O iginal A icle
P e alence o Pa ien s Eligible o An i-IL-5
T ea men in a Coho o Adul -Onse As hma
Pinja Ilma inen, PhD
a
, Leena E. Tuomis o, MD, PhD
a
, Onni Niemelä, MD, PhD
b,c
, and Hannu Kankaan an a, MD, PhD
a,c
Seinäjoki and Tampe e, Finland
Wha is al eady known abou his opic? An ibodies agains he IL-5 pa hway ha e been de eloped o he ea men o
la e-onse eosinophilic co icos e oid- esis an as hma. Es ima es o 5% o 10% on he p e alence o se e e as hma ha e
been p oposed wi h unclea basis.
Wha does his a icle add o ou knowledge? The p e alence o se e e as hma was 5.9%, and 2% ulfilled he c i e ia
o an i-IL-5 he apy in an unselec ed coho o adul -onse as hma. Only 1 pa ien me c i e ia o bo h g oups, and bo h
g oups ep esen a high bu den o heal h ca e.
How does his s udy impac cu en managemen guidelines? This s udy on he p e alence o se e e as hma and
an i-IL-5 eligible pa ien s indica es ha o 100 pa ien s wi h adul -onse as hma, 6 ha e se e e as hma and 2 a e eligible o
an i-IL-5 he apy.
BACKGROUND: An ibodies agains he IL-5 pa hway ha e been
de eloped o he ea men o la e-onse eosinophilic co icos e-
oid- esis an as hma. Howe e , he p e alence o se e e as hma
and he p opo ion o pa ien s who could benefi om such
ea men among he gene al popula ion o as hma ics emain
unknown.
OBJECTIVE: To e alua e he p e alence and cha ac e is ics o
pa ien s eligible o an i-IL-5 ea men and se e e as hma in an
unselec ed coho o adul -onse as hma.
METHODS: Seinäjoki Adul As hma S udy is a 12-yea ollow-up
s udy o pa ien s wi h new-onse adul as hma (n [203). P e -
alence was es ima ed based on in o ma ion collec ed a 12-yea
ollow-up isi . Heal h ca e use was collec ed om he whole
12-yea ollow-up pe iod.
RESULTS: The p e alence o an i-IL-5- ea able pa ien s was
2%, when he ollowing c i e ia we e used: daily use o medium-
o-high inhaled co icos e oid (ICS) dose and long-ac ing
b
2
-
agonis , ‡2 exace ba ions/p e ious yea and blood eosinophil
coun ‡300 cells/
m
L o ac ion o exhaled ni ic oxide ‡50
ppb. The p e alence o se e e as hma, as defined acco ding o
Eu opean Respi a o y Socie y/Ame ican Tho acic Socie y, was
5.9%, and only 1 pa ien me c i e ia o bo h g oups. When
compa ed wi h an i-IL-5 eligible pa ien s, se e e as hma ics
we e mo e o en cu en smoke s a diagnosis, obese, used
highe ICS dose, and had highe blood neu ophils 12 yea s
a e diagnosis. Bo h g oups di e ed om nonse e e as hma by
a highe numbe o all and unplanned espi a o y- ela ed isi s
o heal h ca e. Se e e as hma ics showed he highes numbe o
hospi aliza ions.
CONCLUSIONS: In a coho o unselec ed consecu i e pa ien s
wi h adul -onse as hma, 5.9% ulfilled c i e ia o se e e as hma
and 2% qualified o an i-IL-5 ea men . Bo h g oups ep esen
a high bu den o heal h ca e and specifically a ge ed ea men
could lead o lowe use o heal h ca e a long e m. Ó2019 The
Au ho s. Published by Else ie Inc. on behal o he Ame ican
Academy o Alle gy, As hma & Immunology. This is an open
access a icle unde he CC BY-NC-ND license (h p://
c ea i ecommons.o g/licenses/by-nc-nd/4.0/). (J Alle gy Clin
Immunol P ac 2019;7:165-74)
Key wo ds: As hma; Adul ; Adul -onse ; P e alence; In e leukin-5;
Eosinophil; Se e e; Mepolizumab; Reslizumab; Ben alizumab
a
Depa men o Respi a o y Medicine, Seinäjoki Cen al Hospi al, Seinäjoki, Finland
b
Depa men o Labo a o y Medicine, Seinäjoki Cen al Hospi al, Seinäjoki, Finland
c
Facul y o Medicine and Li e Sciences, Uni e si y o Tampe e, Tampe e, Finland
The analysis and w i e-up o his s udy was unded by As aZeneca, Mölndal,
Sweden. As aZeneca was gi en an oppo uni y o commen he s udy epo
be o e i was submi ed o publica ion. The Seinäjoki Adul As hma S udy
(SAAS) p ojec has been unded by Finnish An i-Tube culosis Associa ion
Founda ion (Helsinki, Finland), Tampe e Tube culosis Founda ion (Tampe e,
Finland), Jalma i and Rauha Ahokas Founda ion (Helsinki, Finland), he Resea ch
Founda ion o he Pulmona y Diseases (Helsinki, Finland), he Compe i i e S a e
Resea ch Financing o he Expe Responsibili y A ea o Tampe e Uni e si y
Hospi al (Tampe e, Finland), and he Medical Resea ch Fund o Seinäjoki Cen al
Hospi al (Seinäjoki, Finland); nei he As aZeneca no he o he unde s ha e any
in ol emen in he planning o execu ion o he SAAS s udy.
Conflic s o in e es : P. Ilma inen, L. E. Tuomis o, and H. Kankaan an a epo a g an om
As aZeneca ela ed o he submi ed wo k. Ou side he submi ed wo k P. Ilma inen
epo s paymen o lec u es om Mundipha ma, O ion Pha ma, and As a Zeneca. L. E.
Tuomis o epo s g an s om Chiesi Pha ma AB and O ion Pha ma and paymen o
lec u es om Filha y, As a Zeneca, and Mundipha ma. O. Niemelä epo s no conflic
o in e es . H. Kankaan an a epo s pe sonal ees and nonfinancial suppo om
Almi all, As aZeneca, and Boeh inge -Ingelheim; pe sonal ees om Chiesi Pha ma
AB, GlaxoSmi hKline, Lei as-Takeda, MSD, No a is, Mundipha ma, Medi h,
Resmed Finland, Roche, and O ion Pha ma; and nonfinancial suppo om In e mune.
Recei ed o publica ion Oc obe 4, 2017; e ised May 22, 2018; accep ed o
publica ion May 23, 2018.
A ailable online June 9, 2018.
