Ironjustic
Wed, May-21-08, 17:16
"Increase in desferrioxamine-chelatable iron levels"
Public release date: 20-May-2008 Contact: Keely Savoie
ksavoie@thoracic.org 212-315-8620 American Thoracic Society
New treatment gives hope for pulmonary fibrosis patients ATS
2008, TORONTO=E2=80=94Patients with idiopathic pulmonary
fibrosis (IPF) may have a new treatment option, according to
researchers in Japan.
In a Phase III, double-blind, placebo-controlled clinical
trial, the investigators discovered that a daily dose of
pirfenidone could slow the progression of IPF, reducing the
loss of lung capacity. The results will be announced at the
American Thoracic Society=E2=80=99s 2008 International
Conference in Toronto on Tuesday, May 20.
=E2=80=9CThe most common treatment for IPF is
anti-inflammatory agents such = as steroids,=E2=80=9D said
lead researcher Takashi Ogura, M.D., of Kanagawa
Cardiovascular and Respiratory Center in Yokohama, Japan.
=E2=80=9CHowever o= ur study confirmed that pirfenidone, the
main action of which is thought to be antifibrotic, achieved a
therapeutic effect on IPF. I expect that our study will serve
as a guide to develop a new therapy for IPF in the
future.=E2=80=9D
The researchers recruited a total of 275 Japanese patients
with mild to moderate IPF and randomized them to a high dose
pirfenidone (1,800
mg/day) group, a low dose pirfenidone group (1,200 mg/day) and
a placebo group. They measured lung capacity (vital
capacity or VC) and progression-free survival, defined as a
period without death or a greater than 10 percent decrease
in VC, to determine the effectiveness of the regimens.
At the end of one year, they found that patients who had
been randomized to the high dose regimen had significantly
lower loss of VC than the placebo group. Furthermore,
pirfenidone slowed the overall deterioration of IPF compared
to the placebo.
=E2=80=9CTaken altogether, our study demonstrated positive
clinical effects = of pirfenidone that suppresses the progress
of IPF and potentially contributes to improving the outcomes
of patients with IPF,=E2=80=9D said Dr= . Ogura.
Pirfenidone represents new hope, not only for IPF patients
who currently have no curative treatment options, but
because it is thought to be an antifibrotic agent, it may be
able to treat other fibrotic lung diseases, such as
interstitial pneumonia with collagen vascular disease and
extrapulmonary fibrosis.
=E2=80=9CWe will continue the follow-up of the patient cohort
included in th= is study to identify whether pirfenidone can
contribute to prolonged survival in patients with
IPF,=E2=80=9D said Dr. Ogura. =E2=80=9COther clini= cal
studies of pirfenidone are also being conducted in the U.S.
and Europe, and we hope that our results will be replicated
there.=E2=80=9D
###
Press Conference: Tuesday, May 20, 7:15 a.m., Room 101, North
Building, Metro Toronto Convention Centre
The research was funded by: Shionogi & Co., Ltd. ----------
-----------------------------------------------------------
---------=
----
Description
Pirfenidone is an orally active small molecule drug that may
inhibit collagen synthesis, down regulate production of
multiple cytokines and block fibroblast proliferation and
stimulation in response to cytokines. Pirfenidone has
demonstrated activity in multiple fibrotic conditions,
including those of the lung, kidney and liver.
Investigational Activity
Pirfenidone for idiopathic pulmonary fibrosis (IPF) has been
studied in multiple Phase 2 clinical trials.
We completed enrollment for CAPACITY, a Phase 3 clinical
program evaluating pirfenidone in patients with IPF, in May
2007.
Investigational, not an FDA approved product.
-------------------------
NEW HOPE FOR IPF PATIENTS? PIRFENIDONE SHOWS PROMISE IN
CLINICAL TRIALS Key Point The novel anti-inflammatory,
antioxidant, and antifibrotic agent pirfenidone may reduce
exacerbations and improve lung function in IPF patients.
