American Journal of Clinical Dermatology

https://doi.org/10.1007/s40257-018-0406-1

ADIS DRUG EVALUATION

Guselkumab: A Review in Moderate to Severe Plaque Psoriasis

Zaina T. Al‑Salama1 · Lesley J Scott1

© Springer Nature Switzerland AG 2018

Abstract
Guselkumab ­(Tremfya®) is a human immunoglobulin G1 λ (IgG1λ) monoclonal antibody (mAb) that blocks the
interleukin-23 (IL-23)-mediated signalling pathway and is the first in its class to be approved in adults with moderate to
severe plaque psoriasis in several countries, including the USA and EU. In the VOYAGE trials, guselkumab was superior to
placebo and to adalimumab at week 16 in terms of the proportion of patients achieving an Investigator Global Assessment
(IGA) score of 0/1 and ≥ 90% improvement from baseline in Psoriasis Area and Severity index score (PASI 90 response),
with benefits of guselkumab over adalimumab maintained at week 24. To date, the beneficial effects of guselkumab
treatment in these trials were maintained for up to 2 years. Inadequate responders to ustekinumab who were then randomized
to guselkumab in NAVIGATE showed better responses than those randomized to ustekinumab between weeks 28–40, with a
significantly greater mean number of visits at which patients had IGA 0/1 and ≥ 2-grade improvement in IGA score, as well
as higher proportions of patients achieving PASI 90 and PASI 100 at week 52. Treatment with guselkumab improved health-
related quality of life (HR-QOL) and patient-reported outcomes in all trials and was generally well tolerated. Guselkumab,
administered by subcutaneous injection, is a useful new option for patients with moderate to severe plaque psoriasis.

Guselkumab: clinical considerations in moderate 1 Introduction

to severe plaque psoriasis 
Fully human IgG1λ mAb to the IL-23 protein; blocks
IL-23-mediated signalling pathway
Better efficacy than adalimumab and provides effective
maintenance therapy, including in adalimumab non-
responders
Improves HR-QOL and patient-reported outcomes
Generally well tolerated
The manuscript was reviewed by: S. R. Feldman, Department
of Dermatology, Wake Forest School of Medicine, Winston-
Salem, NC, USA; L. Grine, Department of Dermatology, Ghent
University Hospital, Ghent, Belgium; B. Kaufman, Department
of Dermatology, Icahn School of Medicine at Mount Sinai, New
York City, NY, USA ; L. Puig, Department of Dermatology,
Hospital de la Santa Creu I Sant Pau, Barcelona, Spain; T. Torres,
Department of Dermatology, Centro Hospitalar do Porto, Porto,
Portugal.
* Zaina T. Al‑Salama
demail@springer.com
1
Springer, Private Bag 65901, Mairangi Bay, Auckland 0754,
New Zealand
Psoriasis is a chronic immune-mediated inflammatory skin
condition that most commonly presents as plaque psoriasis,
which is characterized by erythematous plaques covered
with a silver scale [1]. Affected patients are at an increased
risk of systemic involvement and a substantial decrease in
health-related quality of life (HR-QOL) [2]. Psoriasis can
affect difficult-to-treat sites such as the nails, scalp, hands
and feet [3]. In psoriasis, activation of inflammatory ­CD11c+
dendritic cells and macrophages in the skin results in the
release of interleukin (IL)-23 (Fig. 1) and IL-12 [4]. IL-23 is
a naturally occurring regulatory cytokine, implicated in nor-
mal inflammatory and immune responses, and when bound
to its cell surface receptor is a key driver of the differentia-
tion, proliferation and survival of pathogenic T cell popula-
tions and innate immune cell subsets in the skin [5, 6]. IL-23
and IL-12 stimulate the release of effector cytokines such as
IL-17A, -17F and -22, tumour necrosis factor (TNF)-α and
interferon (IFN)-γ from epidermal T cells [4]. The effects of
these cytokines (except TNF-α) on keratinocytes and their
key role in psoriatic skin inflammation have been identified.
The IL-23/T17 pathway (Fig. 1) is central in the patho-
genesis of psoriasis and represents a key immune process
that contributes to the histological features and chronic

Vol.:(0123456789)

