ORIGINAL ARTICLES

Efficacy and safety of guselkumab,

an anti-interleukin-23 monoclonal
antibody, compared with adalimumab
for the continuous treatment of patients
with moderate to severe psoriasis:
Results from the phase III,
double-blinded, placebo- and active
comparatorecontrolled VOYAGE 1 trial
Andrew Blauvelt, MD, MBA,a Kim A. Papp, MD, PhD,b Christopher E. M. Griffiths, MD,c
Bruce Randazzo, MD, PhD,d,e Yasmine Wasfi, MD, PhD,d Yaung-Kaung Shen, PhD,d
Shu Li, PhD,d and Alexa B. Kimball, MPH, MDf
Portland, Oregon; Waterloo, Ontario, Canada; Manchester, United Kingdom; Spring House and
Philadelphia, Pennsylvania; and Boston, Massachusetts

Background: Guselkumab, an interleukin-23 blocker, was superior to adalimumab in treating moderate to

severe psoriasis in a phase II trial.

Objectives: We sought to compare efficacy and safety of guselkumab with adalimumab and placebo in
patients with psoriasis treated for 1 year.

From the Oregon Medical Research Centera; K. Papp Clinical
Research and Probity Research Inc, Waterloob; Dermatology
Center, Salford Royal Hospital, University of Manchester, Man-
chester Academic Health Science Centerc; Janssen Research &
Development LLC, Spring Housed; Department of Dermatology,
University of Pennsylvania School of Medicine, Philadelphiae;
and Department of Dermatology, Harvard Medical School and
Beth Israel Deaconess Medical Center, Boston.f
Supported by Janssen Research & Development LLC, Spring
House, PA.
Disclosure: Dr Blauvelt has served as a scientific adviser and clinical
study investigator for AbbVie, Amgen, Boehringer Ingelheim,
Celgene, Dermira, Genentech, GSK, Janssen, Eli Lilly, Merck,
Novartis, Pfizer, Regeneron, Sandoz, Sanofi-Genzyme, Sun, UCB,
and Valeant, and as a paid speaker for Eli Lilly. Dr Papp has
received honoraria or clinical research grants as a consultant,
speaker, scientific officer, advisory board member, and/or
steering committee member for AbbVie, Akesis, Akros, Aller-
gan, Alza, Amgen, Anacor, Artax, Astellas, AstraZeneca, Baxalta,
Baxter, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb,
CanFite, Celgene, Celtic, Cipher, Dermira, Dow Pharmaceuticals,
Eli Lilly, Ferring Pharmaceuticals, Formycon, Forward Pharma,
Funxional Therapeutics, Fujisawa, Galderma, Genentech, Gen-
exion, Genzyme, Gilead, GSK, Janssen, Kyowa Hakko Kirin, Leo,
Lypanosys, Medimmune, Meiji Seika Pharma, Merck (MSD),
Merck-Serono, Mitsubishi Pharma, Mylan, Novartis, NovIm-
mune, Pan Genetics, Pfizer, Regeneron, Roche, Sanofi-Aventis,
Stiefel, Takeda, UCB, Vertex, and Valeant. Dr Griffiths
has received honoraria and/or grants as an investigator,
speaker, and/or advisory board member for AbbVie, Eli Lilly,
Janssen, Leo, Novartis, Pfizer, Sandoz, and Sun Pharma. Dr
Kimball has received honoraria as a consultant for AbbVie, BMS,
Dermira, Eli Lilly ICOS LLC, Merck, and Novartis; and received
grants and/or funding for research or the residency/fellowship
program as a principal investigator for AbbVie, Amgen,
Boehringer Ingelheim, Dermira, Janssen, Merck, and Novartis.
Drs Randazzo, Wasfi, Shen, and Li are all employees of Janssen
Research & Development LLC (subsidiary of Johnson & John-
son) and own stock in Johnson & Johnson.
Some of the data reported in this article were presented at the
25th European Academy of Dermatology and Venereology
Congress (Vienna, Austria; September 28-October 2, 2016), the
35th Anniversary Fall Clinical Dermatology Conference (Las
Vegas, NV; October 20-23, 2016), and Skin Disease Education
Foundation 17th Annual Las Vegas Dermatology Seminar (Las
Vegas, NV; November 10-12, 2016).
Accepted for publication November 19, 2016.
Reprint requests: Andrew Blauvelt, MD, MBA, Oregon Medical
Research Center, 9495 SW Locust St, Suite G, Portland, OR
97223. E-mail: ablauvelt@oregonmedicalresearch.com.
Published online January 2, 2017.
0190-9622
Ó 2016 by the American Academy of Dermatology, Inc. Published
by Elsevier, Inc. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
nd/4.0/).
http://dx.doi.org/10.1016/j.jaad.2016.11.041

405
406 Blauvelt et al J AM ACAD DERMATOL
MARCH 2017

Methods: Patients were randomized to guselkumab 100 mg (weeks 0 and 4, then every 8 weeks; n = 329);
placebo/guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20, then every 8 weeks;
n = 174); or adalimumab (80 mg week 0, 40 mg week 1, then 40 mg every 2 weeks through week 47;
n = 334). Physician-reported outcomes (Investigator Global Assessment, Psoriasis Area and Severity Index
[PASI]), patient-reported outcomes (Dermatology Life Quality Index, Psoriasis Symptoms and Signs Diary),
and safety were evaluated through week 48.

Results: Guselkumab was superior (P \ .001) to placebo at week 16 (85.1% vs 6.9% [Investigator Global
Assessment score of 0/1 (cleared/minimal)] and 73.3% vs 2.9% [90% or greater improvement in PASI score
from baseline (PASI 90)]). Guselkumab was also superior (P \.001) to adalimumab for Investigator Global
Assessment 0/1 and PASI 90 at week 16 (85.1% vs 65.9% and 73.3% vs 49.7%), week 24 (84.2% vs 61.7% and
80.2% vs 53.0%), and week 48 (80.5% vs 55.4% and 76.3% vs 47.9%). Furthermore, guselkumab significantly
improved patient-reported outcomes through week 48. Adverse event rates were comparable between
treatments.

Limitations: Analyses were limited to 48 weeks.

Conclusions: Guselkumab demonstrated superior efficacy compared with adalimumab and was well
tolerated in patients with psoriasis through 1 year. ( J Am Acad Dermatol 2017;76:405-17.)

Key words: adalimumab; efficacy; guselkumab; hand and foot psoriasis; nail psoriasis; psoriasis; safety;
scalp psoriasis; VOYAGE 1; VOYAGE 2.

Psoriasis is a common, with adalimumab, a widely

chronic, immune-mediated CAPSULE SUMMARY used TNF-a inhibitor, and
skin disease that is painful, placebo in patients with pso-
disfiguring, and disabling, d Phase II data demonstrated superior riasis treated continuously
thereby negatively impacting efficacy of guselkumab compared with for 1 year. Findings from
health-related quality of life adalimumab in moderate to severe VOYAGE 2, which included
(HRQoL) to a significant psoriasis. a randomized withdrawal
extent.1 Psoriasis affecting d The phase III VOYAGE 1 study validates period, are published
23
body regions such as the scalp, the superiority of guselkumab compared separately.
nails, hands, and feet can be with adalimumab, including in difficult-
particularly challenging to to-treat regional disease, through 1 year
treat.2-5 Elucidation of the of treatment. METHODS
pathogenesis of psoriasis6-8 Patients
d Our results, which show guselkumab is
has led to effective biologic Eligible patients (aged
superior to adalimumab for clearing
treatments targeting tumor ne- $18 years) had moderate to
moderate to severe psoriasis, will help
crosis factor-alpha (TNF-a),9-11 severe plaque psoriasis
clinicians make informed treatment
both interleukin (IL)-12 and (ie, Investigator Global
decisions.
IL-23,12,13 and, most recently Assessment [IGA] score $3,
IL-1714-16 and IL-23 alone.17-21 Psoriasis Area and Severity
Guselkumab (CNTO Index [PASI] score $12,
1959; Janssen Research & Development LLC, Spring body surface area involvement $10%) for at least
House, PA) is a fully human IgG1 lambda mono- 6 months and were candidates for systemic
clonal antibody that binds to the p19 subunit of IL-23 therapy or phototherapy. Patients were ineligible if
and inhibits the intracellular and downstream they had a history or current signs of a severe,
signaling of IL-23, which is required for terminal progressive, or uncontrolled medical condition or
differentiation and survival of T helper (Th)17 cells.22 had current or history of malignancy, except
To confirm earlier findings, we conducted 2 pivotal, nonmelanoma skin cancer, within 5 years. Patients
phase III trials: VOYAGE 1 and VOYAGE 2. We report with history or symptoms of active tuberculosis were
efficacy, safety, and patient-reported outcome find- excluded. Patients could not participate if they
ings from VOYAGE 1, which compared guselkumab received guselkumab or adalimumab previously;
J AM ACAD DERMATOL
VOLUME 76, NUMBER 3
Abbreviations used:
AE: adverse event
DLQI: Dermatology Life Quality Index
f-PGA: Fingernail Physician Global Assessment
HRQoL: health-related quality of life
IGA: Investigator Global Assessment
IL: interleukin
ISR: injection site reaction
NAPSI: Nail Psoriasis Severity Index
PASI: Psoriasis Area and Severity Index
PASI 75: 75% or greater improvement in Psoria-
sis Area and Severity Index score from
baseline
PASI 90: 90% or greater improvement in Psoria-
sis Area and Severity Index score from
baseline
PASI 100: 100% improvement in Psoriasis Area
and Severity Index score from baseline
PGA: Physician Global Assessment
PSSD: Psoriasis Symptoms and Signs Diary
Th: T helper
TNF-a: tumor necrosis factor-alpha
other antieTNF-a therapy (within 3 months); other
treatment targeting IL-12/23, IL-17, or IL-23
(6 months); or any systemic immunosuppressants
(eg, methotrexate) or phototherapy (4 weeks).
Study design
VOYAGE 1 (NCT02207231) was a phase III, ran-
domized, double-blind, placebo- and active compa-
ratorecontrolled trial conducted at 101 global sites
(December 2014-April 2016). The study comprised
an active-comparator period when guselkumab was
compared with adalimumab (week 0-48) and a
placebo-controlled period (weeks 0-16), after which
patients taking placebo crossed over to receive
guselkumab through week 48 (Fig 1). Patients were
randomized using a permuted block method at
baseline in a 2:1:2 ratio to guselkumab 100 mg at
weeks 0, 4, 12, and every 8 weeks through week 44;
placebo at weeks 0, 4, and 12 followed by
guselkumab 100 mg at weeks 16 and 20, and every
8 weeks through week 44; or adalimumab 80 mg at
week 0, 40 mg at week 1, and 40 mg every 2 weeks
through week 47. Central randomization was
implemented using an interactive World Wide Web
response system (Perceptive Informatics, East
Windsor, NJ). To maintain the blind, matching
placebos were used. An institutional review board
or ethics committee approved the study protocol at
participating sites; patients provided written
informed consent before study initiation.
Assessments
Efficacy was evaluated using the IGA, PASI,24 scalp-
specific IGA, fingernail Physician Global Assessment
Blauvelt et al 407
(f-PGA), Nail Psoriasis Severity Index (NAPSI),25 and
Physician Global Assessment (PGA) of the hands and/
or feet (Table I). Patient-reported outcomes were
assessed using the Dermatology Life Quality Index
(DLQI)26 and Psoriasis Symptoms and Signs Diary
(PSSD)27,28 (Table I). Safety monitoring included
collection of adverse events (AEs) and laboratory
testing. Antibodies to guselkumab were detected
using a highly sensitive and drug-tolerant electro-
chemiluminescence immunoassay (sensitivity: 3.1 ng/
mL in guselkumab-free serum and 15 ng/mL with
serum guselkumab concentrations #3.125 g/mL,
exceeding mean trough serum guselkumab levels).
Statistical analyses
Coprimary end points were the proportions of
patients achieving an IGA score of cleared/minimal
disease (IGA 0/1) and 90% or greater improvement in
PASI score from baseline (PASI 90) at week 16 in the
guselkumab group compared with placebo. The
primary and major secondary analyses were tested in
a fixed sequence to control for multiplicity (Table II).
All randomized patients were included in the primary
and selected secondary efficacy analyses; data were
analyzed by randomized treatment group.
The coprimary end points and binary major
secondary end points were analyzed using a
Cochran-Mantel-Haenszel x 2 statistical test stratified
by investigator site. With a sample size of approxi-
mately 750 patients, the power to detect a significant
difference was more than 99% for both coprimary
end points. Continuous response parameters were
compared using an analysis of variance model with
investigator site as a covariate. All statistical testing
was performed 2-sided (a = 0.05).
Patients who discontinued study agent because of
lack of efficacy or an AE of psoriasis worsening or who
started a protocol-prohibited psoriasis treatment were
considered nonresponders (binary end points) or had
baseline values carried over (continuous end points).
Other patients with missing data were considered
nonresponders for binary end points (nonresponder
imputation) and had last observation carried forward
for continuous end points (and all PSSD end points).
Safety analyses included all patients receiving at
least 1 study agent administration and were summa-
rized by actual treatment. The proportion of patients
with antibodies to guselkumab was summarized for
those receiving at least 1 dose of the biologic.
RESULTS
At baseline, 837 patients were randomized to
placebo (n = 174), guselkumab (n = 329), or
adalimumab (n = 334). Overall, 6.9% (12 of 174),
8.5% (28 of 329), and 15.6% (52 of 334) of patients
408 Blauvelt et al
Fig 1. Psoriasis. Study schema.
discontinued treatment in the placebo, guselkumab,
and adalimumab groups, respectively, through week
48 (Fig 2). Demographic and disease characteristics
were comparable across treatment groups at
baseline (Tables III and IV).
Clinical responses
Guselkumab was superior to placebo and/or ada-
limumab for the coprimary end points and all major
secondary end points (all P \ .001). Compared with
placebo, significantly higher proportions of patients
taking guselkumab achieved IGA 0/1 (6.9% vs 85.1%)
and PASI 90 (2.9% vs 73.3%) at week 16 (Fig 3 and
Table V). In addition, the proportions achieving 75%
or greater improvement in PASI score from baseline
(PASI 75) along with IGA 0 and 100% improvement in
PASI score from baseline (PASI 100) were significantly
higher for guselkumab versus placebo at week 16
(Fig 3 and Table V). Guselkumab was superior to
adalimumab as measured by the proportion of pa-
tients achieving IGA 0/1 (85.1% vs 65.9%), PASI 90
(73.3% vs 49.7%), and PASI 75 (91.2% vs 73.1%) at
week 16 (Fig 3 and Table V). Significantly better
responses to guselkumab compared with adalimumab
were maintained at week 24 (IGA 0 [52.6% vs 29.3%],
IGA 0/1 [84.2% vs 61.7%], and PASI 90 [80.2% vs
53.0%]) and at week 48 (50.5% vs 25.7%, 80.5% vs
55.4%, and 76.3% vs 47.9%, respectively) (Fig 3 and
Table V). Likewise, PASI 100 responses in the gusel-
kumab group were significantly better than those in
the adalimumab group at weeks 24 and 48 (P \.001).
J AM ACAD DERMATOL
MARCH 2017
In addition, higher proportions of patients taking
guselkumab attained response in higher PASI cate-
gories compared with adalimumab at week 48 (Fig 4).
After initiating guselkumab at week 16, patients in the
placebo cross-over group achieved responses similar
to those observed in the guselkumab group (Fig 3).
Regional psoriasis measures
Regional psoriasis was evaluated based on
assessments using scalp-specific IGA; f-PGA; NAPSI;
and PGA of the hands and/or feet as described in
Table I. The proportion of patients in the guselkumab
group achieving scalp-specific IGA 0/1 (absent/very
mild scalp psoriasis) was significantly higher
compared with placebo (83.4% vs 14.5%, P \ .001)
at week 16; significantly better responses to guselku-
mab versus adalimumab were observed at weeks 24
and 48 (both P \.001) (Table V). The proportion of
patients achieving f-PGA 0/1 (cleared/minimal) and
percent improvement in NAPSI score were
significantly higher for guselkumab versus placebo
at week 16 (P \.001) (Table V). Although the f-PGA
responses were comparable at week 24, guselkumab
was superior to adalimumab by week 48 (P = .038,
Table V). Mean percent improvements in NAPSI
score were comparable between guselkumab and
adalimumab at weeks 24 and 48 (Table V). The
proportion of patients achieving PGA 0/1 of the
hands and/or feet (clear/almost clear) was signifi-
cantly higher for guselkumab versus placebo at week
16, and responses to guselkumab were superior to
J AM ACAD DERMATOL
VOLUME 76, NUMBER 3
Table I. Overall psoriasis, regional psoriasis, and health-related quality of life assessments
Assessment
IGA Investigator Global Assessment
PASI Psoriasis Area and Severity Index
ss-IGA Scalp-Specific Investigator
Global Assessment
NAPSI Nail Psoriasis Severity Index
f-PGA Fingernail Physician Global Assessment
hf-PGA Physician Global Assessment
of Hands and/or Feet
DLQI Dermatology Life Quality Index
PSSD Psoriasis Symptoms and Signs Diary
BSA, Body surface area.
adalimumab at week 24 (P \ .001) and week 48
(P \.045) (Table V).
HRQoL measures
At week 16, improvement from baseline in DLQI
score was significantly greater for guselkumab
compared with placebo (mean change
11.2 vs

0.6), as were the proportions of patients achieving
DLQI score 0/1 (no impact of psoriasis on HRQoL)
(both P \.001) (Table V). At weeks 24 and 48, both
improvements from baseline in DLQI score and
proportions of patients achieving DLQI 0/1 were
significantly higher for guselkumab versus adalimu-
mab (P \.001) (Table V).
At week 16, the improvement from baseline in
PSSD symptom score was significantly greater for
guselkumab versus placebo (mean change
41.9 vs

3.0); mean changes in PSSD sign score were
Blauvelt et al 409
Description and rating scale
At a given time point, psoriatic lesions are graded by the investigator
for induration, erythema, and scaling on a scale of 0-4: cleared (0),
minimal (1), mild (2), moderate (3), or severe (4).
The severity of psoriatic lesions is assessed in 4 body regions: the
head, trunk, and upper and lower extremities, which account for
10%, 30%, 20%, and 40% of the total BSA, respectively. Each of
these areas is assessed separately for erythema, induration, and
scaling, which are each rated on a scale of 0-4. Total score ranges
from 0-72; a higher score indicates more severe disease.
Scalp lesions are assessed in terms of clinical signs of redness,
thickness, and scaliness and are scored on a 5-point scale:
0 = absence of disease, 1 = very mild disease, 2 = mild disease,
3 = moderate disease, 4 = severe disease.
A target nail (ie, the nail most affected by psoriasis) is divided into
quadrants, which are examined for the presence of nail matrix
psoriasis (ie, pitting, leukonychia, red spots in the lunula, nail plate
crumbling) and nail bed psoriasis (ie, onycholysis, oil drop
dyschromia, splinter hemorrhages, subungual hyperkeratosis) on a
scale of 0-4; total score ranges from 0-8; higher scores indicate
more severe disease.
The overall condition of the fingernails is assessed on a 5-point scale:
0 = clear, 1 = minimal, 2 = mild, 3 = moderate, and 4 = severe.
The severity of psoriasis plaques on the palms and soles is scored on a
5-point scale: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate,
and 4 = severe.
Ten questions related to the effect of skin problems on aspects of life
(ie, symptoms and feelings, daily activities, leisure, work or school
performance, personal relationships, and treatment) during the
previous week are answered by the patient, for an overall score of
0-30. A higher score indicates more severe disease.
Symptoms (ie, itch, pain, stinging, burning, and skin tightness) and
signs (skin dryness, cracking, scaling, shedding or flaking, redness,
and bleeding) of psoriasis are graded (0-10 scale) by the patient in a
daily diary. A higher score indicates more severe symptoms and
signs of psoriasis.
similarly favorable for guselkumab (both P \ .001)
(Table V). Likewise, at weeks 24 and 48, mean
changes in PSSD scores for guselkumab were
significantly greater than those for adalimumab
(P \ .001) (Table V). The proportions of patients
achieving a PSSD symptom score of 0 with
guselkumab and adalimumab, respectively, were
36.3% and 21.6% at week 24, and the significantly
better response to guselkumab was maintained at
week 48 (P \.001). Similar results were observed for
the proportions of patients achieving a PSSD sign
score of 0 at weeks 24 and 48 (P \.001) (Table V).
Safety outcomes
During the placebo-controlled period (weeks 0-
16), the proportion of patients with at least 1 AE was
comparable across treatment groups, and the most
commonly reported events were nasopharyngitis and
410 Blauvelt et al J AM ACAD DERMATOL
MARCH 2017

Table II. Coprimary and major secondary end points tested using a fixed-sequence method
Guselkumab Guselkumab
vs placebo vs adalimumab Study visit no.
Coprimary end points*
(1) Proportion of patients who achieve IGA 0/1 and PASI 90 O d Wk 16
Major secondary end points*
(2) Proportion of patients who achieve IGA 0 d O Wk 24
(3) Proportion of patients who achieve IGA 0/1 d O Wk 24
(4) Proportion of patients who achieve PASI 90 d O Wk 24
(5) Proportion of patients who achieve IGA 0 d O Wk 48
(6) Proportion of patients who achieve IGA 0/1 d O Wk 48
(7) Proportion of patients who achieve PASI 90 d O Wk 48
(8) Change from baseline in DLQI score O d Wk 16
(9) Proportion of patients who achieve IGA 0/1yz d O Wk 16
(10) Proportion of patients who achieve PASI 90yz d O Wk 16
(11) Proportion of patients who achieve PASI 75yz d O Wk 16
(12) Proportion of patients who achieve ss-IGA 0/1x O d Wk 16
(13) Change from baseline in PSSD symptom score O d Wk 16
(14) Proportion of patients who achieve PSSD symptom score 0k d O Wk 24

DLQI, Dermatology Life Quality Index; IGA 0, Investigator Global Assessment score of 0 (cleared); IGA 0/1, Investigator Global Assessment
score of 0 (cleared) or 1 (minimal); PASI 75, 75% or greater improvement from baseline in Psoriasis Area and Severity Index score; PASI 90,
90% or greater improvement from baseline in Psoriasis Area and Severity Index score; PSSD, Psoriasis Symptoms and Signs Diary; ss-IGA 0/1,
scalp-specific Investigator Global Assessment score of 0 (absence of disease) or 1 (very mild disease).
*To control the overall type 1 error rate, the primary analysis and major secondary analyses were tested using a fixed sequence method.
Specifically, the first major secondary end point was tested only if the coprimary end points were positive, and subsequent end points were
tested only if the preceding end point was positive.
y
Tested for noninferiority of the guselkumab group compared with the adalimumab group.
z
Tested for superiority of the guselkumab group compared with the adalimumab group.
x
Included only randomized patients with scalp psoriasis who had an ss-IGA score $2 at baseline and who achieved $2-grade improvement.
k
Included only randomized patients with PSSD symptom score $1 at baseline.

Fig 2. Psoriasis. Consolidated Standards of Reporting Trials diagram.

J AM ACAD DERMATOL Blauvelt et al 411
VOLUME 76, NUMBER 3

Table III. Demographic and disease characteristics at baseline; randomized patients

Placebo Guselkumab Adalimumab Total
Randomized patients, n 174 329 334 837
Age, y
Mean 6 SD 44.9 6 12.90 43.9 6 12.74 42.9 6 12.58 43.7 6 12.72
Men 119 (68.4) 240 (72.9) 249 (74.6) 608 (72.6)
Race
White 145 (83.3) 262 (79.6) 277 (82.9) 684 (81.7)
Asian 23 (13.2) 51 (15.5) 47 (14.1) 121 (14.5)
Black 3 (1.7) 6 (1.8) 8 (2.4) 17 (2.0)
BMI, kg/m2
Mean 6 SD 28.9 6 6.89 29.7 6 6.22 29.8 6 6.48 29.6 6 6.47
Median (IQR) 27.3 (24.1-33.1) 28.7 (25.5-32.9) 28.7 (25.2-33.5) 28.4 (25.2-33.2)
Duration of psoriasis, y
Mean 6 SD 17.6 6 12.44 17.9 6 12.27 17.0 6 11.27 17.5 6 11.91
Body surface area involvement, %
Mean 6 SD 25.8 6 15.93 28.3 6 17.10 28.6 6 16.66 27.9 6 16.70
IGA score, 0-4
Mild, 2 0 0 3 (0.9) 3 (0.4)
Moderate, 3 131 (75.3) 252 (76.6) 241 (72.2) 624 (74.6)
Severe, 4 43 (24.7) 77 (23.4) 90 (26.9) 210 (25.1)
PASI score, 0-72
Mean 6 SD 20.4 6 8.74 22.1 6 9.49 22.4 6 8.97 21.9 6 9.15
Median (IQR) 17.4 (14.4-23.1) 18.6 (15.6-25.5) 20.0 (16.0-26.1) 19.0 (15.4-25.4)
Psoriatic arthritis 30 (17.2) 64 (19.5) 62 (18.6) 156 (18.6)
Prior treatments
Topical agents 154 (88.5) 299 (90.9) 309 (92.8) 762 (91.1)
Phototherapy 86 (49.4) 188 (57.3) 180 (53.9) 454 (54.3)
Conventional systemic agents 92 (52.9) 210 (63.8) 215 (64.4) 517 (61.8)
Biologic agents 34 (19.5) 71 (21.6) 70 (21.0) 175 (20.9)
DLQI score [0-30], n 170 322 328 820
Mean 6 SD 13.3 6 7.12 14.0 6 7.48 14.4 6 7.29 14.0 6 7.33
PSSD score [0-100], n 129 249 274 652
Symptom score
Mean 6 SD 48.3 6 23.77 54.4 6 24.63 53.9 6 25.79 53.0 6 25.03
Sign score
Mean 6 SD 53.6 6 20.34 56.9 6 21.30 58.5 6 21.73 56.9 6 21.34

Values are reported as n (%), unless otherwise indicated.

BMI, Body mass index; DLQI, Dermatology Life Quality Index; IGA, Investigator Global Assessment; IQR, interquartile range; PASI, Psoriasis Area
and Severity Index; PSSD, Psoriasis Symptoms and Signs Diary.

upper respiratory tract infection (Table VI). Serious
AEs and AEs leading to study agent discontinuation
occurred infrequently and in similar proportions of
patients for each treatment (Table VI). Rates of overall
infections and infections requiring antibiotic treat-
ment were comparable across treatment groups
(Table VI). Two patients in the adalimumab group
experienced serious infections (both cellulitis). One
nonmelanoma skin cancer (ie, basal cell carcinoma)
was reported in the guselkumab group, and no other
malignancies occurred in any group. One myocardial
infarction (ie, major adverse cardiovascular event)
occurred in each of the guselkumab and adalimumab
groups through week 16.
The types and patterns of AEs reported through
week 48 were similar to those reported during the
placebo-controlled period (Table VI). The propor-
tions of patients with at least 1 AE, an AE leading to
discontinuation, or a serious AE were similar in the
guselkumab and adalimumab groups (Table VI).
Between weeks 16 and 48, serious infections were
reported in 2 patients in the guselkumab group (ie,
thigh abscess and cellulitis with postoperative
wound infection) and 2 patients in the adalimumab
group (ie, abdominal abscess and staphylococcal
pneumonia with a fatal outcome). Overall infections
and infections requiring antibiotic treatment
occurred at comparable rates across treatment
groups (Table VI). Two additional nonmelanoma
skin cancers (ie, 1 basal cell carcinoma each in the
guselkumab and adalimumab groups) and 2 malig-
nancies (ie, prostate and breast in the guselkumab
412 Blauvelt et al J AM ACAD DERMATOL
MARCH 2017

Table IV. Regional psoriasis characteristics at baseline; randomized patients

Placebo Guselkumab Adalimumab Total
Randomized patients, n 174 329 334 837
ss-IGA score, 0-4 150 (86.2) 291 (88.4) 295 (88.3) 736 (87.9)
Very mild, 1 5 (3.3) 14 (4.8) 9 (3.1) 28 (3.8)
Mild, 2 31 (20.7) 49 (16.8) 54 (18.3) 134 (18.2)
Moderate, 3 89 (59.3) 171 (58.8) 175 (59.3) 435 (59.1)
Severe, 4 25 (16.7) 57 (19.6) 57 (19.3) 139 (18.9)
f-PGA score, 0-4 99 (56.9) 198 (60.2) 194 (58.1) 491 (58.7)
Minimal, 1 11 (11.1) 24 (12.1) 21 (10.8) 56 (11.4)
Mild, 2 33 (33.3) 62 (31.3) 66 (34.0) 161 (32.8)
Moderate, 3 42 (42.4) 83 (41.9) 90 (46.4) 215 (43.8)
Severe, 4 13 (13.1) 29 (14.6) 17 (8.8) 59 (12.0)
NAPSI score, 0-8 99 (56.9) 194 (59.0) 191 (57.2) 484 (57.8)
Mean 6 SD 4.7 6 1.94 4.9 6 2.03 4.6 6 2.03 4.7 6 2.01
hf-PGA score, 0-4 44 (25.3) 100 (30.4) 101 (30.2) 245 (29.3)
Almost clear, 1 1 (2.3) 10 (10.0) 6 (5.9) 17 (6.9)
Mild, 2 15 (34.1) 34 (34.0) 37 (36.6) 86 (35.1)
Moderate, 3 21 (47.7) 42 (42.0) 45 (44.6) 108 (44.1)
Severe, 4 7 (15.9) 14 (14.0) 13 (12.9) 34 (13.9)

Values are reported as n (%), unless otherwise indicated.

f-PGA, Fingernail Physician Global Assessment; hf-PGA, Physician Global Assessment of hands and/or feet; NAPSI, Nail Psoriasis Severity Index;
ss-IGA, scalp-specific Investigator Global Assessment.

group) were reported through week 48. No addi-
tional major adverse cardiovascular event occurred
after week 16. A single suicide attempt was reported
in a patient taking adalimumab. Incidence rates of
candidiasis and neutropenia were low and compa-
rable between groups, and no events of Crohn’s
disease were reported through week 48.
Through week 48, the proportion of patients with
an injection site reaction (ISR) (2.2% vs 9.0%) and the
proportion of injections associated with ISRs (0.5% vs
1.2%) were lower for guselkumab compared with
adalimumab; most ISRs were mild. Rates of abnormal
laboratory results were low, and no between-group
differences were noted. Antibodies to guselkumab
were detected in 26 of 492 patients (5.3%) through
week 44; titers were generally low (81% #1:320). No
association was observed between antibody deve-
lopment and reduced efficacy or ISR occurrence.
DISCUSSION
Our findings, together with the VOYAGE 2
results,23 confirm that 2 injections of guselkumab
100 mg (weeks 0 and 4) and maintenance therapy
every 8 weeks effectively treats moderate to severe
psoriasis. Guselkumab was superior to placebo by
substantial margins at week 16 using 2 rigorous end
points (IGA 0/1 and PASI 90). The onset of action of
guselkumab was rapid, with significant response as
early as week 2 compared with placebo. Guselkumab
was also superior to adalimumab, which is a widely
used and effective subcutaneous TNF-a inhibitor, at
the week-16 end points of IGA 0/1, PASI 90, and PASI
75. Response rates continued to improve with gusel-
kumab beyond week 16. At weeks 24 and 48,
approximately half of all patients in the guselkumab
group achieved complete clearance (IGA 0), which is
associated with optimal HRQoL for patients with
psoriasis.29,30 Patient-reported outcome end points
(PSSD and DLQI) based on total change, or indicating
minimal/no impact on HRQoL or no symptoms or
signs of psoriasis, demonstrated guselkumab re-
sponses superior to placebo at week 16 and adali-
mumab at weeks 24 and 48.
This study assessed multiple body areas where
psoriasis is challenging to treat, and guselkumab was
highly effective in all regions. Guselkumab was
superior to placebo at week 16 and to adalimumab
at weeks 24 and 48, indicating complete or nearly
complete clearance of scalp and hand/foot psoriasis
in at least 75% of guselkumab-treated patients. Based
on both the proportion of patients with clear/
minimal fingernail psoriasis (f-PGA 0/1) and the
mean percent improvement in NAPSI score, gusel-
kumab was superior to placebo at week 16. Nail
responses were comparable between active treat-
ments at weeks 24 and 48, and guselkumab was
superior to adalimumab for f-PGA 0/1 at week 48.
Rates and types of AEs, serious AEs, and abnormal
laboratory results were generally comparable between
the guselkumab and placebo groups through week 16,
and between the guselkumab and adalimumab
groups through week 48. Rates of serious infections,
J AM ACAD DERMATOL Blauvelt et al 413
VOLUME 76, NUMBER 3

IGA 0 / 1 IGA 0
100

Proportion of patients (%)

80

†
60 †

40
†
†
20

*
0 *
2 4 8 12 16 20 24 28 32 36 40 44 48 2 4 8 12 16 20 24 28 32 36 40 44 48
A Week B Week

PASI 75 PASI 90 PASI 100

100
Proportion of patients (%)

80

† †

60 †
†

40
† †

20

* * *
0
2 4 8 12 16 20 24 28 32 36 40 44 48 2 4 8 12 16 20 24 28 32 36 40 44 48 2 4 8 12 16 20 24 28 32 36 40 44 48

C Week D Week E Week

Placebo Placebo Guselkumab Guselkumab Adalimumab

(n = 174) (n = 165) (n = 329) (n = 334)

* P < 0.001 for guselkumab vs. placebo

† P < 0.001 for guselkumab vs. adalimumab

Fig 3. Psoriasis. Clinical efficacy through week 48. Proportion of patients achieving (A) IGA 0/1,
(B) IGA 0, (C) PASI 75, (D) PASI 90, and (E) PASI 100 responses. IGA 0/1, Investigator Global
Assessment score of cleared (0) or minimal (1); IGA 0, Investigator Global Assessment score of
0 (cleared); PASI 75, 75% or greater improvement in Psoriasis Area and Severity Index score from
baseline; PASI 90, 90% or greater improvement in Psoriasis Area and Severity Index score from
baseline; PASI 100, 100% improvement in Psoriasis Area and Severity Index score from baseline.

malignancies, and major adverse cardiovascular group. The number of injections and proportions of
events were low and comparable across treatment patients with ISRs were higher for adalimumab
groups. No notable differences in the incidence of compared with guselkumab. The size and duration
neutropenia or candidiasis were observed between of this study may not allow for assessment of uncom-
the guselkumab and control groups. No AEs of mon events or those with a long latency; however,
Crohn’s disease occurred in any treatment group, longer-term guselkumab treatment is being evaluated
and 1 suicide attempt was reported in the adalimumab in ongoing study extensions.
 414 Blauvelt et al
Table V. Physician- and patient-reported outcomes at weeks 16, 24, and 48; randomized patients
Wk 16 Wk 24 Wk 48
Placebo Guselkumab Adalimumab Guselkumab Adalimumab Guselkumab Adalimumab
Physician-reported outcomes
IGA, n 174 329 334 329 334 329 334
IGA 0 2 (1.1) 157 (47.7) 88 (26.3) 173 (52.6) 98 (29.3) 166 (50.5) 86 (25.7)
IGA 0/1 12 (6.9) 280 (85.1) 220 (65.9) 277 (84.2) 206 (61.7) 265 (80.5) 185 (55.4)
PASI, n 174 329 334 329 334 329 334
PASI 100 1 (0.6) 123 (37.4) 57 (17.1) 146 (44.4) 83 (24.9) 156 (47.4) 78 (23.4)
PASI 90 5 (2.9) 241 (73.3) 166 (49.7) 264 (80.2) 177 (53.0) 251 (76.3) 160 (47.9)
PASI 75 10 (5.7) 300 (91.2) 244 (73.1) 300 (91.2) 241 (72.2) 289 (87.8) 209 (62.6)
Baseline ss-IGA score $2, n 145 277 286 277 286 277 286
ss-IGA 0/1* 21 (14.5) 231 (83.4) 201 (70.3) 234 (84.5) 198 (69.2) 217 (78.3) 173 (60.5)
Baseline f-PGA score $2, n 88 174 173 174 173 174 173
f-PGA 0/1* 14 (15.9) 68 (39.1) 88 (50.9) 98 (56.3) 108 (62.4) 130 (74.7) 107 (61.8)
NAPSI, n 99 194 191 194 191 194 191
Mean percent improvement
0.9 6 57.89 34.4 6 42.46 38.0 6 53.87 49.8 6 44.16 49.4 6 60.04 68.1 6 43.00 61.4 6 49.20
Baseline hf-PGA score $2, n 43 90 95 90 95 90 95
hf-PGA 0/1* 6 (14.0) 66 (73.3) 53 (55.8) 71 (78.9) 54 (56.8) 68 (75.6) 59 (62.1)
Patient-reported outcomes
DLQI, n 170 322 328 322 328 322 328
Change in DLQI
0.6 6 6.36
11.2 6 7.24
9.3 6 7.80
11.6 6 7.55
9.5 6 7.89
11.8 6 7.87
9.2 6 8.27
DLQI score [1 at baseline, n 168 320 319 320 319 320 319
DLQI 0/1 7 (4.2) 180 (56.3) 123 (38.6) 195 (60.9) 126 (39.5) 200 (62.5) 124 (38.9)
PSSD score, n 129 249 274 249 274 249 274
Change in symptom score
3.0 6 19.56
41.9 6 24.61
35.4 6 28.45
44.0 6 24.57
36.0 6 28.36
45.3 6 25.51
32.5 6 31.14
Change in sign score
4.1 6 17.87
44.6 6 22.00
39.7 6 26.44
47.2 6 22.19
40.1 6 26.49
47.9 6 23.08
36.6 6 29.28
Baseline PSSD symptom score $1, n 129 248 273 248 273 248 273
Symptom score of 0 1 (0.8) 67 (27.0) 45 (16.5) 90 (36.3) 59 (21.6) 104 (41.9) 63 (23.1)
Baseline PSSD sign score $1, n 129 248 274 248 274 248 274
Sign score of 0 0 50 (20.2) 32 (11.7) 73 (29.4) 40 (14.6) 89 (35.9) 51 (18.6)

J AM ACAD DERMATOL
Values are reported as n (%) or mean 6 SD.
DLQI, Dermatology Life Quality Index score; f-PGA, fingernail Physician Global Assessment; hf-PGA, Physician Global Assessment of hands and/or feet; IGA, Investigator Global Assessment; NAPSI, Nail
Psoriasis Severity Index; PASI, Psoriasis Area and Severity Index; PASI 75, 75% or greater improvement from baseline in Psoriasis Area and Severity Index; PASI 90, 90% or greater improvement from
baseline in Psoriasis Area and Severity Index; PASI 100, 100% or greater improvement from baseline in Psoriasis Area and Severity Index; PSSD, Psoriasis Symptoms and Signs Diary; ss-IGA, scalp-

MARCH 2017
specific Investigator Global Assessment.
*Includes only patients also achieving $2-grade improvement in ss-IGA and hf-PGA scores and $1-grade improvement in f-PGA score.
J AM ACAD DERMATOL Blauvelt et al 415
VOLUME 76, NUMBER 3

Fig 4. Psoriasis. Distribution of PASI responses at week 48. PASI, Psoriasis Area and Severity Index;
PASI 50, 50% or greater improvement in Psoriasis Area and Severity Index score from baseline; PASI
75, 75% or greater improvement in Psoriasis Area and Severity Index score from baseline; PASI 90,
90% or greater improvement in Psoriasis Area and Severity Index score from baseline; PASI 100,
100% improvement in Psoriasis Area and Severity Index score from baseline.

Table VI. Cumulative rates of key safety events; treated patients

Wk 0-16 Wk 0-48
Placebo-controlled period Active comparatorecontrolled period Wk 16-48
Placebo Guselkumab Adalimumab Guselkumab Adalimumab Placebo /guselkumab
Patients treated, n 174 329 333 329 333 165
Mean duration 15.88 16.27 16.14 46.47 45.56 31.88
of follow-up, wk
At least 1 AE 86 (49.4) 170 (51.7) 170 (51.1) 243 (73.9) 248 (74.5) 107 (64.8)
Common AEs*
Nasopharyngitis 17 (9.8) 30 (9.1) 35 (10.5) 83 (25.2) 74 (22.2) 34 (20.6)
Upper respiratory 9 (5.2) 25 (7.6) 16 (4.8) 47 (14.3) 42 (12.6) 17 (10.3)
tract infection
Injection-site erythema 1 (0.6) 6 (1.8) 15 (4.5) 8 (2.4) 22 (6.6) 3 (1.8)
Headache 7 (4.0) 12 (3.6) 13 (3.9) 18 (5.5) 25 (7.5) 1 (0.6)
Arthralgia 3 (1.7) 11 (3.3) 9 (2.7) 18 (5.5) 16 (4.8) 2 (1.2)
Pruritus 10 (5.7) 5 (1.5) 7 (2.1) 8 (2.4) 12 (3.6) 0
Back pain 2 (1.1) 6 (1.8) 4 (1.2) 12 (3.6) 17 (5.1) 1 (0.6)
Discontinued study 2 (1.1) 4 (1.2) 3 (0.9) 9 (2.7) 12 (3.6) 1 (0.6)
agent because of AE
At least 1 SAE 3 (1.7) 8 (2.4) 6 (1.8) 16 (4.9) 15 (4.5) 5 (3.0)
Infections 44 (25.3) 85 (25.8) 85 (25.5) 172 (52.3) 167 (50.2) 76 (46.1)
Requiring treatment 13 (7.5) 20 (6.1) 24 (7.2) 54 (16.4) 60 (18.0) 25 (15.2)
Serious infections 0 0 2 (0.6) 2 (0.6) 3 (0.9) 1 (0.6)
Malignanciesy 0 0 0 2 (0.6) 0 0
NMSCz 0 1 (0.3) 0 2 (0.6) 1 (0.3) 0
MACEx 0 1 (0.3) 1 (0.3) 1 (0.3) 1 (0.3) 0

Values are reported as n (%).

AE, Adverse event; MACE, major adverse cardiovascular events; NMSC, nonmelanoma skin cancers; SAE, serious adverse event.
*Occurred in at least 5% of patients in any treatment group through wk 48.
y
Includes malignancies other than NMSC (ie, prostate and breast cancer).
z
Includes 3 basal cell carcinomas.
x
Includes sudden cardiac death, myocardial infarction, and stroke.
416 Blauvelt et al
VOYAGE 1 confirms the role of IL-23 in the
pathogenesis of psoriasis. When compared with
TNF-a blockade, selective targeting of the IL-23
pathway provides more psoriasis-specific cytokine
inhibition with a higher degree of efficacy while
maintaining a favorable safety profile.31 IL-23 is a
key driver of Th17 cell differentiation and survival and
an upstream regulator of IL-17A, a central proinflam-
matory effector cytokine implicated in psoriasis
pathogenesis.32-34 Moreover, IL-23 stimulates
production of other Th17 cytokines (eg, IL-22) by
other cell types, including innate lymphoid type 3 cells
and gd T cells.35-37 Therefore, inhibition of IL-23
blocks downstream production of IL-17A and IL-22 by
Th17 cells and other cell types. Because many IL-17A-
producing cells are dependent on IL-23 for survival,
inhibition of IL-23 may reduce the number of these
pathogenic cells.38 This may explain the long duration
of effect and allow for the convenient dosing interval
of guselkumab compared with both antieTNF-a and
anti-IL-17 agents.39-43
Our findings, together with those from VOYAGE
2,23 demonstrate the superior efficacy of guselkumab
compared with adalimumab in psoriasis, including
regional disease of the scalp, nails, and hands/feet,
and a positive safety profile. Although the well-
characterized long-term safety findings reported for
a related treatment that blocks both IL-12 and IL-23
(ustekinumab)44-46 provides relevant information for
selective blockade of IL-23 with guselkumab,
ongoing study extensions will be important for
defining the efficacy and safety of guselkumab
beyond the 1-year period reported here.
The authors thank Cynthia Arnold, Janssen Scientific
Affairs LLC, Spring House, PA, and Cynthia Guzzo, MD,
HireGenics, Duluth, GA, for their editorial assistance and
writing support and Philippe Szapary, MD, MSCE, and
Michael Song, MD, Janssen Research & Development LLC,
Spring House, PA, for their critical review of this
manuscript.
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