The Latest News in Rheumatology
12/5/2002
Dangers of Methotrexate Overdose
Inflammatory
Joint Manifestations are Prevalent in Psoriasis: Prevalence Study of Joint and
Axial Involvement in Psoriatic Patients, and Evaluation of a Psoriatic and
Arthritic Questionnaire
The Use of
Infliximab in Academic Rheumatology Practice: An Audit of Early Clinical
Experience
Misleading Pharmaceutical Drug
Ads Persist
Study Suggests Replacing Joints
Earlier
New York (Reuters Health) -- The Institute of Safe Medication Practices (ISMP)
warned clinicians to take special care prescribing or administering oral
methotrexate to guard against accidental overdose in light of two tragic
methotrexate mix-ups in the last month.
Methotrexate is typically given in low weekly or twice-a-week doses for
treating conditions like spondylitis, but it is also given in much higher daily
doses for fighting cancer. Some patients are accidentally receiving the drug
daily when they were intended to only receive it once a week. A mix-up could
result in disability or even death, particularly in elderly patients. Recently,
a 79-year-old patient died after receiving nine doses of 15mg methotrexate daily
instead of weekly.
ISMP has been warning the medical community for years about the potential for
errors with oral methotrexate. They caution that "because of the number of
fatalities...clinicians should consider it a higher alert medication regardless
of the indication."
ISMP recommends tips for doctors to ensure that they are prescribing the correct
dosage, but patients should also make sure they are receiving the medication
treatment appropriate for their condition. When receiving the initial
prescription, confirm the dosage with the doctor, ask a pharmacist to explain
the dangers of extra methotrexate doses, and make sure that correct dosage
patterns are followed.
"We're very concerned...and it isn't just methotrexate," said ISMP
President Michael Cohen. "The doctors and pharmacists are just so used to
one tablet daily. If they're not really focusing on what they're doing, they do
it almost automatically."
Researchers sought to examine the prevalence of inflammatory arthritis in
people with psoriasis since previous studies place the amount of psoriatic
patients with arthritis anywhere between 7 and 40%.
Gerd-Marie Alenius and colleagues from the University Hospital in Umea, Sweden
published their findings in a recent issue of The Journal of
Rheumatology.
Results: 202 psoriatic patients from the County of Vasterbotten,
Sweden, participated in clinical examinations, testing, and a questionnaire. The
researchers also wanted to evaluate a population who did not know whether they had an arthritic disease, so
patients with known arthritic disease were excluded from the questionnaire
section of the study.
They found a high prevalence of inflammatory joint/axial disease
as well as non-inflammatory joint involvement in this group of psoriatic
patients, although almost half of the patients with peripheral arthritis and/or
axial disease had not previously been diagnosed. Only about 40% of the psoriatic
patients could be classified as healthy based on the absence of joint/back
pain.
Of the undiagnosed patients with peripheral arthritis, 71% had active disease
and almost half had radiologically detectable erosive and/or deforming disease.
This suggests that many patients are not diagnosed at an appropriate time, so
they are not getting sufficient treatment for their joint disease.
While Infliximab (Remicade®) is seen as a major advance by many for patients
with severe arthritic disease, there is not much reported experience in actual
clinical practice as opposed to the setting of a clinical research trial.
Researchers Mary-Ann Fitzcharles and colleagues from McGill University, Ontreal,
Quebec, Canada published their findings in a recent issue of The Journal of
Rheumatology.
Results: Forty-one people took part in the study, most of whom had rheumatoid arthritis, although 20% had a
spondyloarthopathy. They observed the following:
- Impressive clinical response in almost all of
the patients continuing treatment--about 96% improved "moderately to
greatly".
- More than half of the patients needed to
adjust their dosage at some point during the study.
- 15% of the patients encountered severe side effects directly related to
the treatment. Such side effects included acute anaphylactoid-like
reactions, vasculitis, and histoplasmosis.
- Less severe side effects that did not preclude continuation of treatment
but frequently required medical intervention were noted in 93%. The most
commonly reported minor side effects were upper respiratory tract symptoms,
mild rash, and itching.
The researchers conclude that much is still unknown about the long-term
consequences of continued infliximab treatment. They found the rate of adverse
side effects to be very high, many of which required immediate medical
intervention. Two patients even had anaphylactoid-like reactions as late as the
fifth and eighth infusions, suggesting that patients may gradually develop a
sensitivity to the non-human component of infliximab.
They agree that infliximab "should be administered under the supervision
and monitoring of physicians experienced in the diagnosis and treatment"
with full resuscitation facilities available in the event of acute reaction.