Guselkumab IL-23
p19
p40
Dendric cells a b
IL-23
Receptor
Macrophages Naive T cell
membrane
When guselkumab binds to the p19 subunit of IL-23, and blocks its interacon with its receptor, the IL-23- mediated signalling pathway
and release of pro-inflammatory cytokines are consequently blocked.
Fig. 1  The mechanism of action of guselkumab in plaque psoria-
sis [4, 7]. a Release of IL-23 by activated dendritic cells and mac-
rophages. b Once IL-23 binds to its cell surface receptor, it triggers
nature of the disease through producing a feedforward
mechanism and a positive cytokine feedback loop [7].
Furthermore, a growing body of evidence suggests that
dysregulated IL-23/IL-17 (IL-17 is produced by T17 cells;
Fig. 1) responses contribute to the chronic inflammation
underlying the pathophysiology of immune-mediated con-
ditions such as psoriasis [4, 8]. Indeed, T-cell infiltrates
(Th1, Th17, Th22) and the levels of IL-23, IL-12, IL-17
and IL-22 are increased in psoriatic lesions [4]. Selec-
tive blockade of IL-23 reduces the cellular and molecular
disease-related biomarkers in the skin, resulting in clinical
improvements in patients with psoriasis [4].
The advent of biological agents targeting cytokines that
are implicated in the pathophysiology of psoriasis has
revolutionized the landscape of therapy for moderate to
severe disease, particularly in patients with an inadequate
response to phototherapy and conventional systemic non-
biological agents [3]. However, issues associated with
treatment discontinuation of agents due to loss of efficacy
over time or the development of adverse events (AEs)
remain and highlight the need for newer agents that are
effective and well tolerated as maintenance therapy [3].
Guselkumab ­( Tremfya ®) is a fully human immuno-
globulin G1 λ (IgG1λ) monoclonal antibody (mAb) that
selectively targets and binds to IL-23; it is the first in its
class and is approved for the treatment of moderate to
severe plaque psoriasis in several countries, including the
USA [6] and EU [5] (Sect. 6). This article provides an
overview of the pharmacological properties of guselkumab
and reviews the clinical data relevant to its use in this
indication.
Z. T. Al‑Salama, L. J. Scott
IL-17A
Keranocyte
T17 cell IL-17F
proliferaon
T22 cell
IL-22
differentiation, proliferation and survival of T cells subsets. T17 cells
include Th17, Tc17, ILC3 and γδ T cells
2 Pharmacodynamic Properties
of Guselkumab
Guselkumab binds with high affinity and specificity to
IL-23 [5]; it selectively binds to the p19 subunit of IL-23
and prevents its interaction with its cell surface receptor,
subsequently blocking the activation of the IL-23-mediated
signaling pathway and the release of pro-inflammatory
cytokines (Sect. 1; Fig. 1).
Analyses of lesional and non-lesional skin biopsy
specimens of patients with moderate to severe plaque
psoriasis demonstrated that a single dose of guselkumab
(10–300 mg) was associated with significant (p < 0.05)
reductions from baseline in the expression of T cell and
inflammatory ­CD11c+ dendritic cell counts and epidermal
thickness, at week 12 [4]. In patients who responded to
guselkumab [with ≥ 50% improvement in the Psoriasis
Area and Severity Index score (PASI 50) at week 12],
significant (p < 0.05) reductions in serum IL-17A lev-
els from baseline were evident at week 1 and week 12
(vs. no change in placebo recipients). Reductions in the
expression of genes associated with the IL-17A pathway
occurred in a dose-dependent fashion. At week 12, mRNA
expression was reduced (2-, 10- and 26-fold change) com-
pared with baseline for IL-17A, IL-22 (reductions were
less consistent than IL-17-targeted genes) and IL-17F, in
guselkumab recipients, and slightly increased for TNF-γ
(produced by Th1), suggesting that guselkumab exerts its
clinical effects by primarily antagonizing the IL-23/Th17
pathway, with limited effects on the IL-12/Th1 pathway.
Guselkumab: A Review
In phase II and III trials in patients with plaque psoriasis,
guselkumab treatment reduced serum IL-17A, IL-17F and
IL-22 levels compared with placebo [5]. In the pivotal VOY-
AGE 1 trial (Sect. 4.1), guselkumab was associated with
significant (p ≤ 0.001) reductions from baseline in serum
levels of IL-17A, IL-17F and IL-22 at week 4 in 40 evalu-
able patients, with these effects sustained at 24 and 48 weeks
(p ≤ 0.001 vs. baseline at both timepoints) [abstract] [9].
Compared with adalimumab (TNF-α inhibitor), guselkumab
was associated with more effective and durable inhibition of
IL-17A, IL-17F and IL-22 cytokines suggesting a greater
inhibition of cells producing these cytokines, including Th17
and Th22 cells, and downstream effects on keratinocytes
(abstract) [10]; guselkumab significantly (p ≤ 0.05) reduced
IL-17F levels from baseline at weeks 4, 24 and 48, and IL-
17A and IL-22 levels at week 48 [9]. These results are con-
sistent with the clinical benefits observed with guselkumab
treatment in the VOYAGE 1 trial (Sect. 4.1).
In VOYAGE 2 in the randomized withdrawal and retreat-
ment period with guselkumab or placebo (Sect. 4.1.3), a
sustained response (i.e. PASI 90) following withdrawal of
guselkumab was associated with continued reductions of
Th17 and Th22 effector cytokine levels (i.e. IL-17A, IL-
17F and IL-22) at 48 weeks, whereas a loss of response (i.e.
PASI < 75) was associated with increased levels of these
effector cytokines at 48 weeks (p ≤ 0.05) [abstract] [11].
3 Pharmacokinetic Properties
of Guselkumab
Subcutaneous guselkumab exhibited linear pharmacokinetics
(PK) across a dose range of 10–300 mg in adults with moder-
ate to severe plaque psoriasis [8]. In a population PK modeling
study in patients with moderate to severe plaque psoriasis, the
PK of guselkumab were described by a one-compartment lin-
ear model, with first order absorption and elimination [12].
The maximum plasma concentration of guselkumab was
reached by 5.0 to 5.5 days after a single 100 mg dose [13];
steady-state concentrations were reached by week 20 follow-
ing guselkumab 100 mg at weeks 0 and 4, and every 8 weeks
thereafter [5].
Following a single guselkumab 100 mg dose in healthy
volunteers, the absolute bioavailability was estimated to be
≈ 49% [5, 6]. According to the final PK model, the apparent
volume of distribution in patients with moderate to severe
plaque psoriasis was 13.5 L and the apparent clearance
was 0.516 L/day [12]; the mean half-life of guselkumab
in patients with plaque psoriasis was ≈ 15–18 days [5,
6]. Given that guselkumab is a human IgG1λ mAb, it is
expected to be degraded into small peptides and amino acids
in the same manner as endogenous IgG.
Guselkumab dose adjustments are not required in elderly
patients [5, 6] or based on body weight [6]; the PK profile
of guselkumab in Japanese patients with moderate to severe
plaque psoriasis [14] appeared to be consistent with that
seen in patients with moderate to severe plaque psoriasis in
a PK study in the USA [8]. The effects of hepatic or renal
impairment on the PK of guselkumab have not been studied
[5, 6]. However, given that IgG mAbs, like guselkumab,
are predominantly eliminated via intracellular catabolism
and that renal elimination of intact mAb is expected to be
low, the effects of hepatic and renal impairment on the PK
of guselkumab are not expected to be clinically relevant [5].
The potential for clinically relevant interactions between
guselkumab and CYP450 substrates in patients with mod-
erate to severe psoriasis appears to be low, albeit results
of a PK study were highly variable because of the limited
number of patients [5, 6].
4 Therapeutic Efficacy of Guselkumab
The clinical efficacy of subcutaneous guselkumab in
the treatment of moderate to severe plaque psoriasis was
assessed in pivotal, large (n > 250), randomized, double-
blind, multinational, phase III trials (VOYAGE 1 [15], VOY-
AGE 2 [16] and NAVIGATE [17]). These data are supported
by results from a phase III Japanese trial (n = 192) [18]
and a dose-ranging phase II trial (n = 293) [19], which are
not discussed further. Landmark and longitudinal exposure-
response analyses support the guselkumab 100 mg once
every 8 weeks regimen used in the phase III trials [20].
Eligible patients were ≥ 18 years of age with moderate
to severe plaque psoriasis for ≥ 6 months who were eligi-
ble for systemic therapy or phototherapy [15–17]. Patients
had an Investigator Global Assessment (IGA) score of ≥ 3,
a PASI score of ≥ 12 and a minimum affected body surface
area (BSA) of ≥ 10%. These studies excluded patients with
guttate, erythrodermic or pustular psoriasis, a history or
symptoms of active tuberculosis (TB), or who had previously
received guselkumab or the active control i.e. adalimumab in
the VOYAGE trials [15, 16] or ustekinumab (mAb directed at
the p40 subunit common to IL-12 and IL-23) in NAVIGATE
[17] or therapeutic agents targeting specific ILs (e.g. IL-17)
within 6 months or phototherapy within 4 weeks [6, 15–17].
Baseline demographics and disease characteristics were
generally similar and well-balanced between treatment
groups in the VOYAGE trials [15, 16] and in the randomized
and nonrandomized treatment groups in NAVIGATE [17].
In VOYAGE 1 [15] and VOYAGE 2 [16], 20.9 and 20.6%
had received a prior biologic, the mean duration of disease
was 17.5 and 17.8 years, and 18.6 and 18.0% patients had
psoriatic arthritis. The mean duration of psoriasis at week 16
was 16.8 years across the randomized and nonrandomized
 Z. T. Al‑Salama, L. J. Scott

