This CT scan shows the "honeycomb"
pattern of scarring in the lungs of a patient with idiopathic pulmonary
fibrosis, a progressive disease with few good treatment options. A new study
has found that a three-drug combination used worldwide to treat IPF is in fact
associated with a high risk of death and hospitalization than placebo. Credit:
University of Michigan Health System
A combination of three drugs used worldwide
as the standard of care for a serious lung disease puts patients in danger of
death or hospitalization, and should not be used together to treat the disease,
called idiopathic pulmonary fibrosis, according to the surprising results of a
rigorous independent study.
The
study, which will appear online May 20 in the New
England Journal of Medicine to coincide with a presentation at the
annual meeting of the American
Thoracic Society, was conducted by IPF Clinical Research Network, funded by
the National Heart, Lung, and Blood Institute of the National Institutes of
Health.
"The
findings show the importance of testing even those treatments that doctors give
routinely for any type of condition -- to see if they truly help, and don't
harm, patients," says University of Michigan Health System lung specialist
Fernando Martinez, M.D., who will present the results.
Martinez
and his colleagues report that patients in the mild to moderate stages of the
progressive lung-scarring disease had a far higher chance of dying or being
hospitalized if they were taking a three-drug combination used worldwide,
compared with those taking a placebo.
What's
more, the three-drug combo yielded no improvement in lung function, or even
slowing of loss of lung function, compared with placebo. Results from a group
taking the single drug, N-acetylcysteine (NAC), are still being gathered and
analyzed.
This
evidence is from a randomized, placebo-controlled, double-blind, federally
funded trial that included patients with a definitive diagnosis of
IPF who were treated at 25 centers taking part in the IPF Clinical Research
Network or IPFNet. The study was stopped early when an interim analysis showed
signs of harm from the three-drug combination of prednisone, azathioprine and
NAC.
The
findings should cause physicians worldwide to stop using this combination to
treat IPF patients similar to those in the trial, say the authors.
And,
the dramatic finding of harm from a standard treatment should cause physicians
to apply rigorous testing methods to other types of treatment, and highlights
the importance of independent federal funding for such studies, says Martinez.
The
authors salute the volunteer IPF patients who agreed to be randomly assigned to
a treatment or placebo for 60 weeks.
Martinez,
an internationally known IPF researcher and clinician in the U-M Medical
School's Division of Pulmonary Medicine, remarks that results will soon be
known for the group taking NAC alone, compared with those taking placebo. The
current paper and presentation do not include results from this group.
In the
results presented this week, the authors report that eight patients in the
group of 77 assigned to the three-drug combination died, compared with one in
the placebo group. A total of 23 of the three-drug patients were hospitalized
during the trial, compared with 7 in the placebo group. There was no sign that
the three-drug combination slowed the progression of IPF or improved lung
function, as measured by forced vital capacity.
The
study is called PANTHER-IPF, for Prednisone, Azathioprine, and
N-Acetylcysteine: a Study That Evaluates Response in Idiopathic Pulmonary Fibrosis.
Except for a donation of NAC and a matched placebo by the company that makes
the drug, there was no industry support for the work.
IPF,
which affects nearly 100,000 Americans, slowly steals the ability to breathe
freely. Its cause or causes are not clear, which is why it is called
"idiopathic." Over time it leads to the buildup of scar tissue in the
lungs that accumulates in a distinctive honeycomb pattern that can be seen on
biopsy or CT scan.
It is
known as an interstitial lung disease because
it affects the tissue around the air sacs in the lungs.
IPF
patients live an average of five years after diagnosis, though a lung
transplant at a center such as U-M's Transplant Center can extend life for
years beyond. Most patients are
over the age of 65 when diagnosed, but IPF can strike younger people as well.
Because lung transplants are such a
dramatic and rarely available therapy, researchers at U-M and other centers are
working to find new treatments while also studying the underlying biological
factors in the disease. The PANTHER-IPF trial was designed to test a standard
therapy in a rigorous way.
Provided
by University
of Michigan Health System
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