Research

JAMA Dermatology | Original Investigation

Comparison of Biologics and Oral Treatments for Plaque Psoriasis

A Meta-analysis
April W. Armstrong, MD, MPH; Luis Puig, MD; Avani Joshi, PhD; Martha Skup, PhD; David Williams, MD;
Junlong Li, PhD; Keith A. Betts, PhD; Matthias Augustin, MD

Editorial
IMPORTANCE The clinical benefits of novel treatments for moderate to severe psoriasis are Supplemental content
well established, but wide variations exist in patient response across different therapies.
In the absence of head-to-head randomized trials, meta-analyses synthesizing data from
multiple studies are needed to assess comparative efficacy among psoriasis treatments.

OBJECTIVE To estimate the relative short-term and long-term efficacy of biologics and oral
agents for the treatment of moderate to severe psoriasis.

DATA SOURCES A systematic literature review was conducted on December 4, 2017,

and updated on September 17, 2018. The Embase, MEDLINE, and Cochrane Central Register
databases were included.

STUDY SELECTION Phase 2, 3, or 4 randomized clinical trials of treatments licensed by the US

Food and Drug Administration and the European Medicines Agency for adults with moderate
to severe psoriasis with data on Psoriasis Area and Severity Index assessment of 75%,
90%, and 100% reductions (PASI 75, 90, and 100) at 10 to 16 weeks (short-term efficacy)
or 44 to 60 weeks (long-term efficacy) from baseline.

DATA EXTRACTION AND SYNTHESIS Data were extracted based on the Preferred Reporting
Items for Systematic Review and Meta-analysis guidelines. A bayesian network meta-analysis
was conducted to estimate short-term PASI response rates; to account for variation across
trials, an ordinal model that adjusted for reference arm response was implemented.
The long-term PASI rates were estimated via a traditional meta-analysis.

MAIN OUTCOMES AND MEASURES PASI 75, 90, and 100 response rates at 10 to 16 weeks
and 44 to 60 weeks from baseline.

RESULTS Sixty trials meeting all inclusion criteria were included. At weeks 10 to 16, the highest
PASI 90 rates were seen with risankizumab-rzaa (71.6%; 95% credible interval [CrI],
67.5%-75.4%), brodalumab (70.8%; 95% CrI, 66.8%-74.6%), ixekizumab (70.6%; 95% CrI,
66.8%-74.6%), and guselkumab (67.3%; 62.5%-71.9%). At weeks 44 to 60, the treatments
with the highest PASI 90 rates were risankizumab-rzaa (79.4%, 95% CI, 75.5%-82.9%),
guselkumab (76.5%; 95% CI, 72.1%-80.5%), brodalumab (74.0%; 95% CI, 69.3%-78.1%), Author Affiliations: Department of
and ixekizumab (73.9%; 95% CI, 69.9%-77.5%). Findings were consistent for short-term and Dermatology, Keck School of
Medicine, University of Southern
long-term PASI 75 and 100 responses.
California, Los Angeles, California
(Armstrong); Department of
CONCLUSIONS AND RELEVANCE This study provides an assessment of the comparative
Dermatology, Hospital de la Santa
efficacy among treatments for moderate to severe plaque psoriasis. The meta-analysis Creu i Sant Pau, Universitat
suggests that brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa were associated Autònoma de Barcelona, Barcelona,
with the highest PASI response rates in both short-term and long-term therapy. Spain (Puig); AbbVie, North Chicago,
Illinois (Joshi, Skup, Williams);
Analysis Group Inc, Boston,
Massachusetts (Li); Analysis Group
Inc, Los Angeles, California (Betts);
Health Care Research in Dermatology
and Nursing, University Medical
Center Hamburg-Eppendorf,
Hamburg, Germany (Augustin).
Corresponding Author: April W.
Armstrong, MD, MPH, Department of
Dermatology, Keck School of
Medicine, University of Southern
California, HC4 2000,
1450 San Pablo, Health Sciences
JAMA Dermatol. doi:10.1001/jamadermatol.2019.4029 Campus, Los Angeles, CA 90033
Published online February 5, 2020. (aprilarmstrong@post.harvard.edu).