TOKYO=E2=80=94New research suggests that pirfenidone, a novel
agent with ant= i- inflammatory, antioxidant, and
antifibrotic properties, may improve lung function and reduce
the number of acute exacerbations in patients with idiopathic
pulmonary fibrosis (IPF). In fact, the study was terminated
early because the reduction in exacerbations was so
significant that the review board wanted to allow all
participants to take the drug.1
STEM CELLS TESTED
Ganesh Raghu, MD, and colleagues randomized 107
corticosteroid-na=C3=AFve IPF patients to receive treatment
with pirfenidone or placebo; follow- up lasted nine months.
All patients were on a dose-titration schedule of 200 mg three
times a day for the first two days, 400 mg three times a day
for the next two days, and 600 mg three times a day (maximum
dose) for the last three days. The maximum dose was maintained
throughout the study in patients who tolerated it. Patients
not tolerating the maximum dose received a reduced dose.
Primary end points included the difference in the change of
the lowest oxygen saturation by pulse oximetry during two
six-minute exercise tests administered at baseline and again
at six months. Secondary end points included lung function
(vital capacity [VC]) and episodes of acute IPF exacerbation.
According to the authors, =E2=80=9CThe most striking and
clinically important findings noted were that the episodes of
acute exacerbation of IPF manifested exclusively in the
placebo group and there was a lesser decline in change in VC
in patients receiving pirfenidone.=E2=80=9D
SECONDARY END POINTS IMPROVE
There were no statistically significant differences between
groups in the change in oxygen saturation during the
six-minute exercise test (the primary end point), though the
pirfenidone group did show an increase from baseline, versus a
decrease in the placebo group. The patients in the pirfenidone
group, however, experienced significant improvements in the
secondary end points. At nine months, the difference in
decline of VC between groups was =E2=80=930.13 L in the
placeb= o group and =E2=80=930.03 L in the treatment group.
Ground-glass and reticular=
opacities on high-resolution CTs were reduced in 15% of
pirfenidone patients versus 7% of placebo patients.
Most importantly, none of the pirfenidone recipients
experienced an acute IPF exacerbation during nine months. In
contrast, 14% of placebo recipients had an exacerbation (one
of whom died). Because of these data, the study was aborted
and the drug was given to placebo patients. =E2=80=9CThe
implication of the prevention of acute exacerbation b= y
pirfenidone is potentially crucial for the prognosis of IPF,
as these episodes often have a fatal outcome despite
aggressive levels of supportive care in the [ICU],=E2=80=9D
stressed the authors.
Compliance rates at both six and nine months were similar
between groups: About 85% of pirfenidone and 81% of placebo
patients were compliant at six months, and 78% of both groups
were adherent at nine months. Pirfenidone, however, was not
without adverse effects; in fact, about half of the patients
were taking a reduced dose at nine months due to side effects.
The most common of these were photosensitivity, vomiting,
fever, and hepatic dysfunction. Most of these symptoms
disappeared once the medication was decreased or stopped.
WHAT DOES THE FUTURE HOLD?
=E2=80=9CAn efficacious treatment regimen for IPF is long
overdue,=E2=80=9D = wrote the authors. In an accompanying
editorial, Roland M. du Bois, MD, cited some dismal results
for trials of interferon-=CE=B3 and mentioned that studies
involving antitumor necrosis factor-=CE=B1 and antiendothelin
dual- receptor antagonists are on the horizon.2 Although the
pirfenidone study looks promising, Dr. du Bois cited the end
point issue and asked, =E2=80=9CWhat is the most appropriate
measure of change to be used in=
clinical trials?=E2=80=9D The study authors acknowledge that
their primary e= nd point needs to be validated, and the
clinical relevance of other outcome measures must be
determined in order for treatments to be tested effectively.
=E2=80=9CIPF has a mortality greater than some cancers,=
=E2=80=9D maintained Dr. du Bois. =E2=80=9CWe need to follow
the model of cancer trial=
n:comparison of current =E2=80=98best therapy=E2=80=99 with
novel drugs,=E2=80=
=9D in large
trials that are powered to provide answers.