(i.e. open-label continuation) groups in NAVIGATE, with
psoriatic arthritis present in 18.3 and 13.2% of patients in
the respective groups and anti-TNF agents previously used
in 21.6 and 10.8% of patients [17].
The primary efficacy population included all patients ran-
domized at week 0 (i.e. baseline) in the VOYAGE trials [15,
16] or at week 16 in NAVIGATE [17]; missing data were
imputed as non-responses. Some additional data are avail-
able as abstracts/posters [21–27].
4.1 VOYAGE Trials
VOYAGE 1 [15] and VOYAGE 2 [16] included a 16-week
placebo-controlled (Sect.  4.1.1) and active comparator-
controlled period (0–24 [16] or 0–48 [15] weeks;
Sect. 4.1.2), with VOYAGE 2 also including a randomized
withdrawal and retreatment period (Sect. 4.1.3), see Table 1
for dosage regimens. The co-primary endpoints were the
proportion of patients achieving an IGA score of 0 (cleared)
or 1 (minimal) [IGA 0/1] and the proportion of patients with
≥ 90% improvement in the PASI score (PASI 90) from base-
line at week 16 for guselkumab compared with placebo [15,
16]. The relative efficacy (non-inferiority and/or superiority)
of guselkumab to adalimumab for the proportion of patients
achieving an IGA 0/1, PASI 75 or PASI 90 was tested at
week 16 and at week 24 (major secondary endpoints) [15,
16]. The co-primary and major secondary endpoints were
tested using a fixed-sequence method.
In VOYAGE 1, an open-label extension period began
where patients who initially received guselkumab after week
48, or placebo and then crossed over to guselkumab at week
16, continued to receive guselkumab 100 mg then every 8
weeks, whereas patients in the adalimumab group, after their
last dose at week 47, crossed over to receive guselkumab at
week 52 and every 8 weeks thereafter [28]. In VOYAGE 2
from week 76, all randomized patients received open-label
guselkumab every 8 weeks [21]. Data through up to week 100
are available for the VOYAGE trials; longer term follow-up
through to 5 years is ongoing.
4.1.1 Placebo‑Controlled Period
At week 16, treatment with guselkumab was superior to pla-
cebo for the co-primary endpoints (Table 2) [15, 16]. Com-
pared with placebo, the onset of action of guselkumab was
rapid, with significant PASI 90 responses evident as early
as week 2 in VOYAGE 1 (no p-value reported) [15], and
VOYAGE 2 (p < 0.001) [16]. Guselkumab treatment was
superior to adalimumab for these disease activity measures
(major secondary endpoints vs. adalimumab) [Table 2]; see
Sect. 4.1.2 for further discussion of this relative efficacy dur-
ing the 16-week placebo-controlled period.
For all other major secondary endpoints assessing dis-
ease activity and patient-reported HR-QOL at 16 weeks,
guselkumab treatment was significantly more effective than
placebo [i.e. for achievement of scalp specific-IGA score of
0 or 1 (ss-IGA 0/1) and improvements in Psoriasis Symp-
toms and Signs Diary (PSSD) and Dermatology Life Quality

Table 1  Subcutaneous dosage regimens in the pivotal randomized, double-blind, multinational, phase III VOYAGE trials
Trial Active comparator (ADA) period Randomized WD and
b re-TX ­perioda
PL-controlled period (wks 0–16) PL crossover ­period (wks 28–72)

VOYAGE 1 [15] GUS wks 0 and 4 → q8w GUS q8w continued to wk 44 NA

PL wks 0, 4 and 12 GUS wks 16 and 20 → q8w to wk 44 NA
ADA 80 mg wk 0, 40mg wk 1 → 40 mg q2w ADA 40 mg q2w continued to wk 47 NA
VOYAGE 2 [16] GUS wks 0 and 4 → q8w GUS at wk 20 R: ­PLc or GUS q8w
NR: GUS q8w
PL wks 0, 4 and 12 GUS at wks 16 and 20 R: ­PLc
NR: GUS q8w
ADA 80 mg wk 0, 40mg wk 1 → 40 mg q2w ADA 40 mg q2w to wk 23; R: ­PLc
no TX wks 24–28 NR: GUS study-wks 28
and 32 → q8w

ADA adalimumab, GUS guselkumab 100 mg, NA not applicable, NR PASI 90 non-responder, PASI 90 ≥ 90% improvement in Psoriasis Area and
Severity Index, PL placebo, pts patients, qxw every x weeks, R PASI 90 responder, re(TX) re(treatment), WD withdrawal, wk/s week/s, → indi-
cates thereafter
a
 VOYAGE 1 wks 16–48; VOYAGE 2 wks 16–28, prior to randomized withdrawal and re-Tx through to wk 72
b
 GUS-treated pts were re-randomized based on PASI response at wk 28; NR = PASI < 90 and R ≥ PASI 90
c
 Upon loss of ≥ 50% of the 28-wk PASI response, pts were switched to GUS (100 mg at wk 0 and 4 → GUS 100 mg q8w)
Guselkumab: A Review

Table 2  Efficacy of subcutaneous guselkumab in adults with moderate to severe plaque psoriasis at the end of the 16-week placebo-
controlled period in the VOYAGE trials (see Table 1 for dosage regimens)
Trial Regimen PASI IGA 0/1 ssIGA 0/1 HR-QOL outcomes
(no. of pts) (% pts) (% pts)b (% pts)a mean change from BL [BL]
75b 90c PSSD ­symptomd DLQId

