Just How Safe are the New Once-Daily Arthritis Drugs?

              SHREVEPORT JOURNAL Tuesday PM YOU* Health SHREVEPORT-BOSSIER CITY, LA., ,
This human hand exhibits the signs of advanced rheumatoid arthritis.
The most noticeable characteristic of the disease is the almost total
dislocation of the joints resulting in the outward turn of the fingers. The
destruction of cartilage has led to narrowing of the joint spaces, a pain-producing
condition. In addition, this hand shows signs of secondary
degenerative disease (osteoarthritis) especially in the thumb (A) where
an osteophyle, or calcified protrusion, has developed.
Just how safe arc the new
once-daily arthritis drugs?
By DONNA O'NEAL
Journal Medical Writer
Two new arthritis drugs hit the market
recently to offer patients a new concept in
arthritis medication — a once-a-day
dosage.
The once-daily dosage is said to be more
convenient and likely to improve dosage
compliance by arthritis patients — whose
medication traditionally has been in mul-tiple
daily dosages.
But one of the new non-steroidal, anti-inflammatory
drugs (NSAID) — Oraflex —
is under scrutiny by a consumer group that
has asked the U.S. government to ban the
drug after 12 deaths allegedly were linked
to it in Great Britain.
And reports of liver or stomach
maladies supposedly linked to NSAIDs
have surfaced in the United States —
including the Shreveport area.
This recent controversy brings to light
the possible harmful side effects of all the
NSAIDs and raises a legitimate question
for arthritis sufferers taking these drugs:
just how safe are they?
The controversy comes amid an in-vestigation
into the NSAIDs by the FDA,
which has said it simply doesn't have
enough evidence against Oraflex to pull it
off the market.
"We don't have enough evidence to real-ly
tie it (Oraflex) down" as to causing the
deaths in Britain, said Ed Nida, FDA
spokesman.
"We are still concerned about liver prob-lems
with the entire class of (NSAID)
drugs," he added. "And that issue is not
resolved yet."
Nida said the FDA has had no reports of
deaths in the United States stemming from
the use of any NSAID. But, he said, NSAIDs
"are known to cause liver damage."
However, Dr. Ian Sheddes of Eli Lilly
and Co., the manufacturer of Oraflex, said
last week there have been two cases in this
country in which elderly patients who both
had been taking Oraflex died. It was not
known if those deaths could be linked to the
drug, he said.
But Wednesday, Lilly announced — with
FDA approval — that elderly patients
should not receive full doses of the drug
because of the reports linking Oraflex to
death by liver and kidney failure in Great
Britain. The company recommended for
the elderly only one-half to two-thirds of
the usual 600 milligram daily dosage.
John Purcell, spokesman for Lilly, said ••
there have been reported cases of liver
toxicity in the United States by persons
using NSAIDs.
Dr. Robert Wolf, associate professor of
medicine and chief of the section of
rheumatology for LSU School of Medicine
in Shreveport, said he recently has treated
patients who developed stomach ulcers —
in one case, a bleeding ulcer — after taking
the NSAIDs.
Whether or not these deaths and dis-orders
specifically can be linked to the
NSAIDs, however, is a question yet to be
answered.
The consumer group asking for the ban,
the Public Citizens' Health Research
Group, was founded by long-time con-sumer
activist Ralph Nader. On June 17, it
asked Health and Human Services Secre-tary
Richard Schweiker to ban sales of
Oralflex because of reports in the British
Medical Journal allegedly linking the
drug to 12 deaths due to liver or kidney
injuries.
But Nida said his information is that of
the 12 cases, nine patients died while three
recovered. Of the nine, only seven deaths
could be traced to the drug, but it is not
certain that Oraflex — which has been in
use in Britain since 1980 — specifically
caused the deaths.
The patients who died reportedly were
elderly, were taking the maximum dosage
of the drug and had had previous problems
with kidney disfunction.
Oraflex — and other NSAIDs such as
Feldene, Clinoril, Naprosyn, Motrin,
Rufen, Nalfon, Tolectin and Meclomen —
are eliminated from the body through
either the kidneys or the liver. Improper
functioning of these organs could cause
toxic buildup of the drug, Wolf said.
