow-up (5 years) is still needed to determine optimum strategies.

To view the entire text, go to the following:
http://www.medscape.com/adis/DTP/2001/v17.n12/dtp1712.02/dtp1712.02.ht

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This brings our first issue to a close. I hope that the newsletter was both informational and possibly helpful to you.
We can never have enough knowledge about the conditions we all have to live with everyday.

Issue 2001-9/03 -1

Jack Nicholas
Cornishpro@a...
P.S. Since the next issue of the newsletter has some very timely
subjects, I
will be issuing by the end of this week.