=E2=80=94Tamara Gibb
References
1. Azuma A, Nukiwa T, Tsuboi E, et al. Double-blind, placebo-
controlled trial of pirfenidone in patients with idiopathic
pulmonary fibrosis. Am J Respir Crit Care Med.
2005;171:1040-1047.
2. du Bois RM. Is idiopathic pulmonary fibrosis now treatable?
Am J Respir Crit Care Med. 2005;171:939-940.
-------------------------
"Increase in desferrioxamine-chelatable iron levels"
Am J Respir Crit Care Med 1996 Jun;153(6 Pt 1):1918-23
Serum indicators of free radical activity in idiopathic
pulmonary fibrosis.
Jack CI, Jackson MJ, Johnston ID, Hind CR The University
Department of Medicine, University of Liverpool, United
Kingdom.
Serum levels of free radical activity were measured in 37
patients with idiopathic pulmonary fibrosis (IPF) and 16
control subjects. Three assays used were (1) simultaneously
measured levels of the 9,11- diene conjugate of linoleic acid
and 9,12-linoleic acid expressed as a percent molar ratio
(%MR), a measure of free-radical-mediated lipid peroxidation;
(2) thiobarbituric acid reactive substances (TBARS), one of
which is malondialdehyde; (3) desferrioxamine-chelatable iron
assay, a measure of the potential iron available to catalyze
free radical generation. Mean %MR, TBARS and
desferrioxamine-chelatable iron were all elevated initially
in patients with IPF compared with control subjects (%MR, p <
.0001; TBARS, p =3D 0.0013; desferrioxamine-chelatable iron,
p =3D .0029). Furthermore, the serum %MR was higher in a
subset of patients with clinically worsening IPF than in
those patients with clinically stable disease (p =3D 0.002).
Treatment did not appear to affect the three different serum
indicators of free radical activity. Thus, lipid peroxidation
appears to be increased in patients with IPF and is
associated with an increase in desferrioxamine-chelatable
iron levels. Serum % MR levels appeared to correlate with
clinical disease activity, and they may have a role in
monitoring disease activity.
PMID: 8665056, UI: 96279783
--------------------------------------------------------------
--------------= =C2=AD-
----
Who loves ya. Tom
Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
Public release date: 20-May-2008 Contact: Keely Savoie
ksavoie@thoracic.org 212-315-8620 American Thoracic Society
New treatment gives hope for pulmonary fibrosis patients ATS
2008, TORONTO=E2=80=94Patients with idiopathic pulmonary
fibrosis (IPF) may have a new treatment option, according to
researchers in Japan.
In a Phase III, double-blind, placebo-controlled clinical
trial, the investigators discovered that a daily dose of
pirfenidone could slow the progression of IPF, reducing the
loss of lung capacity. The results will be announced at the
American Thoracic Society=E2=80=99s 2008 International
Conference in Toronto on Tuesday, May 20.
=E2=80=9CThe most common treatment for IPF is
anti-inflammatory agents such = as steroids,=E2=80=9D said
lead researcher Takashi Ogura, M.D., of Kanagawa
Cardiovascular and Respiratory Center in Yokohama, Japan.
=E2=80=9CHowever o= ur study confirmed that pirfenidone, the
main action of which is thought to be antifibrotic, achieved a
therapeutic effect on IPF. I expect that our study will serve
as a guide to develop a new therapy for IPF in the
future.=E2=80=9D
The researchers recruited a total of 275 Japanese patients
with mild to moderate IPF and randomized them to a high dose
pirfenidone (1,800
mg/day) group, a low dose pirfenidone group (1,200 mg/day) and
a placebo group. They measured lung capacity (vital
capacity or VC) and progression-free survival, defined as a
period without death or a greater than 10 percent decrease
in VC, to determine the effectiveness of the regimens.
At the end of one year, they found that patients who had
been randomized to the high dose regimen had significantly
lower loss of VC than the placebo group. Furthermore,
pirfenidone slowed the overall deterioration of IPF compared
to the placebo.
=E2=80=9CTaken altogether, our study demonstrated positive
clinical effects = of pirfenidone that suppresses the progress
of IPF and potentially contributes to improving the outcomes
of patients with IPF,=E2=80=9D said Dr= . Ogura.
