S
SPIRIV
VA® (TIO
OTROP
PIUM BROMI
B
DE)
MEDIA BACKG
GROUND
DER
What is Spiriv
va*?
Spiriva® (tiotropium
m bromide) is the mosst prescribed COPD maintenance
m
e treatment worldwide to
relieve symptoms of patients
s with Chro
onic Obstru
uctive Pulm
monary Diseease (COP
PD).1 Spiriva
a®
addressses the ke
ey goals off COPD m
maintenance
e treatmentt, deliveringg long-term
m benefits to
patientss, reducing COPD exa
acerbationss and impro
oving quality
y of life, m
making it a foundation
f
of
mainten
nance treatm
ment.
Spiriva® is availab
ble in two marketed fformulations
s in many countries, eeach in its own uniqu
ue
device:
andiHaler® iis a breath-actuated, single-dose dry powderr
 Spiriva® 18 µg via Ha
inhaler.
®
R
Soft
S Mist™ IInhaler 2.5 μg (2 puffs, once daily)) is a prope
ellant Spiriva® Respimat
free, new generation inhaler tha
at combines innovative technologyy with the prroven
efficacy off Spiriva®.2 The device
e delivers a slow moving soft mist, offering a gentle
g
and pleassant inhalation which iss easy for pa
atients to in
nhale.3,4,5,6
Otropium Safety and Performance
P
e In Respim
mat® (TIOSP
PIR™) Triall, a landma
ark global triial
The TIO
®
in more
e than 17,00
00 patients,, has shown
n Spiriva has
h a comparable safeety and effic
cacy profile in
®
®
the two available fo
ormulations
s – HandiHa
aler (18 μg) and Respimat (2.5 μ
μg, 2 puffs, once daily)).7
prehensive trial data de
emonstratin
ng an exten
nsive wealthh of experie
ence since its
i
Spiriva® has comp
†
introducction over 10 years ago and m ore than 40 million pa
atient-yearss of real life
e experiencce
supportting its safety and efficacy profile.‡‡,2,7,8,9,10,11,122 Spiriva® is
s the numbeer one presc
cribed COP
PD
1
®
mainten
nance thera
apy worldw
wide. Spirivva is the first inhaled
d anticholinnergic drug
g (long-actin
ng
muscarrinic antagonist / LAMA
A) to provide
e significant and sustained improvvements in lung functio
on
with oncce-daily dossing.13,14
Mode
e of actio
on / administratio
on
Spiriva® is the first once-daily
y maintenan
nce treatme
ent COPD medication that provid
des sustaine
ed
24-hourr bronchodiilation (ope
ening of the
e airways) through
t
pro
olonged M33 receptor blockade.
b
M
M3
recepto
ors help to mediate
m
airw
way smooth
h-muscle tone in the lung, which ccontrols narrrowing of th
he
1
13,14
airway.
*
Spiriva® (tiotropium) was
w discovere
ed and develop
ped by Boehriinger Ingelheim
m and is co-prromoted world
dwide
with Pfiizer Inc.
†
®
18 µg delivered via HandiHaler
H
‡
Combin
ned figures forr HandiHaler® and Respima t®
1
Through this prolo
onged block
kade of the M3 recepto
ors, Spiriva® reduces ssmooth-mus
scle tone an
nd
13,14
dilates tthe airwayss, resulting in significan
nt and susta
ained improv
vements in lung functio
on.
What does the
e GOLD report s ay?
In the updated GOLD
G
report (internat ional guide
elines deve
eloped by tthe Global Initiative for
f
g Disease)) long-actin
ng anticho
olinergics are the oonly therapeutic classs
Obstrucctive Lung
recomm
mended forr every pattient requiriing mainten
nance therapy (as a first choice
e for Patie
ent
Groupss B-D relatin
ng to all butt the lowestt risk COPD
D patients and an alternnative choic
ce for Patie
ent
Group A
A).15
GOLD report classifie
es COPD patients into group
ps A-D,
ased on a combinattion of spirometry results,
r
seeverity
ba
15
of sy
ymptoms, and risk of exacerb
bations
2
What are the clinical
c
benefits
b
of Spiriv
va®?
