LA Times article today:
Thursday, December 17, 1998
New Drugs Attack Pain of Arthritis
For those with rheumatoid form of the disease, suffering can
be extreme. But four treatments, each targeting a different
stage of the illness, are revolutionizing research.
By THOMAS H. MAUGH II, Times Medical Writer
ADVERTISEMENT
llene Goodman can remember the precise day her
arthritis began taking control of her life.
On Aug. 3, 1987, Goodman, a medical
transcriptionist, began to shiver uncontrollably, unable
to warm her hands and feet. Then her feet began to
swell. A trip to the nearest rheumatologist, 158 miles
from her home in Caledonia, Miss., confirmed that she
suffered from rheumatoid arthritis, and that day marked
the beginning of a steady acceleration of her disease.
The worst part, she recalls, was the pain. "No one
but God can understand the horror of what I
experienced for several years," she said. "My
nightmares were present awake and asleep. I dreamed
that my joints were being pulled apart by torturers and
screamed aloud, awakening to find my joints . . .
locked."
But Goodman, 68, has found relief during clinical
trials of a new drug called Enbrel, approved by the U.S.
Food and Drug Administration last month.
It is one of four new types of drugs that are
changing the face of arthritis research. Each of the four
attacks the disease at a different stage of its
progression, and most do not produce the side effects
associated with conventional therapy.
None of the new approaches represents a cure, and
most are substantially more expensive than existing
treatments. But they offer relief for people in desperate
need of it.
"This is about as exciting a time as we have ever
had in rheumatology," said Dr. Michael Weinblatt of
Brigham and Womens Hospital in Boston.
"This is a tremendous time," added Dr. Brian
Butcher of the Arthritis Foundation. "We have gone
from where we could not offer much hope to people to
where we can diagnose, provide early treatment, and
stop the progression of the disease."
The new drugs primarily will benefit the 2.1 million
Americans who suffer from rheumatoid arthritis, but
also may help some of the 37 million who have
osteoarthritis.
Osteoarthritis is caused by the general wear and tear
of aging. In rheumatoid arthritis--a more serious form
of the disease--the patient's immune system goes awry,
attacking the joints and causing inflammation and
stiffness. Cartilage is destroyed, and joints often freeze,
preventing patients from carrying out such routine tasks
as getting out of bed or washing their hair. An estimated
40% of rheumatoid arthritis patients are unable to hold
a job six years after diagnosis.
Existing drugs can be effective against arthritis but
carry bothersome side effects. Most arthritis patients
take so-called non-steroidal anti-inflammatory drugs, or
NSAIDs, such as aspirin, acetaminophen and
ibuprofen. NSAIDs reduce pain, fever and
inflammation by blocking the production of
prostaglandins, chemicals that mediate pain. But they
can cause stomach irritation, bleeding ulcers and
decreased kidney function.
About 13 million Americans take these NSAIDs
regularly, but an estimated 76,000 of them are
hospitalized every year for ulcers produced by the
drugs and 7,600 die from them.
Patients with more severe forms of arthritis take
steroids, which are better at reducing inflammation but
cause more severe side effects, such as high blood
pressure, weight gain, diabetes, bone loss, mood
changes and susceptibility to infection.
The third class of drugs are the so-called disease
modifying anti-rheumatic drugs, which interfere with the
proliferation of white blood cells that mediate the
immune attack. These drugs, such as methotrexate,
gold salts and imuran, typically lessen symptoms rather
than eliminate them.
* * *
Perhaps the most promising of the new drugs are
the so-called COX-2 inhibitors, which are expected to
treat a variety of diseases beyond arthritis, such as
angina pectoris and Alzheimer's disease. Like NSAIDs,
these so-called super-aspirins ease pain and
inflammation by blocking the release of prostaglandins,
but they are more selective in their action.
Dr. Harvey R. Herschman of UCLA and
researchers at Brigham Young University and the
University of Rochester discovered that aspirin and
other NSAIDs block the action of two enzymes,
cyclooxygenase-1 and cyclooxygenase-2. Blocking
COX-2 inhibits the production of prostaglandins, but
blocking COX-1 inhibits an enzyme that protects the
kidneys and the lining of the stomach.
