1130-0108/2020/112/7/555-558 • REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
© Copy igh 2020. SEPD y © ARÁN EDICIONES, S.L.
REV ESP ENFERM DIG 2020:112(7):555-558
DOI: 10.17235/ eed.2020.7130/2020
Del Pino Bellido P, Bel is Jiménez M, Cas o La ia L, Maldonado Pé ez B, Sáez Díaz
A, Caunedo Ál a ez A, A güelles-A ias F. Vedolizumab esponse in in lamma o y
bowel disease. Two yea s o ollow-up. Re Esp En e m Dig 2020;112(7):555-558
DOI: 10.17235/ eed.2020.7130/2020
Vedolizumab esponse in in lamma o y bowel disease. Two yea s
o ollow-up
ORIGINAL PAPERS
Pila del Pino Bellido1, Ma ía Bel is Jiménez1, Luisa Cas o La ia1, Belén Maldonado Pé ez1, An onia Sáez Díaz1,
Ángel Caunedo Ál a ez1 and Fede ico A güelles-A ias1,2
1Gas oen e ology and Hepa ology Depa men . Hospi al Uni e si a io Vi gen Maca ena. Se illa, Spain. 2Facul ad de Medicina. Uni e sidad de Se illa.
Se illa, Spain
Recei ed: 15/04/2020 · Accep ed: 04/06/2020
Co espondence: Pila del Pino Bellido. Gas oen e ology and Hepa ology Depa men . Hospi al Uni e si a io Vi gen
Maca ena. C/ D . Fed iani, 3. 41009 Se illa, Spain. e-mail: [email p o ec ed]
ABSTRACT
Backg ound: edolizumab is an α4β7 in eg in an agonis .
The aim o his s udy was o e alua e he clinical esponse
and emission a es wi h edolizumab.
Me hods: his was a e ospec i e s udy o in lamma o y
bowel disease (IBD) pa ien s who ecei ed edolizumab
be ween 2016 and 2019. Response and emission a es
we e analyzed a h ee, six, 12, 18 and 24 mon hs a e
induc ion.
Resul s: i y- i e pa ien s we e included. Clinical emis-
sion a es in CD and UC a h ee, six, 12, 18 and 24 mon hs
we e 19.35 %, 26.67 %, 30.43 %, 30 %, 38.89 % and 29.17 %,
26.09 %, 19.05 %, 26.67 % and 20 %, espec i ely.
Conclusions: edolizumab is e ec i e o induc ion and
main enance o clinical emission, bo h in C ohn’s disease
and ulce a i e coli is.
Keywo ds: Vedolizumab. Response. Remission.
INTRODUCTION
Vedolizumab is a ully humanized monoclonal IgG-1 an i-
body ha selec i ely inhibi s he in e ac ion be ween α4β7
in eg in and mucosal add essin cell adhesion molecule-1
(MAdCAM-1). The e o e p e en ing lymphocy e anslo-
ca ion om he blood in o he in lamed gu issue, which
esul s in a educ ion in local in lamma ion (1). In he GEMI-
NI s udies, edolizumab p o ed o be e ec i e as an induc-
ion and main enance he apy in mode a ely o se e ely
ac i e ulce a i e coli is (UC) and C ohn’s disease (CD) (2,3).
Immunogenici y o edolizumab appea s o be low (4) and
i seems o ha e a a o able sa e y p o ile (5).
The p ima y aim o his s udy was o explo e, acco ding o
he clinical p ac ice, he esponse and emission a es o
edolizumab in ou cen e a e 24 mon hs. The seconda y
aim was o assess whe he he e we e any p edic o s o
esponse o edolizumab.
MATERIALS AND METHODS
S udy design and pa ien popula ion
A e ospec i e, single cen e , obse a ional s udy was pe -
o med a he Hospi al Uni e si a io Vi gen Maca ena, Se ille,
Spain. Adul pa ien s (≥ 18 yea s) wi h CD o UC ecei ing
edolizumab ( i s line o a e p e ious biologic ailu e)
be ween Janua y 1s 2016 and July 1s 2019 we e included.
Inclusion c i e ia we e:
1. A con i med diagnosis o CD o UC.
2. Pa ien s who ecei ed a leas a comple ed induc ion
egimen o in a enous (IV) edolizumab. The s anda d
dosing egimen consis ed in induc ion (300 mg IV a
ze o, wo and six weeks), ollowed by main enance
(300 mg IV e e y eigh weeks).
Ou comes and de ini ions
Response and emission de ini ions we e based on he Ha -
ey B adshaw index (HBI) and Mayo sco ing index (MSI).
Clinical emission was conside ed when MSI was ≤ 2 and
HBI was ≤ 4. Clinical esponse was de ined as a dec ease o
a leas wo poin s in he HBI o MSI index om hei p e i-
ous sco e. Clinical esponse and emission we e analyzed
a h ee, six, 12, 18 and 24 mon hs.
