SYSTEMATIC REVIEW
published: 15 Janua y 2021
doi: 10.3389/ med.2020.618163
F on ie s in Medicine | www. on ie sin.o g 1Janua y 2021 | Volume 7 | A icle 618163
Edi ed by:
F ancesco Ciccia,
Uni e si y o Campania Luigi
Van i elli, I aly
Re iewed by:
Ra aele Sca pa,
Uni e si y o Naples Fede ico II, I aly
Ennio Lub ano,
Uni e si y o Molise, I aly
*Co espondence:
Tiago To es
[email p o ec ed]
†These au ho s ha e con ibu ed
equally o his wo k
Special y sec ion:
This a icle was submi ed o
Rheuma ology,
a sec ion o he jou nal
F on ie s in Medicine
Recei ed: 16 Oc obe 2020
Accep ed: 26 No embe 2020
Published: 15 Janua y 2021
Ci a ion:
To es T, Ba celos A, Filipe P and
Fonseca JE (2021) A Sys ema ic
Re iew Wi h Ne wo k Me a-Analysis
o he A ailable Biologic The apies o
Pso ia ic Disease Domains.
F on . Med. 7:618163.
doi: 10.3389/ med.2020.618163
A Sys ema ic Re iew Wi h Ne wo k
Me a-Analysis o he A ailable
Biologic The apies o Pso ia ic
Disease Domains
Tiago To es1,2*†, Anabela Ba celos3,4,5†, Paulo Filipe6,7,8 and João Eu ico Fonseca9,10
1Depa men o De ma ology, Cen o Hospi ala Uni e si á io do Po o, Po o, Po ugal, 2Mul idisciplina Medical Resea ch
Uni , Ins i u o de Ciências Biomédicas Abel Salaza , Uni e si y o Po o, Po o, Po ugal, 3Rheuma ology Depa men , Cen o
Hospi ala do Baixo Vouga, A ei o, Po ugal, 4NOVA Na ional School o Public Heal h, Public Heal h Resea ch Cen e,
Uni e sidade NOVA de Lisboa – Po ugal, Lisbon, Po ugal, 5Comp ehensi e Heal h Resea ch Cen e (CHRC), Uni e sidade
NOVA de Lisboa – Po ugal, Lisbon, Po ugal, 6Se iço de De ma ologia e Vene eologia, Hospi al de San a Ma ia, Cen o
Hospi ala Uni e si á io Lisboa No e, Lisbon, Po ugal, 7Unidade de In es igação em De ma ologia, Ins i u o de Medicina
Molecula João Lobo An unes, Faculdade de Medicina, Uni e sidade de Lisboa, Lisbon, Po ugal, 8Clínica Uni e si á ia de
De ma ologia, Faculdade de Medicina da Uni e sidade de Lisboa, Lisbon, Po ugal, 9Se iço de Reuma ologia e Doenças
Ósseas Me abólicas, Hospi al de San a Ma ia, Cen o Hospi ala Uni e si á io Lisboa No e, Lisbon, Po ugal, 10 Unidade de
In es igação em Reuma ologia, Ins i u o de Medicina Molecula João Lobo An unes, Faculdade de Medicina, Uni e sidade
de Lisboa, Lisbon, Po ugal
In oduc ion: Se e al new ea men s ha e been de eloped o pso ia ic disease, an
in lamma o y condi ion ha in ol es skin and join s. No wi hs anding, ew s udies ha e
made di ec compa isons be ween ea men s and he e o e i is di icul o selec he
ideal ea men o an indi idual pa ien . The aim o his sys ema ic e iew wi h ne wo k
me a-analysis (NMA) was o analyze a ailable and app o ed biologic he apies o each
domain o pso ia ic disease: skin, pe iphe al a h i is, axial a h i is, en hesi is, dac yli is,
and nail in ol emen .
Me hods: Da a om andomized clinical ials (RCTs) we e included. A sys ema ic e iew
was pe o med using he MEDLINE da abase (July 2020) using PICO c i e ia. Bayesian
NMA was conduc ed o compa e he clinical e icacy o biological he apy in e ms o
he Ame ican College o Rheuma ology c i e ia (ACR, 24 weeks) and Pso iasis A ea and
Se e i y Index (PASI, 10–16 weeks).
Resul s: Fi y- ou RCTs we e included in he sys ema ic e iew. Due o he design o
he RCTs, namely, ou comes and ime poin s, ne wo k me a-analysis was pe o med
o skin and pe iphe al a h i is domains. Fo he skin domain, 30 s udies epo ing
PASI100 we e included. The pe iphe al a h i is domain was analyzed h ough ACR70
in 12 s udies. F om he he apies app o ed o bo h domains, secukinumab and
ixekizumab we e he ones wi h he highes p obabili y o eaching he p oposed
ou comes. The e is a lack o ou come uni o miza ion in he dac yli is, en hesi is, and
nail domains, and he e o e, an objec i e compa ison o he s udies was no easible.
Ne e heless, secukinumab was he ea men wi h he bes comp omise be ween he
numbe o s udies in each domain and he esul s ob ained in he di e en ou comes.
To es e al. Biologic The apy o Pso ia ic Disease
Conclusion: Secukinumab and ixekizumab we e he ea men s wi h he highes
p obabili y o eaching bo h PASI100 and ACR70 ou comes. Due o he lack o a s anda d
e alua ion o ou comes o he o he pso ia ic disease domains, a ne wo k me a-analysis
o all he domains was no possible o pe o m.
Keywo ds: pso iasis, pso ia ic a h i is, pso ia ic disease, biologic he apy, sys ema ic e iew, ne wo k
me a-analysis
INTRODUCTION
Pso iasis (PsO) a ec s 1–3% o he wo ld popula ion. Pso ia ic
a h i is (PsA) occu s in a hi d o he pa ien s wi h PsO. These
wo condi ions sha e clinical, gene ic, and pa hogenic ac o s and
can be conside ed a single en i y—pso ia ic disease (PsD) (1–3).
PsD in ol es ch onic in lamma ion o he skin, nails, and
join s (a h i is, en hesi is, dac yli is, and spondyli is) (4).
Au oimmune mechanisms a e in ol ed in PsA pa hogenesis, and
his is ul ima ely ela ed wi h he sys emic na u e o he disease
and aised he concep o a Sys emic Pso ia ic Disease. This
ac highligh s he he e ogenei y o he disease and he need o
op imizing i s managemen (5).
Op imal managemen o PsD equi es ea ly diagnosis,
moni o ing o he disease ac i i y, and ea men wi h e ec i e
and sa e he apies. O e he las 20 yea s, a ge ed he apies
eme ged in he ea men o PsD, namely, biologic agen s such as
umo nec osis ac o inhibi o s (TNFi), IL-17 inhibi o s (IL-17i),
and IL-12/23 inhibi o s (IL-12/23i), and small molecules, such as
Janus Kinase (JAK) o phosphodies e ase 4 (PDE4) inhibi o s (6).
The G oup o Resea ch and Assessmen o Pso iasis and
Pso ia ic A h i is (GRAPPA) is a global associa ion o mo e
han 500 heuma ologis s, de ma ologis s, and pa ien esea ch
pa ne s ha publish ea men ecommenda ions o PsD
(2). The ea men o six domains—pe iphe al a h i is, axial
disease, en hesi is, dac yli is, skin disease, and nail disease—
a e included in he ecommenda ions di ec ed o anyone
in ol ed in he ea men o pa ien s wi h PsD (2). Based on
hese ecommenda ions, we pe o med a sys ema ic e iew and
ne wo k me a-analyses assessing he main esul s o andomized
clinical ials (RCT) including biologic he apies in he ea men
o pa ien s wi h PsD.
METHODS
Li e a u e Sea ch
A li e a u e sea ch acco ding o he Popula ion, In e en ion,
Compa a o , Ou comes (PICO) amewo k was pe o med
es ablishing c i e ia o s udy eligibili y. The popula ion was
de ined as adul (≥18 yea s) pa ien s wi h he PsD (PsO and/o
PsA) and he in e en ion as any biologic he apy: adalimumab
(ADA), e ane cep (ETN), in liximab (IFX), golimumab (GOL),
ce olizumab (CZP), us ekinumab (UST), secukinumab (SEC),
ixekizumab (IXE), guselkumab (GUS), b odalumab (BRD),
isankizumab (RIS), and ild akizumab (TIL), in all o mula ions
and ea men du a ions. The compa a o was he same d ug
(di e en dose o egimen), any di e en d ug, o placebo.
Ou comes conside ed we e Ame ican College o Rheuma ology
(ACR) o Pso iasis A ea Se e i y Index (PASI) o dac yli is
assessmen o en hesi is assessmen o nail pso iasis assessmen .
The MEDLINE da abase sea ch was pe o med on 1 July 2020,
wi h he il e s “Humans,” “Clinical T ials,” “Phase III,” and
“English,” wi h no da e limi s. In line wi h he GRAPPA and
EULAR ecommenda ions, we did no include aba acep in his
sys ema ic e iew. In addi ion, as his sys ema ic e iew was
ocused only on biologic ea men s ap emilas and o aci inib
we e no analyzed.
S a is ics and Ne wo k Me a-Analyses
Ne wo k me a-analyses (NMA) we e ca ied ou using he
web applica ion CINeMA 1.9.0 (Con idence in Ne wo k Me a-
Analysis) om Coch ane (7). This applica ion is based on a
desc ibed me hodological amewo k ha conside s six domains:
wi hin-s udy bias, epo ing bias, indi ec ness, imp ecision,
he e ogenei y, and incohe ence (8). NMAs based on he Bayesian
amewo k using he ixed-e ec s model we e pe o med o
pool all he di ec and indi ec e idence oge he . Odds a io
(OR) wi h 95% c edible in e als (C I) was used o e alua e
compa isons. Only compa isons showing high con idence in he
six domains we e conside ed o he esul s.
Assessmen o Bias
Assessmen o bias was pe o med using he la es e sion o
RoB2—Coch ane (9).
RESULTS
A de ailed lowcha wi h he esul s o he li e a u e e iew
is shown in Figu e 1. Ou o he 232 e e ences e ie ed, 82
s udies we e selec ed o da a (1,11–57). Fo NMAs, only s udies
epo ing ACR20, ACR50, ACR70 (pe iphe al a h i is domain),
PASI75, PASI90, o PASI100 (skin domain) we e included. Fo
he pe iphe al a h i is domain, only 24 weeks we e included.
Fo he skin domain, esul s be ween 10 and 16 weeks we e
conside ed. Mo eo e , he doses o he d ugs o he sys ema ic
e iew and NMAs, o he pe iphe al a h i is and skin domains,
we e he ones app o ed by he egula o y au ho i ies. The s udies
included in he NMAs a e iden i ied in Table 1. Ex ension s udies
a e speci ied in Table 2 (48,58–84). In Figu e 2 he d ugs
ha ha e been s udied speci ically o each domain o PsD
we e included.
Pe iphe al A h i is
The pe iphe al a h i is domain is p edominan ly assessed by
ins umen s, such as ACR20, ACR50, and ACR70 c i e ia, which
F on ie s in Medicine | www. on ie sin.o g 2Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
FIGURE 1 | PRIMA low diag am. Adap ed om (10).
speci y he imp o emen o 20, 50, o 70% in he numbe o
ende and swollen join s, espec i ely, and a 20, 50, o 70%
imp o emen in h ee o he ollowing i e c i e ia: pa ien
global assessmen , physician global assessmen , unc ional abili y
measu e (mos o en Heal h Assessmen Ques ionnai e—HAQ),
isual analog pain scale, and e y h ocy e sedimen a ion a e o
C- eac i e p o ein (85). The main esul s o he ACR esponse
in RCTs, a 24 weeks, a e included in Table 3 (1,11,18,
24,26,28,31,32,37,38,47,51,55). The head- o-head
compa ison o he ACR esponses o SEC s. ADA a week
F on ie s in Medicine | www. on ie sin.o g 3Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
TABLE 1 | RCT included in he sys ema ic e iew and NMA, ocusing on he ou comes o GRAPPA domains.
