PSORIATIC ARTHRITIS NEWSLETTER NO. 56

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PSORIATIC ARTHRITIS NEWS AND VIEWS

VOL. 3 ISSUE 22 - December 15, 2003

PSORIATIC ARTHRITIS MEDICAL NEWS

NEW PSORIASIS TREATMENTS WORK-

RAPTIVA, ARTHRITIS DRUG ENBREL - EFFECTIVE AND SAFE

Nov. 19, 2003 -- Not so long ago, psoriasis sufferers had few options. Now

three already-available drugs offer relief from the agonizing skin disease.

The new drugs are Enbrel, Raptiva, and Amevive. All are " biological " drugs --

they use recent scientific breakthroughs to target specific body functions.

Psoriasis is an autoimmune disease; the new drugs block harmful immune

responses. Amevive and Raptiva were approved earlier this year as psoriasis

treatments. Enbrel was approved in 1998 to treat rheumatoid arthritis. Enbrel's

manufacturer, Wyeth, has filed for formal approval as a psoriasis treatment.

Separate clinical studies of psoriasis patients treated with Enbrel and

Raptiva appear in the Nov. 20 issue of The New England Journal of Medicine. So

does

an editorial by S. Kupper, MD, of Brigham and Women's Hospital in

Boston.

" At this point, there are insufficient data to support claims that one of

these agents is superior to another, " Kupper writes. " There may be groups of

people who have a better response to one or the other of these agents. "

All of these drugs likely must be taken for long periods of time -- perhaps

for life. Because they interfere with the immune system, there is a danger that

they will raise patients' risk of infections and maybe even cancer. It's not

clear how the drugs will work over years and years of treatment. But in the

short term, all have remarkable safety records. That's particularly true for

Enbrel, which has been used in more than 150,000 patients -- including long-term

safety studies in 2,000 patients.

Enbrel: From Arthritis to Psoriasis

Enbrel is a man-made protein that blocks a chemical messenger called TNF

(tumor necrosis factor). Blocking TNF quiets the abnormal immune responses seen

in

arthritis -- and in psoriasis.

Craig L. Leonardi, MD, of St. Louis University, and colleagues tested three

different doses of Enbrel in 652 adult patients with moderate-to-severe

psoriasis. After 24 weeks of treatment:

59% of high-dose patients (50 mg injections twice a week) had at least 75%

improvement -- 55% reported " clear " or " almost clear " status.

44% of medium-dose patients (25 mg injections twice a week) had at least 75%

improvement -- 39% reported " clear " or " almost clear " status.

25% of low-dose patients (25 mg injections once a week) had at least 75%

improvement -- 26% reported " clear " or " almost clear " status.

" Rapid clearing of skin lesions is an important aspect of effective psoriasis

management and may correlate with the patient's satisfaction with treatment, "

Leonardi and colleagues write. " After two weeks of treatment, [Enbrel]

produced statistically significant and clinically meaningful improvements in

patients' global assessments of disease and in the quality of life. "

Raptiva: Targeting T Cells

Raptiva is a man-made antibody. It goes against T cells, the quarterbacks of

the immune system. It doesn't kill the T cells -- instead, it blocks T cells

from moving from the blood into the skin.

Mark Lebwohl, MD, of Mt. Sinai School of Medicine in New York, and colleagues

treated nearly 600 moderate-to-severe psoriasis patients with two different

doses of Raptiva. After 12 weeks of treatment:

28% of high-dose patients (2 mg/kg body weight injections once a week) had at

least 75% improvement.

22% of low-dose patients (2 mg/kg body weight injections every other week)

had at least 75% improvement.

" Continued [Raptiva] therapy provided continued benefit, " Lebwohl and

colleagues report. " In addition, extending the [Raptiva] treatment from 12 to 24

weeks resulted in improved responses in many subjects who did not initially have

improvement of 75% or more. "

Treatments, Not Cures

Both studies -- and earlier reports of Amevive's efficacy -- are good news

for psoriasis patients. None of the treatments offers a cure. But they offer

significant relief. And they're a sign of more good things to come.