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 Research Original Investigation
T
he treatment options for patients with moderate to se-
vere psoriasis have expanded greatly over the past
decade.1-4 Among the treatments, biologics provide
targeted inhibition of immune-mediated pathways involving
specific cytokines, such as tumor necrosis factor (TNF), inter-
leukin (IL)-17, and IL-23. 5,6 Biologics licensed by the US
Food and Drug Administration and the European Medicines
Agency for the treatment of moderate to severe psoriasis
include the tumor necrosis factor inhibitors adalimumab,
etanercept, infliximab, and certolizumab pegol; the IL-12/23
inhibitor ustekinumab; the IL-17 inhibitors secukinumab,
ixekizumab, and brodalumab; and the IL-23 inhibitors
tildrakizumab-asmn, guselkumab, and risankizumab-rzaa.7-9
Although the increased options of biologics and oral treat-
ments for moderate to severe psoriasis have provided sub-
stantial benefit to patients, it can be challenging for clinicians
to determine how the medications compare with one an-
other. Variations exist across different therapies with regard
to efficacy, safety, and dosing profiles.10,11
Although several head-to-head trials exist,12-22 they are not
available for all possible comparisons. In the absence of head-
to-head trials across the entire set of comparators, studies that
combine and analyze data from multiple studies are needed
to determine comparative efficacy. The overall objective in this
study is to evaluate the comparative efficacy of systemic treat-
ments for psoriasis, including newly developed biologics.
Specifically, the short-term, relative rates of Psoriasis Area
and Severity Index (PASI) response are estimated via a net-
work meta-analysis (NMA), and the long-term PASI response
rates following maintenance therapy are estimated via a tra-
ditional meta-analysis.
Methods
Search Strategy
A systematic literature review was performed on December 4,
2017, and updated on September 17, 2018, to identify random-
ized clinical trials of treatments licensed by the US Food and
Drug Administration and the European Medicines Agency for
adults with moderate to severe psoriasis. This systematic re-
view was conducted based on the Preferred Reporting Items
for Systematic Review and Meta-Analysis guidelines for Net-
work Meta-Analysis (PRISMA-NMA) using Embase, MEDLINE,
and the Cochrane Central Register of Controlled Trials.23 Iden-
tified studies were independently assessed by 2 reviewers for
inclusion at each stage of study selection. Any discrepancies
between the inclusion/exclusion decisions were resolved by
a third independent reviewer.
Inclusion Criteria
To be included in the analyses, studies were required to (1) be
a phase 2, 3, or 4 randomized clinical trial on adults with mod-
erate to severe psoriasis who were eligible for systemic thera-
pies and phototherapy, (2) include European Medicines Agen-
cy–licensed treatments and dosages for moderate to severe
psoriasis, and (3) report at least 1 of the efficacy outcomes of
interest (PASI 75, 90, and 100, indicating 75%, 90%, or 100%
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Comparison of Biologics and Oral Treatments for Plaque Psoriasis
Key Points
Question What is the short-term and long-term comparative
efficacy among biologics and oral agents for plaque psoriasis?
Findings In a network meta-analysis of 60 clinical trials for
short-term efficacy, brodalumab, guselkumab, ixekizumab,
and risankizumab-rzaa had the highest Psoriasis Area and
Severity Index response rates at 10 to 16 weeks from baseline.
A meta-analysis of long-term efficacy suggested that brodalumab,
guselkumab, ixekizumab, and risankizumab-rzaa had the highest
response rates at 44 to 60 weeks.
Meaning This study provides an assessment of both short-term
and long-term comparative efficacy among treatments for
moderate to severe plaque psoriasis which can help health care
stakeholders optimize treatment regimens.
reductions) at the end of the primary response period (10-16
weeks from baseline) or at the end of the maintenance period
(44-60 weeks from baseline).
Comparators
Comparators for the base case analyses included anti-TNF
agents (etanercept, 25 mg, twice weekly or 50 mg once weekly,
or etanercept, 50 mg twice weekly until week 12, then once
weekly; adalimumab, 80 mg, at week 0, then 40 mg every
2 weeks starting at week 1; certolizumab pegol, 400 mg, at
weeks 0, 2, and 4, then 200 mg every 2 weeks; certolizumab
pegol, 400 mg, every 2 weeks; infliximab, 5 mg/kg, at weeks
0, 2, and 6, then every 8 weeks), apremilast, 30 mg, twice daily
after initial titration schedule; dimethyl fumarate, ustekinumab
weight-based dosage (45 mg ≤100 kg, 90 mg >100 kg at weeks
0 and 4, then every 12 weeks), anti-IL-17 agents (secukinumab,
300 mg, at weeks 0, 1, 2, and 3, then every 4 weeks starting
at week 4; ixekizumab, 160 mg, at week 0, then 80 mg every
2 weeks; brodalumab, 210 mg, at weeks 0, 1, and 2, then ev-
ery 2 weeks), and anti-IL-23 agents (tildrakizumab-asmn,
100 mg, at weeks 0, 4, then every 12 weeks; tildrakizumab-
asmn, 200 mg, at weeks 0, 4, then every 12 weeks; guselkumab,
100 mg, at weeks 0, 4, then every 8 weeks; risankizumab-
rzaa, 150 mg, at weeks 0, 4, then every 12 weeks). Different
dosing schedules of etanercept with 25 mg twice weekly and
50 mg once weekly were assumed to have the same clinical ef-
ficacy, and the 2 dosages were pooled into a single etaner-
cept, 25 mg twice weekly/50 mg once weekly, treatment arm.
For the outcomes at the end of the maintenance period, a dose
of 50 mg twice weekly until week 12 then once weekly (ap-
proved by the US Food and Drug Administration and also as
an alternative dosage licensed by the European Medicines
Agency) was used. In addition, the following conventional sys-
temic treatments were included in a sensitivity analysis for the
short-term analyses: acitretin, 0.4 mg/kg daily, cyclosporine,
2.5-3 mg/kg/d (initial dose), fumaric acid esters (licensed in Ger-
many only), low-dose methotrexate (initial dose of 5-7.5 mg
once weekly, increased as needed and as tolerated up to a maxi-
mum of 15-25 mg once weekly), and high-dose methotrexate
(initial dose of 15 mg once weekly, increased as needed up to
a maximum of 20-22.5 mg once weekly).
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 Comparison of Biologics and Oral Treatments for Plaque Psoriasis Original Investigation Research