VOYAGE 1 [5, 15] GUS (329) 91*† 73*† 85*† 83* − 42* [54] − 11* [14]
ADA (334) 73 50 66 70 − 35 [54] − 9 [14]
PL (174) 6 3 7 15 − 3 [48] < − 1 [13]
VOYAGE 2 [5, 16] GUS (496) 86*† 70*† 84*† 81* − 40* [54] − 11* [15]
ADA (248) 69 47 68 67 − 33 [54] − 10 [15]
PL (248) 8 2 9 11 − 8 [59] − 3 [15]

ADA adalimumab, BL baseline value, DLQI Dermatology Life Quality Index, GUS guselkumab, HR-QOL health-related quality of life, IGA
Investigator Global Assessment (0 = cleared; 1 = minimal), PASI Psoriasis Area and Severity Index, PASI x improvement of ≥ x% from BL in
PASI score, PL placebo, PSSD Psoriasis Symptoms and Signs Diary, pts patients, qxw every x weeks, ssIGA scalp-specific IGA (0 = absence; 1
= very mild), UST ustekinumab
*p ≤ 0.001 vs. PL; †p < 0.001 vs. ADA
a
 Major secondary outcome GUS vs. PL. Assessed in pts with BL ss-IGA score of ≥ 2 who had a ≥ 2-grade improvement; included 277, 286 and
145 pts in the GUS, ADA and PL groups, respectively, in VOYAGE 1 and 408, 194 and 202 pts in VOYAGE 2. No statistical comparisons per-
formed for GUS vs. ADA
b
 Major secondary outcome for GUS vs. ADA
c
 Co-primary endpoint for GUS vs. PL at wk 16 in the VOYAGE trials; major secondary endpoint for GUS vs. ADA
d
 Major secondary outcome for GUS vs. PL: mean change from BL in PSSD symptom score assessed in 249, 274 and 129 pts in the GUS, ADA
and PL groups, respectively, in VOYAGE 1 and 411, 201 and 198 pts in VOYAGE 2; mean change from BL in DLQI score assessed in 322, 328
and 170 pts in the GUS, ADA and PL groups, respectively, in VOYAGE 1 and 496, 248 and 248 pts in VOYAGE 2

Index (DLQI) scores] (Table 2) [15, 16]. PASI 75 (Table 1),
PASI 100 (37 vs. < 1% [15]; 34 vs. < 1% [16]) and IGA 0
response rates (48 vs. 1% [15]; 43 vs. <1% [16]) were also
significantly (p < 0.001) higher in guselkumab than placebo
recipients at 16 weeks. In addition to ss-IGA 0/1 response
rates, in evaluable patients with regional-specific psoriasis,
significantly (p < 0.001) more guselkumab than placebo
recipients achieved a hand and foot psoriasis (hf-) Physi-
cian Global Assessment (PGA) score of 0/1 (cleared/almost
cleared) or a fingernail PGA (f-PGA) score of 0/1 (cleared/
minimal) at 16 weeks [15, 16], with a higher mean percent-
age improvement in Nail Psoriasis Severity Index (NAPSI)
score in the guselkumab group [5]. For HR-QOL scores,
guselkumab recipients also achieved significantly greater
improvements in PSSD symptom and sign scores and signifi-
cantly more guselkumab than placebo recipients achieved a
DLQI score of 0/1 (no impact of psoriasis on HR-QOL) or a
PSSD symptom or sign score of 0 (all p < 0.001) [15, 16]. In
VOYAGE 2, compared with placebo, guselkumab treatment
was associated with better (p < 0.001) improvements from
baseline in SF-36 physical and mental component summary
scores, and all measures on the Work Limitations Question-
naire and Hospital Anxiety and Depression Scale scores at
16 weeks [5, 13, 16].
Results from pooled analyses of the VOYAGE trials in
the overall population (n = 825 and 422 in the guselkumab
and placebo groups) were consistent with those in individual
trials for IGA 0/1 response rates, and irrespective of gender,
ethnicity (including in Hispanic and non-Hispanic patients
[23]), age, bodyweight by quartiles and body mass index
(BMI) [29].
4.1.2 Active Comparator‑Controlled Period
Guselkumab treatment was superior to adalimumab for
major secondary endpoints assessing disease activity dur-
ing the 16-week placebo-controlled period (Table 2; IGA0/1,
PASI 90 and PASI 75 response rates), with these benefits
sustained at 24 [15, 16] or 48 weeks [15] (all p < 0.001 vs.
adalimumab at 24 and/or 48 weeks; at which times, these
were major or other secondary endpoints).
In VOYAGE 1, patients who were switched from placebo
to guselkumab at week 16 (placebo→guselkumab; n = 165)
achieved generally similar responses (i.e. proportion of
patients achieving IGA 0/1, IGA 0, PASI 75, PASI 90, PASI
100) to those in patients receiving guselkumab continuously
throughout the 48-week period [15].
At week 16, guselkumab recipients experienced generally
more favorable improvements for the majority of regional
psoriasis disease scores and patient-reported outcomes than
adalimumab recipients [15, 16]; no statistical comparisons
were conducted at 16 weeks between the guselkumab and
adalimumab groups for ss-IGA 0/1, hf-PGA 0/1 and f-PGA
0/1 responses, improvements in NAPSI score, changes in