S udy En olled pa ien s NMA
Au ho Yea ND ug Dosage Ou comes
IMPACT 2 (1) An oni 2005 200 IFX 5 mg/kg ①②③④
⑤⑥⑦⑧
YES
PLB
ADEPT (11) Mease 2005 313 ADA 40 mg ①②③
④⑤⑥
YES
PLB
(12) Reich 2005 378 IFX 5 mg/kg ④⑤
⑥⑩
YES
PLB
(13) Geno ese 2007 100 ADA 40 mg ①②③
⑦⑨
NO
PLB
(14) Ty ing 2007 618 ETN 50 mg ④⑤⑥ YES
PLB
PHOENIX 1 (15) Leona di 2008 766 UST 45 mg ④⑤⑥ YES
UST 90 mg
PLB
PHOENIX 1 (16) Papp 2008 1,230 UST 45 mg ④⑤⑥ YES
UST 90 mg
PLB
(17) Rich 2008 378 IFX 5 mg/kg ⑩NO
PLB
(18) Ka anaugh 2009 405 GOL 50 mg ①②③
④⑤⑥
⑧⑨⑩
YES
GOL 100 mg
PLB
(19) Ba ke 2011 868 IFX 5 mg/kg ④⑤⑥ YES
MTX 15 mg
(20) Go lieb 2011 347 BRK 200 mg ⑤⑥⑦ YES
ETN 50 mg
PLB
(21) S obe 2011 350 BRK 200 mg ⑤⑥⑦ YES
ETN 50 mg
PLB
RESPOND (22) Ba anauskai e 2012 115 IFX +MTX 5 mg/kg ①②③
⑤⑧⑨
NO
MTX 15 mg
(23) Go lieb 2012 478 MTX +ETN 15 mg +50 mg ④⑤⑥ NO
PSUMMIT 1 (24) McInnes 2013 615 UST 45 mg ①②③
⑥⑧⑨
YES
UST 90 mg
PLB
ERASURE (25) Langley 2014 738 SEC 150 mg ⑤⑥⑦ YES
SEC 300 mg
PLB
FIXTURE (25) Langley 2014 1,306 SEC 150 mg ⑤⑥⑦ YES
SEC 300 mg
ETN 50 mg
PLB
RAPID-PsA (26) Mease 2014 409 CZP 200 mg ①②③
④⑤⑥
⑧⑨⑩
YES
CZP 400 mg
PLB
PHOENIX 1 (27) Rich 2014 766 UST 45 mg ④⑤
⑥⑩
YES
UST 90 mg
PLB
(Con inued)
F on ie s in Medicine | www. on ie sin.o g 4Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
TABLE 1 | Con inued
S udy En olled pa ien s NMA
Au ho Yea ND ug Dosage Ou comes
PSUMMIT 2 (28) Ri chlin 2014 312 UST 45 mg ①②③
⑤⑧⑨
YES
UST 90 mg
PLB
UNOCOVER 2 (29) G i i hs 2015 1,224 IXE 80 mg 2 w ⑤⑥⑦ YES
IXE 80 mg 4 w
ETN 50 mg
PLB
UNOCOVER 3 (29) G i i hs 2015 1,346 IXE 80 mg 2 w YES
IXE 80 mg 4 w ⑤⑥⑦
ETN 50 mg
PLB
AMAGINE-2 (30) Lebwohl 2015 1,831 BRD 140 mg ⑤⑦ YES
BRD 210 mg
UST 45/95 mg
PLB
AMAGINE-3 (30) Lebwohl 2015 1,881 BRD 140 mg ⑤⑦ YES
BRD 210 mg
UST 45/95 mg
PLB
FUTURE 2 (31) McInnes 2015 397 SEC 75 mg ①②③
⑤⑥⑧
YES
SEC 150 mg
SEC 300 mg
PLB
(32) Mease 2015 606 SEC 10 mg/kg ①②⑤
⑥⑧⑨
YES
SEC 75 mg
SEC 150 mg
PLB
CLEAR (33) Thaçi 2015 676 SEC 300 mg ⑤⑥⑦ YES
UST 45/90 mg
BELIEVE (34) Thaçi 2015 730 ADA 40 mg ⑩NO
PLB
AMAGINE-1 (35) Papp 2016 661 BRD 140 mg ⑤⑥⑦ YES
BRD 210 mg
PLB
VOYAGE 1 (36) Blau el 2017 837 GUS 100 mg ⑤⑥⑦⑩ YES
ADA 40 mg
PLB
SPIRIT-P1 (37) Mease 2017 417 IXE 80 mg 2 w ①②⑤ YES
IXE 80 mg 4 w ⑥⑦⑧
ADA 40 mg ⑨⑩
PLB
SPIRIP-P2 (38) Nash 2017 363 IXE 80 mg 2 w ①②③ YES
IXE 80 mg 4 w ⑤⑥⑦
PLB ⑧⑨⑩
eSURFACE 1 (39) Reich 2017 772 TIL 100 mg ⑤⑥⑦ YES
TIL 200 mg
PLB
(Con inued)
F on ie s in Medicine | www. on ie sin.o g 5Janua y 2021 | Volume 7 | A icle 618163

To es e al. Biologic The apy o Pso ia ic Disease
TABLE 1 | Con inued
S udy En olled pa ien s NMA
Au ho Yea ND ug Dosage Ou comes
eSURFACE 2 (39) Reich 2017 1,090 TIL 100 mg ⑤⑥⑦ YES
TIL 200 mg
ETN 50 mg
PLB
IXORA-S (40) Reich 2017 302 IXE 80 mg ⑤⑥⑦ YES
UST 45/90 mg
CLARITY (41) Bagel 2018 1102 SEC 300 mg ⑤⑥⑦ YES
UST 45/90 mg
(42) Elewski 2018 217 ADA 40 mg ⑩NO
PLB
Ul IMMa-1 (43) Go don 2018 506 RIS 150 mg ⑤⑥⑦ YES
UST 45/90 mg
PLB
Ul IMMa-2 (43) Go don 2018 491 RIS 150 mg ⑤⑥⑦ YES
UST 45/90 mg
PLB
CIMPASI-1 (44) Go lieb 2018 234 CZP 200 mg ⑥⑦ YES
CZP 400 mg
PLB
CIMPASI-2 (44) Go lieb 2018 227 CZP 200 mg ⑥⑦ YES
CZP 400 mg
PLB
CIMPACT (45) Lebwohl 2018 559 CZP 200 mg ⑤⑥ YES
CZP 400 mg
ETN 50 mg
PLB
TRANSFIGURE (46) Reich 2018 198 SEC 150 mg ⑤⑥
⑦⑩
YES
SEC 300 mg
PLB
FUTURE 5 (47) Mease 2018 774 SEC 150 mg ①②③
⑤⑦⑧
YES
SEC 300 mg
PLB
Sus aIMM (48) Oh suki 2019 171 RIS 75 mg ⑤⑥⑦ YES
RIS 150 mg
PLB
ECLIPSA (50) A aujo 2019 47 UST 45/90 mg ⑨NO
TNFi
IMM en (52) Reich 2019 605 RIS 150 mg ⑤⑥⑦ YES
ADA 40 mg
ECLIPSE (53) Reich 2019 1048 GUS 100 mg ⑤⑥⑦ YES
SEC 300 mg
DISCOVER-2 (49) Mease 2020 741 GUS 100 mg ①②③⑤
⑥⑦⑧⑨
NO
PLB
SPIRIT H2H (51) Mease 2020 566 ADA 40 mg ①②③⑤
⑥⑧⑨⑩
YES
IXE 80 mg
DISCOVER-1 (54) Deodha 2020 624 GUS 100 mg ①②③⑤
⑥⑦⑧⑨
NO
PLB
EXCEED (55) McInnes 2020 853 SEC 300 mg ①②③⑤ NO
ADA 40 mg ⑥⑦⑧⑨
(Con inued)
F on ie s in Medicine | www. on ie sin.o g 6Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
TABLE 1 | Con inued
S udy En olled pa ien s NMA
Au ho Yea ND ug Dosage Ou comes
ORION (56) Fe is 2020 78 GUS 100 mg ⑤⑥⑦ YES
PLB
IMMe ge (57) Wa en 2020 327 RIS 150 mg ⑤⑥⑦ YES
SEC 300 mg
N, numbe ; NMA, ne wo k me a-analysis; GRAPPA, G oup o Resea ch and Assessmen o Pso iasis and Pso ia ic A h i is; RCT, andomized clinical ial; ADA, adalimumab; ETN,
e ane cep ; INF, in liximab; GOL, golimumab; CZP, ce olizumab; UST, us ekinumab; SEC, secukinumab; IXE, ixekizumab; GUS, guselkumab; BRD, b odalumab; RIS, isankizumab; TIL,
ild akizumab; BRK, b iakinumab; MTX, me ho exa e; PLB, placebo.
①ACR20, ②ACR50, ③ACR70, ④PASI50, ⑤PASI75, ⑥PASI90, ⑦PASI100, ⑧dac yli is assessmen , ⑨en hesi is assessmen , ⑩nail assessmen .
YES— he s udy was in NMA; NO— he s udy was no included in NMA.
TABLE 2 | Ex ension s udies om RCT ocusing on ou comes o GRAPPA domains.
S udy En olled pa ien s NMA
Au ho Yea NTime o ou come
(weeks)
D ug Dosage Ou comes
IMPACT 2 (58) Ka anaugh 2007 200 52 IFX 5 mg/kg ①②③④
⑤⑥⑧⑨
PLB
(59) Men e 2008 1,212 52 ADA 40 mg ⑥⑦
PLB
REVEAL (60) Go don 2012 522 156 ADA 40 mg PASI imp o emen
PLB
GO-REVEAL (61) Ka anaugh 2012 405 52 GOL 50 mg ①②③④
⑤⑧⑨⑩
GOL 100 mg
PLB
PHOENIX 1 (62) Kimball 2012 766 156 UST 45 mg ④⑤⑥
UST 90 mg
PLB
GO-REVEAL (63) Ka anaugh 2013 405 104 GOL 50 mg ①②③④
⑤⑧⑨⑩
GOL 100 mg
PLB
PHOENIX 1 (64) Kimball 2013 766 260 UST 45 mg ④⑤⑥
UST 90 mg
PLB
GO-REVEAL (65) Ka anaugh 2014 405 268 GOL 50 mg ①②③④
⑤⑧⑨⑩
GOL 100 mg
PLB
PSUMMIT 1 Ka anaugh 2014 927 52 UST 45 mg Radiog aphic p og ession
PSUMMIT 2 (66) UST 90 mg
PLB
PSUMMIT 1 (67) Ka anaugh 2015 615 100 UST 45 mg ①②③⑤
⑥⑧⑨
UST 90 mg
PLB
PHOENIX 2 (68) Langley 2015 1,212 260 UST 45 mg ⑤⑥
UST 90 mg
PLB
UNCOVER 3 (69) Dennehy 2016 491 60 IXE 80 mg 2 w ⑩
IXE 80 mg 4 w
ETN 50 mg
PLB
(Con inued)
F on ie s in Medicine | www. on ie sin.o g 7Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
TABLE 2 | Con inued
S udy En olled pa ien s NMA
Au ho Yea NTime o ou come
(weeks)
D ug Dosage Ou comes
UNCOVER 2 (70) Go don 2016 1,224 60 IXE 80 mg 2 w ⑤⑥⑦
IXE 80 mg 4 w
ETN 50 mg
PLB
UNCOVER 3 (70) Go don 2016 1,346 60 IXE 80 mg 2 w ⑤⑥⑦
IXE 80 mg 4 w
ETN 50 mg
PLB
(71) an de Heijde 2016 606 52 SEC 10 mg/kg Radiog aphic p og ession
SEC 75 mg
SEC 150 mg
PSTELLAR (72) Blau el 2017 325 112 UST q12 wk ⑤⑥⑦
UST q24 wk
UNCOVER 3 (73) Blau el 2017 1,346 108 IXE 80 mg 2 w ⑤⑥⑦
IXE 80 mg 4 w
ETN 50 mg
PLB
CLEAR (74) Blau el 2017 676 52 SEC 300 mg ⑤⑥⑦
UST 45/90 mg
FUTURE 2 (75) McInnes 2017 397 104 SEC 75 mg ①②③
⑥⑧⑨
SEC 150 mg
SEC 300 mg
PLB
(76) Mease 2017 422 54 TOF 5 mg ①②③
⑤⑧⑨
TOF 10 mg
ADA 40 mg
PLB
LIBERATE (77) Reich 2017 250 52 APR 30 mg ④⑤
⑥⑩
ETN 50 mg
PLB
UNCOVER 3 (78) an de Ke kho 2017 809 60 IXE 80 mg 2 w ⑩
IXE 80 mg 4 w
ETN 50 mg
PLB
(79) G i i hs 2018 100 GUS 100 mg ⑤⑥⑦
ADA 40 mg
PLB
UNCOVER 3 (80) Leona di 2018 1,346 156 IXE 80 mg 2 w ⑤⑥⑦
IXE 80 mg 4 w
ETN 50 mg
PLB
(81) Oh suki 2018 191 52 GUS 50 mg ④⑤⑥
⑦⑩
GUS 100 mg
PLB
LIBERATE (82) Reich 2018 250 104 APR 30 mg ⑤⑩
ETN 50 mg
PLB
(Con inued)
F on ie s in Medicine | www. on ie sin.o g 8Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
TABLE 2 | Con inued
S udy En olled pa ien s NMA
Au ho Yea NTime o ou come
(weeks)
D ug Dosage Ou comes
UNCOVER 2/3
(83)
Kemény 2019 2570 156 IXE 80 mg 2 w ⑤⑥⑦
IXE 80 mg 4 w
ETN 50 mg
PLB
IXORA-S (84) Paul 2019 302 52 IXE 80 mg ⑤⑥⑦
UST 45/90 mg
SUSTaIMM (48) Oh suki 2019 171 52 RIS 75 mg ⑤⑥⑦
RIS 150 mg
PLB
N, numbe ; NMA, ne wo k me a-analysis; GRAPPA, G oup o Resea ch and Assessmen o Pso iasis and Pso ia ic A h i is; RCT, andomized clinical ial; ADA, adalimumab;
ETN, e ane cep ; IFX, in liximab; GOL, golimumab; UST, us ekinumab; SEC, secukinumab; IXE, ixekizumab; GUS, guselkumab; RIS, isankizumab; APR, ap emilas ; TOF, o aci inib;
PLB, placebo.