" One thing is certain -- we have not seen the last of biologic therapies for

psoriasis, " Kupper notes. " This will ultimately be a boon to patients with

this chronic, debilitating disease. "

SOURCES: Kupper, T.- The New England Journal of Medicine, Nov. 20, 2003.

© 2003 WebMD Inc..

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COST OF TREATING RHEUMATIC CONDITIONS EXCEEDS THAT FOR OBESITY IN U.S. By

Karla Gale - NEW YORK (Reuters Health)

Arthritis and other rheumatic conditions, the leading cause of disability in

the U.S., costs the country upwards of $116 billion annually -- more than 1%

of the gross domestic product -- investigators report in the Morbidity and

Mortality Weekly Report for November 21.

" Most people with arthritis are working age, " senior author Dr. G.

Helmick told Reuters Health. " So governments, businesses and health care plans

have an interest in knowing where direct costs are incurred. If they can invest

in programs to prevent some of the disease progression and disability, they

may be able to save on direct costs in the long run. "

Using data from the 1997 Medical Expenditure Panel Survey, Dr. Helmick's

group determined the " attributable fraction " of costs due to arthritis alone

after

factoring out costs for other conditions, such as heart disease and diabetes.

" Of all the medical expenditures, 10% are attributable to arthritis care, "

co-author Dr. Louise said. Included in these estimates are costs to treat

osteoarthritis, rheumatoid arthritis and systemic lupus erythematosus, she

noted, " as well as conditions not typically thought of in this category, such as

carpel tunnel syndrome and fibromyalgia. "

In fact, " we were surprised when we compared our findings with the results of

a recent study that looked at the costs associated with obesity, " she added.

In 2002 dollars, the obesity is estimated to cost the US $85.2 billion,

compared with the 2002 cost of $128.4 billion for arthritic conditions.

" This number is as big as many other chronic conditions that get a lot more

attention, such as cancer and heart disease, " Dr. Helmick noted. " Because

arthritis is so prevalent, even though it doesn't kill you, it racks up a lot of

costs. "

He expects the costs of treating arthritis to increase faster than health

care expenditures in general, because of expensive new COX-2 inhibitors and

biologic response modifiers. However, these costs may be offset by increasing

the

number of individuals able to return to work and by implementing

self-management programs to increase physical activity and maintain a healthy

weight.

Copyright © 2003 Reuters Limited.

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FATIGUE OFTEN PRECEDES HEART ATTACKS IN WOMEN

By Karla Gale - NEW YORK (Reuters Health)

Most women who have a heart attack have experienced telltale symptoms, such

as extreme fatigue and sleep disturbance, during the weeks leading up to the

attack, investigators report.

Chest pain, however, is not usually one of these symptoms.

According to their report the American Heart Association's journal

Circulation, Dr. C. McSweeney and her colleagues believe that doctors

sometimes

don't recognize that a woman is having a heart attack because the symptoms don't

match those of men, who more commonly experience severe chest pain.

To further investigate, McSweeney, with the University of Arkansas for

Medical Sciences, Little Rock, and colleagues telephoned 515 women who had had a

heart attack within the previous 4 to 6 months. The women were asked what

symptoms they experienced before and during the heart attack.

Ninety-five percent of the subjects reported unusual symptoms during the

weeks leading up to the heart attack.

" These are symptoms that change in intensity or frequency, or they're a brand

new appearance, starting in the period prior to their heart attack, "

McSweeney told Reuters Health.

The most frequently reported were unusual fatigue (71 percent) and sleep

disturbance (48 percent). Shortness of breath, indigestion and anxiety were also

common. Less than a third reported chest discomfort, and when they did, it was

most often described as pressure, aching or tightness.