Da a collec ion
Da a o pa ien s ea ed wi h edolizumab om Janua y 2016
o July 2019 we e collec ed. All pa ien s we e ollowed in
ou in lamma o y bowel disease (IBD) uni du ing he s udy
P. del Pino Bellido e al.
REV ESP ENFERM DIG 2020:112(7):555-558
DOI: 10.17235/ eed.2020.7130/2020
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pe iod. An anonymous da abase was c ea ed ha included
demog aphic a iables, smoking s a us, disease du a ion,
disease pheno ype, p e ious and concu en IBD ea men s
a baseline and clinical measu es o disease ac i i y a edol-
izumab induc ion and a mon hs h ee, six, 12, 18, 24.
S a is ical analysis
Baseline demog aphic cha ac e is ics we e analyzed wi h
s anda d desc ip i e s a is ics. Fo he analysis o quan i a-
i e a iables, he non-pa ame ic U Mann-Whi ney es was
used o he compa ison o he g oups. S a is ical signi i-
cance was conside ed when p < 0.05. The p opo ion o clin-
ical esponde s o edolizumab was compa ed a each ime
poin using he Pea son’s Chi‐squa ed es . Uni a ia e and
mul i a iable logis ic eg ession analyses we e pe o med
o e alua e p edic o s o clinical and objec i e emission a
h ee, six, 12, 18 and 24 mon hs. Wi h ega d o he esponse
and emission a e analysis, pa ien s who had ad e se e ec s
and hose who had no ye comple ed ollow-up we e exclud-
ed. The e o e, he analysis included pa ien s wi h ea men
ailu e (including hose equi ing su ge y).
RESULTS
Baseline pa ien cha ac e is ics
Fi y- i e pa ien s (31 CD, 24 UC) we e included in he s udy.
Figu e 1 summa izes he pa ien lowcha o he s udy and
demog aphics a e summa ized in able 1; 83.9 % (26/31)
o he pa ien s wi h CD and 100 % o he pa ien s wi h CU
had ecei ed an i-TNFα he apies p io o ini ia ing edol-
izumab. Mos o he pa ien s had ecei ed wo di e en
an i-TNFα he apies (46.2 % CD, 62.5 % UC). The main ea-
son o he onse o edolizumab was he lack o esponse
o p e ious ea men s (64.5 % CD, 95.8 % UC), ollowed
by ad e se e ec s o p e ious he apy (19.4 % CD, 4.2 %
CU). In addi ion, 12.9 % s a ed edolizumab as a i s line
he apy due o concomi an diseases.
Table 1. Baseline pa ien demog aphics
C ohn’s disease
(n = 31)
Ulce a i e coli is
(n = 24)
Gende (n, %)
Men
Women
8 (25.8)
23 (74.2)
13 (54.2)
11 (45.8)
Age (mean ± SD)
41.7 ± 12.9 41.4 ± 14.9
Smoking s a us (n, %)
Smoke s
Non smoke s
Ex-smoke
9 (29)
17 (54.8)
5 (16.1)
1 (4.2)
21 (87.5)
2 (8.3)
Mon eal
(n, %)
Age
A1: 8 (25.8)
A2: 16 (51.6)
A3: 7 (22.6)
Loca ion
L1: 6 (19.4)
L2: 12 (38.7)
L3: 12 (38.7)
L3+L4: 1 (3.2)
E1: 5 (20.8)
E2: 14 (58.3)
E3: 5 (20.8)
Beha io
B1: 13 (41.9)
B2: 10 (32.3)
B3: 8 (25.8)
S1: 7 (29.2)
S2: 10 (41.7)
S3: 7 (29.2)
Basal Ha ey B adshaw index
(mean ± SD)
7.81 ± 2.02 --
Basal Mayo sco ing index
(mean ± SD)
-- 6,42 ± 2.3
Pe ianal disease (n, %)
11 (35.5) 1 (4.2)
Ex ain es inal mani es a ions
(n, %)
17 (54.8) 8 (33.3)
P e ious an i-TNF ea men
In liximab
Adalimumab
IFX y ADA
IFX, ADA and golimumab
IFX, ADA and ce olizumab
ADA and ce olizumab
26 (83.9)
1 (3.8)
6 (23.1)
12 (46.2)
1 (3.8)
5 (19.2)
1 (3.8)
24 (100)
5 (20.8)
1 (4.2)
15 (62.5)
3 (12.5)
0 (0)
0 (0)
Concomi an ea men
AZT
MTX
Co icos e oids
2 (6.5)
4 (12.9)
22 (71)
5 (20.8)
3 (12.5)
16 (66.7)
Fig. 1. S udy lowcha .