Co esponding au ho : Pinja Ilma inen, PhD, Depa men o Respi a o y Medicine,
Seinäjoki Cen al Hospi al, FIN-60220 Seinäjoki, Finland. E-mail: pinja.
ilma inen@epshp.fi.
2213-2198
Ó2019 The Au ho s. Published by Else ie Inc. on behal o he Ame ican Academy
o Alle gy, As hma & Immunology. This is an open access a icle unde he CC
BY-NC-ND license (h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/).
h ps://doi.o g/10.1016/j.jaip.2018.05.032
165
Abb e ia ions used
ACT- As hma Con ol Tes
ATS- Ame ican Tho acic Socie y
CI- Confidence in e al
ERS- Eu opean Respi a o y Socie y
FeNO- F ac ion o exhaled ni ic oxide
FEV
1
- Fo ced expi a o y olume in 1 second
GINA- Global Ini ia i e o As hma
ICS- Inhaled co icos e oid
LABA- Long-ac ing
b
2
-agonis
OCS- O al co icos e oid
SA- Se e e as hma
SAAS- Seinäjoki Adul As hma S udy
Recen ly, as hma has been conside ed o mani es in di e en
pheno ypes equi ing di e en ea men app oaches. Age a
onse is a c i ical ac o sepa a ing di e en pheno ypes. As hma
s a ing in childhood o en coexis s wi h a opy/alle gy, is domi-
na ed by Th2 inflamma ion, and esponds well o he apy wi h
inhaled co icos e oids (ICS). Howe e , as hma s a ing a
adul hood is mo e o en nona opic, less esponsi e o ICS
ea men , and has less a o able p ognosis. Adul -onse
as hma has been p oposed o consis o subpheno ypes such as
obesi y- ela ed, smoking, se e e obs uc i e, mild- o-mode a e/
well-con olled, and a opic as hma.
1-3
La e-onse eosinophilic
(o en se e e) as hma has been conside ed o be one o he
adul -onse as hma pheno ypes.
1,3
La e-onse eosinophilic as hma is cha ac e ized by pe sis en
eosinophilic ai way inflamma ion despi e he use o co icos e-
oid he apy. I is associa ed wi h a lowe a e o alle gy;
equen ly he e is no ob ious amily his o y o as hma and i is
o en se e e om onse .
3
Many o hese pa ien s su e om
equen exace ba ions and may espond poo ly o inhaled s e-
oid he apy. This condi ion is associa ed wi h subs an ial heal h
ca e cos s due o unplanned heal h ca e isi s, eme gency
depa men isi s, and hospi al admissions. P e ious s udies ha e
emphasized he impo ance o eosinophils in media ing exace -
ba ions,
4
and he e o e he esolu ion o eosinophilic inflam-
ma ion has been sugges ed as a p omising he apeu ic s a egy o
educe exace ba ions. IL-5 is a c i ical cy okine o eosinophil
ma u a ion, su i al, and ac i a ion.
5,6
Neu aliza ion o i s e -
ec s by an i-IL-5 an ibodies such as mepolizumab o eslizumab
leads o he educed numbe o eosinophils. Ben alizumab is an
an i-IL5 ecep o an ibody ha deple es eosinophils h ough
an ibody-dependen cell-medica ed cy o oxici y. In clinical ials
in pa ien s wi h se e e glucoco icoid- esis an eosinophilic
as hma, hese an ibodies dec eased exace ba ion a e, had a
glucoco icoid-spa ing e ec , and imp o ed as hma- ela ed
quali y o li e and lung unc ion.
7-11
Typically, inclusion c i e ia o an i-IL-5 s udies ha e been he
use o mode a e- o-high ICS dose oge he wi h long-ac ing
b
2
-
agonis (LABA) o ano he con olle and a leas 2 exace ba ions
equi ing o al co icos e oid (OCS) du ing he p e ious yea .
7-11
Fo blood eosinophil le els, 150, 300, o 400 cells/
m
L ha e
been used as a c i e ion o inclusion o al e na i ely, ac ion o
exhaled ni ic oxide (FeNO) 50 ppb, o spu um eosinophil
coun 3%.
7-11
The p opo ion o pa ien s wi h eosinophilic
as hma who could benefi om an i-IL-5 he apy among a
gene al popula ion o adul -onse as hma ics has, howe e ,
emained unknown.
The p opo ion o pa ien s wi h se e e as hma (SA) has been
app oxima ed o be 5% o 10% among all pa ien s wi h
as hma.
12
Howe e , he e ha e been di ficul ies in assessing he
ue p e alence due o he lack o accu a e defini ion
13
and
exclusion o significan pa ien g oups (smoking, aged in-
di iduals, and pa ien s wi h significan como bidi ies) om mos
published clinical coho s. A Eu opean Respi a o y Socie y/
Ame ican Tho acic Socie y (ERS/ATS) commi ee defined SA as
as hma equi ing ea men wi h high ICS dose oge he wi h
add-on medica ion o OCS o p e en i om becoming un-
con olled o which emains uncon olled despi e his he apy.
12
This s udy was ca ied ou o e alua e he p opo ion o
pa ien s ulfilling combina ions o possible clinical c i e ia o he
use o an i-IL-5 he apies as well as he p e alence o SA in a eal-
li e coho o pa ien s wi h clinically defined adul -onse as hma
12 yea s a e diagnosis. Ano he aim was o compa e he clinical
cha ac e is ics o pa ien s wi h non-SA and SA and hose ul-
filling c i e ia o an i-IL-5 he apy.
METHODS
S udy design and pa ien s
This s udy is pa o Seinäjoki Adul As hma S udy (SAAS).
SAAS (ClinicalT ials.go ID NCT02733016) is a p ospec i e,
single-cen e (Seinäjoki Cen al Hospi al, Seinäjoki, Finland) 12-
yea ollow-up s udy o a coho o pa ien s ha ing new-onse
as hma diagnosed a adul age (15 yea s). Ins i u ional pe mis-
sions we e ob ained and he pa icipan s ga e w i en in o med
consen o he s udy p o ocol app o ed by he e hics commi ee o
Tampe e Uni e si y Hospi al, Tampe e, Finland. Mo e han 94%
o he pa ien s diagnosed wi h no el as hma in he s udy si e we e
ec ui ed o he s udy.
14
In 2001, he s udy popula ion ep esen ed
>38% o no el diagnoses o as hma made o adul s in he whole
geog aphical a ea. The p o ocol, inclusion and exclusion c i e ia,
and he backg ound da a o he SAAS s udy ha e been published
sepa a ely.
14
B iefly, as hma was diagnosed by a espi a o y specialis
du ing 1999-2002 based on ypical symp oms, and diagnosis was
confi med by objec i e lung unc ion measu emen s.