" A lot of women ignore these symptoms, thinking it's just because they're

'getting older,' " McSweeney commented. " But even when they do go to a physician,

their physicians may overlook these symptoms. "

These warning signs can be overwhelming, she said, and shouldn't be shrugged

off. Some of the subjects said they had been so tired they couldn't finish

making a bed without having to rest. Others said they had trouble climbing

stairs.

" Women need to explain to their doctor how these symptoms are impacting their

daily life. They should specifically say what they can't do, so that

physicians can judge how severe this fatigue is. "

When the heart attack occurred, the acute symptoms most commonly reported

were shortness of breath, weakness, unusual fatigue, cold sweat and dizziness.

If

they had chest discomfort, they rarely described is as " pain. "

Most women also had conventional risk factors, such as a history of

cardiovascular disease, diabetes and high blood pressure.

" I'm trying to get women and physicians to look not only at these symptoms

but also at their cardiovascular risk factors, such as hypertension or a strong

family history of heart disease, " to decide what diagnostic tests should be

performed, McSweeney concluded.

Copyright © 2003 Reuters Limited.

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ARTERIAL WALL THICKENING ACCELERATED IN RHEUMATOID ARTHRITIS PATIENTS

NEW YORK (Reuters Health) 12/04/03

Thickening of the arterial wall occurs faster in rheumatoid arthritis (RA)

patients than in healthy subjects, Japanese researchers report. In such

patients, inflammation and calcium mobilization are strongly associated with

arterial

thickening.

Mortality from cardiovascular causes is known to be increased in RA patients.

However, it was unclear if atherosclerosis is accelerated in such patients.

The findings, which are published in the November issue of Arthritis and

Rheumatism, are based on a study of 62 women with stable RA and 63 healthy

female

controls. Ultrasound was used to assess the intima-media thickness of the

common carotid artery at baseline and again at least 18 months later. Blood

markers of inflammation and calcium mobilization were measured at baseline.

Dr. Masaaki Inaba, from Osaka City University, and colleagues found that RA

patients experienced a greater increase in arterial wall thickness during the

study period than did the controls.

On multivariate analysis, the C-reactive protein level -- a marker of

inflammation -- and the urinary calcium-to-creatinine ratio -- an indicator of

calcium mobilization -- were both significant independent predictors of the rise

in

arterial wall thickness seen in RA patients.

" This is the first prospective study demonstrating accelerated arterial

thickening in patients with RA, " the researchers state. " Further studies are

needed

to examine whether strict control of RA can prevent atherosclerosis and

reduce the risk of death from cardiovascular causes, " they add. Copyright © 2003

Reuters Limited.

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DISABILITY LEVELS IN RHEUMATOID ARTHRITIS ARE DECLINING IN U.S. NEW YORK

(Reuters Health)

The results of a recent study suggest that average disability levels in

rheumatoid arthritis (RA) have declined in the US since 1977.

" If newer, more aggressive treatment strategies in RA are more effective,

long-term outcomes in RA should be improving substantially, " investigators write

in the October 1st issue of the American Journal of Medicine.

In a longitudinal study, Dr. F. Fries of the Stanford University School

of Medicine, California, and Dr. Eswar Krishnan of the Clinical Research

Center of Reading, West Reading, Pennsylvania, examined disability trends in RA

patients.

The researchers assessed data on functional disability from 3035 RA patients

who developed the disease between 1977 and 1998. They used the Health

Assessment Questionnaire disability index to collect disability data on a

semiannual

basis. The mean follow-up was 5.3 years.

The average disability was estimated for each patient, and the mean

disability for each calendar year was computed by averaging the values from all

of the

patients in that calendar year. In addition, the team evaluated the relation

of successive annual cohorts and subsequent disability after adjusting for a

number of variables.

" Average disability declined by about 2% to 3% per calendar year of disease

onset, " they report. After controlling for confounding factors, they found that

the mean disability index declined by a rate of 2.0% for each calendar year.

The trend toward a reduction in functional disability was consistent by sex,

race, education level, disease duration, length of follow-up, and baseline

disability.