Outcomes Figure 1. Study Screening and Selection Flow

In this analysis, the outcomes of interest were the proportion
of patients that achieved 75%, 90%, and 100% reductions in 11 476 Identified
PASI and the associated number needed to treat (NNT) at the 6916 Embase
end of the primary response period (10-16 weeks from base- 2392 MEDLINE
2168 Cochrane
line) and at the end of the maintenance period (44-60 weeks
3439 Duplicates
from baseline).
8037 Screened based on title,
abstract
Statistical Analysis 7324 Excluded
Short-term Efficacy: NMA 2807 Population
2216 Review, editorial
An ordinal bayesian random effects NMA24 was conducted to
1680 Study design
compare the relative PASI 75, 90, and 100 responses at the end 543 Intervention
of the primary response period (10-16 weeks from baseline) 52 Animal or in vitro
26 Non-English language
across treatments. To account for heterogeneity across trials,
713 Screened based on full text
a model that adjusted for reference-arm response was
364 Excluded
implemented.25,26 The base-case analysis included all biolog-
172 Abstract superseded
ics, apremilast, and dimethyl fumarate. The estimated PASI re- by full article
sponse rates were summarized using posterior medians and 67 Study design
66 Population
their associated 95% credible intervals (CrIs). The NNT for each 19 Intervention
treatment was calculated as the reciprocal of the treatment ef- 14 Outcomes
10 Comparator
fect difference vs placebo. Pairwise comparisons of the esti- 6 Non-English language
mated treatment effects relative to risankizumab-rzaa, ixeki- 6 Review, editorial
4 Full text not obtained
zumab, brodalumab, and guselkumab were summarized using
odds ratios (ORs) and their associated 95% CrIs. All analyses 63 Additions
59 September 2018 update
were conducted using R, version 3.5.1 statistical software 4 Hand searching
(R Foundation) and WinBUGS, version 1.4.3 with noninforma-
tive priors, 40 000 burn-in iterations, a thinning factor of 10,
412 Included (160 studies)
and 3 chains each with 100 000 posterior iterations. Three sen- 60 Studies included in NMA
sitivity analyses were conducted: 1 that included only global 100 Studies excluded from NMA
trials (country-specific trials were excluded to assess the as-
sociations of homogeneous populations with the study re- NMA indicates network meta-analysis.
sults), 1 that included only phase 3 trials, and 1 that focused
on an expanded treatment space that also included conven-
tional systemic treatments (acitretin, cyclosporine, fumaric acid
esters, and methotrexate).
Results
Long-term Efficacy: Meta-analysis
Most of the psoriasis trials feature crossover (typically, the Literature Search
placebo arm switching to the active treatment) after the pri- A total of 11 476 studies were systematically identified. Fol-
mary short-term end point. In addition, some psoriasis trials lowing elimination of duplicate studies, 8037 studies were
rerandomize patients based on the level of PASI response screened based on title and abstract and 713 full-text studies
achieved. Owing to the relative dearth of trials that did not fea- were evaluated. An updated search on September 17, 2018,
ture crossover or rerandomization, a traditional random- identified an additional 59 randomized clinical trials of treat-
effects meta-analysis27 was conducted to estimate the PASI 75, ments and dosages licensed by the European Medicines Agency
90, and 100 response rates at the end of the maintenance pe- for adults with moderate to severe psoriasis. A total of 412 pub-
riod (44-60 weeks from baseline). Only data from trial treat- lications covering 160 studies met the inclusion criteria
ment arms in which baseline treatment assignment was (Figure 1). The full list of clinical trials13,15-21,28-86 and their re-
maintained during the maintenance period were used. ported efficacy data that were analyzed are summarized in
Each intervention’s response rate and its associated 95% CI eTable 1 in the Supplement.
were summarized. Pairwise comparisons of the estimated
response rates relative to brodalumab, guselkumab, ixeki- Short-term Efficacy
zumab, and risankizumab-rzaa were summarized using ORs The evidence network for the base-case NMA of short-term
and their associated 95% CIs. Three sensitivity analyses were efficacy 10 to 16 weeks from baseline is illustrated in
conducted: an analysis of only global trials (country-specific Figure 2.13,15-21,30-35,37-47,49-69,71-74,83,84 A total of 60 trials meet-
trials were excluded to assess the association between the ing all inclusion criteria were included in the base-case NMA.
homogeneous populations and the study results), 1 that in- The median posterior probability of each intervention achiev-
cluded only phase 3 trials, and 1 that included only trials that ing at least the given PASI response (PASI 75, 90, and 100) is
reported nonresponse imputed (NRI) data. presented in the Table. The estimated PASI 90 response rates