Eli Lilly and Co. dismisses the consumer
group's charges against Oraflex as "sensa-tional"
and "irresponsible." They point out
that NSAIDs are used by millions of people
with little or no ill effects.
The other new drug, Feldene, is manu-factured
by Pfizer. The Health Research
Group has not challenged it, nor has the
FDA received any negative reports about
it, Nida said. Both Feldene and Oraflex
were approved for the United States drug
market on April 19.
Journal Photo by Louis DeLuca
Dr. Robert Wolf
However, both the new drugs' manufac-turers
admit that side effects ranging from
gastrointestinal disorders to liver and
kidney prdblems to photosetisitivity of the
skin are possible with the new medications.
But such side effects have been found
with most, if not all, of the NSAID arthritis
drugs, LSU Med School physician Wolf
said.
The once-daily dosage concept Oraflex
and Feldene offer is a "breakthrough" for
patients who previously have been faced
with taking multiple arthritic medication
dosages (including aspirin) — anywhere
from two to 20 daily doses — for relief
from pain.
The new drugs' manufacturers, along
with local doctors and pharmacists, say the
once-a-day dosage is more convenient and
likely will improve patient compliance of
taking recommended daily dosages — a
familiar problem in the medical field.
But the admitted side effects of these
new drugs — along with older NSAIDs,
which first appeared on the market in 1965
— raises the question as to their safety.
Wolf said that "all drugs have potential
side effects. Severe reactions and deaths
have occurred in patients with the vast
majority of (all kinds of) drugs. Weighing
the potential risk with the potential benefit
is what the physician has to do with any
drug, including the NSAIDs."
But, he added, arthritis patients have a
legitimate reason to question the safety of
such drugs when controversy such as that
surrounding Oraflex arises. And for
arthritis patients over the age of 70, "some
considerations need to be made about
Oraflex therapy," Wolf said, since reported
ill effects with the drug seem to be cor-related
to the age of the patient.
Arthritis afflicts some 31 million Ameri-cans
— one out of every seven people — of
all age groups, making it the nation's
number one crippling disease. To the 31
million are added one million more
arthritis victims each year.
It's an often-degenerative disease of the
joints and connective tissues that's costing
Americans some $14 billion annually in
medical bills, lost wages or other costs. So
far, doctors are mystified as to both its
cause and its cure; they can only treat the
pain and inflammation of the disease.
The most common forms of arthritis are
osteoarthritis and rheumatoid arthritis.
Osteoarthritis, also called a degenerative
joint disease, is primarily a wear-and-tear
disease of the weight-bearing joints that
comes with old age. Usually the disorder is
mild and not generally inflammatory. But
pain can be intense.
Rheumatoid arthritis is less common. An
inflammatory disease, it is very painful
and can lead to permanent disability. Al-though
it primarily attacks the joints, it
can also cause disease in the lungs, skin,
muscles and heart. The unpredictable dis-ease
tends to subside and then flare up
suddenly, often causing progressive dam-age
to tissues. Rheumatoid arthritis is a
much more commonly disfiguring disease
than osteoarthritis.
Drug treatment of both these forms of
arthritis is aimed at reducing the pain and
inflammation or otherwise slowing and
controlling the symptoms. Such anti-arthritic
agents used to treat the disease
range from aspirin to NSAIDs to steroids
to even a diverse group of drugs such as
penicillamine and gold salts.
One complication of steroids such as
cortisone, however, is they can cause
cataracts and thinning of bones, Wolf said.
The NSAIDs don't cause such problems,
but they have side effects of their own — as
does aspirin taken in large dosages.
Wolf said both the new NSAIDs, Oraflex
and Feldene, treat osteoarthritis and
rheumatoid arthritis by being metabolized
in the bloodstream more slowly than other
NSAIDs on the market — hence the once-a-day
dosage.
Both drugs, like most NSAIDs, help
block the synthesis of a body product of
inflammation called prostaglandins, Wolf
said. Oraflex, although a little weaker in
inhibiting the production of prostaglan-dins,
also blocks the production of a dif-ferent
mediator of inflammation called
leukotrienes, he said.