" More aggressive use of disease-modifying anti-rheumatic drug treatment might

be expected to reduce average disability and the rate of progression of

disability in rheumatoid arthritis, " they conclude. Copyright © 2003 Reuters

Limited.

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TROPICAL JUICE THAT STOPS THE PAIN OF ARTHRITIS

Daily Mail. 12/10/03. Submitted by our group member from London,

Szczygiel.

An exotic fruit juice from the South Sea islands of the Pacific can offer

pain relief to people suffering from arthritis.

Noni juice has anti-inflammatory chemicals and antibacterial compounds that

work to block the causes of joint pain, it is claimed.

The fruit - which is found in places such as Tahiti and Hawaii - has been

taken by inhabitants of the islands for centuries.

But it is only in the past ten years that doctors and scientists have been

looking at Noni - a member of the citrus family - to see exactly what conditions

it can treat.

'A lot of extravagant claims have been made for Noni curing or helping all

sorts of conditions,' says London-based nutritionist Gareth Zeal.

'Not all have been substantiated, but we are fairly confident that Noni will

help people with arthritic pain.' As many as eight million people in the UK

suffer from arthritis, and although there are a variety of prescription drugs

for the condition, many have to be taken with care because of the side effects.

Others are denied some of the latest, less harmful drugs on grounds of cost.

Large numbers seek alternative treatments for their pain.

Noni has been found to contain a number of chemicals and enzymes that act

against the inflammatory response that causes joints to become arthritic.

Bromelain, an enzyme that is known to be anti-inflammatory, is also found in

the stalks of the pineapple family. A licensed pharmaceutical drug is being

developed from pineapple bromelain for treating victims of severe burns in

hospitals.

Mr. Zeal adds:' We also know that Noni contains complex sugars, known as

mucopolysaccharides.

It is known that people with arthritis have high levels of certain bacteria

in their bowel, which get into the bloodstream and are thought to play a key

role in causing the inflammation in joint arthritis.

'Mucopolysaccharides help promote the production of " good " bacteria in the

bowel that drive out the " bad " bacteria which is thought to be responsible for

the inflammatory response.

'We also think that bacteria and bromelain are working against the release of

tumor necrosing factor [TNF], which is part of the body's over-response to an

attack on the immune system.' Financial Times Limited,

Copyright © 2003

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TREATING DEPRESSION MAY EASE ARTHRITIS

By Warner - WebMD Medical News Reviewed By Brunilda Nazario, MD

Fighting Elderly Depression Reduces Pain and Improves Quality of Life

(New York) -- Improving the treatment of depression among the elderly not

only boosts their outlook on life, but it may also reduce the pain and

disability

caused by arthritis.

Both depression and arthritis are common and disabling conditions among the

elderly, and a new study shows that better depression care can benefit more

than just the person's depression -- it can also help ease the pain and

suffering

caused by arthritis. Researchers found that giving older people adequate

treatment for their depression lessened the negative impact arthritis had on

their

lives.

" In addition to better mood, their pain interference with daily activities

was also less, " says researcher Lin, MD, MPH, of the Center for Health

Studies, Group Health ative, in Seattle, Wash. " We also saw improvement

in patients reporting that they had better overall quality of life. "

Lin presented the results of the study, which appears in the Nov. 12 issue of

The Journal of the American Medical Association, at an American Medical

Association briefing on pain management held here.

Treat One, Ease the Other

Researchers say depression affects about one in six older adults, and nearly

a third of adults older than 65 suffer from arthritis, making it one of the

leading causes of disability among the elderly.

In this study researchers looked at whether enhancing care for depression

improved pain and other aspects of daily life in 1,001 adults over 60 who were

being treated for both depression and arthritis at 18 primary care clinics

across the U.S.

At the start of the study, less than half of the participants were taking

antidepressant medications and 57% were taking pain medications.

During the course of the study, participants were randomly assigned to usual

care such as antidepressant drugs or an intervention designed to improve

depression treatment by using antidepressant medication and/or six to eight

sessions of problem-solving psychotherapy.