DLQI score, or the percentage of patients with PSSD sign or
symptom scores of 0 [5]. At weeks 24 and 48, guselkumab
treatment was generally associated with greater improve-
ments in regional psoriasis disease scores and HR-QOL
measures than adalimumab [15, 16]. In patients with at least
mild scalp or hand/feet psoriasis (ss-IGA or hf-PGA score
≥ 2) at baseline, significantly (p < 0.05) more guselkumab
than adalimumab recipients had an ss-IGA or hf-PGA
of 0/1 at week 24 [15, 16] and week 48 [15]. In patients
with at least mild fingernail psoriasis (f-PGA ≥ 2) at base-
line, the f-PGA 0/1 response was generally similar in the
guselkumab and adalimumab groups at week 24 [15, 16];
significantly (p < 0.05) more guselkumab than adalimumab
recipients had an f-PGA score of 0/1 at week 48 [15]. In the
guselkumab and adalimumab groups, generally similar mean
percent improvements in the NAPSI score were evident at 24
[15, 16] and 48 [15] weeks. Significantly (p < 0.001) more
guselkumab than adalimumab recipients had a DLQI score
of 0/1 and PSSD sign or symptom score of 0, and signifi-
cantly greater mean changes from baseline in PSSD sign or
symptom score at week 24 [15, 16] and week 48 [15].
Results from pooled analyses of the VOYAGE trials in
the overall population (n = 825 and 582 in the guselkumab
and adalimumab groups) were consistent with those in indi-
vidual trials, including IGA 0/1, IGA 0, PASI 75, PASI 90
and PASI 100 response rates [21, 25, 29]. Guselkumab pro-
vided better efficacy than adalimumab at 16 and 24 weeks
in terms of IGA 0/1 and IGA 0 responses, irrespective of
gender, ethnicity [apart from in the limited number of Black
or African American randomized patients (n = 25)], age,
bodyweight by quartiles and BMI [29]. The relative effi-
cacy of guselkumab to that of adalimumab was also con-
sistent between Hispanic and non-Hispanic patients [23].
Guselkumab treatment was also generally associated with
a shorter median time to achieve a PASI 75 (≤ 8 weeks
both groups), PASI 90 (≤ 12 vs. ≤ 16 weeks) and PASI
100 (≤ 24 weeks vs. could not be determined) response
than adalimumab treatment (i.e. median time to ≥ 50% of
patients achieving each PASI response), based on Kaplan-
Meier estimates [25].
4.1.3 Randomized Withdrawal and Retreatment Period
In VOYAGE 2 at week 28, patients were re-randomized/
retreated according to PASI 90 response (Table 1). At 48
weeks, PASI 90 response rates were significantly higher in
the maintenance group (those who continued every 8 weeks
guselkumab treatment throughout the study) than the with-
drawal group (patients who switched from guselkumab to
placebo at 28 weeks) (Table 3); the median time to loss
of PASI 90 response was 15.2 weeks in the withdrawal
group [16]. PASI 90 response rates in the withdrawal group
began to diverge from the maintenance group 4 weeks after
Z. T. Al‑Salama, L. J. Scott
Table 3  Efficacy of guselkumab at week 48 in patients with mod-
erate to severe plaque psoriasis in the VOYAGE 2 trial [16]
Regimen at week 28 [no. of pts] PASI IGA
(% pts) response
(% pts)
75 90 100 0/1 0
GUS→GUS (maintenance) [193] 96*a 89* 59*a 92*a 65*a
GUS→PL (withdrawal) [182] 61a 37 20a 46a 22a
ADA→GUS (switch) [112] 66 29
See Table 1 for dosage regimens
ADA adalimumab, GUS guselkumab, IGA Investigator Global
Assessment (0 = cleared; 1 = minimal), PASI Psoriasis Area and
Severity Index, PASI 90/100 improvement of ≥ 90/ ≥ 100% in PASI
score from baseline, PL placebo, pts patients, wk week, → indicates
switched to
*p < 0.001 vs. GUS→PL
a
 Values estimated from a graph
re-randomization (i.e. at week 32). PASI 100, PASI 75, IGA
0/1 and IGA 0 clinical responses were also higher in the
maintenance group than the withdrawal group (Table 3). At
48 weeks, significantly (p < 0.001) greater improvements
in DLQI and PSSD symptom and sign scores were also
observed in the maintenance than in the withdrawal group.
In adalimumab PASI 90 non-responders who were
switched to guselkumab at week 28 (n = 112), the majority
of patients achieved a PASI 90 response at week 48 (Table 3)
with more patients achieving a PASI 100 response at week
48 than at week 28 [16].
4.1.4 Longer‑Term Treatment
The efficacy of guselkumab in terms of clinical responses
(IGA 0, IGA 0/1, PASI 90 and PASI 100) was consistent at
weeks 24 and 100 across the VOYAGE trials [21]. At week
100, efficacy outcomes were also generally consistent across
the continuous guselkumab, placebo→guselkumab and
adalimumab→guselkumab groups in both trials [21]. IGA
0/1 response was achieved by 73, 81 and 83% of patients in
the continuous guselkumab (n = 329), placebo→guselkumab
(n = 165) and adalimumab→guselkumab (n = 280) groups,
respectively, in VOYAGE 1 and by 75, 76 and 81% of
patients in corresponding groups (n = 494, 233 and 220) in
VOYAGE 2 [21].
Robust clinical responses were demonstrated through
week 100 of continuous guselkumab treatment [28]. Fur-
thermore, in the adalimumab→guselkumab group, efficacy
outcomes improved from weeks 52 to 100 in VOYAGE 1,
with improvements in clinical responses (PASI 75, PASI
90, PASI 100, IGA0/1 and IGA 0 responses) and HR-
QOL outcomes (DLQI 0/1 response) [28]. In adalimumab
PASI 90 non-responders who initiated guselkumab at week
Guselkumab: A Review
52 (n = 138) in VOYAGE 1 and at week 28 in VOYAGE