①ACR20, ②ACR50, ③ACR70, ④PASI50, ⑤PASI75, ⑥PASI90, ⑦PASI100, ⑧dac yli is assessmen , ⑨en hesi is assessmen , ⑩nail assessmen .
FIGURE 2 | GRAPPA domains—e alua ed he apies.
52 in he EXCEED s udy is also lis ed bu no included on
he NMA (55).
An NMA was pe o med o he h ee ou comes (ACR20,
ACR50, and ACR70). The included s udies a e iden i ied in
Table 1. A ne wo k plo o ACR70 is included in Figu e 3, as
an example o he ne wo k plo s o hese h ee NMAs.
The NMA esul s om he ne wo k o biologic he apies o
he ou come ACR70 esponse a e included in Table 4.
Axial Disease
Da a including biologic he apies o axial disease, in he con ex
o PsD, a e sca ce, possibly because he e is no alida ed
ins umen o assess his domain. Nowadays, he only ial
add essing speci ically PsD pa ien s wi h he axial disease is
s ill ongoing and his da a is no ye published. This ial—
MAXIMIZE—e alua es he e icacy and sa e y o SEC 300
o 150 mg in managing axial mani es a ions in pa ien s wi h
PsA, who ha e ailed o espond o a leas 2 non-s e oidal
an i-in lamma o y d ugs (NSAIDs) o e 4 weeks, acco ding o
Assessmen o Spondyloa h i is In e na ional Socie y (ASAS)
ecommenda ions o he ea men o axial spondyloa h i is
(ClinicalT ials.go NCT02721966) (86).
En hesi is
The e a e a leas 6 indices o e alua e en hesi is ou comes
(4-poin en hesi is measu e, Leeds En hesis Index (LEI),
F on ie s in Medicine | www. on ie sin.o g 9Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
TABLE 7 | Con inued
Imp o emen
PASI75 PASI90 PASI100
S udy Weeks D ug n/ o al (%) n/ o al (%) n/ o al (%)
G i i hs 2015
UNCOVER 2 (29)
12 PLB 4/168 (2.4) 1/168 (0.6) 1/168 (0.6)
12 IXE Q4W* 269/347 (77.5) 267/347 (76.9) 107/347 (30.8)
12 ETA 149/358 (41.6) 67/358 (18.7) 19/358 (5.3)
p- alue <0.0001 <0.0001 <0.0001
G i i hs 2015
UNCOVER 3 (29)
12 PLB 14/193 (7.2) 6/193 (3.1) 0/193 (0.0)
12 IXE* 325/386 (84.2) 352/386 (91.2) 135/386 (35.0)
12 ETA 201/382 (52.6) 98/382 (25.6) 19/358 (5.3)
p- alue <0.0001 <0.0001 <0.0001
Lebwohl 2015 12 PLB 25/309 (8.1) 12/309 (3.9) 2/309 (0.6)
AMAGINE 2 (30) 12 UST 210/300 (70.0) 141/300 (47.0) 65/300 (21.7)
12 BRD 210 mg* 528/612 (86.3) 428/612 (69.9) 272/612 (44.4)
p- alue <0.001 <0.001 <0.001
Lebwohl 2015 12 PLB 19/315 (6.0) 6/315 (1.9) 1/315 (0.3)
AMAGINE 3 (30) 12 UST 217/313 (69.3) 141/313 (45.0) 58/313 (18.5)
12 BRD* 531/624 (85.1) 430/624 (68.9) 229/624 (36.7)
p- alue <0.001 <0.001 <0.001
Thaci 2015 12 SEC 311/334 (93.1) 264/334 (79.0) 148/334 (44.3)
CLEAR (33) 12 UST 277/334 (82.9) 277/334 (82.9) 130/334 (38.9)
p- alue <0.0001 <0.0001 =0.003
Go don 2016 12 PLB 17/431 (3.9) 7/431 (1.7) 0/431 (0.0)
UNCOVER 1 (70) 12 IXE Q4W 357/432 (82.6) 279/432 (64.6) 145/432 (33.6)
p- alue <0.001 <0.001 <0.001
Papp 2016 12 PLB 6/220 (2.7) 2/220 (0.9) 1/220 (0.5)
(35) 12 BRD 185/222 (83.3) 156/220 (70.9) 93/222 (41.9)
p- alue <0.001 <0.001 <0.001
Blau el 2017 16 PLB 10/174 (5.7) 5/174 (2.9) 1/174(0.6)
VOYAGE 1 16 GUS* 300/329 (91.2) 241/329 (73, 3) 123/329 (37.4)
(36) 16 ADA 244/334 (73.1) 166/334 (49.7) 57/334 (17.4)
p- alue <0.001 <0.001 <0.001
Mease 2017 12 PLB 5/67 (7.5) 1/67 (1.5) 1/67 (1.5)
SPIRIT 1 12 IXE Q4W* 55/73 (75.3) 38/73 (52.0) 23/73 (31.5)
(37) 12 ADA 23/68 (33.8) 15/68 (22.1) 10/68 (14.7)
p- alue ≤0.01 ≤0.01 ≤0.01
Reich 2017 12 PLB 9/154 (5.8) 4/154 (3.0) 2/154 (1.3)
eSURFACE 1 (39) 12 TIL 100 mg 197/309 (63.8) 107/309 (35.0) 43/309 (13.9)
p- alue <0.0001 <0.0001 <0.0001
Reich 2017 12 PLB 9/156 (5.8) 2/156 (1.3) 0/156 (0.0)
eSURFACE 2 (39) 12 TIL 100 mg* 188/307 (61.2) 119/307 (38.8) 38/307 (12.4)
12 ETA 151/313 (48.2) 67/313 (21.4) 15/313 (4.8)
p- alue 0.0001 0.0001 0.0001
Reich 2017 12 IXE 120/136 (88.2) 99/136 (72.8) 49/136 (36.0)
IXORA-S (40) 12 UST 114/166 (68.7) 70/166 (42, 2) 24/166 (14.5)
p- alue 0.001 0.001 0.001
Bagel 2018 16 SEC 504/550 (91.7) 421/550 (76.6) 249/550 (45.3)
CLARITY (41) 16 UST 440/552 (79.8) 299/552 (54.1) 147/552 (26.7)
p- alue <0.0001 <0.0001 <0.0001
Go don 2018 12 PLB 10/102 (9.8) 2/102 (2.0) 0/102 (0.0)
(Con inued)
F on ie s in Medicine | www. on ie sin.o g 16 Janua y 2021 | Volume 7 | A icle 618163

To es e al. Biologic The apy o Pso ia ic Disease
TABLE 7 | Con inued
Imp o emen
PASI75 PASI90 PASI100
S udy Weeks D ug n/ o al (%) n/ o al (%) n/ o al (%)
Ul iMMa 1 (43) 12 UST* 70/100 (70) 42/100 (42.0) 12/100 (12.0)
12 RIS* 264/304 (86.8) 229/304 (75.3) 109/304 (35.9)
p- alue <0.0001 <0.0001 <0.0001
Go don 2018 12 PLB 8/98 (8.1) 2/98 (2.0) 2/98 (2.0)
Ul iMMa 2 (43) 12 UST 69/99 (69.7) 47/99 (47.5) 24/99 (24.2)
12 RIS 261/294 (88.8) 220/294 (74.9) 149/294 (50.7)
p- alue <0.0001 <0.0001 <0.0001
Go lieb 2018 16 PLB 3/51 (6.5) 0/51 (0.0) 0/51 (0.0)
CIMPASI 1 (44) 16 CZP 200 mg 63/95 (66.3) 34/95 (35.8) 13/95 (13.7)
p- alue <0.0001 <0.0001 <0.0001
Go lieb 2018 16 PLB 6/49 (11.6) 2/49 (2.2) 1/49 (1.8)
CIMPASI 2 (44) 16 CZP 200 mg 74/92 (81.4) 48/91 (52.6) 14/91 (15.4)
p- alue <0.0001 <0.0001 <0.0001
Lebwohl 2018 16 PLB 3/57 (5.3) 5/57 (0.0) –
CIMPACT (45) 16 CZP 200 mg 113/165 (68.5) 66/165 (40.0) –
p- alue <0.0001 <0.0001
Reich 2018 16 PLB 3/65 (4.6) 1/65 (1.5) 0/65 (0.0)
TRANSFIGURE (46) 16 SEC 300 mg 56/66 (84.8) 48/66 (72.7) 22/66 (33.3)
p- alue <0.001 <0.001
Mease 2018 16 PLB 40/332 (12.3) 31/332 (9.3) –
FUTURE 5 (47) 16 SEC 150 mg 132/220 (60.0) 81/220 (36.8) –
16 SEC 300 mg 155/222 (70.0) 119/222 (53.6) –
p- alue <0.05 <0.05
Reich 2019 16 RIS 150 mg 237/301 (91) 218/301 (72) 120/301 (40)
IMM en (52) 16 ADA 218/304 (72) 144/304 (47) 70/304 (23)
p- alue <0.0001 <0.0001 <0.0001
Reich 2019 12 GUS 477/534 (89) 369/534 (69) 311/534 (58)
ECLIPSE (53) 12 SEC 471/514 (92) 391/514 (76) 249/514 (48)
p- alue NA NA NA
Oh suki 2019
Sus aIMM (48)
16 RIS 75 mg* 52/58 (89.8) – 13/58 (22.4)
16 RIS 150 mg* 52/55 (94.5) – 18/55 (32.7)
16 PLB 5/58 (8.6) – 0/0
p- alue <0.001 <0.001
Mease 2020 16 ADA 195/238 (68.9) 158/283 (55.8) 132/283 (46.6)
SPIRIT H2H (51) 16 IXE 227/283 (80.2) 203/283 (71.7) 170/283 (60.1)
p- alue p=0.002 <0.001 <0.001
McInnes 2020 52 SEC 170/215 (79) 140/215 (54) 99/215 (46)
EXCEED (55) 52 ADA 123/202 (61) 87/202 (43) 61/202 (30)
p- alue 0.0002 <0.0001 0.0007
Fe is 2020 16 GUS 55/62 (88.7) 47/62 (75.8) 31/62 (50.0)
ORION (56) 16 PLB 0/16 (0) 0/16 (0) 0/16 (0)
p- alue <0.001 <0.001 <0.001
Wa en 2020 16 RIS 92/164 (56.1) 74/164 (45.1) 44/164 (26.9)
IMMe ge (57) 16 SEC 80/163 (49.1) 66/163 (40.5) 34/163 (20.9)
PASI, Pso iasis A ea Se e i y Index; ADA, adalimumab; ETN, e ane cep ; IFX, in liximab; GOL, golimumab; CZP, ce olizumab; UST, us ekinumab; SEC, secukinumab; IXE, ixekizumab;
GUS, guselkumab; BRD, b odalumab; RIS, isankizumab; TIL, ild akizumab; BRK, b iakinumab; MTX, me ho exa e; PLB, placebo; * s. placebo.
F on ie s in Medicine | www. on ie sin.o g 17 Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
FIGURE 4 | Ne wo k plo o PASI100 showing di ec compa isons, a weeks
10–16. The wid h o he edge is p opo ional o he numbe o s udies, and he
node size is p opo ional o he sample size.
ecen ly published ne wo k me a-analysis (94–96). Al hough he
numbe o RCTs epo ing PASI100 esponse (Table 7) (15,
16,20,21,25,29,30,33,35–37,39–41,43,44,46,48,51–
53,56,57,59,70) as an ou come was supe io o he ones
epo ing ACR70 esponse, he con idence in he NMA was no
supe io . Since 2015 some head- o-head ials we e designed
o e alua e he e icacy o speci ic d ugs in he PASI esponse
ou come (33,40,41,51–53,55,57), and signi ican di e ences
we e ound (Table 7).