After 12 months, researchers found that patients in the intervention group

not only had improved depression scores but they also had lower average scores

for pain intensity and reported less interference with daily activities due to

arthritis or pain in general. In addition, the patients who received the

enhanced depression care had better overall health and quality of life compared

to

those who received the standard treatment with antidepressant drugs.

Researchers say that about 80% of the patients in the intervention group

received antidepressant medications and about a third participated in the

psychotherapy. The estimated cost of the intervention was about $550 per

patient.

But Lin says treating depression adequately saves money in the long run

because previous studies have shown that older adults with depression use health

care services 50% more than those without depression. She says future studies

will look at the cost-effectiveness of implementing this treatment approach at

other primary care clinics.

SOURCES: Lin, E. The Journal of the American Medical Association, Nov. 12,

2003; vol 290: pp 2428-2434. Lin, MD, MPH, Center for Health Studies,

Group Health ative, Seattle, Wash. © 2003 WebMD Inc. All rights reserved.

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CHILL OUT, OR FACE RISING HEALTH RISKS

News release, Health Behaviors News Service.

When Hostility Rises With Age, so Do Unhealthy Behaviors

People who don't mellow out with age may face rising health risks as they get

older.

A new study shows that men and women who become more hostile as they age may

double their risk of obesity, depression, and poor social support.

Not only does their health suffer, but researchers also found that the

careers of increasingly hostile people may also fail to live up to their

expectations.

Researchers say the vast majority of people mellow out and become less

hostile with age, but a significant number of men and women hold on to their

hostility or become more hostile.

Tracing Hostility Through Life

Hostility is one of a number of psychosocial risk factors that is linked to

an increased risk of a number of illnesses, such as heart disease. In this

study, researchers looked at whether changes in hostility levels over time might

predict health-related risks.

Researchers collected information on physical and mental health and

personality traits from more than 2,200 University of North Carolina college

students

who started college between 1964 and 1965 and then interviewed them again in

1998.

They found that nearly two-thirds of the alumni became less hostile as they

aged, but about 18% maintained the same hostility level or become more hostile.

People who had high levels of hostility were more likely to:

Smoke

Drink more than two alcoholic drinks per day

Have low levels of social support

Become depressed

Achieve less than they had expected in their career and relationships

Report that their family life had changed for the worse

Researchers say all of those factors could add up to a higher risk of heart

disease.

Alumni who became more hostile after college had a significantly higher risk

of:

Obesity

Feeling socially isolated

Avoiding exercise

Eating a high-fat diet

Negative changes in economic life, work life, and physical health

In addition, women who became more hostile also reported a lower income than

those who had mellowed out.

Researchers say having higher levels of hostility at midlife raises risk of

health problems, and future research should look at developing interventions to

help people reduce hostility.

SOURCES: Siegler, I. Psychosomatic Medicine, Sept/Oct. 2003; vol 65.

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Editor's note: The following information, compliments of Ron Dotson, will

give you a tiny peak into the world of science and a perspective on potential

future medical advances.

IRONING OUT BLOOD IMPURITIES

By Louise Knapp - Dec. 08, 2003

Magnetized nanoparticles may one day be the treatment of choice for people

needing to detox -- whether they be a soldier in the field contaminated by

anthrax or a civilian who has partied way too hard and is suffering from a drug

overdose.

The nanoparticles, designed at the Argonne National Laboratory, come fitted

with receptors designed to identify, and then latch onto, target molecules. The

nanoparticles are injected into the bloodstream, where they circulate through

the body, picking up their target toxins as they go.

Once they have made their rounds, all that's needed to remove the particles

from the body are a magnet housed in a handheld unit and a small, dual-channel

shunt inserted into an arm or leg artery.

" Dual channel means a tube within a tube. You stick it into an artery and the

blood will pass from the body into an inner diameter tube and then flow back

into the body through an outer tube, " said Kaminski, one of the

architects behind the project and an engineer at Argonne National Laboratory's

chemical engineering division.