2 (n = 112), switching to guselkumab treatment was asso-
ciated with sustained improvements in the proportion of
patients achieving clinical responses of PASI 90 and PASI
100 and achieving IGA scores of 0/1 or 0 through week
100, as well as a higher proportion of patients achieving
a DLQI score of 0/1 and PSSD sign or symptom score of
0 [26].
4.2 NAVIGATE
The enrichment design of open-label treatment followed
by randomization was used to investigate the efficacy of
guselkumab in patients with moderate to severe plaque
psoriasis who had responded inadequately (IGA ≥ 2) to
doses of ustekinumab (45 or 90 mg injections for patients
weighing ≤ 100 or > 100 kg; n = 871) at weeks 0 and 4 in
NAVIGATE [17]. At 16 weeks, 585 patients had an IGA of
0/1 and continued to receive open-label ustekinumab and
268 patients with an IGA ≥ 2 were randomized in a dou-
ble-blind fashion to receive guselkumab 100 mg (n = 135)
or to continue on ustekinumab (n = 133). Randomization
was stratified by study site and baseline weight (≤ 100 vs.
> 100 kg). The primary endpoint was the mean number of
visits between weeks 28 and 40 with an IGA 0/1 response
and ≥ a 2-grade improvement in IGA score out of a total
of four possible visits relative to week 16 [17].
Treatment with guselkumab was associated with a sig-
nificantly greater mean number of visits at which patients
had achieved an IGA of 0/1 response and ≥ a 2-grade
improvement between weeks 28–40 than ustekinumab
(1.5 vs. 0.7; p ≤ 0.001) [primary endpoint] [17]. Signifi-
cantly (p ≤ 0.001) more guselkumab than ustekinumab
recipients achieved an IGA of 0/1 with ≥ 2-grade improve-
ment from week 16 to week 28 (31 vs. 14%), with this
significant between-group difference maintained at week
52 (36 vs. 17%) [17]. Between weeks 28 and 40, treat-
ment with guselkumab was associated with a significantly
(p ≤ 0.001) higher mean number of visits at which patients
achieved PASI 90 response relative to baseline (2.2 vs.
1.1) or an IGA score of 0 (0.9 vs. 0.4) than ustekinumab
treatment [17].
Switching to guselkumab following an inadequate
response to ustekinumab improved overall HR-QOL and the
severity of the signs and symptoms of psoriasis, as assessed
by DLQI scores and PSSD sign or symptom scores [17]. At
week 52, amongst randomized patients with week 16 DLQI
scores of > 1 and PSSD sign or symptom scores of > 0,
significantly (p < 0.05) more guselkumab than ustekinumab
recipients were sign- (9 vs. 3%) or symptom-free (20 vs.
10%) and achieved a DLQI score of 0/1 (39 vs. 19%; nomi-
nal p-value only) [17].
5 Tolerability of Guselkumab
Guselkumab was generally well tolerated in adults with
moderate to severe plaque psoriasis in pivotal trials
[15–17], and in the pooled analyses of the VOYAGE tri-
als [13]; the tolerability/safety profile of guselkumab in
individual trials was generally consistent with that of the
pooled analysis. There were no new safety signals identi-
fied during long-term (through 2 years/100 weeks) therapy
[26–28]. The pooled safety analysis set of the VOYAGE
trials included 1367 patients who had received ≥ 1 injec-
tion of guselkumab, with 1036 and 592 patients treated for
6 months and 1 year [13].
During the placebo-controlled period, AEs occurred in
49, 50 and 47% of patients in the guselkumab (n = 823
[5]), adalimumab (n = 581) and placebo (n = 422) groups
[13]. The most common adverse reactions reported in
≥ 1% of patients in the guselkumab group and at a higher
rate than in the placebo group in the pooled analysis
included upper respiratory infections [which included
nasopharyngitis, pharyngitis, upper respiratory tract infec-
tion (URTI) and viral URTI; 14 and 13% of guselkumab
and placebo recipients], headache (5 and 3%), injection-
site reactions (ISRs; 5 and 3%), arthralgia (3 and 2%),
diarrhea (2 and < 1%), gastroenteritis (1 and < 1%), herpes
simplex infections (1 and <1%) and tinea infections (1 and
0%) [6]. Although gastroenteritis occurred more frequently
in the guselkumab than in the placebo group during the
placebo-controlled period, events of gastroenteritis were
not serious and did not lead to guselkumab discontinuation
through week 48 [5]. Elevated liver enzymes were reported
in 3 and 2% of patients in the guselkumab and placebo
groups; the majority of cases in the guselkumab group
were mild or moderate in severity and did not lead to treat-
ment discontinuation. Serious AEs (SAEs) occurred in 2
and 1% of patients in the guselkumab and placebo groups
[6.3 and 4.7 events/100 patient-years (PYs) of follow-up]
[6].
During the randomized withdrawal and retreatment
period in VOYAGE 2 (weeks 28–48), 52 and 45% of
patients in the maintenance and withdrawal groups
reported ≥ 1 AE, but no patients discontinued study agent
because of an AE; SAEs were reported by a similar pro-
portion of patients (1.0–1.6%) in the maintenance and
withdrawal groups [16].
Through year 1 in the VOYAGE trials (974 and 461
total PYs of follow-up in the guselkumab and adalimumab
groups), the exposure-adjusted event rate of AEs per 100
PYs in the guselkumab 100 mg group (n = 1221; includ-
ing placebo-crossover patients) was 259.42 compared with
332.84 in the adalimumab group [13, 27]. The most com-
mon (≥ 5.0/100 PYs’ exposure) AEs in the guselkumab