Both prostaglandins and leukotrienes al-low
the production of fluid and more
inflammation in the joints, thus causing
arthritic pain, he said.
Neither drug appears to be significantly
more helpful in treating arthritis than the
other drug — or than other NSAIDs, Wolf
noted. "Some people will be helped by
these (new) medications who will not be
helped by any of the others." But some
won't, he said.
The same is true for side effects. "There
is not any one that has drastically fewer
side effects," he said.
Side effects of NSAIDs include gastroin-testinal
disorders, occurring in about 20
percent of patients in laboratory tests;
ulceration or bleeding of the stomach lin-ing,
occurring in less than 1 percent of
patients in lab tests; photosensitivity, in
which the patient feels a temporary burn-ing
or itching sensation on the skin after
prolonged exposure to sunlight.
Purcell, Wolf, Nida with the FDA and
Ray O'Rourke, spokesman for Pfizer, all
agree that the NSAIDs are generally safe.
"In general, they're far safer than the
cortisone-like (steroids) drugs," Nida said.
Wolf called the drugs "in general... very
safe." O'Rourke said gastrointestinal side
effects caused by taking Feldene for
arthritis actually were 10 to 20 percent
lower than those caused by taking aspirin.
Purcell said his company doesn't believe
"that people who are taking (Oraflex) de-serve
to be alarmed by sensational and
irresponsible accusations." Considering
the large number of people taking the drug
— more than 500,000 in the United King-dom
— the percentage of those experienc-ing
serious side effects is very low, Purcell
said.
Both Purcell and O'Rourke said their
companies will continue to test their new
products. Nida said the FDA has been
studying potential problems with NSAIDs
for nine months and will be working with
British officials to gather all available
data on the alleged Oraflex-related deaths
before making a final decision- on the
drug's future in the U.S. market.
Until then, however, the FDA's Arthritis
Advisory Committee this month has asked
all NSAID manufacturers to include in-formation
warning arthritis patients of the
potential for liver toxicity, Nida said.
But the Public Citizens' Health Research
Group isn't happy with the FDA's decision.
Dr. Eve Bargmann, medical researcher for
the group, said although it's "too soon to
tell" if Oraflex may pose any serious
health problems to arthritis sufferers,
"we'd just as soon it be withdrawn before
that's found out."
She also criticized the Health and Hu-man
Services Secretary Richard
Schweiker's proposal last week for speed-ups
in the drug approval process that he
claimed would reduce paperwork as much
as 70 percent.
Bargmann is worried such changes
would lead to greater risks for consumers
from harmful and insufficiently tested
drugs. "When you set time limits," she said,
"you run the risk of compromising safety."
She added she thinks aspirin should be "a
drug of first choice" for arthritis victims.
"It's as effective (as NSAIDs) and has been
around far longer," she said.
But Wolf said .aspirin taken in large
doses of 10 to 20 daily — common for most
arthritis victims — has problems of its
own, including liver disorders. "Most of the
(anti-arthritic) drugs can cause liver prob-lems,"
he said. "In essence, if a person is
overdosed, then liver problems can oc-cur
... That is a toxic reaction."
However, he added, liver problems with
anti-arthritic drugs are rare. "There is no
need to be overly concerned about serious
side effects," Wolf said. But, he added,
"Until more information is fully available
on some of these problems with Oraflex, I
think there needs to be some degree of
caution in using Oraflex, particularly with
elderly people."
Meanwhile, the FDA office in
Shreveport has received no local com-plaints
on the new drugs, which seem to be
selling well in this area, according to local
pharmacists.
Although Oraflex and Feldene are more
expensive than other NSAIDs on the mar-ket
— $1 to $1.50 per pill — the reduced
dosage makes them comparable in price to
the others, pharmacists say.
Most of the pharmacists reported that
comments from purchasers on the two new
drugs' effectiveness have been mixed, but
mainly favorable. Some buyers also have
reported experiencing side effects such as
photosensitivity — for which doctors are
prescribing a sunscreen.
"Everyone is grasping at straws with
arthritis," a pharmacist with Medic Phar-macy
said. "They have heard there's no
cure, but they're just hoping there's some-thing
better."
B