All the blood circulates through this handheld unit. The magnetic field in

the unit pulls the particles out of the blood and deposits them into a

detachable chamber.

Around 40 minutes later the treatment is finished and the soldier is ready to

get back to his mission while the reveler can return to his party.

The fact that the system is small and portable, and that the treatment can be

done quickly, scores it points over hemodialysis -- the method commonly used

to treat advanced and permanent kidney failure.

During hemodialysis the blood flows, a few ounces at a time, through a

machine with a special filter that removes wastes and extra fluids. The clean

blood

is then returned to the body. The treatment takes up to seven hours, since the

process requires several circulations before all the impurities are drawn out

of the blood.

" Hemodialysis is very complex. It's not only done to remove toxins but also

to balance salt (and) water levels. It's a really, really sophisticated system

and uses a huge machine to do this, " Kaminski said.

Hemodialysis is also limited: The process can filter out only certain kinds

of toxins.

" Hemodialysis works great for kidney failure but is useless for most other

kinds of detoxification, " said Axel Rosengart, the other architect behind the

new magnetic treatment and an assistant professor of neurology and surgery at

the University of Chicago.

Kaminski said his treatment is far more versatile. " It could be used to

remove excess chemotherapy (drugs), or for diseases called autoimmune disease --

rheumatoid arthritis is one, " he said.

In autoimmune diseases, the body's natural immune system does not operate as

it should. Instead, the immune system attacks healthy tissue. In rheumatoid

arthritis, the assault causes inflammation and joint damage.

Kaminski's treatment could help if the nanoparticles' receptors were designed

to pinpoint the pathogenic antibodies that cause inflammation.

The team's nanoparticles are between 100 nanometers and 5,000 nanometers.

(The head of a pin measures 1 million nanometers.) The particles are small

enough

to pass through blood vessels but large enough to avoid being filtered from

the bloodstream by the kidneys.

The particles are made of polylactic acid, a biodegradable material. " We are

looking to take out all of the particles but we can't expect to reach 100

percent, so they need to be biodegradable, " Kaminski said. " We don't want to be

introducing anything that could be harmful to the body. "

Small iron crystals of magnetite, a magnetic mineral, are added to the

particles along with a number of receptors, or antibodies, designed to bind to

the

toxic target.

" One of these particles has thousands of antibodies attached to it, " Kaminski

said. " We make sure there are enough receptors to remove or account for more

than 10 times the lethal dose of toxin in the body. "

The whole particle is then coated with polyethylene glycol, a substance that

can hoodwink the immune system into thinking the particle is just part of the

body.

" In a rat, ordinary particles may last 12 to 20 minutes, but with

polyethylene glycol they can last up to five hours, " Kaminski said.

Kaminski admitted the process of making the particles sounds complicated but,

he said, the process is simple.

" It's a solvent-extraction technique -- the same method as making Italian

dressing, " Kaminski said. " If I were to make a batch today it will take 24 hours

to completely make it. The batch can be as big as the reactor vessel you have

-- right now we can make several kilograms of the stuff. "

" The reactor vessel is the same sort of thing you'd brew beer in -- stainless

steel vessels, " Kaminski said.

The samples can then be freeze-dried and stored for up to a year.

" I think this technology may have the potential to work -- maybe not for

removing antibodies but other molecules you don't want like TNF (tumor necrosis

factor), an inflammatory molecule that produces inflammation in the joints in

arthritic patients, " said Dr. Daikh of the rheumatology division at the

University of California Medical Center.

" This is a very clever and creative way of doing something, " said Dr. Bill

Buchholz of the Buchholz Medical Group, a cancer clinic in California.

Buchholz did not, however, think it would work with chemotherapy.

Chemotherapy employs drugs that destroy cancer cells by preventing them from

multiplying.

But chemotherapy has a drawback: Healthy cells also can be harmed at the same

time, especially those that divide quickly.