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 Research Original Investigation Comparison of Biologics and Oral Treatments for Plaque Psoriasis

Figure 2. Evidence Network for Network Meta-analysis (NMA) of Short-term Psoriasis Area and Severity Index (PASI) (Base Case)

PSOR-010/LIBERATE

Apremilast 30 mg
CIMPASI-1
CIMPASI-2 reSURFACE-1
Etanercept 25 mg twice
CIMPACT Papp 2015
weekly, 50 mg once weekly
PSOR-008/ESTEEM-1 reSURFACE-2
Certolizumab pegol 400 mg PSOR-009/ESTEEM-2
Tildrakizumab 200 mg
PSOR-010/LIBERATE
PSOR-005
CIMPASI-1 Ohtsuki 2017
CIMPASI-2
Certolizumab pegol 200 mg CIMPACT Leonardi 2003 reSURFACE-1 Tildrakizumab 100 mg
NCT00245765 Papp 2005 Papp 2015
van de Kerkhof 2008 reSURFACE-2
Gottlieb 2003 reSURFACE-1
CIMPASI-1
PSOR-010/LIBERATE Papp 2015
CIMPASI-2
reSURFACE-2
CIMPACT EXPRESS
EXPRESS II
SPIRIT
Dimethyl fumarate Chaudhari 2001 Infliximab 5 mg/kg
BRIDGE Torii 2010
VOYAGE-1 Yang 2012 LOTUS
VOYAGE-2 PEARL
ORION PHOENIX 1
Ohtsuki 2018 PHOENIX 2
Placebo Igarashi 2012
Asahina 2010
PHOENIX 1
Guselkumab 100 mg Bissonnette 2013 Ustekinumab 45 mg
PHOENIX 2
REVEAL
Nakagawa 2016 Igarashi 2012 ACCEPT
VOYAGE-1 CHAMPION
Papp 2012 PHOENIX 1
VOYAGE-2 Gordon 2006 ERASURE
AMAGINE-1 PHOENIX 2
Cai 2017 FEATURE
AMAGINE-2 Igarashi 2012
X-PLORE FIXTURE
UltIMMa1 AMAGINE-3 UNCOVER 1
VOYAGE-1 JUNCTURE
UltIMMa2
VOYAGE-2 UNCOVER 2 Ustekinumab 90 mg
IMMhance
VIP-U UNCOVER 3
AMAGINE-2
Adalimumab 40 mg AMAGINE-3
UltIMMa1
UltIMMa2
IMMvent