Drug companies seized on this discovery, designing
drugs that inhibit COX-2 but leave COX-1 largely
untouched. Clinical trials showed that these
drugs--Celebrex, developed by Searle, and Vioxx,
developed by Merck & Co.--are as effective as
NSAIDs at relieving pain, but have far fewer side
effects.
"It's an advance in safety, not an advance in
effectiveness," said Dr. David Fox of the University of
Michigan.
An FDA advisory committee recommended this
month that Celebrex be approved, and Vioxx is
expected to be submitted to the panel in the next six
months. Celebrex is taken orally twice a day, Vioxx
once, and they are expected to cost $2 to $4 per day.
The Enbrel that patient Goodman takes binds to a
naturally occurring chemical called tumor necrosis
factor. The factor is released by white blood cells as
they multiply to attack joints, and it stimulates the
production of more white cells, escalating the arthritic
process.
Trials in more than 1,000 patients showed that
Enbrel reduced pain and swelling in 62% of patients,
usually within the first two weeks of treatment. Side
effects were rare, primarily mild reactions at the
injection site.
Enbrel, marketed by Wyeth-Ayerst, is taken by
injection twice weekly and is expected to cost as much
as $10,000 per year. Centocor has a similar drug, called
Remicade, that is already approved for treating Crohn's
disease and may soon be approved for arthritis. Other
drugs are in earlier stages of development.
* * *
The third new drug is Arava, which blocks the
proliferation of immune cells that attack the joints.
Clinical trials showed that Arava, manufactured by
Hoechst Marion Roussel, is as effective as
methotrexate at reducing pain and inflammation and
slowing the progression of the disease, but has fewer
side effects such as diarrhea and rashes.
Arava has been approved by the FDA and is taken
orally once a day. It costs about $240 per month.
The final new treatment is expected to be reserved
for the most severe 10% of rheumatoid arthritis
patients. The Prosorba column, a device manufactured
by Cypress Bioscience Inc. of San Diego, is targeted at
antibodies that attack the joints.
The device works something like a dialysis machine.
Once a week, the patient comes in and blood is drawn
out through one arm. Blood cells are separated out and
the remaining plasma is circulated through a device that
removes the antibodies. The plasma and blood cells are
then reunited and infused back into the patient.
Clinical trials showed that 12 weeks of such
treatments allowed patients--all of whom were severely
ill at the beginning--to go without drugs for as long as
75 weeks, according to Dr. Jay Kranzler, Cypress
president. The clinical trial was halted a year early
because the results were so good, he said.
Prosorba was approved by an FDA advisory
committee in October. Final approval is expected soon.
As for Allene Goodman, she is feeling much better
these days. She still has pain, but has been able to
resume many daily activities, such as brushing her teeth
and ironing her husband's clothes. She is even able to
begin writing stories about her early life for her
grandchildren so that they will know what the
Depression was like.
"What I want so badly," she added, "is future
research. They need to develop a sequel to Engrel or
modify it so the next generation has a cure."
* * *
New Weapons to Fight Arthritis Pain
Rheumatoid arthritis strikes joints, causing pain,
swelling and deformity. Four new treatment attack the
problem in different ways.
The normal course of arthritis
1. Inappropriate signal triggers immune cells to
multiply.
2. The multiplying cells produce tumor necrosis
fac-tor (TNF), which signals for more.
3. The cells also produce prosta-glandins, which
cause pain and swelling in the affected tissues.
4. Antibodies attack tissue at the joint.
New treatments
A) Arava and methotrexate inhibit multiplication of
immune cells.
B) Enbrel binds to and removes TNF.
C) COX-2 inhibitors block binding of
prostaglandins.
D) Prosorba removes antibodies from blood.
* * *
Sources: Arthritis Foundation
Copyright 1998 Los Angeles Times. All Rights Reserved
Search the archives of the Los Angeles Times for similar stories
about:
ARTHRITIS, PAIN, MEDICAL RESEARCH, MEDICAL
TREATMENTS. You will not be charged to look for stories, only to
retrieve one.
|
