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November 2, 2000
ROTTA'S GLUCOSAMINE PREVENTS DAMAGE IN OA
Osteoarthritis is the most prevalent form of arthritis,
affecting approximately 10-12% of the world's
population. As a pharmaceutical market, it is much
larger than rheumatoid arthritis, which afflicts
approximately 1% of the population.
It is more common in the elderly, affecting about 85% of
people aged over 70, and is one of the leading causes of
disability in this group. In the US, OA is conservatively
estimated to account for 46 million physician visits, 3.7
million hospital admissions, 185 million bed days and 68
million work days lost every year.
Often described as "wear and tear", osteoarthritis
involves a complex degeneration of the joints. The
cartilage becomes thin and flaky, and begins to split,
and the bone underneath thickens and starts to
protrude from the edges of the joint, restricting
movement. The joints become swollen, stiff and painful,
and in severe cases, are permanently deformed.
Rotta's glucosamine sulphate has significantly reduced the
progression of osteoarthritis (OA) in a three-year placebo-controlled
study reported at the recent American College of
Rheumatology meeting in Boston. The Italian firm markets
glucosamine sulphate as a prescription product, but the
substance is also widely sold over-the-counter by many
different manufacturers as a "nutraceutical".
"This is the first time that any product has shown a structure
modification effect in osteoarthritis," commented lead
investigator Jean-Yves Reginster, professor of
epidemiology and public health at the University of Liege,
Belgium (and also the Belgian representative at the EMEA).
Noting that glucosamine also had effects on symptoms, he
proposed calling it a disease-modifying agent for OA.
There are no such drugs at present - all existing disease-modifying
agents are for rheumatoid arthritis. Current
treatment of osteoarthritis is
aimed at pain and symptom
relief, and involves
analgesics (NSAIs), and
intra-articular injections of
steroids or hyaluronic acid,
as well as advice on weight
loss and exercise.
. . . significant X-ray
differences
The three-year study
involved 212 patients with
osteoarthritis of the knee,
and X-rays of the affected
joint were taken on
enrolment, after one year
and after three years.
Symptoms were scored
every four months on the
WOMAC index (a composite
of pain, stiffness and
physical function).
The difference between
treated and placebo groups for the three-year X-rays was
significant and remained significant regardless of whether the
data were analysed on an intention-to-treat analysis or on a
per protocol basis (including only patients who completed
the three-year study - 71 on placebo and 68 on
glucosamine). Although no significant difference was seen
between groups in the one year X-rays, there was a trend in
favour of the treated group, Professor Reginster noted.
Placebo-treated patients had an average joint space
narrowing of 0.08-0.1mm/year, while the group taking
glucosamine sulphate 1,500mg once daily saw no significant
joint space narrowing, he said. In addition, there was an
improvement in symptoms, with scores for pain and agility
significantly better in the treated group compared with those
on placebo. In the placebo group, a "slight worsening of the
symptoms was evident at the end of treatment, compared
with the improvement observed after glucosamine".
. . . Rotta markets as medicine
Rotta markets glucosamine sulphate as a prescription
medicine under several different trade names - including
Dona, Viartril and Arthryl - throughout Europe, South
America and Southeast Asia. In many countries, it is the
best-selling prescription product for osteoarthritis,
the company says. It is number one in Germany, where it
was launched in the 1980s, number two in Italy,
and number four in Spain, where it was launched three
years ago (as Xicil). It is the company's best-selling product,
bringing in sales of $49 million last year.
Rotta has further OA studies underway in Europe, including
another three-year pivotal study. The company intends to
apply for approval of glucosamine in other markets
worldwide, including the US, and will license it out in
countries where it has only a small presence. Rotta
emphasises that its product is a "chemically well defined
and pure substance", and should be clearly differentiated
from other products which are undefined macromolecular
derivatives or extracts from animal cartilage.
. . . many nutraceuticals
Glucosamine is also widely available as a "nutraceutical", sold
over-the-counter in health shops and pharmacies, both alone
and in combination with chondroitin. Many of the products
available in the US contain
glucosamine hydrochloride,
which differs from the
sulphate form in bioavailability
and recommended doses.
Glucosamine is an amino
sugar precursor to
glycosaminoglycans, which
are large polysaccharides
found in articular cartilage.
Chondroitin sulphate is the
most abundant
glycosaminoglycan found in
articular cartilage (the other
is hyaluronic acid). Although
their mechanisms of actions
are not well understood,
glucosamine is thought to
increase the production of
glycosaminoglycans and
related substances that make
up the collagen matrix in
cartilage, while chondroitin is
believed to inhibit enzymes that degrade cartilage.
These products have become increasingly popular with
patients in recent years. This has led both to criticism
from medical circles over "hype" which suggests a "cure"
for arthritis, and accusations from the other side that
medics are ignoring a "rational and safe therapeutic
strategy" because it is not a patentable drug. But the
growing interest from patients, and those supplying them
with the products, has forced the medical community to
sit up and take note. In the US, so many OA patients are
taking these supplements that recruitment to placebo
groups in clinical trials is proving difficult, one
investigator commented.
Last year in the US, the National Center for Complementary
and Alternative Medicine (part of the NIH), convened a group
of experts, including representatives from the FDA, who
declared that "there is a real and urgent public health need
to test these agents in a rigorous way". As a result, a large
NIH-funded study is planned. The first US multicentre study
of glucosamine and chondroitin sulphate in knee
osteoarthritis will be a Phase III study which will last four
years, involving more than 1,000 patients to test for efficacy,
safety and side-effects. The $6.6 million research contract
was awarded in September to the University of Utah School
of Medicine.
Zosia Chustecka
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