A comple e ea men o a pa ien wi h PsD should be ideally
based on a single d ug ha is e ec i e in all he mani es a ions.
Cu en ly, om he he apies included in he PASI100 NMAs,
only ADA, CZP, IXE, SEC, and UST we e app o ed o PSO
and PsA. Thus, in in eg a i e analysis o NMA esul s, and
based only on compa isons o he d ugs wi h placebo, hose
wi h he highes p obabili y o eaching he p oposed ou come
o skin and join domains a e SEC and IXE. Fo SEC, OR
(95% C I) a e 9.430 (5.455, 16.302) and 42.897 (26.848, 68.539)
e sus placebo o ACR70 and PASI100, espec i ely. Fo IXE,
OR a e 9.315 (4.206, 20.627) and 64.027 (39.805, 102.997)
e sus placebo o ACR70 and PASI100, espec i ely. E en
hough a ew p e ious NMAs analyzed ea men op ions in
PsD including ACR and PASI ou comes, mos o hem did no
ind signi ican di e ences in he e icacy and sa e y be ween he
d ugs, only de ec ing ha ea men s we e mo e e icacious han
placebo (97–101).
As epo ed in Table 5, da a ega ding he en hesi is domain
we e no so consis en as skin and pe iphe al a h i is esul s
(1,13,18,22,24,26,28,31,32,37,38,47,50,51,55,61,65,76).
In addi ion o he ou come no being s anda dized, he e we e
s udies epo ing mo e han one ou come wi hou consis en
esul s (50,51). The e we e d ugs ha e en in compa ison wi h
he placebo did no show a consis en signi ican bene i (22,
28,31,38,76). Long- e m e alua ion o en hesi is showed ha
he bene i was main ained wi h IFX a week 54 (58). Al hough
he bene i o UST was no consis en a weeks 24 and 52(28),
a week 100 he e was a 100% imp o emen o MASES om
baseline (67) and he same was ue o SEC esul s, which
showed inconsis en da a a week 24 (31,32), bu a week 104
he e was 100% esolu ion o en hesi is in 70% o he pa ien s
who had en hesi is a baseline (75). En hesopa hy a ec s 35–
50% o pa ien s wi h PsA and should be managed ca e ully
since i can a ec he quali y o li e and wo k p oduc i i y
e en in he ea ly s ages o he disease (102). A ecen s udy
showed ha en hesi is is he pheno ypes o PsD ha con ibu e
mos o Quali y o Li e Sco es and ha his domain should be
e alua ed, bila e ally, in all PsD pa ien s, pa icula ly in hose
e e ing join pain (103). Ne e heless, he clinical e alua ion
o en hesi is is no s anda dized and lacks accu acy and he
eliabili y is highly dependen on he obse e (104). A ecen
s udy compa ed MASES, SPARCC, and LEI, he h ee en hesi is
index, and showed ha MASES had a be e co ela ion wi h
disease ac i i y and unc ional measu es (105). On he o he
hand, ano he s udy has epo ed a be e pe o mance in LEI
and SPARCC indices, which showed a highe disc imina o y
abili y and ea men esponses sugges ed o be ela ed o he
ac ha MASES e alua es ewe pe iphe al si es, which may
be clinically ele an in he con ex o PsA, a p edominan ly
pe iphe al disease (106).
Simila ly o en hesi is, he ou comes measu ed in he dac yli is
domain we e no s anda dized as is explici in Table 6 (1,18,
24,26,28,31,32,37,38,47,51,55,61,76). Mo eo e , he e
we e da a wi h he same d ug in di e en s udies ha we e
no consis en (31,32,37,38). Long- e m da a showed ha he
bene i wi h IFX was main ained a week 54 (58). Fo UST, he
median pe cen imp o emen in he en hesi is sco e a week
100 was 100% (67) whe eas o SEC ea men 90% o he
pa ien s p esen ed comple e dac yli is esolu ion a week 104
(75). A majo limi a ion in dac yli is e alua ion is ha physical
examina ion is he basis o he clinical assessmen o dac yli is
and imaging ools ha e been used only o complemen he clinical
examina ion. Ne e heless, he c i e ia o image esolu ion a e
no uni o m and he e o e da a om di e en s udies a e no
compa able (107,108). Like en hesi is, dac yli is also has a
huge impac on he quali y o li e and in he s uc u al impac
o PsD, and da a om en hesi is and dac yli is highligh he
di icul y in ea ing hese mani es a ions and he long pe iod
o ea men ha is needed o achie e emission. Recen ly, a
eal-wo ld PsA popula ion mul ina ional s udy has shown ha
en hesi is, dac yli is, in lamma o y back pain, and sac oilii is
a e signi ican ly associa ed wi h he wo sening o he pa ien ’s
quali y o li e and/o wo k p oduc i i y, h ough e alua ion o an
ex ensi e pa ien - epo ed ou comes (PROs) lis —namely EQ-
5D, HAQ-DI, Pso ia ic A h i is Impac o Disease (PsAID)12,
and Wo k P oduc i i y and Ac i i y Impai men (WPAI) (109).
F on ie s in Medicine | www. on ie sin.o g 18 Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
TABLE 8 | NMA esul s om he ne wo k o biologic he apies in he ou come PASI100.
ADA BRK BRD CZP ETN GUS IXE PLB RIS SEC TIL UST
ADA 0.511
(0.247–1.057)
0.412
(0.279–0.610)
3.005
(0.531–16.998)
4.078
(2.825–5.887)
0.518
(0.363–0.738)
0.514
(0.393–0.671)
32.891
(20.602–52.505)
0.426
(0.320–0.567)
0.767
(0.556–1.058)
1.590
(0.830–3.047)
1.152
(0.831–1.597)
BRK 1.956
(0.946–4.046)
0.807
(0.374–1.740)
5.877
(0.929–37.192)
7.977
(4.211–15.111)
1.013
(0.476–2.155)
1.005
(0.501–2.017)
64.335
(29.280–141.359)
0.833
(0.395–1.758)
1.500
(0.722–3.116)
3.110
(1.332–7.263)
2.253
(1.076–4.717)
BRD 2.424
(1.640–3.548)
1.239
(0.575–2.673)
7.285
(1.276–41.571)
9.887
(6.322–15.462)
1.256
(0.847–1.862)
1.245
(0.837–1.854)
79.742
(48.415–131.341)
1.033
(0.718–1.486)
1.859
(1.329–2.601)
3.855
(1.925–7.718)
2.793
(2.230–3.498)
CZP 0.333
(0.059–1.883)
0.170
(0.027–1.077)
0.137
(0.024–0.783)
1.357
(0.237–7.759)
0.172
(0.030–0.984)
0.171
(0.030–0.969)
10.946
(2.063–58.067)
0.142
(0.025–0.805)
0.255
(0.045–1.444)
0.529
(0.087–3.225)
0.383
(0.068–2.168)
ETN 0.245
(0.170–0.354)
0.125
(0.066–0.237)
0.101
(0.065–0.158)
0.737
(0.129–4.212)
0.127
(0.083–0.193)
0.126
(0.094–0.169)
8.066
(4.866–13.368)
0.104
(0.070–0.157)
0.188
(0.129–0.274)
0.390
(0.222–0.686)
0.282
(0.191–0.418)
GUS 1.931
(1.355–2.752)
0.987
(0.464–2.100)
0.796
(0.537–1.181)
5.801
(1.016–33.129)
7.873
(5.169–11.994)
0.992
(0.678–1.452)
63.510
(38.479–104.815)
0.823
(0.576–1.175)
1.481
(1.177–1.862)
3.070
(1.554–6.065)
2.224
(1.602–3.087)
IXE 1.947
(1.490–2.544)
0.995
(0.496–1.998)
0.803
(0.539–1.195)
5.849
(1.032–33.159)
7.938
(5.908–10.667)
1.008
(0.689–1.476)
64.027
(39.805–102.997)
0.829
(0.589–1.168)
1.493
(1.063–2.095)
3.095
(1.664–5.758)
2.243
(1.605–3.134)
PLB 0.030
(0.019–0.049)
0.016
(0.007–0.034)
0.013
(0.008–0.021)
0.091
(0.017–0.485)
0.124
(0.075–0.206)
0.016
(0.010–0.026)
0.016
(0.010–0.025)
0.013
(0.008–0.021)
0.023
(0.015–0.037)
0.048
(0.024–0.097)
0.035
(0.022–0.056)
RIS 2.347
(1.763–3.125)
1.200
(0.569–2.531)
0.968
(0.673–1.393)
7.052
(1.242–40.037)
9.571
(6.376–14.368)
1.216
(0.851–1.736)
1.206
(0.856–1.698)
77.192
(47.727–124.861)
1.800
(1.330–2.436)
3.732
(1.908–7.299)
2.704
(2.022–3.616)
SEC 1.304
(0.945–1.800)
0.667
(0.321–1.385)
0.538
(0.385–0.753)
3.919
(0.693–22.174)
5.319
(3.650–7.749)
0.675
(0.537–0.850)
0.670
(0.477–0.940)
42.897
(26.848–68.539)
0.556
(0.411–0.752)
2.074
(1.077–3.992)
1.502
(1.165–1.938)
TIL 0.629
(0.328–1.205)
0.322
(0.138–0.751)
0.259
(0.130–0.519)
1.890
(0.310–11.518)
2.565
(1.458–4.511)
0.326
(0.165–0.643)
0.323
(0.174–0.601)
20.687
(10.326–41.438)
0.268
(0.137–0.524)
0.482
(0.251–0.928)
0.724
(0.374–1.405)
UST 0.868
(0.626–1.203)
0.444
(0.212–0.929)
0.358
(0.286–0.448)
2.608
(0.461–14.746)
3.540
(2.390–5.242)
0.450
(0.324–0.624)
0.446
(0.319–0.623)
28.551
(17.930–45.468)
0.370
(0.277–0.495)
0.666
(0.516–0.858)
1.380
(0.712–2.676)
OR and C I a e p esen ed. Compa isons wi h high con idence a ing based on CINeMA e alua ion a e iden i ied in bold. OR highe han 1 a o he in e en ion speci ied in he ow.
NMA, ne wo k me a-analysis; PASI, Pso iasis A ea Se e i y Index; CINeMA, Con idence in Ne wo k Me a-Analysis; OR, odds a io; C I, c edible in e al; ADA, adalimumab; ETN, e ane cep ; IFX, in liximab; GOL, golimumab; CZP,
ce olizumab; UST, us ekinumab; SEC, secukinumab; IXE, ixekizumab; GUS, guselkumab; BRD, b odalumab; RIS, isankizumab; TIL, ild akizumab; BRK, b iakinumab; MTX, me ho exa e; PLB, placebo.
F on ie s in Medicine | www. on ie sin.o g 19 Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
TABLE 9 | Nail pso iasis assessmen in pa ien s wi h pso iasis.