Brodalumab 210 mg

Risankizumab 150 mg Secukinumab 300 mg AMAGINE-2

AMAGINE-3
UltIMMa1 Ixekizumab 80 mg
UltIMMa2
CLEAR
CLARITY IXORA-S

Ustekinumab 45 mg ≤100 kg
90 mg >100 kg

The reference citations for the NMA are as follows: PSOR-010/LIBERATE: reference 20; CIMPASI-1: reference 65; CIMPASI-2: reference 65; CIMPACT: reference 66;
reSURFACE-1: reference 68; Papp 2005: reference 38; reSURFACE-2: reference 68; PSOR-008/ESTEEM-1: reference 71; PSOR-009/ESTEEM-2: reference 72;
PSOR-005: reference 73; Ohtsuki 2017: reference 74; NCT00245765: reference 67; Papp 2015: reference 69; Leonardi 2003: reference 37; van de Kerkhof 2008:
reference 39; Gottlieb 2003: reference 40; EXPRESS: reference 41; EXPRESS II: reference 42; SPIRIT: reference 43; Chaudhari 2001: reference 44; Torii 2010:
reference 45; Yang 2012: reference 46; BRIDGE: reference 31; VOYAGE-1: reference 17; VOYAGE-2: reference 18; ORION: reference 60; Ohtsuki 2018: reference 61;
LOTUS: reference 54; PEARL: reference 55; PHOENIX 1: reference 56; PHOENIX 2: reference 57; Igarashi 2012: reference 58; Asahina 2010: reference 30;
Bissonnette 2013: reference 31; REVEAL: reference 32; CHAMPION: reference 33; Gordon 2006: reference 34; Cai 2017: reference 35; X-PLORE: reference 58;
ACCEPT: reference 53; Nakagawa 2016: reference 62; Papp 2012: reference 63; AMAGINE-1: reference 64; AMAGINE-2: reference 19; AMAGINE-3: reference 19;
ERASURE: reference 50; FEATURE: reference 51; FIXTURE: reference 50; JUNCTURE: reference 52; UltIMMa-1: reference 15; UltIMMa-2: reference 15; IMMhance:
reference 83; UNCOVER 1: reference 47; UNCOVER 2: reference 48; UNCOVER 3: reference 48; VIP-U: reference 59; IMMvent: reference 21; CLEAR: reference 13;
CLARITY: reference 26; and IXORA-S: reference 16.

at 10 to 16 weeks from baseline were 71.6% (95% CrI, 67.5%-
75.4%) for risankizumab-rzaa; 70.8% (95% CrI, 66.8%-
74.6%) for brodalumab; 70.6% (95% CrI, 66.8%-74.6%) for
ixekizumab; 67.3% (95% CrI, 62.5%-71.9%) for guselkumab;
61.4% (95% CrI, 57.2%-65.6%) for secukinumab; 57.4%
(95% CrI, 52.2%-62.8%) for infliximab; 45.6% (39.3%-52.2%)
for certolizumab pegol, 400 mg; 43.9% (40.2%-47.9%) for
ustekinumab; 43.7% (95% CrI, 40.0%-47.4%) for adalim-
umab; 40.2% (95% CrI, 33.5%-47.2%) for certolizumab pegol,
200 mg; 38.8% (95% CrI, 33.3%-44.7%) for tildrakizumab-
asmn, 200 mg; 36.8% (31.4%-42.5%) for tildrakizumab-
asmn, 100 mg; 17.9% (CrI, 14.9%-21.4%) for etanercept; 12.1%
(95% CrI, 9.9%-14.7%) for apremilast; 11.4% (95% CrI, 7.5%-
16.7%) for dimethyl fumarate; and 1.1% (95% CrI, 1.0%-1.3%)
for placebo. In addition, the ORs of achieving the given PASI
response (PASI 75, 90, and 100) for each intervention vs bro-
dalumab, guselkumab, ixekizumab, and risankizumab-rzaa are
illustrated in eFigure 1 in the Supplement.

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 Comparison of Biologics and Oral Treatments for Plaque Psoriasis Original Investigation Research

Table. Estimated Response Rates From the NMA of Short-term PASI (Base Case)

Posterior Median, % (95% CrI)