Pirfenidone represents new hope, not only for IPF patients
who currently have no curative treatment options, but
because it is thought to be an antifibrotic agent, it may be
able to treat other fibrotic lung diseases, such as
interstitial pneumonia with collagen vascular disease and
extrapulmonary fibrosis.
=E2=80=9CWe will continue the follow-up of the patient cohort
included in th= is study to identify whether pirfenidone can
contribute to prolonged survival in patients with
IPF,=E2=80=9D said Dr. Ogura. =E2=80=9COther clini= cal
studies of pirfenidone are also being conducted in the U.S.
and Europe, and we hope that our results will be replicated
there.=E2=80=9D
###
Press Conference: Tuesday, May 20, 7:15 a.m., Room 101, North
Building, Metro Toronto Convention Centre
The research was funded by: Shionogi & Co., Ltd. ----------
-----------------------------------------------------------
---------=
----
Description
Pirfenidone is an orally active small molecule drug that may
inhibit collagen synthesis, down regulate production of
multiple cytokines and block fibroblast proliferation and
stimulation in response to cytokines. Pirfenidone has
demonstrated activity in multiple fibrotic conditions,
including those of the lung, kidney and liver.
Investigational Activity
Pirfenidone for idiopathic pulmonary fibrosis (IPF) has been
studied in multiple Phase 2 clinical trials.
We completed enrollment for CAPACITY, a Phase 3 clinical
program evaluating pirfenidone in patients with IPF, in May
2007.
Investigational, not an FDA approved product.
-------------------------
NEW HOPE FOR IPF PATIENTS? PIRFENIDONE SHOWS PROMISE IN
CLINICAL TRIALS Key Point The novel anti-inflammatory,
antioxidant, and antifibrotic agent pirfenidone may reduce
exacerbations and improve lung function in IPF patients.
TOKYO=E2=80=94New research suggests that pirfenidone, a novel
agent with ant= i- inflammatory, antioxidant, and
antifibrotic properties, may improve lung function and reduce
the number of acute exacerbations in patients with idiopathic
pulmonary fibrosis (IPF). In fact, the study was terminated
early because the reduction in exacerbations was so
significant that the review board wanted to allow all
participants to take the drug.1
STEM CELLS TESTED
Ganesh Raghu, MD, and colleagues randomized 107
corticosteroid-na=C3=AFve IPF patients to receive treatment
with pirfenidone or placebo; follow- up lasted nine months.
All patients were on a dose-titration schedule of 200 mg three
times a day for the first two days, 400 mg three times a day
for the next two days, and 600 mg three times a day (maximum
dose) for the last three days. The maximum dose was maintained
throughout the study in patients who tolerated it. Patients
not tolerating the maximum dose received a reduced dose.
Primary end points included the difference in the change of
the lowest oxygen saturation by pulse oximetry during two
six-minute exercise tests administered at baseline and again
at six months. Secondary end points included lung function
(vital capacity [VC]) and episodes of acute IPF exacerbation.
According to the authors, =E2=80=9CThe most striking and
clinically important findings noted were that the episodes of
acute exacerbation of IPF manifested exclusively in the
placebo group and there was a lesser decline in change in VC
in patients receiving pirfenidone.=E2=80=9D
SECONDARY END POINTS IMPROVE
There were no statistically significant differences between
groups in the change in oxygen saturation during the
six-minute exercise test (the primary end point), though the
pirfenidone group did show an increase from baseline, versus a
decrease in the placebo group. The patients in the pirfenidone
group, however, experienced significant improvements in the
secondary end points. At nine months, the difference in
decline of VC between groups was =E2=80=930.13 L in the
placeb= o group and =E2=80=930.03 L in the treatment group.
Ground-glass and reticular=
opacities on high-resolution CTs were reduced in 15% of
pirfenidone patients versus 7% of placebo patients.