14
A e diag-
nosis, he pa ien s we e ea ed and moni o ed by hei own
physician acco ding o he p inciples o Finnish As hma P og am
15
and guidelines.
16
The o al coho consis ed o 257 pa ien s and 203
pa ien s e u ned o he 12-yea ollow-up isi .
17
A his isi ,
as hma s a us and con ol, como bidi ies, and medica ion we e
e alua ed using s uc u ed ques ionnai es, and lung unc ion and
inflamma o y pa ame e s we e measu ed. The basic cha ac e is ics,
12-yea p ognosis ( emission and as hma con ol), de ailed smoking
cha ac e is ics, and como bidi ies o he s udy coho ha e been
p e iously published.
17-19
Da a we e also ga he ed om all as hma- ela ed isi s o heal h
ca e (p ima y ca e, p i a e heal h ca e, and hospi al clinics), exac-
e ba ions, acu e espi a o y ac in ec ions, and hospi aliza ions
du ing he whole 12-yea ollow-up pe iod. Da a om he 12-yea
ollow-up isi and he ime in be ween he isi s we e used in
assessing he p opo ion o an i-IL-5 eligible pa ien s and SA. To
assess adhe ence in hese pa ien s, he numbe s o ICS-con aining
inhale s/canis e s and OCS bough om pha macies in 2012-2013
we e e ie ed om Social Insu ance Ins i u ion o Finland.
Exace ba ions and medica ion
The numbe o exace ba ions was sel - epo ed employing a
s uc u ed ques ionnai e filled a 12-yea ollow-up isi o e alua ed
om he pa ien eco ds (p e ious yea ). Medica ion o as hma was
J ALLERGY CLIN IMMUNOL PRACT
JANUARY 2019
166 ILMARINEN ET AL
sel - epo ed a s uc u ed ques ionnai e. I he in o ma ion was
missing, medica ion was e alua ed om he p e ious as hma- ela ed
isi o heal h ca e.
Lung unc ion, in lamma o y pa ame e s, and o he
clinical measu emen s
Lung unc ion measu emen s we e pe o med wi h a spi ome e
acco ding o in e na ional ecommenda ions.
20
De ailed in o ma-
ion on he lung unc ion measu emen s, de e mina ion o inflam-
ma o y pa ame e s, como bidi ies, and on o he clinical
measu emen s can be ound in his a icle’s Online Reposi o y a
www.jaci-inp ac ice.o g.
Se e e as hma
SA was defined acco ding o he ATS/ERS Task Fo ce as as hma
equi ing ea men wi h high ICS dose oge he wi h add-on
medica ion o OCS o p e en i om becoming uncon olled o
which emains uncon olled despi e his he apy.
12
Uncon olled
as hma was defined as one o he ollowing a he 12-yea ollow-up
isi : (1) poo symp om con ol (As hma Con ol Tes [ACT] sco e
<20), (2) equen exace ba ions (2 bu s s o OCS in he p e ious
yea ), (3) se ious exace ba ions (1 hospi aliza ion in he p e ious
yea due o as hma), and (4) ai flow limi a ion (p ee o ced expi a-
o y olume in 1 second (FEV
1
)<80% p edic ed).
12
P ima y and seconda y endpoin s
The p ima y endpoin o his s udy was o assess he p opo ion
o pa ien s who could benefi om an i-IL-5 he apy, ha is,
pa ien s ulfilling he ollowing c i e ia: (1) daily use o medium- o-
high ICS dose (800
m
g budesonide equi alen ) and LABA, (2) 2
exace ba ions pe p e ious yea be o e he 12-yea ollow-up isi ,
and (3) blood eosinophil le el 300 cells/
m
L o FeNO 50 ppb a
he 12-yea ollow-up isi in he SAAS coho .
The seconda y endpoin s we e o assess he p opo ion o pa ien s
wi h SA ( ulfilling ERS/ATS c i e ia) and he p opo ion o pa ien s
ulfilling di e en combina ions o he clinical c i e ia ela ed o
eligibili y o an i-IL-5 ea men . A u he aim was o see whe he
an i-IL-5 eligible pa ien s and SA o e lap. A compa ison o basic and
clinical cha ac e is ics and heal h ca e use o pa ien s ulfilling c i e ia
o an i-IL-5 he apy o hose ulfilling c i e ia o SA and o he
pa ien s wi h non-SA was also assessed as a seconda y endpoin .
S a is ical analysis
Con inuous da a a e exp essed as mean s anda d de ia ion o
median and in e qua ile ange. A compa ison be ween 3 g oups was
pe o med by using 1-way analysis o a iance wi h Tukey’s pos
hoc, K uskal-Wallis, o
c
2
es . Boo s apping
21
was used o es ima e
95% confidence in e al (CI) o he p ima y/seconda y ou come
es ima e. By his me hod, 1000 samples wi h eplacemen we e
d awn om he o iginal da ase o he same size as he o iginal
sample allowing us o quan i y mo e p ecisely he accu acy o p i-
ma y ou come es ima e. S a is ical analyses we e pe o med using
SPSS so wa e, e sion 23 (IBM SPSS, A monk, NY). P alue <.05
was ega ded as s a is ically significan .
RESULTS
Pa ien cha ac e is ics
The cha ac e is ics o pa ien s a 12-yea ollow-up isi a e
shown in Table I. Pa ien s we e mos ly emales, nona opic,
o e weigh , and app oxima ely hal had smoking his o y. The
p opo ion o daily ICS use s was 76.4%. As hma was uncon-
olled in 29.6% o pa ien s. Two pa ien s (1%) we e using
con inuous OCS o as hma indica ion a 12-yea ollow-up isi ,
and 2 pa ien s (1%) o o he indica ion.
Pa ien s eligible o an i-IL-5 he apy
The p ima y endpoin o his s udy was ulfilled by 4 o 203
(2% o pa ien coho ) (Figu e 1,A). Wi h blood eosinophil
cu o se om 150 o 400 cells/
m
L, p opo ion a ied be ween
1% and 3% (Figu e 1,A). When c i e ia o exace ba ions and
medica ion use we e emo ed, 20.3% o pa ien s ulfilled c i e ia
o blood eosinophils 300 cells/
m
L o FeNO 50 ppb. Wi h
blood eosinophil cu o s om 150 o 400, p opo ion a ied
om 58.7% o 14.5% (Figu e 1,B).
Some imes as hma exace ba ion may be con used wi h acu e
espi a o y ac in ec ion, and consequen ly, an ibio ics o
doubling o ICS dose is p esc ibed ins ead o OCS. The e o e,
we applied an explo a i e app oach. In addi ion o he pa ien s
who we e p esc ibed OCS a leas wice pe yea , he ex ended
defini ion included also pa ien s wi h 2 acu e isi s o heal h
ca e whe e an ibio ics o doubling o ICS dose was p esc ibed
du ing he p e ious yea . In he coho , 11.3% o he pa ien s
ulfilled c i e ia o ex ended defini ion o exace ba ions and used
medium o high ICS dose and LABA o hei daily he apy.
When c i e ia o ele a ed eosinophils (300 cells/
m
L) o FeNO
(50 ppb) we e added, 3% (n ¼6) pa ien s emained.
TABLE I. Cha ac e is ics o pa ien s a 12-yea ollow-up as
p e iously epo ed
17
Cha ac e is ic Coho a ollow-up (n [203)
Age (y) 58 (14)
Male gende , n (%) 85 (41.9)
BMI (kg/m
2
) 28.1 (24.4-31.2)
BMI <25, n (%) 59 (29.0)
BMI 25-29.99, n (%) 73 (36.0)
BMI 30, n (%) 71 (35.0)
Smoke s (incl. ex), n (%) 107 (52.7)
Smoking his o y, pack-yea 16 (7-30)
To al IgE (kU/L) 61 (24-163)
Daily ICS use, n (%) 155 (76.4)
Blood eosinophils (10
9
/L) 0.17 (0.10-0.27)
Blood eosinophils 0.3, n (%) 35 (17.3)
P e-BD FEV
1
% 86 (76-96)
P e-BD FEV
1
<80% p edic ed, n (%) 61 (30.0)
P e-BD FVC % 96 (87-106)
P e-BD FEV
1
/FVC 0.73 (0.66-0.79)
Pos -BD FEV
1
% 90 (80-98)
Pos -BD FEV
1
<80% p edic ed, n (%) 48 (23.6)
Pos -BD FVC % 99 (88-107)
Pos -BD FEV
1
/FVC 0.75 (0.69-0.80)
DL
CO
(%) 92 (19)
DL
CO
/VA (%) 94 (17)
AQ20 sco e 4 (2-7)
ACT sco e 22 (19-24)
ACT sco e <20, n (%) 56 (27.6)
ACT, As hma Con ol Tes ; AQ20, Ai ways Ques ionnai e 20; BD, b onchodila o ;
BMI, body mass index; DL
CO
, di using capaci y; DL
CO
/VA, di using capaci y
adjus ed by he al eola olume; FEV
1
, o ced expi a o y olume in 1 s; FVC, o ced
i al capaci y; GINA, Global Ini ia i e o As hma; ICS, inhaled co icos e oid.
Shown a e mean (s anda d de ia ion) o median (25 h-75 h pe cen ile).
As hma con ol was e alua ed by GINA 2010.
22
J ALLERGY CLIN IMMUNOL PRACT
VOLUME 7, NUMBER 1
ILMARINEN ET AL 167
P e alence o se e e as hma
We used he ATS/ERS Task Fo ce
12
defini ion o SA. O he
pa ien s, 14 (6.9%) we e using high-in ensi y medica ion o
as hma (high ICS dose plus second con olle and/o OCS o
50% o he p e ious yea ) and 12 (5.9%) s ill emained un-
con olled ulfilling c i e ia o SA.
12
The p opo ion o pa ien s
defined as uncon olled acco ding o he ACT sco e <20, 2
exace ba ions las yea , o p eb onchodila o FEV
1
<80% p e-
dic ed a e shown in Figu e 2. The e was only 1 pa ien who
ulfilled c i e ia o bo h SA and an i-IL-5 eligibili y due o
di e en c i e ia o ICS dose, and in u he analyses, his pa-
ien was included only in o he an i-IL-5 g oup. Th ee an i-IL-5
eligible pa ien s we e no ega ded as ha ing SA due o ICS dose
no classified as high acco ding o ERS/ATS c i e ia.
Cha ac e is ics o pa ien s wi h nonse e e as hma,
se e e as hma, and hose eligible o an i-IL-5
he apy
Pa ien s wi h non-SA, SA, and hose eligible o an i-IL-5
he apy we e simila in espec o gende , age o as hma onse ,
and lung unc ion pa ame e s a diagnosis and 12-yea ollow-up
isi (Table II and Table E1, a ailable in his a icle’s Online
Reposi o y a www.jaci-inp ac ice.o g). Pa ien s wi h SA we e
mo e o en cu en smoke s a diagnosis (Table E1) and had
FIGURE 1. P e alence o pa ien s ul illing di e en combina ions o he clinical c i e ia ela ed o eligibili y o an i-IL-5 he apy in he
coho o adul -onse as hma (n ¼203). A, P e alence o pa ien s ul illing di e en c i e ia o he le el o blood eosinophils o FeNO,
exace ba ions, and use o medica ion. B, P e alence o pa ien s ul illing di e en c i e ia o he le el o blood eosinophils (B-eos) o FeNO
wi hou he need o ul ill c i e ia o equen exace ba ions o use o medium- o-high ICS dose o as hma. FeNO, F ac ion o exhaled
ni ic oxide; ICS, inhaled co icos e oid; LABA, long-ac ing
b
2
-agonis .
J ALLERGY CLIN IMMUNOL PRACT
JANUARY 2019
168 ILMARINEN ET AL
highe body mass index a he 12-yea ollow-up isi (Table II)
when compa ed wi h he 2 o he g oups. In addi ion, pa ien s
wi h SA had mo e o en sys emic heuma ic disease, hy oid
diso de , o ea ed dyspepsia as como bidi y a 12-yea ollow-
up isi (Table E2, a ailable in his a icle’s Online Reposi o y
a www.jaci-inp ac ice.o g). Di e ences exis ed in pa ame e s
ela ed o as hma medica ion, exace ba ions, symp oms, and
as hma con ol, which was expec ed because hese pa ame e s
we e used in he ca ego iza ion o pa ien s (Tables II and III).
FeNO and o al IgE le el we e he highes in pa ien s ulfilling
c i e ia o an i-IL-5 he apy and lowes in pa ien s wi h SA
(Table II). Ins ead, blood neu ophils we e highes in pa ien s
wi h SA and lowes in an i-IL-5 eligible pa ien s a 12-yea
ollow-up isi (Table II). To assess adhe ence o s e oid ea -
men he numbe s o ICS-con aining inhale s/canis e s as well as
packages o OCS bough om pha macies a ound he ollow-up
isi (2012-2013) we e e ie ed. All an i-IL-5-eligible pa ien s
had bough se e al ICS-con aining inhale s annually (mean 8.2/
yea ) and a leas 1 OCS package (mean bough o al OCS dose
1688 mg p ednisolone equi alen /2 yea s co esponding o >5
en-day cou ses o 30 mg o al p ednisolone daily). One pa ien
classified as ha ing SA had low adhe ence a he ollow-up isi
bu be e adhe ence in long e m. All o he emaining 10 pa-
ien s classified as ha ing SA had bough (2012-2013) annually
se e al ICS-con aining inhale s/canis e s (mean 13.5/yea ) and 8
had bough a leas 1 package o OCS. Two we e on a con in-
uous OCS he apy. The mean bough o al OCS dose was 1975
mg p ednisolone equi alen /2 yea s in hose 6 pa ien s no being
on a con inuous OCS he apy.
Use o heal h ca e in pa ien s wi h nonse e e
as hma, se e e as hma, and hose eligible o an i-
IL-5 ea men
Du ing he 12-yea ollow-up pe iod, he use o heal h ca e
was di e en be ween non-SA, SA, and an i-IL-5 g oups: num-
be o all as hma- ela ed isi s o heal h ca e and numbe o
unplanned isi s ( isi s due o exace ba ions and espi a o y ac
in ec ions) we e highe in SA and an i-IL-5 eligible pa ien s when
compa ed wi h nonse e e pa ien s (Figu e 3). Pa ien s wi h SA
also had mo e equen planned isi s o heal h ca e han pa ien s
wi h non-SA (Figu e 3,B). Howe e , he e was no s a is ically
significan di e ence be ween SA and an i-IL-5 eligible pa ien s
in he numbe o all planned o unplanned heal h ca e isi s. In
addi ion, all an i-IL-5 eligible pa ien s had 3 sick lea es in he
pas 2 yea s be o e he 12-yea ollow-up isi , whe eas he
p opo ion was 16.7% in pa ien s wi h SA (Table III). Howe e ,
pa ien s wi h SA had mos hospi aliza ions du ing he whole
12-yea ollow-up pe iod (Table III).
In o al, an i-IL-5 eligible pa ien s accoun ed o 4.7% o all
as hma- ela ed isi s o heal h ca e and 7.9% o unplanned
as hma- ela ed isi s o heal h ca e, being 2- o 4- old highe han
expec ed. Pa ien s wi h SA accoun ed o 13% o 13.9% o all
and unplanned as hma- ela ed isi s o heal h ca e being mo e
han double han would be expec ed. In e es ingly, he mos
d as ic di e ence was ound in hospi aliza ions: al hough an i-IL-
5 eligible pa ien s accoun ed o only 2% o all hospi al admis-
sions ( he same as expec ed), pa ien s wi h SA accoun ed o 31%
o all hospi aliza ions, which is 5- old mo e han expec ed.
Es ima ion o con idence in e al o he p e alence
o an i-IL-5 eligible pa ien s and se e e as hma
O he o al coho o adul -onse as hma, 2% we e eligible o
an i-IL-5 he apy and 5.9% we e classified as ha ing SA. By
using he boo s apping me hod, he 95% CI limi s o hese
es ima es a e 0.5% o 4.1% o an i-IL-5 eligible pa ien s and
2.9% o 9.4% o SA.
DISCUSSION
In his s udy, we ha e e alua ed he p e alence o pa ien s
eligible o an i-IL-5 he apy in a coho o adul -onse as hma
wi h inclusion o all le els o as hma se e i y and pa ien g oups
such as smoke s and hose wi h como bidi ies. O he o al
coho , 2% we e ound o ulfill he c i e ia o an i-IL-5 eligi-
bili y, namely daily use o medium- o-high ICS dose and LABA,
a leas 2 exace ba ions du ing he p e ious yea , blood eosino-
phils 300 cells/
m
L, and/o FeNO 50 ppb. In addi ion, we
e alua ed he p e alence o SA as defined by he ERS/ATS
c i e ia in his coho , being 5.9% o all pa ien s (Figu e 4).
Fu he mo e, only 1 pa ien ulfilled c i e ia o bo h g oups
(Figu e 4). Pa ien s wi h SA and hose who ulfilled c i e ia o
an i-IL-5 eligibili y we e sepa a ed om nonse e e pa ien s by
highe use o heal h ca e (all and unplanned as hma- ela ed isi s
o heal h ca e), showing ha bo h o hese pa ien g oups
ep esen a majo bu den o heal h ca e. In addi ion, when
compa ing pa ien s wi h SA wi h an i-IL-5 eligible pa ien s,
se e e as hma ics we e mo e o en cu en smoke s a diagnosis
and we e obese, used highe ICS dose, and had highe blood
neu ophils 12 yea s a e diagnosis.
Epidemiological s udies on di e en as hma pheno ypes a e
a e. To ou knowledge, his is he fi s s udy whe e he p e a-
lence o an i-IL-5- ea able as hma among pa ien s wi h adul -
onse as hma was e alua ed. The p e alence o an i-IL-5
eligibili y among SA has been assessed in a Belgian SA
coho including smoking pa ien s and hose wi h como bidi ies
and 30% o pa ien s wi h SA we e ound o be eligible o
an i-IL-5.
23
The c i e ia o an i-IL-5 eligibili y we e simila o
FIGURE 2. P e alence o se e e as hma (SA) in pa ien s wi h
adul -onse as hma. High-in ensi y medica ion e e s o daily use
o high ICS dose oge he wi h second con olle (LABA, LTRA, o
heophylline), o sys emic s e oid o a leas 50% o he p e ious
yea . De ini ion o se e e as hma includes he use o high-
in ensi y medica ion and uncon olled as hma as de ined by ACT
sco e <20, 2 exace ba ions p e ious yea , and/o p e-
b onchodila o FEV
1
<80% p edic ed. ACT, As hma con ol es ;
FEV
1
, o ced expi a o y olume in 1 second; ICS, inhaled co i-
cos e oid; LABA, long-ac ing
b
2
-agonis ; LTRA, leuko iene
ecep o an agonis .
J ALLERGY CLIN IMMUNOL PRACT
VOLUME 7, NUMBER 1
ILMARINEN ET AL 169

he c i e ia used in he p ima y endpoin o ou s udy bu wi h
highe ICS dose equi emen (880
m
gflu icasone equi alen )
and wi h inclusion o spu um eosinophils 3%. A mul icen e
s udy also assessed eligibili y o an i-IL-5 an ibodies mepolizu-
mab and eslizumab among “ eal-wo ld”pa ien s wi h SA and
ound eligibili ies o 20% and 6% o hese agen s, espec i ely.
24
Howe e , he esul s a e di ficul o compa e wi h ou esul due
o di e en pa ien coho s (se e e s gene al) and di e en
c i e ia used o eligibili y (eosinophil coun 150 o mepoli-
zumab o 400 cells/
m
L o eslizumab s 300 cells/
m
L in ou
TABLE II. Cha ac e is ics o pa ien s wi h nonse e e as hma, se e e as hma, and hose eligible† o an i-IL-5 he apy a 12-yea
ollow-up isi
Cha ac e is ic Nonse e e Se e e Eligible o an i-IL-5 P alue
No. o pa ien s 188 11 4
Female, n (%) 108 (57.4%) 7 (63.6%) 3 (75.0%) .726
Age a onse (y) 47 (37-56) 52 (41-55) 49 (40-70) .748
BMI (kg/m
2
) 28.4 (5.5) 32.5 (5.8)*25.6 (5.1) .033
Wi h smoking his o y, n (%) 97 (51.6 %) 8 (72.7%) 2 (50.0%) .392
Cu en smoke s, n (%) 26 (13.8%) 4 (36.4%) 0 .086
Pack-yea s o smoke s 16 (7-30) 18 (15-21) 31 (42) .799
A opic, n (%) 63 (37.3%) 3 (30%) 2 (50.0%) .778
Lung unc ion
P e-BD FEV
1
(% p ed) 86 (18) 81 (19) 79 (16) .557
Pos -BD FEV
1
(% p ed) 89 (17) 83 (19) 81 (18) .399
Pos -FEV
1
/FVC 0.76 (0.69-0.81) 0.72 (0.68-0.74) 0.71 (0.51-0.79) .150
DL
CO
/VA, % p edic ed 96 (16) 92 (18) 87 (25) .462
Daily medica ion
ICS, n (%) 140 (74.5%) 11 (100%) 4 (100%) .081
LABA, n (%) 82 (43.6%) 10 (90.9%)*4 (100%) .001
LTRA, n (%) 22 (11.7%) 5 (45.5%)*0.005
LAMA, n (%) 5 (2.7%) 2 (18.2%)*1 (25%)*.003
Theophylline, n (%) 2 (1.1%) 2 (18.2%) 0 <.001
No. o add-on d ugs 1 (0-1) 2 (1-2)*1.5 (1-2) <.001
ICS dosez786 (406) 2140 (844)*1333 (577)** <.001
High ICS dose,xn (%) 4 (2.1%) 11 (100%)*1 (25 %)*
,
** <.001
Sys emic s e oid, n (%) 1 (0.5%) 3 (27.3%) 0 <.001
Symp oms/quali y o li e
AQ20 sco e 4 (1-7) 8 (4-15)*8 (3-10) .005
ACT sco e 22 (20-24) 16 (10-19)*18.5 (13.3-23.8) <.001
ACT 20 144 (76.6%) 1 (9.1%)*2 (50%) <.001
ACT 16-19 26 (13.8%) 5 (45.5%) 0
ACT <16 18 (9.6%) 5 (45.5%) 2 (50%)
As hma con ol, GINA 2010, n (%) .055
Con olled 68 (36.2%) 1 (9.1%) 0
Pa ially con olled 69 (36.7%) 4 (36.4%) 1 (25.0%)
Uncon olled 51 (27.1%) 6 (54.5%) 3 (75.0%)
Inflamma ion
Blood eosinophils (10
9
/L) 0.17 (0.10-0.27) 0.13 (0.10-0.28) 0.46 (0.12-0.71) .203
Blood eosinophils 0.3 10
9
/L 31 (16.6%) 2 (18.2%) 2 (50.0%) .217
FeNO (ppb) 11 (5-18) 8 (6-15) 41 (13-56) .043
FeNO 50 ppb 8 (4.5%) 0 2 (50.0 %)*
,
** <.001
To al IgE (kU/L) 61 (25-161) 22 (9-76) 307 (67-552) .038
Blood neu ophils (10
9
/L) 3.9 (1.4) 6.3 (2.5)*2.5 (0.6)** <.001
ACT, As hma Con ol Tes ; AQ20, Ai ways Ques ionnai e 20; ATS, Ame ican Tho acic Socie y; BD, b onchodila o ; BMI, body mass index; DL
CO
/VA, di using capaci y adjus ed
by he al eola olume; ERS, Eu opean Respi a o y Socie y; FeNO, ac ion o exhaled ni ic oxide; FEV
1
, o ced expi a o y olume in 1 s; FVC, o ced i al capaci y; GINA, Global
Ini ia i e o As hma; ICS, inhaled co icos e oid; LAMA, long-ac ing musca inic ecep o an agonis ; LABA, long-ac ing
b
2
-agonis ; LTRA, leuko iene ecep o an agonis .
Shown a e n (%) o ca ego ical a iables, and mean (s anda d de ia ion) o median (in e qua ile ange) o con inuous a iables.
Bold indica es s a is ical significance (P<.05).
*P<.05 s nonse e e.
**P<.05 s se e e g oup.
†An i-IL-5 eligible pa ien s e e o hose who ulfill c i e ia o he p ima y endpoin o his s udy (daily use o medium- o-high ICS dose and LABA, 2 exace ba ions pe
p e ious yea , and blood eosinophil le el 300 cells/
m
L o FeNO 50 ppb).
zICS dose as budesonide equi alen s (
m
g).
xBased on ERS/ATS c i e ia.
14
J ALLERGY CLIN IMMUNOL PRACT
JANUARY 2019
170 ILMARINEN ET AL
s udy, exace ba ion equency 2 o mepolizumab and in ou
s udy, 1 o eslizumab). In addi ion, c i e ia o FeNO we e
no included in ha s udy consis en ly wi h he Food and D ug
Adminis a ioneapp o ed c i e ia o an i-IL-5 an ibodies. ERS/
ATS c i e ia
12
(used in ou s udy) o high ICS dose in SA we e
e y s ic and much highe han ha defined by Global Ini ia i e
o As hma (GINA), and as a consequence mos an i-IL-5 eligible
pa ien s we e no defined as se e e as hma ics in ou s udy. Only
1 pa ien o e lap in hese 2 g oups is a su p ising and in e es ing
finding and eflec s he s ic c i e ia o SA by ATS/ERS and
con using cu en s a e o mul iple defini ions o high ICS dose.
Despi e no belonging o he g oup o SA, all an i-IL-5- ea able
pa ien s ulfilled 1 o mo e ea u es o uncon olled as hma (3
pa ien s uncon olled, 1 pa ially con olled acco ding o GINA
2010). I pa ien s wi h SA and hose wi h an i-IL-5 eligibili y a e
combined, he p opo ion o an i-IL-5 eligible pa ien s in his
g oup is 27%, simila ly o he Belgian egis y.
We also e alua ed he p e alence o eosinophilic pheno ype o
adul -onse as hma in he whole s udy coho by using di e en
cu o poin s. The p opo ions o eosinophilic as hma by using
TABLE III. Cha ac e is ics o pa ien s wi h nonse e e as hma, se e e as hma, and hose eligible† o an i-IL-5 he apy du ing he 12-yea
ollow-up pe iod
Cha ac e is ic Nonse e e Se e e Eligible o an i-IL-5 P alue
No. o pa ien s 188 11 4
Lung unc ion decline pe yea z
D
FEVz(mL) 46 (36) 65 (43) 65 (31) .152
D
FEV
1
(% p edic ed) 0.5 (1.0) 1.0 (1.4) 1.2 (0.9) .183
Exace ba ions
Use o o al s e oid cou sesx56 (30.1%) 5 (50%) 4 (100%)*.006
No. o OCS bu s s/2 y{1 (1-2) 3 (1-7) 5 (3-9)*.002
3 sick lea es/2 y#3 (2.0%) 1 (16.7%) 3 (100%)††*<.001
Use o heal h ca e
Hospi aliza ions, n 0 (0-0) 2 (0-4)*0.5 (0-1.75) .005
1 hospi aliza ion, any espi a o y eason (planned and unplanned) 43 (23.0%) 6 (54.5%) 2 (50.0%) .033
1 hospi aliza ion, any espi a o y eason (unplanned) 17 (9.1%) 4 (36.4%)*1 (25.0%) .013
1 hospi aliza ion, as hma- ela ed (planned and unplanned) 29 (15.6%) 4 (36.4%) 1 (25.0%) .185
1 hospi aliza ion, as hma- ela ed (unplanned) 10 (5.4%) 1 (9.1%) 0 .774
Hospi al days, any espi a o y eason (planned and unplanned) 0 (0-0) 2 (0-22)*1.5 (0-4.5) .015
Hospi al days, any espi a o y eason (unplanned) 0 (0-0) 0 (0-21)*0 (0-2) .007
Hospi al days, as hma- ela ed (planned and unplanned) 0 (0-0) 0 (0-14) 0 (0-4) .134
Hospi al days, as hma- ela ed (unplanned) 0 (0-0) 0 (0-0) 0 (0-0) .746
FeNO, F ac ion o exhaled ni ic oxide; FEV
1
, o ced expi a o y olume in 1 s; ICS, inhaled co icos e oid; LABA, long-ac ing
b
2
-agonis ; OCS, o al co icos e oid.
Shown a e n (%) o ca ego ical a iables, and mean (s anda d de ia ion) o median (in e qua ile ange) o con inuous a iables.
Bold indica es s a is ical significance (P<.05).
*P<.05 s nonse e e.
†An i-IL-5 eligible pa ien s e e o hose who ulfill c i e ia o he p ima y endpoin o his s udy (daily use o medium- o-high ICS dose and LABA, 2 exace ba ions pe
p e ious yea , and blood eosinophil le el 300 cells/
m
L o FeNO 50 ppb).
zDecline in FEV
1
om he poin o maximal lung unc ion wi hin 2.5 y a e diagnosis (and s a o he apy) o he 12-yea ollow-up isi .
xPa ien s who ha e used o al s e oid bu s s a leas once du ing he 12-yea ollow-up pe iod.
{Numbe o o al s e oid bu s s in p e ious 2 y be o e 12-y ollow-up isi among hose who needed o al s e oid bu s s.
#Sick lea es ela ed o as hma in he pas 2 y be o e he 12-y ollow-up isi .
††One pa ien wi h missing in o ma ion.
FIGURE 3. A, As hma- ela ed isi s o heal h ca e in pa ien s wi h nonse e e as hma, se e e as hma, and eligible o an i-IL-5 he apy. B,
Planned isi s include as hma- ela ed ollow-up isi s. C, Unplanned isi s include isi s ela ed o exace ba ions and acu e espi a o y
ac in ec ions. An i-IL-5 eligible pa ien s e e o hose who ul ill c i e ia o he p ima y endpoin o his s udy (daily use o medium- o-
high ICS dose and LABA, 2 exace ba ions pe p e ious yea , and blood eosinophil le el 300 cells/
m
L o FeNO 50 ppb). FeNO,
F ac ion o exhaled ni ic oxide; ICS, inhaled co icos e oid; LABA, long-ac ing
b
2
-agonis .
J ALLERGY CLIN IMMUNOL PRACT
VOLUME 7, NUMBER 1
ILMARINEN ET AL 171
he cu -poin o 300 o 400 cells/
m
L o blood eosinophils we e
17.3% and 10.4%, espec i ely. P e ious s udies ound 26.4%
25
and 16%
26
p e alence by using he same cu o s, espec i ely,
bu used selec ed coho s (exclusion o pa ien s wi h coexis ing
ch onic obs uc i e pulmona y disease
26
o inclusion o hose
wi h egula ea men [medium- o-high ICS dose] o as hma
25
).
So a , li le is known abou he p e alence o SA among all
as hma ics e en hough es ima es o 5% o 10% ha e o en been
p oposed wi h unclea basis o he es ima e. P e ious pha macy-
based s udies ha e ound he p e alence o SA om 3.6% (Du ch
s udy)
13
o 4.6% (Is aeli s udy).
27
In he Du ch s udy, only
3.6% we e defined as ha ing SA a e excluding hose wi h poo
adhe ence o an inco ec inhala ion echnique. In ou s udy wi h
pa ien s ha ing as hma diagnosis clinically confi med by espi-
a o y specialis and lung unc ion measu emen s, 5.9% (CI
2.9% o 9.4%) we e classified as ha ing SA acco ding o he
defini ion ag eed by he ATS/ERS Task Fo ce.
12
E en hough
he p e alence es ima es (3.6% o 4.6%) ob ained om he
pha macy-based s udies
13,27
a e somewha lowe , hey all wi hin
he 95% CI (2.9% o 9.4%) o SA ob ained in he p esen
s udy, and sugges ha pha macy da abase s udies may be a way
o wa d o ob ain c ude es ima es o SA. Di e ences in he age o
as hma onse , lack o objec i e as hma diagnosis, exclusion o
hea y smoke s, and defini ion o SA may a ec he di e ence
seen be ween he p e alence o SA in ou and he p e ious
s udies.
13,27
SA is no a single disease, bu a he e ogeneous g oup wi h
many subpheno ypes. Age a disease onse has been ound as a
di e en ia ing ac o o as hma pheno ypes in many s udies,
sepa a ing alle gic and a opic ea ly-onse pheno ype om less
alle gic adul -onse pheno ypes.
1,3,28,29
Adul -onse sub-
pheno ypes such as eosinophilic inflamma ion-p edominan ,
mild- o-mode a e well-con olled, obese noneosinophilic,
smoking as hma, and se e e obs uc i e as hma ha e been
iden ified by se e al clus e analyses.
1
La e-onse se e e eosin-
ophilic as hma ep esen s only 1 subpheno ype, and in a s udy
o his size, a andom p edominance o a pa icula pheno ype
may ha e a ec ed he p opo ion o subjec s iden ified as an i-
IL-5 eligible. In he Belgian SA egis y,
23
hep e alenceo he
eosinophilic pheno ype (blood eosinophils 300 cells/
m
L) in
he SA coho was 36%. Inflamma ion in ou pa ien s wi h SA
was o en neu ophil p edominan . This is in conco dance wi h
p e ious s udies in which SA has been associa ed wi h
neu ophilic ai way inflamma ion.
30,31
Whe he neu ophilic
inflamma ion is due o di e en pa hological mechanisms in
SA, o a esponse o high-dose glucoco icoid ea men in
hese pa ien s, emains unknown. Neu ophilia as well as low
numbe o pa ien s wi h SA wi h ele a ed blood eosinophils in
ou coho may also be ela ed o good adhe ence o ICS
ea men .
To ou knowledge, he e exis no s udies wi h compa ison
be ween SA and an i-IL-5 eligible pa ien s. Se e e (uncon olled)
as hma has been associa ed wi h he inc eased use o heal h ca e,
obesi y, and smoking in p e ious s udies when compa ed wi h
nonse e e as hma ics,
27
being consis en wi h ou esul s.
Numbe o hospi al admissions and isi s o gene al p ac i ione
and as hma specialis ha e been epo ed o be highe in pa ien s
wi h SA as compa ed wi h nonse e e pa ien s in ollow-up o 1
yea .
27
In a US s udy wi h 11-mon h ollow-up, pa ien s wi h
eosinophilic (400 cells/
m
L) SA (se e i y defined solely by use o
medica ion) we e epo ed o be mo e o en hospi alized bu had
no mo e ou pa ien o eme gency oom isi s when compa ed
wi h hose wi h no mal eosinophils.
32
In con as , in ou s udy,
an i-IL-5 eligible pa ien s isi ed heal h ca e equen ly, had he
high numbe o o al s e oid cou ses and sick lea es, bu hospi-
aliza ions we e no inc eased as compa ed wi h SA. F equency o
hospi aliza ions in pa ien s wi h SA may be pa ly explained by
obesi y and smoking as well as como bidi ies, all being associa ed
wi h poo ou come o as hma.
17,19,33
The es ima e o an i-IL-5 eligible pa ien s in his gene al
popula ion o as hma ics was 2%. A majo limi a ion o his
s udy is he ela i ely small sample size. Howe e , by using
boo s ap analysis ela i ely na ow, 95% CI o 0.5% o 4.1%
o an i-IL-5 eligibili y was ob ained. Ano he limi a ion
a ec ing he gene alizabili y o ou findings is he ela i ely low
a e o pa ien s wi h uncon olled as hma in ou coho (29.6%)
when compa ed wi h p e ious s udies a ying om 27% o
74%.
34-37
Di e en pa ien popula ion and me hod o assessing
con ol o as hma as well as be e adhe ence o ea men in ou
s udy may explain he di e ence. On he o he hand, good
adhe ence o ea men is essen ial when conside ing biological
d ugs and can be conside ed as a s eng h when assessing he
p e alence o an i-IL-5 eligibili y. Many pa ien s wi h SA su e
om mul imo bidi y (including eflux disease o sinusi is),
38
and
i como bidi ies a e add essed p ope ly, his can lead o es o-
a ion o as hma con ol and ob ia e he need o p esc ibing a
biologic agen . Ou an i-IL-5 eligible pa ien s had e y ew
como bidi ies al oge he , and none o he 4 an i-IL-5 eligible
pa ien s epo ed eflux disease. Sinusi is was no objec i ely
e alua ed in he ollow-up isi in each pa ien bu du ing he
12-yea ime, 3 o he 4 an i-IL-5 eligible pa ien s had had
se e al isi s o heal h ca e because o sinus p oblems and we e
p esc ibed pe manen nasal s e oid o long- e m hini is.
Howe e , we canno exclude he possibili y ha sinus p oblems
ha e a ec ed as hma de elopmen in o se e e o m and whe he
hey could ha e been be e add essed. In addi ion, ou s udy
excluded childhood-onse as hma ics, also limi ing he gene al-
izabili y o he findings.
FIGURE 4. P e alence o an i-IL-5 eligible as hma, se e e as hma,
and nonse e e as hma in coho o adul -onse as hma (SAAS).
One pa ien o e lap exis ed in he g oups o an i-IL-5 eligibili y and
se e e as hma. CI, Con idence in e al; SAAS, Seinäjoki Adul
As hma S udy.
J ALLERGY CLIN IMMUNOL PRACT
JANUARY 2019
172 ILMARINEN ET AL
This s udy was ca ied ou by using c i e ia equi alen o he
clinical indica ions app o ed o used in s udies. Despi e he
clinical benefi s o an i-IL-5 ea men , he d ugs a e cos ly, and
acco ding o a p elimina y cos -e ec i eness analysis o mepoli-
zumab, i may exceed commonly used h esholds.
39
The p e-
limina y cos -e ec i eness analysis has been based on da a
a ailable om clinical ials. Thus, i is possible ha in he u u e
an i-IL-5 he apy will be a ge ed di e en ly. Recen s udies
sugges ha he cha ac e is ics o pa ien s ob aining be e benefi
may include hose wi h highe eosinophil le els
40,41
and as hma
onse a e 40 yea s.
42
In summa y, in an unselec ed coho o adul -onse as hma,
we ha e shown 2% p e alence o eosinophilic s e oid- esis an
exace ba ion-p one as hma ha could benefi om hean i-IL-
5 an ibody and 5.9% p e alence o SA. Only 1 pa ien me
c i e ia o bo h g oups. Pa ien s wi h SA and hose eligible o
an i-IL-5 he apy di e ed by cu en smoking, obesi y, and
mo e neu ophil-p edominan disease in pa ien s wi h SA.
Acco ding o ou esul s including excep ionally long 12-yea
ollow-up da a o heal h ca e use, bo h g oups a e a high
bu den o heal h ca e, sugges ing ha he cu en ea men s
a e ine ec i e o hese pa ien s. I is impo an o iden i y
hese pheno ypes as ea ly as possible because hey may benefi
om a ge ed ea men ha could lead o lowe long- e m use
o heal h ca e.
Acknowledgmen
Aino Sepponen, RN, is g a e ully acknowledged o he help
h ough all he s ages o his wo k.
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