Treatment PASI 75 PASI 90 PASI 100
Risankizumab-rzaa, 150 mg 89.2 (86.9-91.3) 71.6 (67.5-75.4) 40.4 (35.9-45.0)
Ixekizumab, 80 mg 88.8 (86.5-90.9) 70.8 (66.8-74.6) 39.5 (35.2-44.0)
Brodalumab, 210 mg 88.7 (86.5-90.8) 70.6 (66.8-74.6) 39.2 (35.2-43.9)
Guselkumab, 100 mg 86.8 (83.8-89.4) 67.3 (62.5-71.9) 35.7 (30.9-40.7)
Secukinumab, 300 mg 83.1 (80.2-85.7) 61.4 (57.2-65.6) 29.9 (26.3-33.9)
Infliximab, 5 mg/kg 80.4 (76.5-84.0) 57.4 (52.2-62.8) 26.5 (22.3-31.4)
Certolizumab pegol, 400 mg 71.1 (65.4-76.5) 45.6 (39.3-52.2) 17.7 (13.8-22.3)
Ustekinumab, 45 mg ≤100 kg, 90 mg >100 kg 69.7 (66.3-73.1) 43.9 (40.2-47.9) 16.7 (14.4-19.3)
Adalimumab, 40 mg 69.5 (66.0-72.6) 43.7 (40.0-47.4) 16.5 (14.2-19.0)
Certolizumab pegol, 200 mg 66.2 (59.6-72.4) 40.2 (33.5-47.2) 14.4 (10.7-18.8)
Tildrakizumab-asmn, 200 mg 64.9 (59.4-70.3) 38.8 (33.3-44.7) 13.6 (10.6-17.1)
Tildrakizumab-asmn, 100 mg 62.9 (57.3-68.4) 36.8 (31.4-42.5) 12.5 (9.7-15.8)
Abbreviations: CrI, credible interval;
Etanercept, 25 mg twice weekly/50 mg once weekly 40.1 (35.4-45.1) 17.9 (14.9-21.4) 4.2 (3.1-5.4)
NMA, network meta-analysis;
Apremilast, 30 mg 30.8 (26.8-35.0) 12.1 (9.9-14.7) 2.4 (1.8-3.1) PASI, Psoriasis Area and Severity
Dimethyl fumarate 29.6 (22.0-38.3) 11.4 (7.5-16.7) 2.2 (1.2-3.8) Index; PASI 75, 90, 100, a 75%,
90% or 100% decrease from
Placebo 5.3 (4.8-5.9) 1.1 (1.0-1.3) 0.1 (0.1-0.1)
baseline PASI.

Among all of the comparators evaluated, brodalumab, gusel-
kumab, ixekizumab, and risankizumab-rzaa had the highest
PASI 75, 90, and 100 rates at the end of the primary response pe-
riod, and there were no statistically significant differences among
these treatments. Brodalumab, guselkumab, ixekizumab, and
risankizumab-rzaa had significantly higher PASI 75, 90, and 100
rates (with 95% probability) compared with adalimumab, apre-
milast, certolizumab pegol, dimethyl fumarate, etanercept,
tildrakizumab-asmn, and ustekinumab. Brodalumab, ixeki-
zumab, and risankizumab-rzaa also had significantly higher rates
compared with infliximab and secukinumab across all PASI out-
comes (with 95% probability).
The NNT to achieve PASI 75, 90, or 100 for each treat-
ment relative to placebo is presented in Figure 3. To achieve a
PASI 75 response, the NNT was 1.19 (95% CrI, 1.16-1.23) with
risankizumab-rzaa, 1.20 (95% CrI, 1.17-1.23) with ixekizumab
and brodalumab, and 1.23 (95% CrI, 1.19-1.27) with gusel-
kumab. The NNT to achieve a PASI 90 response was 1.42
(95% CrI, 1.35-1.51) with risankizumab-rzaa, 1.43 (95% CrI, 1.36-
1.52) with ixekizumab, 1.44 (95% CrI, 1.36-1.52) with bro-
dalumab, and 1.51 (95% CrI, 1.41-1.63) with guselkumab. The
NNT to achieve a PASI 100 response was 2.48 (95% CrI, 2.23-
2.79) with risankizumab-rzaa, 2.54 (95% CrI, 2.28-2.85) with
ixekizumab, 2.56 (95% CrI, 2.28-2.85) with brodalumab, and
2.81 (95% CrI, 2.46-3.25) with guselkumab.
Sensitivity Analyses: Short-term Efficacy
Among the 60 trials included in the base-case, 10 are country-
specific trials and were excluded from this sensitivity analy-
sis. The median posterior probability of PASI 75, 90, and 100
rates for each intervention are presented in eTable 2 in the
Supplement. Overall, the results from the sensitivity analysis
including only global trials were consistent with the base-
case analysis.
Among the 60 trials included in the base case, 47 were
phase 3 trials that were included in the following sensitivity
analysis. The median posterior probability of PASI 75, 90, and
100 rates for each intervention are presented in eTable 2 in the
Supplement. The results from the sensitivity analysis based
on phase 3 trials were consistent with those from the base-
case analysis.
For the sensitivity analysis of the expanded treatment
space, a total of 70 trials were included. The median posterior
probability of PASI 75, 90, and 100 rates for each intervention are
presented in eTable 2 in the Supplement. The results from the
sensitivity analysis of the expanded treatment space were also
consistent with those from the base-case analysis.
Long-term Efficacy
A total of 22 trials on 10 treatments meeting all inclusion cri-
teria were included in the meta-analysis. The estimated re-
sponse rates (PASI 75, 90, and 100) of each intervention are
presented in Figure 4.13,15-18,20,21,34,41,42,47,50-52,73,74,84-86 The
estimated PASI 90 response rates at 44 to 60 weeks from base-
line were 79.4% (95% CI, 75.5%-82.9%) for risankizumab-
rzaa, 76.5% (95% CI, 72.1%-80.5%) for guselkumab, 74.0%
(95% CI, 69.3%-78.1%) for brodalumab, 73.9% (95% CI, 69.9%-
77.5%) for ixekizumab, 71.3% (95% CI, 64.2%-77.5%) for
secukinumab, 52.4% (95% CI, 47.1%-57.7%) for ustekinumab,
46.2% (95% CI, 38.6%-53.9%) for adalimumab, 40.1% (95% CI,
30.0%-51.1%) for infliximab, 33.4% (95% CI, 28.5%-38.7%) for
etanercept, and 16.0% (95% CI, 10.7%-23.3%) for apremilast.
In addition, the ORs of achieving PASI 75, 90, and 100 for each
intervention vs brodalumab, guselkumab, ixekizumab, and
risankizumab-rzaa are presented in eFigure 2 in the Supple-
ment. Among the comparators, the highest estimated PASI
75, 90, and 100 response rates at 44 to 60 weeks from base-
line occurred following treatment with brodalumab, gusel-
kumab, ixekizumab, risankizumab-rzaa, and secukinumab,
which were significantly higher than those corresponding
to adalimumab, apremilast, etanercept, infliximab, and
ustekinumab. In addition, risankizumab-rzaa had significantly

