Lumiracoxib, the newest medicine
for the control of arthritis pain, has just made its
entrance on Canadian pharmacists' shelves. Initially
approved for osteoarthritis of the knee, it will soon
be offered for hip pain too.
Beyond that, lumiracoxib is likely
to become a popular anti-inflammatory for all sorts
of bone-related pain relief. But it first had to live
down its name. Any drug ending in the suffix -coxib
has raised alarms since the first wave of Cox-2 inhibitors
began to lose their lustre in a welter of recrimination
over unexpected cardiovascular events.
TAKE
THREE
When Cox-2 inhibitors first came onto the market, they
didn't promise extra efficacy but a reduced risk of
gastrointestinal (GI) bleeding. Unfortunately, the trials
that backed that safety claim failed to pick up an increase
in blood pressure in a small subset of patients. The
increase meant extra heart attacks, a trade-off that
went largely unnoticed until the drugs had been on the
market for years.
Lumiracoxib is the first in a third
wave of anti-inflammatories, designed to fix the problems
of the second. It retains the safer gastrointestinal
profile, but also promises not to cause more cardiovascular
events than traditional anti-inflammatories like naproxen
and ibuprofen.
SAFETY
IN NUMBERS
Dr John Wade, a rheumatologist at the University of
British Columbia, is optimistic about the drug's safety
profile — with qualifiers. "The TARGET trial, which
tested both GI and cardiovascular safety, used a 400mg
dose of lumiracoxib which is four times higher than
the approved dose, so there's reason to hope that the
actual safety will be somewhat better than demonstrated
in the trial," he says.
The data showed a very slight but
nonsignificant increase in cardiovascular risk over
naproxen, but not over other NSAIDs. "I think there
are definitely fewer grounds for concern about cardiovascular
issues than with other Cox inhibitors," Dr Wade says.
On the GI front, lumiracoxib does
as well as other Cox inhibitors, which is very well.
"Before Cox-2 drugs came along, 1-2% of osteoarthritis
patients on NSAIDs would suffer GI bleeds every year.
These drugs have largely lived up to their promise of
dramatically cutting those numbers," says Dr Wade.
In the TARGET trial, patients taking
lumiracoxib had 79% fewer gastrointestinal ulcers than
those taking ibuprofen or naproxen. Over 18,000 patients
participated in this study, and a further 16,000 in
efficacy trials — marking it in the history books
as the largest pre-launch trial of an anti-inflammatory.
But Dr Wade insists physicians
take heed: anyone giving this drug should carefully
monitor blood pressure at the outset, he says. Health
Canada isn't taking any chances either: Lumiracoxib's
manufacturer, Novartis, must conduct a post-marketing
study of 10,000 patients on the drug, as well as another
10,000 patients on older NSAIDs and provide regular
updates to the regulatory body as a condition of their
approval.
REAL
EXPECTATIONS
Physicians will undoubtedly welcome the addition to
their range of treatment options. In spite of the onslaught
of information and marketing that's sure to come, Dr
Wade warns it's important not to set your sights too
high.
"I wouldn't say that any of these
new drugs are more effective painkillers than traditional
NSAIDs," he says. "Once you've turned off inflammation,
you've gone about as far as you can go down that road.
What's new is doing it without a high burden of adverse
events."
It's always possible, of course,
that a new drug will achieve results in a patient who
hasn't responded to other drugs in the same class. Dr
Wade doesn't exactly rule this out, but he doesn't sound
entirely convinced either. "There may be subpopulations
who are more responsive to one coxib than to another.
It's always worth trying different drugs when one fails."
According to the recent Canadian
Consensus Conference on evidence-based prescribing of
NSAIDs, one-third of Canadian osteoarthritis patients
aren't getting adequate pain relief.
|