But using magnetic nanoparticles to rid the body of the potentially harmful

anticancer drug would mean either the drug would have to be removed from the

body before it had time to destroy the cancer cells, or that it would be removed

once the damage to the healthy cells already had been done.

" If you have a loud sound that triggered an avalanche, blocking the sound

after the avalanche occurred would do nothing, " Buchholz said.

Buchholz, however, said the principle behind the Argonne technique was sound

and that the process could work with other toxins.

Kaminski has so far limited his trials to tests on rats but the results have

been very promising. " Our initial tests have been very successful -- I am very

confident that we will be able to remove 99 point something of the

particles, " he said.

Kaminski said Food and Drug Administration trials will start in five years.

The research is sponsored by the Defense Advanced Research Projects Agency and

the U.S. Department of Energy.

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TULARIK INITIATES PHASE 2 CLINICAL TRIAL OF T487 IN PSORIASIS

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Dec. 10, 2003

Tularik Inc. today announced the initiation of a Phase 2 efficacy and safety

study with T487 for the treatment of patients with psoriasis. T487 is an

orally administered therapy that has a novel mechanism of action and is expected

to

reduce inflammation in conditions such as psoriasis.

The Phase 2 double blind, randomized, placebo-controlled study will enroll

approximately 40 patients with moderate to severe psoriasis. Patients will

receive T487 or placebo once daily for 28 days. Efficacy endpoints include an

improvement in the Psoriasis Area and Severity Index (PASI) score and measures

of

inflammatory cell infiltration in psoriasis skin lesions. The study will be

conducted at multiple centers in Europe.

" Based on our preclinical data we expect T487 will block a step in the

cascade of events leading to chronic autoimmune disease. Building on the

strength of

these data and the success of Phase 1 studies, we are excited to advance T487

into Phase 2, " said Levy, MD, Vice President of Development and Chief

Medical Officer of Tularik. " The availability of a new oral therapy that is

convenient, safe and effective would be an important addition to currently

available treatment options for patients with psoriasis. "

T487 acts by binding to CXCR3, a receptor found on the surface of

lymphocytes. The binding of T487 to CXCR3 inhibits the migration of lymphocytes

into

inflamed tissue. Thus, T487 is expected to provide symptomatic relief and block

the progression of diseases such as rheumatoid arthritis, inflammatory bowel

disease, multiple sclerosis and psoriasis. In preclinical studies, T487 blocked

immune cell migration and demonstrated excellent potency, high selectivity and

good oral bioavailability. In Phase 1 studies, all doses of T487 were well

tolerated and no serious adverse events were observed.

T487 was developed by Tularik scientists as part of a collaboration initiated

in 1999 with ChemoCentryx. ChemoCentryx is a private, California-based

company dedicated to chemokine-related drug discovery. Tularik retains worldwide

commercialization rights to T487, while ChemoCentryx will receive certain

payments in connection with the development and marketing of T487.

About Tularik

Tularik is engaged in the discovery and development of a broad range of novel

and superior orally available medicines that act through the regulation of

gene expression. Tularik's scientific platform is focused on three therapeutic

areas: cancer, immunology and metabolic disease. The Company currently has four

drug candidates in clinical trials. In the cancer area, Tularik is currently

conducting a pivotal study of T67 for the treatment of hepatocellular

carcinoma (HCC) and Phase 2 trials with T607 for the treatment of HCC, ovarian

cancer,

gastric cancer and esophageal cancer. T487 for the treatment of psoriasis is

in Phase 2 trials. T487 for the treatment of rheumatoid arthritis, and T131

for the treatment of type 2 diabetes, are moving into Phase 2 trials.

This press release contains " forward-looking " statements. For this purpose,

any statements contained in this press release that are not statements of

historical fact may be deemed to be forward-looking statements. Thanks Micky

from

London

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May each one of you and your families have a great holiday season.

Good Health to all,

Jack

Newsletter Editor

Cornishpro@...

Issue 2003 12/15/03-22