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 E6
Figure 3. Estimated Number Needed to Treat (95% Credible Interval) Relative to Placebo for Short-term Psoriasis Area and Severity Index (PASI) (Base Case)

PASI 75 PASI 90 PASI 100

Fewer Needed More Needed Fewer Needed More Needed Fewer Needed More Needed
Response Rate to Treat to to Treat to Response Rate to Treat to to Treat to Response Rate to Treat to to Treat to
(95% Crl), % Achieve PASI 75 Achieve PASI 75 (95% Crl), % Achieve PASI 90 Achieve PASI 90 (95% Crl), % Achieve PASI 100 Achieve PASI 100
Risankizumab-rzaa 150 mg 1.19 (1.16-1.23) 1.42 (1.35-1.51) 2.48 (2.23-2.79)
Ixekizumab 80 mg 1.20 (1.17-1.23) 1.43 (1.36-1.52) 2.54 (2.28-2.85)
Brodalumab 210 mg 1.20 (1.17-1.23) 1.44 (1.36-1.52) 2.56 (2.28-2.85)
Research Original Investigation

Guselkumab 100 mg 1.23 (1.19-1.27) 1.51 (1.41-1.63) 2.81 (2.46-3.25)

Secukinumab 300 mg 1.29 (1.24-1.34) 1.66 (1.55-1.78) 3.36 (2.96-3.82)
Infliximab 5 mg/kg 1.33 (1.27-1.40) 1.78 (1.62-1.96) 3.79 (3.21-4.50)
Certolizumab pegol 400 mg 1.52 (1.41-1.66) 2.25 (1.96-2.62) 5.68 (4.50-7.30)
Ustekinumab 1.55 (1.48-1.64) 2.34 (2.14-2.56) 6.02 (5.21-6.99)
45 mg ≤100 kg
90 mg > 100 kg
Adalimumab 40 mg 1.56 (1.49-1.64) 2.35 (2.16-2.57) 6.10 (5.29-7.09)
Certolizumab pegol 200 mg 1.64 (1.49-1.84) 2.56 (2.17-3.09) 6.99 (5.35-9.43)
Tildrakizumab-asmn 200 mg 1.68 (1.54-1.85) 2.65 (2.30-3.11) 7.41 (5.88-9.52)
Tildrakizumab-asmn 100 mg 1.74 (1.58-1.92) 2.80 (2.42-3.30) 8.06 (6.37-10.42)
Etanercept 25 mg twice 2.87 (2.52-3.32) 5.95 (4.93-7.25) 24.39 (18.87-32.26)

JAMA Dermatology Published online February 5, 2020 (Reprinted)

weekly, 50 mg once weekly
Apremilast 30 mg 3.92 (3.37-4.63) 9.09 (7.41-11.36) 43.48 (33.33-58.82)
Dimethyl fumarate 4.12 (3.03-5.99) 9.71 (6.41-15.63) 47.62 (27.03-90.91)

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1 2 4 8 1 2 5 10 20 1 5 10 50 100
Number Needed to Treat Number Needed to Treat Number Needed to Treat

PASI 75, 90, 100, indicates 75%, 90%, or 100% decrease from baseline.

© 2020 American Medical Association. All rights reserved.