Adjustments to dosage and scheduling treatments were made at the time of the
infusion, which they think is essential in providing the best close follow-up
medical care.
According to a new government report, pharmaceutical companies are continuing
to deliver misleading drug ads to consumers. Officials place the blame on delays
in the FDA's review process, and repeated violations by some drug companies.
The amount spent on consumer advertising of prescription medicines has
tripled in recent years, and prescription drug spending is the fastest growing
component of healthcare spending, as mentioned in the recent report by the U.S.
General Accounting Office (GAO).
The FDA requires pharmaceutical companies to submit all drug ads when the ads are first
released to the public. If the FDA finds the ad to be misleading or it if fails
to represent both the benefits and risks of the medication, the FDA will issue a
regulatory letter requesting that the company either withdraw or revise the ad.
A warning letter may be issued for more serious violations.
Between August 1997 and August 2002, the FDA issued 88 regulatory letters and
four warning letters for pharmaceutical ads that violated its standards. The FDA says that the companies stop the misleading advertisements, but
the GAO report shows that a letter from the FDA is not always enough to make the
pharmaceutical companies change their ways.
For example, between 1997 and 2002, the FDA issued 14 regulatory letters to
GlaxoSmithKline, 6 to Schering Coporation, 5 to Merck, and 4 to Pfizer.
Some companies even received multiple letters for new ads with misleading
claims about the same drug, such as in a situation involving Glaxo Wellcome from
1999 and 2000 for the allergy drug Flonase, and another involving Pfizer's
cholesterol-lowering drug Lipitor.
Researchers also found that a recent change in the review process has significantly
increased the time between the FDA's identification of a misleading ad and a
letter to the company. Some regulatory letters may not even be issued until
after the ad campaign has run its course. The change was implemented in January
2002 by the Bush administration to require lawyers at the Department of Health
and Human Services (HHS) to review the letters before they can be issued. The
HHS plans to speed up this process to reduce the number of days letters are
under review.
While Bruce Kuhlik (general counsel for the Pharmaceutical Research and Manufacturers
of America) agrees with the GAO's findings that the review process needs to move
more quickly, he says that the drug ads are already subject to the most
stringent regulatory processes as compared to other types of advertising.
"Out of the hundreds and hundreds of ads under review, the FDA has only
issued a small number of letters and only four of the more serious warning
letters," says Kuhlik. "And companies have uniformly complied in
response to those letters."
Other findings from the GAO reports:
- In 2001, pharmaceutical companies spent $30.3 billion on research and
development, and $19.1 billion on promotional activities (including $2.7
billion on advertising)
- From 1997 to 2001, ad spending grew by 145%; research and development
increased by only 59%
- The bulk of the rise in prescription drug spending is due to more people
using the medications, not necessarily price increases.
- Prescription drug use has grown at an average rate of 6% a year since
1992, thanks to an aging population, more effective medications, and
increased insurance coverage for medications.
- Between 1999 and 2000, the number of prescriptions written for the most
heavily advertised drugs grew by 25%; drugs that were not heavily advertised
only increased by 4%.
Patients fare best when they undergo joint replacement surgery for knees and
damaged hips in the early stages of osteoarthritis, as concluded in a recent
study published in the December issue of Arthritis & Rheumatism. This
type of surgery is usually reserved as a last-ditch effort for people with the
most pain and least movement, but research shows that getting the operation
before it's "needed" may actually yield longer-lasting benefits.
Jeffrey N. Katz, MD of Harvard School, explains that physicians are
traditionally taught to hold back and wait before replacing a joint--it is
viewed as the "last resort". But he and other colleagues found that
the longer a person waits, the more disabled he/she becomes, and the surgery
outcome is worse. "They don't catch up in their ease of movement and
quality of life compared to their counterparts who were operated on at an
earlier stage."
Results: 165 people with osteoarthritis bad enough to need joint
replacement surgery were divided into two groups prior to surgery: those able to
go about their day and those unable to maintain their normal lives due to
arthritis pain.
All enjoyed similar relief in the first six months after surgery, but after
two years, those with low functioning prior to surgery were five times more
likely to need assistance moving around.
Dr. Katz says, "If you wait until you have trouble with basic activities
like moving room-to-room, your outcome may be worse than if you get your joint
replaced when you begin to notice trouble moving in recreational activities or
moving about the community."
According to the American Academy of Orthopaedic Surgeons, hip and knee
replacements are highly popular and successful procedures that bring relief to
more than 90% of the 435,000 American who receive them each year.
Dr. Katz believes that part of the reason for surgery delays is
because of misinformation on the risks and benefits of the procedure. There is a
1% or less death rate for joint-replacement surgeries, which is very good, but
causes some people to take pause.