S udy Au ho Yea In e en ion Ou come Time o
ou come
Resul
(12) Reich 2005 IFX s. placebo Pe cen age o
imp o emen NAPSI
Week 10 26.0 (42.3) s. −5.9 (54.3) (p<0.0001)
Week 24 56.3 (43.3) s. −3.2 (62.3) (p<0.0001)
(18) Ka anaugh 2009 GOL 50 mg s. placebo Pe cen age o
change NAPSI
Week 14 25% s. 0% (p=0.015)
GOL 100 mg s. placebo 53% s. 0% (p<0.001)
GOL 50 mg s. placebo Week 24 33% s. 0% (p<0.001)
GOL 100 mg s. placebo 54% s. 0% (p<0.001)
GO-REVEAL (61) Ka anaugh 2012 GOL 50 mg s. placebo NAPSI (pe cen age
change om
baseline)
Week 52 51.6 ±46.8 s. 56.2 ±48.1
GOL 100 mg s. placebo 65.8 ±51.9 s. 56.2 ±48.1
O onne 2013 ETN 50 mg BIW NAPSI Week 12 −13.6 (−16.7 o −10.5)
ETN 50 mg QW −15.7 (−19,0 o −12.5)
PHOENIX 1 (27) Rich 2014 UST 45 mg s. placebo NAPSI baseline sco e Week 12 26.7% s. 11.8% (p<0.001)
UST 90 mg s. placebo 24.9% s. 11.8% (p<0.001)
UST 45 mg s. placebo Week 24 46.5% s. 29.1%
(65) Ka anaugh 2014 GOL 50 mg s. placebo NAPSI Week 256 1.7 ±2.5 s. 1.1 ±1.9
GOL 100 mg s. placebo 1.1 ±1.8 s. 1.1 ±1.9
BELIEVE (33) Thaci 2015 ADA NAPSI baseline
educ ion
Week 8 15.1%
Week 16 39.5%
(26) Mease 2015 CZP 200 mg Q2W s. placebo mNAPSI change om
baseline
Week24 – 1.6 VS. −1.1 (p=0.003)
CZP 400 mg Q4W s. placebo −2.0 s. −1.1 (p<0.001)
UNCOVER 3 (69) Dennehy 2016 IXE Q2W s. placebo s. ETN Imp o emen in nail
pso iasis
Week 12 38% s. 28% s. −4.7%
IXE Q4W s. placebo s. ETN 40% s. 48% s. −4,7%
SPIRIT-P1 (37) Mease 2017 IXE Q2W s. placebo s. ADA NAPSI Week 12 −7.7 (1.4) s. −1.1 (1.4) s. −6.8 (1.4) p<0.05*
IXE Q4W s. placebo s. ADA −15.5 (1.5) s. −2.4 (1.7) s. −10.7 (1.5)
p<0.05*
IXE Q2W s. placebo s. ADA Week 24 −8.4 (1.5) s. −1.1 (1.4) s. −6.8 (1.4) p<0.05*
IXE Q4W s. placebo s. ADA −14.0 (1.5) 2.4 (1.7) s. −10.7 (1.5) p<0.05*
SPIRIT-P2 (38) Nash 2017 IXE Q2W s. placebo P opo ion o pa ien s
who had a esponse
Week 24 34.8% s. 11.0% (p<0.0005)
IXE Q4W s. placebo 20% s. 7.0% (p<0.0001)
UNCOVER 3 (78) an de
Ke kho
2017 IXE Q2W s. placebo NAPSI om baseline Week 12 35.2% s. −34.3% p<0.001
IXE Q4W s. placebo 36.7% s. −34.3% p<0.001
IXE Q2W s. ETN 35.2 (6.9) s. 20.0 (5.9) p>0.005
IXE Q4W s. ETN 36.7% s. 20% p=0.048
IXE Q2W s. placebo NAPSI =0 Week 12 17.5% s. 4.3% p<0.001
IXE Q4W s. placebo 19.7% s. 4.3% p<0.001
IXE Q2W s. ETN 17.5% s. 10.2% p<0.05
IXE Q4W s. ETN 19.7% s. 10.2% p<0.05
(36) Blau el 2017 GUS s. placebo s. ADA NAPSI pe cen
imp o emen
Week 16 34.4 ±42.46 s. −0.9 ±57.89 s. 38.0 ±53.87
p<0.001**
GUS s. ADA Week 24 49.8 ±44.16 s. 49.4 ±60.04
GUS s. ADA Week 48 68.1 ±43.00 s. 61.4 ±49.20
(Con inued)
F on ie s in Medicine | www. on ie sin.o g 20 Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
TABLE 9 | Con inued
S udy Au ho Yea In e en ion Ou come Time o
ou come
Resul
LIBERATE (77) Reich 2017 APR s. placebo NAPSI (pe cen age o
change)
Week 16 −18.7 (40.2) s. −17.0 (25.0) p=0.4959
ETN s. placebo −35.9 (28.9) s. −17.0 (25.0) p=0.0024
(42) Elewski 2018 ADA s. placebo mNAPSI75 Week 26 46.6% s. 3.4% (p<0.001)
Imp o emen NAPSI Week 26 56.2% s. 11.5% (p<0.01)
UST 90 mg s. placebo 48.7% s. 29.1%
(81) Oh suki 2018 GUS 50 mg s. placebo Change in NAPSI Week 16 −1.2 (1.61) s. −0.2 (1.13) p<0.001
GUS 100 mg s. placebo −1.5 (1.78) s. −0.2 (1.13) p<0.001
TRANSFIGURE (46) Reich 2018 SEC 150 mg s. placebo NAPSI (pe cen age o
change)
Week 16 −37.9% s. −10.8% (p<0.001)
SEC 300 mg s. placebo −45.3% s. −10.8% (p<0.001)
(88) Elewski 2019 ADA Pe cen age o
achie emen
mNAPSI75
Week 16 27.3
Week 26 53.4
Week 52 65.0
SPIRIT H2H (51) Mease 2020 IXE s. ADA Finge nails
NAPSI =0
Week 24 58.1% s. 71.7% (p<0.001)
ADA, adalimumab; ETN, e ane cep ; IFX, in liximab; GOL, golimumab; CZP, ce olizumab; UST, us ekinumab; SEC, secukinumab; IXE, ixekizumab; GUS, guselkumab; RIS, isankizumab;
PLB, placebo; NAPSI, Nail Pso iasis Se e i y Index; mNAPSI, modi ied Nail Pso iasis Index. *IXE s. placebo, **GUS s. placebo.
In lamma o y back pain and sac oilii is a e common axial
mani es a ions in PsA pa ien s and can a ise in 30 o 70%
o pa ien s (110,111). The e is an ongoing discussion on
whe he axial mani es a ions in PsA a e equi alen o hose
seen in axial spondyloa h i is and consequen ly i hey may
be ea ed in he same way (112). In ac , he e idence o
he e icacy o biologic he apies in he PsA axial domain
is s ill sca ce. Howe e , some s udies and case epo s ha e
sugges ed a posi i e impac o TNFi, IL-17i, and IL-12/23i in
axial in ol emen - ela ed ou comes in PsD pa ien s, namely,
BASDAI and ASAS-PR, showing ha i could be possible
o achie e emission and minimal disease ac i i y (113–
115). To ou knowledge, he only andomized clinical ial
add essing ea men e icacy in his speci ic domain pa ien
p o ile is he MAXIMIZE ial (ClinicalT ials.go NCT02721966)
(86)—a s udy e alua ing SEC e icacy in axial mani es a ions
imp o emen in PsA pa ien s. In ac , om he da a eleased
in he la es in e na ional cong esses, esul s sugges ha IL-
17 inhibi ion, namely, wi h SEC, is e ec i e in axial PsA
ea men , e alua ed by ASAS esponse and Be lin MRI
sco e (116).
Nail pso iasis is common among pa ien s wi h mode a e-
o-se e e PsO and mo e p e alen in pa ien s wi h PsA (117).
Di e en s udies assessed he e icacy o biologic agen s in he
ea men and esolu ion o nail pso iasis (Table 9) (12,18,
26,27,34,37,38,42,46,51,61,65,69,73,77,78,81,88).
All o hem showed he bene i o he es ed d ug compa ed
o he placebo. The head- o-head compa ison be ween IXE
and ADA showed supe io i y a week 24 o IXE (51). The
esponse is sus ained in long- e m s udies (46,69,81). O
no e, mos s udies epo ing NAPSI ep esen subg oup analysis
including ec ui ed pa ien s who had mani es a ions o nail
pso iasis. Howe e , om he da a desc ibed he e a e only
d ugs wi h s udies designed speci ically o e alua e nail Pso iasis:
ETN (89), ADA (42), and SEC (46). Impo an ly, hese s udies
we e speci ically designed o e alua e nail ou comes and ha e
demanding ec ui men c i e ia, wi h NAPSI sco es mo e se e e
and, he e o e, much mo e di icul o ea . The e o e, he esul s
ob ained wi h hese 3 d ugs may be conside ed mo e obus and
signi ican conce ning hei impac on nail ea men . O no e, all
s udies demons a ed an imp o emen in he e alua ed sco es.
Howe e , sco es and ime poin s we e no he same, making
compa isons impossible.
Taking all he esul s om he sys ema ic e iew and ne wo k
me a-analysis oge he in Figu e 2, IL-17i a e he d ugs es ed
in mo e mani es a ions, namely, SEC ha had speci ic s udies
o all he domains, e en hough axial domain da a we e no
ye published.
This esul is in line wi h wha was ecen ly published in wo
NMA (98,118). The i s one concluded ha SEC demons a ed
good e icacy ac oss he e alua ed ou comes (ACR, PASI, and
PsARC a 12–16 weeks) and all he ea men s demons a ed
supe io i y o placebo (98). The o he s udy demons a ed ha
SEC may be he mos e icacious and he sa es biologic o
sho - e m ea men o PsA (118).
Limi a ions
One o he main limi a ions o his s udy is he high
a iabili y o s udy designs, inclusion and exclusion
c i e ia, and pa ien s’ cha ac e is ics. I is impo an o
F on ie s in Medicine | www. on ie sin.o g 21 Janua y 2021 | Volume 7 | A icle 618163

To es e al. Biologic The apy o Pso ia ic Disease
no e ha o en hesi is, dac yli is, and nail pso iasis he
e alua ed ou comes a e he e ogeneous and do no allow he
pe o mance o a ne wo k me a-analysis. The esul s o he
NMAs highligh he limi a ions o his me hod, and cau ion
is needed in he in e p e a ion o hese esul s o a oid
misleading in e ences.
CONCLUSIONS
PsD is a e y complex disease in which he same pa ien
may p esen se e al mani es a ions wi h a g ea impac
on unc ional and quali y o li e. Nowadays, we should
be mo e demanding in he analysis o he apeu ic
ou comes, ocusing on achie ing emission in all
PsD mani es a ions.
Al hough he e a e se e al e ec i e he apies, his s udy
showed ha he concep o a holis ic and e icacious ea men o
pa ien s wi h PsD is achie able and ha IL-17i a e he d ugs mos
ex ensi ely es ed in his con ex . Speci ically, SEC demons a ed
good e icacy in all he e alua ed GRAPPA domains, allowing
a comple e sho - e m ea men o pa ien s wi h mul iple
mani es a ions o he disease.
DATA AVAILABILITY STATEMENT
The o iginal con ibu ions p esen ed in he s udy a e included
in he a icle/supplemen a y ma e ials, u he inqui ies can be
di ec ed o he co esponding au ho /s.
AUTHOR CONTRIBUTIONS
TT and AB concep ualized he s udy, designed PICO c i e ia,
managed he li e a u e sea ch, and w o e he i s d a o he
manusc ip . PF and JF in e p e ed he da a and c i ically e ised
he manusc ip . All he au ho s app o ed he inal manusc ip .
FUNDING
Suppo o his assis ance was unded by No a is
Fa ma Po ugal.
ACKNOWLEDGMENTS
Edi o ial assis ance in he p epa a ion o his a icle was p o ided
by I ina Dua e Ph.D. o X2-Science Solu ions.
REFERENCES
1. An oni C, K uege GG, de Vlam K, Bi ba a C, Beu le A, Guzzo C,
e al. In liximab imp o es signs and symp oms o pso ia ic a h i is:
esul s o he IMPACT 2 ial. Ann Rheuma Dis. (2005) 64:1150–7.
doi: 10.1136/a d.2004.032268
2. Coa es LC, Ka anaugh A, Mease PJ, So iano ER, Lau a Acos a-Felque
M, A ms ong AW, e al. G oup o esea ch and assessmen o
pso iasis and pso ia ic a h i is 2015. T ea men ecommenda ions o
pso ia ic a h i is. A h Rheuma ol. (2016) 68:1060–71. doi: 10.1002/a .
39573
3. Sca pa R, Caso F, Cos a L, Peluso R, Del Puen e A, Oli ie i I. Pso ia ic
disease 10 yea s la e . J Rheuma ol. (2017) 44:1298–301. doi: 10.3899/j heum.
161402
4. Sakkas LI, Za i iou E, Bogdanos DP. Mini e iew: new ea men s in pso ia ic
a h i is. Focus on he IL-23/17 Axis. F on Pha macol. (2019) 10:872.
doi: 10.3389/ pha .2019.00872
5. Chimen i MS, Caso F, Ali e nini S, De Ma ino E, Cos a L, Tolusso
B, e al. Ampli ying he concep o pso ia ic a h i is: he ole o
au oimmuni y in sys emic pso ia ic disease. Au oimmun Re . (2019) 18:565–
75. doi: 10.1016/j.au e .2018.11.007
6. Raychaudhu i SP, Wilken R, Sukho AC, Raychaudhu i SK, Ma e akis
E. Managemen o pso ia ic a h i is: ea ly diagnosis, moni o ing o
disease se e i y and cu ing edge he apies. J Au oimmun. (2017) 76:21–37.
doi: 10.1016/j.jau .2016.10.009
7. [So wa e]. CCiNM-A. Ins i u e o Social and P e en i e Medicine,
Uni e si y o Be n (2017).
8. Salan i G, Del Gio ane C, Chaimani A, Caldwell DM, Higgins JPT.
E alua ing he quali y o e idence om a ne wo k me a-analysis. PLoS ONE.
(2014) 9:e99682. doi: 10.1371/jou nal.pone.0099682
9. Cu en Ve sion o RoB 2. (2019). A ailable online a : h ps://si es.google.
com/si e/ isko bias ool/welcome/ ob-2-0- ool/cu en - e sion-o - ob-2
(accessed July 15, 2020).
10. Mohe D. Libe a i A, Te zia J, Al man DG, The PRISMA G oup
(2009). P e e ed epo ing i ems o sys ema ic e iews and
me a-analysis: he PRISMA s a emen . PLoS Med. 6:e1000097.
doi: 10.137/jou nal.pmed1000097
11. Mease PJ, Gladman DD, Ri chlin CT, Rude man EM, S ein eld SD, Choy
EH, e al. Adalimumab o he ea men o pa ien s wi h mode a ely o
se e ely ac i e pso ia ic a h i is: esul s o a double-blind, andomized,
placebo-con olled ial. A h Rheuma . (2005) 52:3279–89. doi: 10.1002/a .
21306
12. Reich K, Nes le FO, Papp K, O onne JP, E ans R, Guzzo C, e al. In liximab
induc ion and main enance he apy o mode a e- o-se e e pso iasis: a
phase III, mul icen e, double-blind ial. Lance . (2005) 366:1367–74.
doi: 10.1016/S0140-6736(05)67566-6
13. Geno ese MC, Mease PJ, Thomson GT, Ki i z AJ, Pe dok RJ, Weinbe g MA,
e al. Sa e y and e icacy o adalimumab in ea men o pa ien s wi h pso ia ic
a h i is who had ailed disease modi ying an i heuma ic d ug he apy. J
Rheuma ol. (2007) 34:1040–50.
14. Ty ing S, Go don KB, Poulin Y, Langley RG, Go lieb AB, Dunn
M, e al. Long- e m sa e y and e icacy o 50 mg o e ane cep wice
weekly in pa ien s wi h pso iasis. A ch De ma ol. (2007) 143:719–26.
doi: 10.1001/a chde m.143.6.719
15. Leona di CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang
Y, e al. E icacy and sa e y o us ekinumab, a human in e leukin-
12/23 monoclonal an ibody, in pa ien s wi h pso iasis: 76-week
esul s om a andomised, double-blind, placebo-con olled ial
(PHOENIX 1). Lance . (2008) 371:1665–74. doi: 10.1016/S0140-6736(08)
60725-4
16. Papp KA, Langley RG, Lebwohl M, K uege GG, Szapa y P, Yeilding
N, e al. E icacy and sa e y o us ekinumab, a human in e leukin-
12/23 monoclonal an ibody, in pa ien s wi h pso iasis: 52-week
esul s om a andomised, double-blind, placebo-con olled ial
(PHOENIX 2). Lance . (2008) 371:1675–84. doi: 10.1016/S0140-6736(08)
60726-6
17. Rich P, G i i hs CE, Reich K, Nes le FO, Sche RK, Li S, e al. Baseline
nail disease in pa ien s wi h mode a e o se e e pso iasis and esponse
o ea men wi h in liximab du ing 1 yea . J Am Acad De ma ol. (2008)
58:224–31. doi: 10.1016/j.jaad.2007.07.042
18. Ka anaugh A, McInnes I, Mease P, K uege GG, Gladman D, Gomez-
Reino J, e al. Golimumab, a new human umo nec osis ac o alpha
an ibody, adminis e ed e e y ou weeks as a subcu aneous injec ion
in pso ia ic a h i is: wen y- ou -week e icacy and sa e y esul s o a
F on ie s in Medicine | www. on ie sin.o g 22 Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
andomized, placebo-con olled s udy. A h Rheuma . (2009) 60:976–86.
doi: 10.1002/a .24403
19. Ba ke J, Ho mann M, Wozel G, O onne JP, Zheng H, an Hoogs a en
H, e al. E icacy and sa e y o in liximab s. me ho exa e in pa ien s
wi h mode a e- o-se e e plaque pso iasis: esul s o an open-label, ac i e-
con olled, andomized ial (RESTORE1). B J De ma ol. (2011) 165:1109–
17. doi: 10.1111/j.1365-2133.2011.10615.x
20. Go lieb AB, Leona di C, Ke del F, Mehlis S, Olds M, Williams DA. E icacy
and sa e y o b iakinumab s. e ane cep and placebo in pa ien s wi h
mode a e o se e e ch onic plaque pso iasis. B J De ma ol. (2011) 165:652–
60. doi: 10.1111/j.1365-2133.2011.10418.x
21. S obe BE, C owley JJ, Yamauchi PS, Olds M, Williams DA. E icacy and
sa e y esul s om a phase III, andomized con olled ial compa ing he
sa e y and e icacy o b iakinumab wi h e ane cep and placebo in pa ien s
wi h mode a e o se e e ch onic plaque pso iasis. B J De ma ol. (2011)
165:661–8. doi: 10.1111/j.1365-2133.2011.10419.x
22. Ba anauskai e A, Ra ayo a H, Kungu o NV, Kubano a A, Venalis A,
Helmle L, e al. In liximab plus me ho exa e is supe io o me ho exa e
alone in he ea men o pso ia ic a h i is in me ho exa e-nai e
pa ien s: he RESPOND s udy. Ann Rheum Dis. (2012) 71:541–8.
doi: 10.1136/a d.2011.152223
23. Go lieb AB, Langley RG, S obe BE, Papp KA, Kleko ka P, C eame
K, e al. A andomized, double-blind, placebo-con olled s udy o
e alua e he addi ion o me ho exa e o e ane cep in pa ien s wi h
mode a e o se e e plaque pso iasis. B J De ma ol. (2012) 167:649–57.
doi: 10.1111/j.1365-2133.2012.11015.x
24. McInnes IB, Ka anaugh A, Go lieb AB, Puig L, Rahman P, Ri chlin
C, e al. E icacy and sa e y o us ekinumab in pa ien s wi h ac i e
pso ia ic a h i is: 1 yea esul s o he phase 3, mul icen e, double-
blind, placebo-con olled PSUMMIT 1 ial. Lance . (2013) 382:780–9.
doi: 10.1016/S0140-6736(13)60594-2
25. Langley RG, Elewski BE, Lebwohl M, Reich K, G i i hs CE, Papp K, e al.
Secukinumab in plaque pso iasis– esul s o wo phase 3 ials. N Engl J Med.
(2014) 371:326–38. doi: 10.1056/NEJMoa1314258
26. Mease PJ, Fleischmann R, Deodha AA, Wollenhaup J, Kh aishi M, Kiela
D, e al. E ec o ce olizumab pegol on signs and symp oms in pa ien s wi h
pso ia ic a h i is: 24-week esul s o a Phase 3 double-blind andomised
placebo-con olled s udy (RAPID-PsA). Ann Rheum Dis. (2014) 73:48–55.
doi: 10.1136/ann heumdis-2013-203696
27. Rich P, Bou cie M, So en H, Fakha zadeh S, Was i Y, Wang Y, e al.
Us ekinumab imp o es nail disease in pa ien s wi h mode a e- o-se e e
pso iasis: esul s om PHOENIX 1. B J De ma ol. (2014) 170:398–407.
doi: 10.1111/bjd.12632
28. Ri chlin C, Rahman P, Ka anaugh A, McInnes IB, Puig L, Li S, e al. E icacy
and sa e y o he an i-IL-12/23 p40 monoclonal an ibody, us ekinumab,
in pa ien s wi h ac i e pso ia ic a h i is despi e con en ional non-
biological and biological an i- umou nec osis ac o he apy: 6-mon h
and 1-yea esul s o he phase 3, mul icen e, double-blind, placebo-
con olled, andomised PSUMMIT 2 ial. Ann Rheum Dis. (2014) 73:990–9.
doi: 10.1136/ann heumdis-2013-204655
29. G i i hs CE, Reich K, Lebwohl M, an de Ke kho P, Paul C, Men e
A, e al. Compa ison o ixekizumab wi h e ane cep o placebo
in mode a e- o-se e e pso iasis (UNCOVER-2 and UNCOVER-3):
esul s om wo phase 3 andomised ials. Lance . (2015) 386:541–51.
doi: 10.1016/S0140-6736(15)60125-8
30. Lebwohl M, S obe B, Men e A, Go don K, Weglowska J, Puig L,
e al. Phase 3 s udies compa ing b odalumab wi h us ekinumab in
pso iasis. N Engl J Med. (2015) 373:1318–28. doi: 10.1056/NEJMoa15
03824
31. McInnes IB, Mease PJ, Ki kham B, Ka anaugh A, Ri chlin CT, Rahman P,
e al. Secukinumab, a human an i-in e leukin-17A monoclonal an ibody,
in pa ien s wi h pso ia ic a h i is (FUTURE 2): a andomised, double-
blind, placebo-con olled, phase 3 ial. Lance . (2015) 386:1137–46.
doi: 10.1016/S0140-6736(15)61134-5
32. Mease PJ, McInnes IB, Ki kham B, Ka anaugh A, Rahman P, an de
Heijde D, e al. Secukinumab inhibi ion o in e leukin-17a in pa ien s wi h
pso ia ic a h i is. N Engl J Med. (2015) 373:1329–39. doi: 10.1056/NEJMoa
1412679
33. Thaçi D, Blau el A, Reich K, Tsai TF, Vanaclocha F, Kingo K, e al.
Secukinumab is supe io o us ekinumab in clea ing skin o subjec s wi h
mode a e o se e e plaque pso iasis: CLEAR, a andomized con olled
ial. J Am Acad De ma ol. (2015) 73:400–9. doi: 10.1016/j.jaad.2015.
05.013
34. Thaçi D, Unneb ink K, Sunda am M, Sood S, Yamaguchi Y. Adalimumab
o he ea men o mode a e o se e e pso iasis: subanalysis o e ec s on
scalp and nails in he BELIEVE s udy. J Eu Acad De ma ol Vene eol. (2015)
29:353–60. doi: 10.1111/jd .12553
35. Papp KA, Reich K, Paul C, Blau el A, Ba an W, Bolduc C, e al. A
p ospec i e phase III, andomized, double-blind, placebo-con olled s udy
o b odalumab in pa ien s wi h mode a e- o-se e e plaque pso iasis. B J
De ma ol. (2016) 175:273–86. doi: 10.1111/bjd.14493
36. Blau el A, Papp KA, G i i hs CE, Randazzo B, Was i Y, Shen YK,
e al. E icacy and sa e y o guselkumab, an an i-in e leukin-23 monoclonal
an ibody, compa ed wi h adalimumab o he con inuous ea men o
pa ien s wi h mode a e o se e e pso iasis: esul s om he phase III, double-
blinded, placebo- and ac i e compa a o -con olled VOYAGE 1 ial. J Am
Acad De ma ol. (2017) 76:405–17. doi: 10.1016/j.jaad.2016.11.041
37. Mease PJ, an de Heijde D, Ri chlin CT, Okada M, Cuchaco ich RS, Shule
CL, e al. Ixekizumab, an in e leukin-17A speci ic monoclonal an ibody,
o he ea men o biologic-nai e pa ien s wi h ac i e pso ia ic a h i is:
esul s om he 24-week andomised, double-blind, placebo-con olled and
ac i e (adalimumab)-con olled pe iod o he phase III ial SPIRIT-P1. Ann
Rheum Dis. (2017) 76:79–87. doi: 10.1136/ann heumdis-2016-209709
38. Nash P, Ki kham B, Okada M, Rahman P, Combe B, Bu mes e GR,
e al. Ixekizumab o he ea men o pa ien s wi h ac i e pso ia ic
a h i is and an inadequa e esponse o umou nec osis ac o inhibi o s:
esul s om he 24-week andomised, double-blind, placebo-con olled
pe iod o he SPIRIT-P2 phase 3 ial. Lance . (2017) 389:2317–7.
doi: 10.1136/ann heumdis-2017-eula .1576
39. Reich K, Papp KA, Blau el A, Ty ing SK, Sinclai R, Thaci D,
e al. Tild akizumab e sus placebo o e ane cep o ch onic plaque
pso iasis ( eSURFACE 1 and eSURFACE 2): esul s om wo
andomised con olled, phase 3 ials. Lance . (2017) 390:276–88.
doi: 10.1016/S0140-6736(17)31279-5
40. Reich K, Pin e A, Lacou JP, Fe andiz C, Micali G, F ench LE,
e al. Compa ison o ixekizumab wi h us ekinumab in mode a e- o-se e e
pso iasis: 24-week esul s om IXORA-S, a phase III s udy. B J De ma ol.
(2017) 177:1014–23. doi: 10.1111/bjd.15666
41. Bagel J, Nia J, Hashim PW, Pa eka M, de Ve a A, Hugo S, e al.
Secukinumab is supe io o us ekinumab in clea ing skin in pa ien s wi h
mode a e o se e e plaque pso iasis (16-week cla i y esul s). De ma ol The .