55 pa ien s
3 mon hs
6 mon hs
12 mon hs
18 mon hs
24 mon hs
31 CD 24 UC
31
29
16
12
10
9
1 non- esponde
1 did no comple e ollow-up
1 su ge y
1 los ollow-up
1 non- esponde
3 non- esponde s
2 did no comple e ollow-up
1 non- esponde
5 did no comple e ollow-up
1 in ole ance
1 in ole ance
1 non- esponde
1 did no comple e ollow-up
1 in ole ance
1 non- esponde
2 did no comple e ollow-up
4 non- esponde s
6 did no comple e ollow up
1 dea h
1 ad e se e en
1 su ge y
23
21
16
9
Vedolizumab esponse in in lamma o y bowel disease. Two yea s o ollow-up
REV ESP ENFERM DIG 2020:112(7):555-558
DOI: 10.17235/ eed.2020.7130/2020
557
Clinical esponse and emission
Clinical esponse and emission a es o edolizumab he a-
py in CD and UC a e summa ized in igu es 1 and 2. O e all,
he e was a dec ease in he Ha ey-B adshaw and Mayo
index alues compa ed o baseline a h ee, six, 12, 18 and
24 mon hs (p < 0.05), as well as a dec ease in C- eac i e p o-
ein. Nine pa ien s (6 CD, 3 UC) equi ed a 4 h dose o edol-
izumab a week 10. Nine pa ien s (29 %) wi h CD equi ed
in ensi ica ion o edolizumab.
P edic o s o clinical and objec i e emission wi h
edolizumab
In he mul i a ia e analysis, no ela ionship was obse ed
wi h age, smoking, ype o disease o p e ious an i-TNF
and highe esponse a es. A 12 mon hs, highe esponse
and emission a es we e obse ed in emales (81.8 %,
p = 0.039), while 87.5 % o pa ien s wi h CD ea ed wi h
co icos e oids did no espond a six mon hs.
Fig. 2. Clinical esponse and emission a es in CD.
Fig. 3. Clinical esponse and emission a es in UC.
P. del Pino Bellido e al.
REV ESP ENFERM DIG 2020:112(7):555-558
DOI: 10.17235/ eed.2020.7130/2020
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Sa e y p o ile o edolizumab
Fi e pa ien s (3 CD, 2 CU) expe ienced an ad e se e en ,
ou equi ed suspension. One pa ien p esen ed abdomi-
nal pain and omi ing, wo pa ien s (1 CD, 1 UC) had skin
lesions and he emaining wo expe ienced headaches and
join pain. One pa ien (CD) died du ing ollow-up due o
a espi a o y ailu e, as a consequence o a neph o ic syn-
d ome in he con ex o a seconda y amyloidosis.
DISCUSSION
Pi o al s udies ha e shown edolizumab o be e ec i e and
sa e, bo h o induc ion and main enance in pa ien s wi h
IBD (2,3). CD pa ien s ea ed wi h edolizumab p esen clin-
ical emission a es o a ound 19 % a h ee mon hs, shown
bo h in a eal-wo ld coho in Canada (6), a p ospec i e
Ge man s udy (7) and he p esen s udy (19.35 %). In UC,
clinical emission a es a h ee mon hs ange be ween 23
and 51 % (6-12). Speci ically, we epo a es o 29.17 % in
ou s udy. The a iance may be due o di e en inclusion
c i e ia and de ini ions o ac i e disease, emission and
esponse, which may cause di e ences in he se e i y o
he disease be ween each popula ion. Fo ins ance, Ko ze
epo ed a clinical emission a e o 51 % in UC. This s udy
included 54 % o UC pa ien s wi h a p e ious biologic ail-
u e, compa ed o 100 % in ou s udy.
A 12 mon hs, clinical emission a es o 30.43 % in CD
we e obse ed in ou s udy. This a e is sligh ly highe han
ha epo ed by Ko ze (6), bu somewha lowe han hose
epo ed in he GEMINI ial (3) and VICTORY conso ium
ial (12). The di e ences wi h he GEMINI ial may be due
o he p opo ion o pa ien s who had ecei ed p io an i-
TNF he apy, which was limi ed o 50 %. Lowe emission
a es we e ound in UC pa ien s han ha epo ed in he
li e a u e (2,6,13,14), bo h a 12 and 18 weeks. The la ge
numbe o pa ien s in his s udy compa ed o ou s may
explain his di e ence.
Subg oup analyses o GEMINI 2 showed highe clinical
emission a es in males, younge pa ien s and CD pa ien s
wi h a sho e disease du a ion (5). Howe e , highe
esponse and emission a es we e obse ed in emales
only a 12 mon hs compa ed o males. Besides, p e ious
s udies sugges ha p io ea men wi h co icos e oid is
associa ed wi h a lack o clinical emission (11,15). This is
consis en wi h ou esul s, as pa ien s wi h concomi an
ea men wi h co icos e oids we e less likely o achie e
clinical emission a six mon hs.
Ou s udy has se e al limi a ions. Fi s ly, he numbe o
pa ien s is educed. Secondly, i is a e ospec i e and sin-
gle-cen e s udy. Howe e , p elimina y in o ma ion was
ob ained ha may ac as a s a ing poin o u u e e alua-
ions o he impac o edolizumab in IBD pa ien s.
In conclusion, ea men wi h edolizumab is e ec i e o
induc ion and main enance o clinical emission in pa ien s
wi h IBD who ha e no esponded o o ole a ed an i-TNF
ea men .
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