Spiriva® has provven clinical efficacy in
n delivering
g long-term
m benefits in reducing
g the risk of
exacerb
bations, imp
proving lung
g function, rreducing sh
hortness of breath and improving the quality of
life in pa
atients with COPD.7,9,10,12,16,17
The TIO
OSPIR™ trrial, one of the largestt COPD tria
als ever conducted, reeinforced th
he safety an
nd
efficacyy of Spiriva®2 in both available
a
fo
ormulations (HandiHale
er® (18 µg,, dry powde
er inhaler) or
Respim
mat® (2.5 μg
g, 2 puffs once daily Soft Mist™
™ Inhaler))) and acrosss all groups of COP
PD
7
®
patientss. Spiriva once-daiily has alsso been shown
s
to significantlly reduce the risk of
exacerb
bations with
h both devic
ces.11,12,16
Breathlessness
m of COPD and is a major cause of disability
y and anxie
ety
Breathlessness is the hallmark symptom
ated with the
e disease. In COPD, b reathlessne
ess is typica
ally persisteent and prog
gressive.15
associa
Spiriva® (18 µg via
a HandiHale
er):
 Provides prompt
p
and sustained reduction of
o breathless
sness.8,18
ctivity induce
ed breathles
ssness vers
sus placeboo.19
 Reduces physical ac
 Improves patients’ ex
xercise end urance.17,199
 After the first
f
dose, provides
p
sig
gnificant red
duction of breathlessneess during exercise
e
19
compared
d with placebo (p<0.05 ).
 In a 1-yyear study
y, Spiriva® maintaine
ed improve
ement in airflow an
nd lung
hyperinfla
ation reductiion during th
he entire co
ourse of the
e trial (p<0.0001).8
Exacerrbations
COPD exacerbatio
ons pose an
n immediat e and ongo
oing threat to
t patients and reducin
ng the risk of
ons is an internationa
ally recomm
mended go
oal of COP
PD treatmen
nt by GOLD.
COPD exacerbatio
®
Spiriva reduces th
he number of exacerb ations and exacerbatio
on-related hhospitalisatiions for up to
four yea
ars, as dem
monstrated in
i the Unde
erstanding Potential
P
Lo
ong-Term Im
mpacts on Function
F
wiith
®
11,§
®
®
Tiotropiium (UPLIF
FT ) study.
Spiriva (18 µg via
v HandiHaler ) also produces a significa
ant
reductio
on in the nu
umber of exacerbation
ns per patie
ent year compared to control (pla
acebo) (14%
%;
p<0.001
1),11,§ as we
ell as provid
ding significcant reductiion in the risk of COPD
D exacerba
ations leadin
ng
to hospitalisation vs. contro
ol (placebo
o) and co
ompared to
o a long-aacting beta
a2 antagonist
(salmetterol).8,16
e-year Prev
vention Of Exacerbatio
ons with Tiotropium P
POET-COPD
D® study, th
he
Resultss of the one
largest head-to-head study de
esigned to ccompare the effects off two long-aacting bronc
chodilators on
o
ate to seve
ere exacerb
bations in C
COPD, sho
ow that – compared
c
tto the long-acting betta2
modera
§
While S
Spiriva 18 µg via HandiHale
er® did not alte
er the rate of decline
d
in lung
g function, a cooprimary endp
point in
the UPL
LIFT® study, itt sustained gre
eater improve
ements in lung
g function vs. placebo.