(2018) 8:571–9. doi: 10.1007/s13555-018-0265-y
42. Elewski BE, Okun MM, Papp K, Bake CS, C owley JJ, Guille G, e al.
Adalimumab o nail pso iasis: e icacy and sa e y om he i s 26 weeks o
a phase 3, andomized, placebo-con olled ial. J Am Acad De ma ol. (2018)
78:90–9.e1. doi: 10.1016/j.jaad.2017.08.029
43. Go don KB, S obe B, Lebwohl M, Augus in M, Blau el A, Poulin Y, e al.
E icacy and sa e y o isankizumab in mode a e- o-se e e plaque pso iasis
(Ul IMMa-1 and Ul IMMa-2): esul s om wo double-blind, andomised,
placebo-con olled and us ekinumab-con olled phase 3 ials. Lance . (2018)
392:650–61. doi: 10.1016/S0140-6736(18)31713-6
44. Go lieb AB, Blau el A, Thaci D, Leona di CL, Poulin Y, D ew J, e al.
Ce olizumab pegol o he ea men o ch onic plaque pso iasis: esul s
h ough 48 weeks om 2 phase 3, mul icen e , andomized, double-
blinded, placebo-con olled s udies (CIMPASI-1 and CIMPASI-2). J Am
Acad De ma ol. (2018) 79:302–14.e6. doi: 10.1016/j.jaad.2018.04.012
45. Lebwohl M, Blau el A, Paul C, So en H, Weglowska J, Pigue V, e al.
Ce olizumab pegol o he ea men o ch onic plaque pso iasis: esul s
h ough 48 weeks o a phase 3, mul icen e , andomized, double-blind,
e ane cep - and placebo-con olled s udy (CIMPACT). J Am Acad De ma ol.
(2018) 79:266–76.e5. doi: 10.1016/j.jaad.2018.04.013
46. Reich K, Sulli an J, A enbe ge P, M owie z U, Jazaye i S, Augus in
M, e al. E ec o secukinumab on he clinical ac i i y and disease
bu den o nail pso iasis: 32-week esul s om he andomized placebo-
con olled TRANSFIGURE ial. B J Me ma ol. (2018) 181:954–66.
doi: 10.1111/bjd.17351
F on ie s in Medicine | www. on ie sin.o g 23 Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
47. Mease P, an de Heijde D, Landewé R, Mpo u S, Rahman P, Tahi H,
e al. Secukinumab imp o es ac i e pso ia ic a h i is symp oms and inhibi s
adiog aphic p og ession: p ima y esul s om he andomised, double-
blind, phase III FUTURE 5 s udy. Ann Rheuma ic Dis. (2018) 77:890–7.
doi: 10.1136/ann heumdis-2017-212687
48. Oh suki M, Fuji a H, Wa anabe M, Suzaki K, Flack M, Huang X, e al. E icacy
and sa e y o isankizumab in Japanese pa ien s wi h mode a e o se e e
plaque pso iasis: esul s om he Sus aIMM phase 2/3 ial. J De ma ol.
(2019) 46:686–94. doi: 10.1111/1346-8138.14941
49. Mease PJ, Rahman P, Go lieb AB, Kollmeie AP, Hsia EC, Xu XL,
e al. Guselkumab in biologic-nai e pa ien s wi h ac i e pso ia ic
a h i is (DISCOVER-2): a double-blind, andomised, placebo-con olled
phase 3 ial. Lance . (2020) 395:1126–36. doi: 10.1016/S0140-6736(20)3
0263-4
50. A aujo EG, Englb ech M, Hoepken S, Finzel S, Kampyla ka E,
Kleye A, e al. E ec s o us ekinumab e sus umo nec osis ac o
inhibi ion on en hesi is: esul s om he en hesial clea ance in pso ia ic
a h i is (ECLIPSA) s udy. Semin A h Rheuma . (2019) 48:632–7.
doi: 10.1016/j.sema h i .2018.05.011
51. Mease PJ, Smolen JS, Beh ens F, Nash P, Liu Leage S, Li L, e al. A head- o-
head compa ison o he e icacy and sa e y o ixekizumab and adalimumab
in biological-naï e pa ien s wi h ac i e pso ia ic a h i is: 24-week esul s
o a andomised, open-label, blinded-assesso ial. Ann Rheum Dis. (2020)
79:123–31. doi: 10.1136/ann heumdis-2019-215386
52. Reich K, Goode ham M, Thaçi D, C owley JJ, Ryan C, K uege
JG, e al. Risankizumab compa ed wi h adalimumab in pa ien s wi h
mode a e- o-se e e plaque pso iasis (IMM en ): a andomised, double-
blind, ac i e-compa a o -con olled phase 3 ial. Lance . (2019) 394:576–86.
doi: 10.1016/S0140-6736(19)30952-3
53. Reich K, A ms ong AW, Langley RG, Fla in S, Randazzo B, Li S, e al.
Guselkumab e sus secukinumab o he ea men o mode a e- o-se e e
pso iasis (ECLIPSE): esul s om a phase 3, andomised con olled ial.
Lance . (2019) 394:831–9. doi: 10.1016/S0140-6736(19)31773-8
54. Deodha A, Helliwell PS, Boehncke WH, Kollmeie AP, Hsia EC,
Sub amanian RA, e al. Guselkumab in pa ien s wi h ac i e pso ia ic
a h i is who we e biologic-nai e o had p e iously ecei ed TNFα
inhibi o ea men (DISCOVER-1): a double-blind, andomised,
placebo-con olled phase 3 ial. Lance . (2020) 395:1115–25.
doi: 10.1016/S0140-6736(20)30265-8
55. McInnes IB, Beh ens F, Mease PJ, Ka anaugh A, Ri chlin C, Nash P,
e al. Secukinumab e sus adalimumab o ea men o ac i e pso ia ic
a h i is (EXCEED): a double-blind, pa allel-g oup, andomised,
ac i e-con olled, phase 3b ial. Lance . (2020) 395:1496–505.
doi: 10.1016/S0140-6736(20)30564-X
56. Fe is LK, O E, Jiang J, Hong HC, Li S, Han C, e al. E icacy and
sa e y o guselkumab, adminis e ed wi h a no el pa ien -con olled
injec o (One-P ess), o mode a e- o-se e e pso iasis: esul s om
he phase 3 ORION s udy. J De ma ol T ea . (2020) 31:152–9.
doi: 10.1080/09546634.2019.1587145
57. Wa en RB, Blau el A, Poulin Y, Beeck S, Kelly M, Wu T, e al. E icacy
and sa e y o isankizumab s. secukinumab in pa ien s wi h mode a e-
o-se e e plaque pso iasis (IMMe ge): esul s om a phase 3, andomised,
open-label, e icacy assesso -blinded clinical ial. B J De ma ol. (2020).
doi: 10.1111/bjd.19341. [Epub ahead o p in ].
58. Ka anaugh A, K uege GG, Beu le A, Guzzo C, Zhou B, Dooley LT, e al.
In liximab main ains a high deg ee o clinical esponse in pa ien s wi h
ac i e pso ia ic a h i is h ough 1 yea o ea men : esul s om he
IMPACT 2 ial. Ann Rheum Dis. (2007) 66:498–505. doi: 10.1136/a d.2006.
058339
59. Men e A, Ty ing SK, Go don K, Kimball AB, Leona di CL, Langley
RG, e al. Adalimumab he apy o mode a e o se e e pso iasis: a
andomized, con olled phase III ial. J Am Acad De ma ol. (2008) 58:106–
15. doi: 10.1016/j.jaad.2007.09.010
60. Go don K, Papp K, Poulin Y, Gu Y, Rozzo S, Sasso EH. Long- e m e icacy
and sa e y o adalimumab in pa ien s wi h mode a e o se e e pso iasis
ea ed con inuously o e 3 yea s: esul s om an open-label ex ension
s udy o pa ien s om REVEAL. J Am Acad De ma ol. (2012) 66:241–51.
doi: 10.1016/j.jaad.2010.12.005
61. Ka anaugh A, an de Heijde D, McInnes IB, Mease P, K uege GG,
Gladman DD, e al. Golimumab in pso ia ic a h i is: one-yea clinical
e icacy, adiog aphic, and sa e y esul s om a phase III, andomized,
placebo-con olled ial. A h Rheuma . (2012) 64:2504–17. doi: 10.1002/
a .34436
62. Kimball AB, Go don KB, Fakha zadeh S, Yeilding N, Szapa y PO, Schenkel
B, e al. Long- e m e icacy o us ekinumab in pa ien s wi h mode a e- o-
se e e pso iasis: esul s om he PHOENIX 1 ial h ough up o 3 yea s. B
J De ma ol. (2012) 166:861–72. doi: 10.1111/j.1365-2133.2012.10901.x
63. Ka anaugh A, McInnes IB, K uege GG, Gladman D, Beu le A, Ga hany
T, e al. Pa ien - epo ed ou comes and he associa ion wi h clinical
esponse in pa ien s wi h ac i e pso ia ic a h i is ea ed wi h golimumab:
indings h ough 2 yea s o a phase III, mul icen e , andomized,
double-blind, placebo-con olled ial. A h Ca e Res. (2013) 65:1666–73.
doi: 10.1002/ac .22044
64. Kimball AB, Papp KA, Was i Y, Chan D, Bissonne e R, So en H, e al. Long-
e m e icacy o us ekinumab in pa ien s wi h mode a e- o-se e e pso iasis
ea ed o up o 5 yea s in he PHOENIX 1 s udy. J Eu Acad De ma ol
Vene eol. (2013) 27:1535–45. doi: 10.1111/jd .12046
65. Ka anaugh A, McInnes IB, Mease P, K uege GG, Gladman D, an de
Heijde D, e al. Clinical e icacy, adiog aphic and sa e y indings h ough 5
yea s o subcu aneous golimumab ea men in pa ien s wi h ac i e pso ia ic
a h i is: esul s om a long- e m ex ension o a andomised, placebo-
con olled ial ( he GO-REVEAL s udy). Ann Rheum Dis. (2014) 73:1689–
94. doi: 10.1136/ann heumdis-2013-204902
66. Ka anaugh A, Ri chlin C, Rahman P, Puig L, Go lieb AB, Li S, e al.
Us ekinumab, an an i-IL-12/23 p40 monoclonal an ibody, inhibi s
adiog aphic p og ession in pa ien s wi h ac i e pso ia ic a h i is:
esul s o an in eg a ed analysis o adiog aphic da a om he
phase 3, mul icen e, andomised, double-blind, placebo-con olled
PSUMMIT-1 and PSUMMIT-2 ials. Ann Rheum Dis. (2014) 73:1000–6.
doi: 10.1136/ann heumdis-2013-204741
67. Ka anaugh A, Puig L, Go lieb AB, Ri chlin C, Li S, Wang Y, e al.
Main enance o clinical e icacy and adiog aphic bene i h ough wo yea s
o us ekinumab he apy in pa ien s wi h ac i e pso ia ic a h i is: esul s
om a andomized, placebo-con olled phase III ial. A h Ca e Res. (2015)
67:1739–49. doi: 10.1002/ac .22645
68. Langley RG, Lebwohl M, K uege GG, Szapa y PO, Was i Y, Chan D, e al.
Long- e m e icacy and sa e y o us ekinumab, wi h and wi hou dosing
adjus men , in pa ien s wi h mode a e- o-se e e pso iasis: esul s om he
PHOENIX 2 s udy h ough 5 yea s o ollow-up. B J De ma ol. (2015)
172:1371–83. doi: 10.1111/bjd.13469
69. Dennehy EB, Zhang L, Ama o D, Goldblum O, Rich P. Ixekizumab
is e ec i e in subjec s wi h mode a e o se e e plaque pso iasis wi h
signi ican nail in ol emen : esul s om UNCOVER 3. J D ugs De ma ol.
(2016) 15:958–61.