Most importantly, none of the pirfenidone recipients
experienced an acute IPF exacerbation during nine months. In
contrast, 14% of placebo recipients had an exacerbation (one
of whom died). Because of these data, the study was aborted
and the drug was given to placebo patients. =E2=80=9CThe
implication of the prevention of acute exacerbation b= y
pirfenidone is potentially crucial for the prognosis of IPF,
as these episodes often have a fatal outcome despite
aggressive levels of supportive care in the [ICU],=E2=80=9D
stressed the authors.
Compliance rates at both six and nine months were similar
between groups: About 85% of pirfenidone and 81% of placebo
patients were compliant at six months, and 78% of both groups
were adherent at nine months. Pirfenidone, however, was not
without adverse effects; in fact, about half of the patients
were taking a reduced dose at nine months due to side effects.
The most common of these were photosensitivity, vomiting,
fever, and hepatic dysfunction. Most of these symptoms
disappeared once the medication was decreased or stopped.
WHAT DOES THE FUTURE HOLD?
=E2=80=9CAn efficacious treatment regimen for IPF is long
overdue,=E2=80=9D = wrote the authors. In an accompanying
editorial, Roland M. du Bois, MD, cited some dismal results
for trials of interferon-=CE=B3 and mentioned that studies
involving antitumor necrosis factor-=CE=B1 and antiendothelin
dual- receptor antagonists are on the horizon.2 Although the
pirfenidone study looks promising, Dr. du Bois cited the end
point issue and asked, =E2=80=9CWhat is the most appropriate
measure of change to be used in=
clinical trials?=E2=80=9D The study authors acknowledge that
their primary e= nd point needs to be validated, and the
clinical relevance of other outcome measures must be
determined in order for treatments to be tested effectively.
=E2=80=9CIPF has a mortality greater than some cancers,=
=E2=80=9D maintained Dr. du Bois. =E2=80=9CWe need to follow
the model of cancer trial=
n:comparison of current =E2=80=98best therapy=E2=80=99 with
novel drugs,=E2=80=
=9D in large
trials that are powered to provide answers.
=E2=80=94Tamara Gibb
References
1. Azuma A, Nukiwa T, Tsuboi E, et al. Double-blind, placebo-
controlled trial of pirfenidone in patients with idiopathic
pulmonary fibrosis. Am J Respir Crit Care Med.
2005;171:1040-1047.
2. du Bois RM. Is idiopathic pulmonary fibrosis now treatable?
Am J Respir Crit Care Med. 2005;171:939-940.
-------------------------
"Increase in desferrioxamine-chelatable iron levels"
Am J Respir Crit Care Med 1996 Jun;153(6 Pt 1):1918-23
Serum indicators of free radical activity in idiopathic
pulmonary fibrosis.
Jack CI, Jackson MJ, Johnston ID, Hind CR The University
Department of Medicine, University of Liverpool, United
Kingdom.
Serum levels of free radical activity were measured in 37
patients with idiopathic pulmonary fibrosis (IPF) and 16
control subjects. Three assays used were (1) simultaneously
measured levels of the 9,11- diene conjugate of linoleic acid
and 9,12-linoleic acid expressed as a percent molar ratio
(%MR), a measure of free-radical-mediated lipid peroxidation;
(2) thiobarbituric acid reactive substances (TBARS), one of
which is malondialdehyde; (3) desferrioxamine-chelatable iron
assay, a measure of the potential iron available to catalyze
free radical generation. Mean %MR, TBARS and
desferrioxamine-chelatable iron were all elevated initially
in patients with IPF compared with control subjects (%MR, p <
.0001; TBARS, p =3D 0.0013; desferrioxamine-chelatable iron,
p =3D .0029). Furthermore, the serum %MR was higher in a
subset of patients with clinically worsening IPF than in
those patients with clinically stable disease (p =3D 0.002).
Treatment did not appear to affect the three different serum
indicators of free radical activity. Thus, lipid peroxidation
appears to be increased in patients with IPF and is
associated with an increase in desferrioxamine-chelatable
iron levels. Serum % MR levels appeared to correlate with
clinical disease activity, and they may have a role in
monitoring disease activity.
PMID: 8665056, UI: 96279783
--------------------------------------------------------------
--------------= =C2=AD-
----
Who loves ya. Tom
Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk