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 comparator

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 phas[.]

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,aKim A Papp, MD, PhD,bChristopher E M Griffiths, MD,c

Bruce Randazzo, MD, PhD,d,eYasmine Wasfi, MD, PhD,dYaung-Kaung Shen, PhD,d

Shu Li, PhD,dand 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 Center c ; Janssen Research &

Development LLC, Spring House d ; Department of Dermatology,

University of Pennsylvania School of Medicine, Philadelphia e ;

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 December 29, 2016.

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

1

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 http://dx.doi.org/10.1016/ j.jaad.2016.11.041.)

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

Psoriasis is a common,

chronic, immune-mediated

skin disease that is painful,

disfiguring, and disabling,

thereby negatively impacting

health-related quality of life

(HRQoL) to a significant

extent.1 Psoriasis affecting

body regions such as the scalp,

nails, hands, and feet can be

particularly challenging to

treat.2-5 Elucidation of the

pathogenesis of psoriasis6-8

has led to effective biologic

treatments targeting tumor

ne-crosis factor-alpha (TNF-a),9-11

both interleukin (IL)-12 and

IL-23,12,13and, most recently

IL-1714-16and IL-23 alone.17-21

1959; Janssen Research & Development LLC, Spring

House, PA) is a fully human IgG1 lambda

mono-clonal antibody that binds to the p19 subunit of IL-23

and inhibits the intracellular and downstream

signaling of IL-23, which is required for terminal

differentiation and survival of T helper (Th)17 cells.22

To confirm earlier findings, we conducted 2 pivotal,

phase III trials: VOYAGE 1 and VOYAGE 2 We report

efficacy, safety, and patient-reported outcome

find-ings from VOYAGE 1, which compared guselkumab

with adalimumab, a widely used TNF-a inhibitor, and placebo in patients with pso-riasis treated continuously for 1 year Findings from VOYAGE 2, which included

a randomized withdrawal

separately.23 METHODS Patients Eligible patients (aged

$18 years) had moderate to severe plaque psoriasis (ie, Investigator Global Assessment [IGA] score $3, Psoriasis Area and Severity Index [PASI] score $12, body surface area involve-ment $10%) for at least 6 months and were candidates for systemic therapy or phototherapy Patients were ineligible if they had a history or current signs of a severe, progressive, or uncon-trolled medical condition or had current or history of malignancy, except nonmelanoma skin cancer, within 5 years Patients with history or symptoms

of active tuberculosis were excluded Patients could not participate if they received guselkumab or adalimumab previously; other antieTNF-a therapy

CAPSULE SUMMARY

d Phase II data demonstrated superior efficacy of guselkumab compared with adalimumab in moderate to severe psoriasis

d The phase III VOYAGE 1 study validates the superiority of guselkumab compared with adalimumab, including in difficult-to-treat regional disease, through 1 year

of treatment

d Our results, which show guselkumab is superior to adalimumab for clearing moderate to severe psoriasis, will help clinicians make informed treatment decisions

(within 3 months); other treatment targeting IL-12/

23, IL-17, or IL-23 (6 months); or any systemic

immunosuppressants (eg, methotrexate) or

photo-therapy (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

(f-PGA), Nail Psoriasis Severity Index (NAPSI),25and 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 x2statistical 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

Abbreviations used:

DLQI: Dermatology Life Quality Index

f-PGA: Fingernail Physician Global Assessment

HRQoL: health-related quality of life

IGA: Investigator Global Assessment

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

TNF-a: tumor necrosis factor-alpha

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 3and

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 3and

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)

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 adalimuguselku-mab were observed at weeks 24 and 48 (both P \.001) (Table V) The proportion of patients achieving f-PGA 0/1 (cleared/minimal) and

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 Fig 1 Psoriasis Study schema

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

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

Table I Overall psoriasis, regional psoriasis, and health-related quality of life assessments

IGA Investigator Global Assessment 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)

PASI Psoriasis Area and Severity Index 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

ss-IGA Scalp-Specific Investigator

Global Assessment

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

NAPSI Nail Psoriasis Severity Index 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

f-PGA Fingernail Physician Global Assessment The overall condition of the fingernails is assessed on a 5-point scale:

0 = clear, 1 = minimal, 2 = mild, 3 = moderate, and 4 = severe hf-PGA Physician Global Assessment

of Hands and/or Feet

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

DLQI Dermatology Life Quality Index 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

PSSD Psoriasis Symptoms and Signs Diary 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

BSA, Body surface area.

Table II Coprimary and major secondary end points tested using a fixed-sequence method

Guselkumab

vs placebo

Guselkumab

vs adalimumab Study visit no. Coprimary end points*

Major secondary end points*

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

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 treattreat-ment 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

Table III Demographic and disease characteristics at baseline; randomized patients

Age, y

Race

BMI, kg/m2

Duration of psoriasis, y

Body surface area involvement, %

IGA score, 0-4

PASI score, 0-72

Prior treatments

Symptom score

Sign score

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.

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,

Table IV Regional psoriasis characteristics at baseline; randomized patients

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.

malignancies, and major adverse cardiovascular

events were low and comparable across treatment

groups No notable differences in the incidence of

neutropenia or candidiasis were observed between

the guselkumab and control groups No AEs of

Crohn’s disease occurred in any treatment group,

and 1 suicide attempt was reported in the adalimumab

group The number of injections and proportions of patients with ISRs were higher for adalimumab compared with guselkumab The size and duration

of this study may not allow for assessment of uncom-mon events or those with a long latency; however, longer-term guselkumab treatment is being evaluated

in ongoing study extensions

0 A G I

B

1 / 0 A G I

A

0 1 I S A P

E

0 I S A P

D

5 I S A P

C

0 20 40 60 80 100

2 4 8 12 16 20 24 28 32

*

†

†

†

†

†

†

*

36 40 44 48

Week

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

Week

0

20

40

60

80

100

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

Week

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

Week

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

Week

Placebo Guselkumab (n = 165)

* P < 0.001 for guselkumab vs placebo

† P < 0.001 for guselkumab vs adalimumab

Placebo (n = 174)

Guselkumab (n = 329)

Adalimumab (n = 334)

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

Table V Physician- and patient-reported outcomes at weeks 16, 24, and 48; randomized patients

Physician-reported outcomes

Mean percent improvement
0.9 6 57.89 34.46 42.46 38.06 53.87 49.86 44.16 49.46 60.04 68.16 43.00 61.46 49.20

Patient-reported outcomes

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

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-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.