group included nasopharyngitis, URTI [27], headache,
arthralgia and hypertension [13]; the exposure-adjusted
event rates for most other AEs were < 1/100 PYs [13].
The exposure-adjusted event rates of AEs leading to dis-
continuation of study drug and of SAEs in the guselkumab
group through the end of the reporting period were 2.36 and
6.05/100 PYs [27]. In the VOYAGE trials through to week
48, laboratory abnormalities were low and occurred with
generally similar rates across treatment groups [15, 16].
After up to 2 years of treatment (2084 total PYs of follow-up),
the safety profile of guselkumab including placebo-
crossover patients (n = 1221) was consistent with that pre-
viously reported through 1 year, as demonstrated by similar
event rates per 100 PYs of follow-up to those previously
reported [27]. The exposure-adjusted event rates of overall
AEs and SAEs at 2 years were 210.41 and 6.29 per 100
PYs of follow-up [27]. Similarly, through week 100 in the
VOYAGE trials (n = 500; 496 PYs of follow-up), the safety
profile in the adalimumab-crossover patients was consistent
with the overall guselkumab safety profile with no unex-
pected/additional safety signals identified [26].
In NAVIGATE (through week 60), there were no new
safety findings observed in patients with an inadequate
response to ustekinumab who were switched to guselkumab
without a wash out period [17]. In the randomized cohorts,
64 and 56% of patients in the guselkumab and ustekinumab
groups had ≥ 1 AE, with 2% of patients in each group dis-
continuing treatment due to an AE, and SAEs were reported
in 7 and 5% of patients [17].
5.1 Adverse Events of Special Interest
In the pooled safety data set, during the 48-week reporting
period, ‘infections and infestations’ was the system organ
class with the highest proportion of AEs in the guselkumab
group (96.57/100 PYs of exposure), with stable rates
observed at 16, 28 and 48 weeks (97.90, 91.32 and 97.69/100
PYs’ exposure, respectively) [13]. Rates of infection in the
guselkumab group were generally similar to the placebo
group at week 16, and to the adalimumab group at weeks 28
and 48 [13]. Serious infections occurred with an event rate
of 1.03 and 1.73 PYs of exposure in patients treated with
guselkumab or adalimumab [13]. There was no increase in
the risk of infections or serious infections through up to 2
years, with exposure-adjusted rates in guselkumab-treated
patients of 81.74 and 1.06/100 PYs [27], and 71.20 and
0.0/100 PYs in adalimumab-crossover patients through
week 100 [26]. Similarly, the most common AE across the
guselkumab and ustekinumab randomized groups in NAVI-
GATE were infections (41 and 35%), with 16 and 10% of
patients requiring oral or parenteral antibacterials; serious
infections occurred in 0.7 and 0% of patients [17].
Z. T. Al‑Salama, L. J. Scott
Given that treatment with guselkumab may increase the
risk of infections, local prescribing information recommend
that guselkumab treatment should not be initiated in patients
with clinically important active infection until resolution
or adequate treatment of the infection [5, 6]. Guselkumab
should be discontinued in patients who develop a clinically
important or serious infection or who are not responding to
standard therapy; close monitoring in these patients is also
recommended [5, 6].
Through week 48, 0.7% of guselkumab injections (vs.
1.3 and 0.3% of adalimumab and placebo injections) were
associated with ISRs in the VOYAGE trials [5]. Injection-
site erythema was the most common ISR and was reported
in 1.5 and 5.3% of guselkumab and adalimumab recipients
[13]; ISRs (erythema and pain) were all mild or moderate
in severity and none were serious or led to discontinuation
of guselkumab [5].
In the pooled analysis, event rates for major adverse car-
diovascular events (MACE) were generally similar in the
guselkumab and adalimumab groups through 28 and 48
weeks [13]. The exposure-adjusted event rates for MACE
per 100 PYs were stable over time, with rates of 0.41/100
PYs’ exposure through 1 year and 0.38/100 PYs’ exposure
through up to 2 years of continuous treatment [27].
Exposure-adjusted event rates per 100 PYs for non-melanoma
skin cancer (NMSC) and malignancies (excluding NMSC) in
the guselkumab group were 0.62 and 0.31 through year 1 (vs.
0.22 and 0/100 PYs in the adalimumab group [13]), and 0.39
and 0.38 through up to 2 years of treatment [27].
In a pooled analysis of patients receiving guselkumab in
phase II and III trials (n = 1730), the overall incidence of
antidrug antibodies (ADAs) was 6% (n = 96) through to week
52; neutralizing antibodies were reported in 7% (7/96) of
these patients [i.e. 0.4% (7/1730) of all patients treated with
guselkumab] [13]. The development of ADAs was not associ-
ated with a loss of clinical response/efficacy or the develop-
ment of ISRs [5, 6]. Moreover, through week 100 in VOYAGE
2, withdrawal and retreatment with guselkumab was not asso-
ciated with a marked increase in the incidence of ADAs, and in
patients who were positive for ADAs, was not associated with
reductions in the systemic exposure or efficacy, or the develop-
ment of clinically meaningful ISRs (abstract plus poster) [30].
6 Dosage and Administration
of Guselkumab
Guselkumab is approved in several countries, including
the USA [6] and EU [5] for the treatment of adults with
moderate to severe plaque psoriasis who are candidates for
systemic therapy (or phototherapy [6]). The recommended
dosage of guselkumab is 100 mg administered by subcu-
taneous injection at weeks 0 and 4, followed by 100 mg
Guselkumab: A Review
every 8 weeks, thereafter [5, 6]. In patients who do not
show a response after 16 weeks of treatment, discontinu-
ation of treatment should be considered [5]. The concomi-
tant administration of live vaccines with guselkumab is not
recommended [5, 6]. Treatment with guselkumab must be
withheld for ≥ 12 weeks after the last dose before live viral
or live bacterial vaccination, with resumption of treatment
≥ 2 weeks after vaccination [5]. The use of guselkumab is
contraindicated in patients with clinically important active
infections [5]. Patients should be evaluated for TB infection
prior to initiating guselkumab treatment, with monitoring for
signs and symptoms of active TB during and after treatment;
guselkumab must not be administered to patients with active
TB infection [5, 6]. There are no data regarding the use of
guselkumab in pregnant women [5, 6]; however, it is prefer-
able to avoid its use during pregnancy and effective con-
traception should be used during and for ≥ 12 weeks after
guselkumab treatment in women of childbearing potential
[5]. Local prescribing information should be consulted for
detailed information regarding drug interactions, warnings
and precautions, and use in special patient populations.
7 Place of Guselkumab in the Management
of Moderate to Severe Plaque Psoriasis
There are currently several treatment options for moderate
to severe plaque psoriasis, including phototherapy, conven-
tional/traditional systemic agents (e.g. methotrexate) and
biological agents [1–3, 31], with the choice dependant on
treatment-related factors (e.g. efficacy, tolerability, ease of
administration, availability) and patient-specific factors (e.g.
comorbidities). Given the chronic nature of psoriasis, long-
term treatment that is aimed at improving the patient’s QOL
and reducing plaque size, scaling and thickness is typically
necessary [32]. Patient access to some treatments remains
limited because of cost and it is likely that the emergence
of biosimilars will be associated with cost savings and
improved access; post-approval monitoring is required to
evaluate long-term safety of these products [33].
The current US [1, 2] and EU [31] guidelines preceded
the approval of guselkumab, and thus do not include a rec-
ommendation for its use. The American Academy of Der-
matology guidelines for the management and treatment of
psoriasis and psoriatic arthritis state that biological agents
are now routinely used in patients where one or more tradi-
tional systemic agents fail to produce an adequate response,
are not suitable because of the presence of comorbidities or
are not tolerated because of adverse effects [2]. For patients
with chronic plaque psoriasis with more than 5% BSA
involvement (without psoriatic arthritis) who are healthy
adult males, women of childbearing potential using appro-
priate contraception or women who are trying to conceive,
the algorithm for treatment suggested includes traditional
systemic agents (e.g. cyclosporine) and biological agents
(e.g. adalimumab, ustekinumab) as first-line options in cases
where UVB (or UV in healthy adult males) is not available.
Second-line options often include a combination of first-line
therapies. Similarly, traditional systemic and/or biological
agents are recommended as first-line therapies in patients
with moderate to severe disease and concurrent psoriatic
arthritis; ustekinumab plus methotrexate is recommended
as second-line therapy [2]. The EU treatment guidelines
recommend that most biological agents (e.g. ustekinumab)
should only be used in patients with plaque psoriasis for
the induction of long-term treatment if they have an inad-
equate response to phototherapy and conventional systemic
agents, or if these agents are contraindicated or not toler-
ated (i.e. second-line medication) [31]. Secukinumab (an
IL-17A antagonist) is currently the only biological agent
recommended as first-line treatment for plaque psoriasis by
the EU guidelines; ixekizumab has also been approved in
the EU for the treatment of adults with moderate to severe
plaque psoriasis who are candidates for systemic therapy
[34]. The National Institute for Health and Care Excellence
(NICE) recommends guselkumab as an option for the treat-
ment of adults with plaque psoriasis only if the disease is
severe, has not responded to other systemic therapies, or if
these options are contraindicated or not well-tolerated [35].
In the VOYAGE trials, in terms of the proportion of
patients achieving an IGA 0/1 and PASI 90 response,
guselkumab treatment was superior to placebo at week 16
(co-primary endpoints) and to adalimumab at weeks 16 and
24 (major secondary endpoints) (Sect. 4.1). The beneficial
effects of guselkumab treatment were maintained for up to
2 years in the VOYAGE trials (Sect. 4.1). Compared with
interrupted guselkumab treatment (i.e. randomized with-
drawal; Table 3), guselkumab maintenance was associated
with higher PASI 75, PASI 90 and PASI 100 responses
and improvements in HR-QOL outcomes at 48 weeks in
VOYAGE 2. Improvements in difficult-to-treat regional
disease were also evident in guselkumab-treated patients
in the VOYAGE trials. In the NAVIGATE trial evaluating
patients with an inadequate response to ustekinumab after
a 16-week run-in period, guselkumab treatment was asso-
ciated with a significantly greater mean number of visits
between weeks 28 and 40 at which patients had achieved an
IGA of 0/1 response and ≥ a 2-grade improvement in IGA
score versus ustekinumab treatment (Sect. 4.2). Guselkumab
treatment was also associated with improvements in HR-
QOL throughout these pivotal phase III trials, as assessed by
DLQI scores and PSSD sign and symptom scores (Sect. 4).
Most guselkumab recipients in phase III trials (Sect. 4) met
the criteria, defined by the European consensus programme
for continuing treatment (i.e. a PASI 75 response after