p
3
agonist salmeterol (50 µg via HFA me
etered-dose inhaler) – Spiriva® (118 µg via HandiHalerr®)
significa
antly delayyed the occ
currence o f the first exacerbatio
on, with a 17% redu
uction in rissk
16
®
®
(p<0.00
01). Spirivva (18 µg via Handi Haler ) als
so reduced the risk oof severe exacerbation
e
ns
requirin
ng hospitalissation by 28
8% (p<0.00 1).16
Spiriva® Respimatt® has also been show
wn to lowerr the rate off exacerbattions relativ
ve to placeb
bo
and sho
own to have
e comparative efficacy to Spiriva® HandiHalerr in the TIO SPIR™ tria
al.7,12
Quality
y of life
Spiriva® (18 µg via
a HandiHale
er®) producces statistically significant improveements in health-relate
h
ed
quality of life for up
u to four years
y
as m
measured by
y the St. George’s
G
Reespiratory Questionnai
Q
re
11,**
®
(SGRQ
Q p<0.001), compared with contro
ol.
Spiriv
va also pro
ovides signnificant improvements in
11,220,**
quality o
of life in CO
OPD patientts new to m aintenance treatment (p<0.05).
(
Spiriva® Respimatt® has dem
monstrated iimproved health-relate
h
ed quality oof life relative to contrrol
12
(placeb
bo).
Surviva
al
urvival has been established in tthe UPLIFT
T® study an
nd
The favvourable efffect of Spiriva® on su
®
®
reinforcced in the TIOSPIR™
T
trial.
t
In UPL
LIFT , a tria
al of nearly 6,000 patieents, Spiriva
a (18 µg via
v
HandiH
Haler®) redu
uced risk off on-treatm
ment mortaliity in COPD patients by 16% ve
ersus contrrol
®
2.5 µg, (2 puffs, onc
(placeb
bo).11,21,†† In
n the TIOSPIR™ trial,, Spiriva® Respimat
R
ce daily) an
nd
®
®
Spiriva HandiHaler 18 µg
g showed similar imp
pact on su
urvival as m
measured by all-causse
mortalitty.7 This effect
e
was confirmed
d in patien
nts with and withoutt a history
y of cardia
ac
7,‡‡
arrhythm
mia.
**
While
e Spiriva 18 µg
µ via HandiHa
aler® did not a
alter the rate of
o decline in lun
ng function, a coprimary endpoint in
®
g
improvvements in lun
ng function vs. placebo.
the UPLIFT study, it sustained greater
††
Mortality, a pre-spe
ecified seconda
ary endpoint, w
was evaluated
d in 3 analyses: 1) on treatm
ment; 2) intenttion to
treat a
at protocol-de
efined end of trreatment (Dayy 1,440); and 3)
3 intention to treat after 30--day follow-up
p (Day
1,470
0). Effect exten
nded to end off treatment pe
eriod (Day 1,44
40), as defined
d by protocol. Effect becam
me nonsignificant within the 30-day follo
ow-up period ( Day 1,470), when,
w
accordin
ng to protocol, patients were
e
discontinued from their
t
study me
edication (ITT analysis endp
point).
‡‡
Results from TIOSP
PIR™, a head-to-head trial iin more than 17,000
1
COPD patients com
mparing the effiicacy and


safetyy of Spiriva Respimat
R
2.5 µg (2 puffs, o
once daily) to Spiriva
S
18 µg via HandiHaller®, powered to
provid
de a precise estimate
e
of mo
ortality rates ass well as COP
PD exacerbatio
on rates.
4
Safety
y and tolerability
y
The sa
afety profile of Spiriva® has been
n well desc
cribed with both HanddiHaler® an
nd Respima
at®
inhaler devices.7,8,222,23
OSPIR™ triial showed Respimat® 2.5 µg, (2 puffs,
p
once daily) to haave a comp
parable safe
ety
The TIO
profile to that of HandiHalerr® (18 µg) in COPD patients with or withoout a historry of cardia
ac
7
arrhythm
mia.
Referrences:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
IMS H
Health, IMS MID
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Boehrringer Ingelheim
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5