70. Go don KB, Blau el A, Papp KA, Langley RG, Luge T, Oh suki M, e al.
Phase 3 ials o ixekizumab in mode a e- o-se e e plaque pso iasis. N Engl J
Med. (2016) 375:345–56. doi: 10.1056/NEJMoa1512711
71. an de Heijde D, Landewe RB, Mease PJ, McInnes IB, Conaghan PG,
P icop L, e al. B ie epo : secukinumab p o ides signi ican and sus ained
inhibi ion o join s uc u al damage in a phase III s udy o ac i e pso ia ic
a h i is. A h Rheuma ol. (2016) 68:1914–21. doi: 10.1002/a .39685
72. Blau el A, Fe is LK, Yamauchi PS, Qu eshi A, Leona di CL, Fa ahi K,
e al. Ex ension o us ekinumab main enance dosing in e al in mode a e-
o-se e e pso iasis: esul s o a phase IIIb, andomized, double-blinded,
ac i e-con olled, mul icen e s udy (PSTELLAR). B J De ma ol. (2017)
177:1552–61. doi: 10.1111/bjd.15722
73. Blau el A, Goode ham M, I e sen L, Ball S, Zhang L, Agada NO, e al.
E icacy and sa e y o ixekizumab o he ea men o mode a e- o-se e e
plaque pso iasis: esul s h ough 108 weeks o a andomized, con olled
phase 3 clinical ial (UNCOVER-3). J Am Acad De ma ol. (2017) 77:855–62.
doi: 10.1016/j.jaad.2017.06.153
74. Blau el A, Reich K, Tsai TF, Ty ing S, Vanaclocha F, Kingo K,
e al. Secukinumab is supe io o us ekinumab in clea ing skin o
subjec s wi h mode a e- o-se e e plaque pso iasis up o 1 yea : esul s
om he CLEAR s udy. J Am Acad De ma ol. (2017) 76:60–9.e9.
doi: 10.1016/j.jaad.2016.08.008
F on ie s in Medicine | www. on ie sin.o g 24 Janua y 2021 | Volume 7 | A icle 618163
To es e al. Biologic The apy o Pso ia ic Disease
75. McInnes IB, Mease PJ, Ri chlin CT, Rahman P, Go lieb AB, Ki kham B,
e al. Secukinumab sus ains imp o emen in signs and symp oms o pso ia ic
a h i is: 2 yea esul s om he phase 3 FUTURE 2 s udy. Rheuma ology.
(2017) 56:1993–2003. doi: 10.1093/ heuma ology/kex301
76. Mease P, Hall S, Fi zGe ald O, an de Heijde D, Me ola JF, A ila-Zapa a F,
e al. To aci inib o adalimumab e sus placebo o pso ia ic a h i is. N Engl
J Med. (2017) 377:1537–50. doi: 10.1056/NEJMoa1615975
77. Reich K, Goode ham M, G een L, Bewley A, Zhang Z, Khanskaya I, e al.
The e icacy and sa e y o ap emilas , e ane cep and placebo in pa ien s
wi h mode a e- o-se e e plaque pso iasis: 52-week esul s om a phase IIIb,
andomized, placebo-con olled ial (LIBERATE). J Eu Acad De ma ol
Vene eol. (2017) 31:507–17. doi: 10.1111/jd .14015
78. an de Ke kho P, Guen he L, Go lieb AB, Sebas ian M, Wu JJ, Foley P,
e al. Ixekizumab ea men imp o es inge nail pso iasis in pa ien s wi h
mode a e- o-se e e pso iasis: esul s om he andomized, con olled and
open-label phases o UNCOVER-3. J Eu Acad De ma ol Vene eol. (2017)
31:477–82. doi: 10.1111/jd .14033
79. G i i hs CEM, Papp KA, Kimball AB, Randazzo B, Song M, Li S, e al.
Long-Te m e icacy o guselkumab o he ea men o mode a e- o-se e e
pso iasis: esul s om he phase 3 Voyage 1 ial h ough wo yea s. J D ugs
De ma ol. (2018) 17:826–32. doi: 10.1136/ann heumdis-2018-eula .5825
80. Leona di C, Maa i C, Philipp S, Goldblum O, Zhang L, Bu kha d N, e al.
Main enance o skin clea ance wi h ixekizumab ea men o pso iasis: h ee-
yea esul s om he UNCOVER-3 s udy. J Am Acad De ma ol. (2018)
79:824–30.e2. doi: 10.1016/j.jaad.2018.05.032
81. Oh suki M, Kubo H, Mo ishima H, Go o R, Zheng R, Nakagawa H.
Guselkumab, an an i-in e leukin-23 monoclonal an ibody, o he ea men
o mode a e o se e e plaque- ype pso iasis in Japanese pa ien s: e icacy
and sa e y esul s om a phase 3, andomized, double-blind, placebo-
con olled s udy. J De ma ol. (2018) 45:1053–62. doi: 10.1111/1346-8138.
14504
82. Reich K, Goode ham M, Bewley A, G een L, Soung J, Pe ic R, e al. Sa e y
and e icacy o ap emilas h ough 104 weeks in pa ien s wi h mode a e o
se e e pso iasis who con inued on ap emilas o swi ched om e ane cep
ea men : indings om he LIBERATE s udy. J Eu Acad De ma ol
Vene eol. (2018) 32:397–402. doi: 10.1111/jd .14738
83. Kemény L, Be gg en L, Dossenbach M, Du onc Y, Paul C. E icacy and sa e y
o ixekizumab in pa ien s wi h plaque pso iasis ac oss di e en deg ees o
disease se e i y: esul s om UNCOVER-2 and UNCOVER-3. J De ma ol
T ea . (2019) 30:19–26. doi: 10.1080/09546634.2018.1473551
84. Paul C, G i i hs CEM, an de Ke kho PCM, Puig L, Du onc Y, Henneges
C, e al. Ixekizumab p o ides supe io e icacy compa ed wi h us ekinumab
o e 52 weeks o ea men : esul s om IXORA-S, a phase 3 s udy. J Am
Acad De ma ol. (2019) 80:70–9.e3. doi: 10.1016/j.jaad.2018.06.039
85. Go lieb A, Me ola JF. Pso ia ic a h i is o de ma ologis s. J De ma ol T ea .
(2019) 2019:1–18. doi: 10.1080/09546634.2019.1605142
86. ClinicalT ials.go . S udy o E icacy and Sa e y o Secukinumab in
Pa icipan s Wi h Ac i e Pso ia ic A h i is Wi h Axial Skele on In ol emen
(MAXIMISE). Be hesda, MD: Na ional Lib a y o Medicine (US) (2000).
A ailable online a : h ps://clinical ials.go /c 2/show/NCT02721966
(accessed June 3, 2020).
87. F ed iksson T, Pe e sson U. Se e e pso iasis–o al he apy wi h a
new e inoid. De ma ologica. (1978) 157:238–44. doi: 10.1159/0002
50839
88. Elewski BE, Bake CS, C owley JJ, Poulin Y, Okun MM, Calimlim B,
e al. Adalimumab o nail pso iasis: e icacy and sa e y o e 52 weeks
om a phase-3, andomized, placebo-con olled ial. J Eu Acad De ma ol
Vene eol. (2019) 33:2168–78. doi: 10.1111/jd .15793
89. O onne JP, Paul C, Be a desca E, Ma ino V, Gallo G, B aul Y, e al. A
24-week andomized clinical ial in es iga ing he e icacy and sa e y o
wo doses o e ane cep in nail pso iasis. B J De ma ol. (2013) 168:1080–7.
doi: 10.1111/bjd.12060
90. Nikolakopoulou A, Higgins JP, Papakons an inou T, Chaimani A, Del
Gio ane C, Egge M, e al. Assessing con idence in he esul s o
ne wo k me a-analysis (Cinema). bioRxi . (2019) 2019:597047. doi: 10.1101/
597047
91. Nikolakopoulou A, Higgins JPT, Papakons an inou T, Chaimani A, Del
Gio ane C, Egge M, e al. CINeMA: an app oach o assessing con idence
in he esul s o a ne wo k me a-analysis. PLoS Med. (2020) 17:e1003082.
doi: 10.1371/jou nal.pmed.1003082
92. Papakons an inou T, Nikolakopoulou A, Higgins JPT, Egge M, Salan i
G. CINeMA: so wa e o semiau oma ed assessmen o he con idence in
he esul s o ne wo k me a-analysis. Campbell Sys Re . (2020) 16:e1080.
doi: 10.1002/cl2.1080
93. Mbuagbaw L, Rochwe g B, Jaeschke R, Heels-Andsell D, Alhazzani
W, Thabane L, e al. App oaches o in e p e ing and choosing he
bes ea men s in ne wo k me a-analyses. Sys Re . (2017) 6:79–.
doi: 10.1186/s13643-017-0473-z
94. Tada Y, Wa anabe R, Noma H, Kanai Y, Nomu a T, Kaneko K. Sho -
e m e ec i eness o biologics in pa ien s wi h mode a e- o-se e e
plaque pso iasis: a sys ema ic e iew and ne wo k me a-analysis.
J De ma ol Sci. (2020) 99:53–61. doi: 10.1016/j.jde msci.2020.
06.003
95. Shi J, Xu J, Chen Y. A ne wo k me a-analysis o he compa ison o
e icacy and sa e y o in e leukin (IL)-23 a ge ed d ugs in he ea men
o mode a e o se e e pso iasis. De ma ol The . (2020) 2020:e13802.
doi: 10.1111/d h.13802
96. Augus in M, Wi h D, Mahlich J, Peppe AN, D uchok C. Cos pe
esponde analysis o guselkumab e sus a ge ed he apies in he ea men
o mode a e o se e e plaque pso iasis in Ge many. J De ma ol T ea . (2020)
2020:1–7. doi: 10.1080/09546634.2020.1793891
97. Kawalec P, Holko P, Mo´
cko P, Pilc A. Compa a i e e ec i eness o aba acep ,
ap emilas , secukinumab and us ekinumab ea men o pso ia ic a h i is: a
sys ema ic e iew and ne wo k me a-analysis. Rheuma ol In . (2018) 38:189–
201. doi: 10.1007/s00296-017-3919-7
98. McInnes IB, Nash P, Ri chlin C, Choy EH, Kan e s S, Thom H,
e al. Secukinumab o pso ia ic a h i is: compa a i e e ec i eness e sus
licensed biologics/ap emilas : a ne wo k me a-analysis. J Comp E ec Res.
(2018) 7:1107–23. doi: 10.2217/ce -2018-0075
99. Song GG, Lee YH. Rela i e e icacy and sa e y o ap emilas , secukinumab,
and us ekinumab o he ea men o pso ia ic a h i is. Zei sch Rheuma ol.
(2018) 77:613–20. doi: 10.1007/s00393-017-0355-8
100. S and V, Elaine Husni M, Be s KA, Song Y, Singh R, G i i h J, e al. Ne wo k
me a-analysis and cos pe esponde o a ge ed immunomodula o s in
he ea men o ac i e pso ia ic a h i is. BMC Rheuma ol. (2018) 2:3.
doi: 10.1186/s41927-018-0011-1
101. Ruyssen-Wi and A, Pe y R, Wa kins C, B aileanu G, Kuma G, Ki i S,
e al. E icacy and sa e y o biologics in pso ia ic a h i is: a sys ema ic
li e a u e e iew and ne wo k me a-analysis. RMD Open. (2020) 6:e001117.
doi: 10.1136/ mdopen-2019-001117
102. We e s K, Luime JJ, Tche e iko I, Ge a ds AH, Kok MR, Appels
CWY, e al. In luence o disease mani es a ions on heal h- ela ed quali y
o li e in ea ly pso ia ic a h i is. J Rheuma ol. (2018) 45:1526–31.
doi: 10.3899/j heum.171406
103. Suna I, A aman S, Nas K, Kilic E, Sa gin B, Kasman SA, e al. En hesi is
and i s ela ionship wi h disease ac i i y, unc ional s a us, and quali y o li e
in pso ia ic a h i is: a mul i-cen e s udy. Rheuma ol In . (2020) 40:283–94.
doi: 10.1007/s00296-019-04480-9
104. K is ensen S, Ch is ensen JH, Schmid EB, Olesen JL, Johansen MB, A esen
KB, e al. Assessmen o en hesi is in pa ien s wi h pso ia ic a h i is using
clinical examina ion and ul asound. Muscles Ligamen s Tendons J. (2016)
6:241–7. doi: 10.11138/ml j/2016.6.2.241
105. Palominos PE, de Campos APB, Ribei o SLE, Xa ie RM, Xa ie JW, de
Oli ei a FB, e al. Co ela ion o en hesi is indices wi h disease ac i i y
and unc ion in axial and pe iphe al spondyloa h i is: a c oss-sec ional
s udy compa ing MASES, SPARCC and LEI. Ad Rheuma ol. (2019) 59:23.
doi: 10.1186/s42358-019-0066-8
106. Mease PJ, Van den Bosch F, Siepe J, Xia Y, Pangan AL, Song IH. Pe o mance
o 3 En hesi is indices in pa ien s wi h pe iphe al spondyloa h i is
du ing ea men wi h adalimumab. J Rheuma ol. (2017) 44:599–608.
doi: 10.3899/j heum.160387
107. Viei a-Sousa E, Al es P. Dac yli is: mo e han jus a h i is. Ac a Reuma ol
Po uguesa. (2015) 40:210–2.
108. Kaeley GS, Ede L, Aydin SZ, Gu ie ez M, Bakewell C. Dac yli is: a
hallma k o pso ia ic a h i is. Semin A h Rheuma . (2018) 48:263–73.
doi: 10.1016/j.sema h i .2018.02.002
F on ie s in Medicine | www. on ie sin.o g 25 Janua y 2021 | Volume 7 | A icle 618163