induction and during maintenance treatment of moderate to
severe plaque psoriasis) [32].
Guselkumab was generally well tolerated in clinical trials,
with upper respiratory infection being the most commonly
reported adverse reaction (Sect. 5). No new safety signals
were identified through up to 2 years of treatment, with the
longer-term safety profile of guselkumab in the VOYAGE
trials during this period consistent with that observed in the
first year (Sect. 5). Longer-term follow-up with exposure
beyond 2 years is ongoing and would be of interest to more
definitively assess the incidence of some uncommon AEs or
those with a long latency such as malignancies. It is note-
worthy that selective inhibition of IL-23 (i.e. guselkumab)
may be associated with a lower malignancy risk and the
potential for fewer severe infections than combined inhibi-
tion IL-12/IL-23 (e.g. ustekinumab), due to sparing of IL-12
which has been implicated in tumour immune surveillance
and in host defense against intracellular pathogens [36].
Furthermore, unlike IL-17A blockade (e.g. secukinumab),
inhibiting IL-23 selectively is not associated with class
effects of Crohn’s disease, neutropenia or mucosal candida
infections [13].
Further support for the efficacy and safety of guselkumab
was demonstrated by a network meta-analysis of data from 45
trials comparing guselkumab with other systemic biological
therapies [35]. Guselkumab was associated with substantially
greater clinical benefits than adalimumab, etanercept, inflixi-
mab and ustekinumab, and with similar clinical benefits as
those provided by secukinumab and ixekizumab. The safety
and tolerability profile of guselkumab was generally similar
to that of other biologic agents [35].
Given that there is currently no specific sequence in
which biological agents should be used, results of the ongo-
ing head-to-head phase III ECLIPSE study (NCT03090100)
evaluating the efficacy and safety of guselkumab versus
secukinumab would be of interest [37], as would other tri-
als comparing the efficacy and tolerability of guselkumab
with other approved targeted immunomodulators (includ-
ing in the long-term setting), as they would assist in better
positioning guselkumab compared with other therapies in
the treatment of plaque psoriasis. Real-world studies would
also be of interest, as would trials investigating the efficacy
of guselkumab in patients with moderate to severe plaque
psoriasis who had an inadequate response to targeted bio-
logical therapies (e.g. IL-17 receptor antagonists).
In a cost per responder analysis, based on US costings
and efficacy data from VOYAGE 1, guselkumab was pre-
dicted to be more cost-effective than adalimumab, with a
lower cost per responder for achieving PASI 75, PASI 90
and PASI 100 responses during the first year of treatment
(poster) [38]. Based on US costings, guselkumab was pre-
dicted to provide a lower cost per responder for achieving
PASI 90 responses than secukinumab (efficacy data from
Z. T. Al‑Salama, L. J. Scott
VOYAGE 1 and ERASURE) [39] and ixekizumab (effi-
cacy data from VOYAGE 1 and UNCOVER 3) [40] during
an indirect comparison of efficacy data in the first year
of treatment of patients with moderate to severe plaque
psoriasis (poster presentations). In the NICE guidance,
guselkumab was considered to have met the criteria to be
recommended using cost comparison with secukinumab
and ixekizumab [35]. Additional pharmacoeconomic data
would be beneficial.
The less frequent dosing regimen of guselkumab (i.e.
weeks 0 and 4 then every 8 weeks) may be advantageous
compared with other subcutaneous immunomodulators
administered more frequently (e.g. secukinumab adminis-
tered weekly for 4 weeks followed by once monthly main-
tenance dosing); the convenience of less frequent dosing
and the option of self-administration may contribute to
better compliance/adherence and thus better outcomes.
Although longer-term data and additional comparative
studies will more definitively position guselkumab in rela-
tion to other biological agents in the treatment of plaque
psoriasis, it is an effective and generally well tolerated
systemic treatment for patients with moderate to severe
plaque psoriasis, and as a first in class anti-IL-23 biologic,
guselkumab represents a useful new addition to the options
available for the management of this population.
Data Selection Guselkumab: 176 records
identified 
Duplicates removed 45
Excluded during initial screening (e.g. press releases; 65
news reports; not relevant drug/indication; preclinical
study; reviews; case reports; not randomized trial)
Excluded during writing (e.g. reviews; duplicate data; 26
small patient number; nonrandomized/phase I/II trials)
Cited efficacy/tolerability articles 18
Cited articles not efficacy/tolerability 22
Search Strategy: EMBASE, MEDLINE and PubMed from 1946
to present. Clinical trial registries/databases and websites were
also searched for relevant data. Key words were guselkumab,
CNTO1959, psoriasis. Records were limited to those in English
language. Searches last updated 23 October 2018.
Acknowledgements  During the peer review process, the manufacturer
of guselkumab was also offered an opportunity to review this article.
Changes resulting from comments received were made on the basis of
scientific and editorial merit.
Compliance with Ethical Standards 
Funding  The preparation of this review was not supported by any
external funding.
Guselkumab: A Review
Conflict of interest  Zaina T. Al-Salama and Lesley J. Scott are salaried
employees of Adis/Springer, are responsible for the article content and
declare no relevant conflicts of interest.
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