Comparison of Biologics and Oral Treatments for Plaque Psoriasis

jamadermatology.com
 Figure 4. Estimated Response Rate From the Meta-analysis of Long-term Placebo for Short-term Psoriasis Area and Severity Index (PASI) (Base Case)

Response Rate PASI 75 Response Rate PASI 90 Response Rate PASI 100
Therapy (95% CI), % (95% CI), % (95% CI), %
Risankizumab-rzaa 150 mg at week 0, 4, then every 12 wk
IMMvent21 (N = 301) 86.7 (8.24-90.1) 75.7 (70.6-80.3) 52.8 (47.2-58.4)
UltIMMa115 (N = 304) 91.8 (88.1-94.4) 81.9 (77.2-85.8) 56.3 (50.6-61.7)

jamadermatology.com
UltIMMa215 (N = 294) 91.5 (87.7-94.2) 80.6 (75.7-84.7) 59.5 (53.8-65.0)
Overall 90.1 (86.3-92.9) 79.4 (75.5-82.9) 56.2 (52.4-59.9)
Guselkumab 100 mg at week 0, 4, then every 8 wk
61
Ohtsuki 2018 (N = 63) 90.5 (80.4-95.7) 77.8 (65.9-86.4) 47.6 (35.7-59.8)
VOYAGE 117 (N = 329) 87.8 (83.8-91.0) 76.3 (71.4-80.6) 47.4 (42.1-52.8)
Overall 88.2 (84.6-91.1) 76.5 (72.1-80.5) 47.4 (42.5-52.4)
Brodalumab 210 mg at week 0, 1, 2, then every 2 wk
AMAGINE-279 (N = 189) 80.0 (73.7-85.1) 75.0 (68.3-80.7) 56.0 (48.8-62.9)
AMAGINE-379 (N = 194) 80.0 (73.8-85.0) 73.0 (66.3-78.8) 53.0 (46.0-59.9)
Overall 80.0 (75.7-83.7) 74.0 (69.3-78.1) 54.5 (49.5-59.4)
Ixekizumab 160 mg at week 0, 80 mg every 2 wk
until week 12, then 80 mg every 4 wk
IXORA-S16 (N = 136) 88.2 (81.6-92.6) 76.5 (68.7-82.9) 52.2 (43.8-60.5)
UNCOVER 348 (N = 385) 83.0 (78.9-86.4) 73.0 (68.3-77.2) 55.0 (50.0-59.9)
Overall 85.0 (79.2-89.4) 73.9 (69.9-77.5) 54.3 (50.0-58.5)
Secukinumab 300 mg at week 0, 1, 2, and 3,
then every 4 wk
Comparison of Biologics and Oral Treatments for Plaque Psoriasis

CLEAR13 (N = 334) 91.6 (88.1-94.1) 74.9 (69.9-79.2) 44.9 (39.7-50.3)

Pooled analysis of four trials 85.2 (82.3-87.7) 68.1 (64.5-7.15) 40.8 (37.2-44.5)
50 51
(ERASURE, FEATURE, FIXTURE, 50
and JUNCTURE52) (N = 686)
Overall 88.6 (80.6-93.6) 71.3 (64.2-77.5) 42.4 (38.5-46.4)
Ustekinumab 45 mg or 90 mg at week 0, 4,
then every 12 wk

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AMAGINE-279 (N = 300) 62.0 (56.4-67.3) 48.0 (42.4-53.7) 30.0 (25.1-35.4)
AMAGINE-379 (N = 313) 63.0 (57.5-68.2) 50.0 (44.5-55.5) 29.0 (24.2-34.3)
CLEAR13 (N = 335) 78.2 (73.5-82.3) 60.6 (55.3-65.7) 36.7 (31.7-42.0)
16
IXORA-S (N = 166) 75.9 (68.8-81.8) 59.0 (51.4-66.3) 35.5 (28.6-43.1)
84
PSTELLAR (N = 69) 82.6 (71.8-89.8) — —
UltIMMa115 (N = 100) 70.0 (60.3-78.2) 44.0 (34.6-53.8) 21.0 (14.1-30.1)
UltIMMa215 (N = 99) 76.8 (67.5-84.0) 50.5 (40.8-60.2) 30.3 (22.1-40.0)
Overall 72.5 (65.9-78.2) 52.4 (4.71-57.7) 31.0 (27.2-35.2)
Adalimumab 80 mg at week 0,
then 40 mg every 2 wk
ADACCESS85 (N = 115) 79.6 (71.3-86.0) 51.0 (41.9-60.0) 29.6 (22.0-38.6)
Gordon 200634 (N = 45) 56.0 (41.4-69.6) 33.0 (20.9-47.8) 16.0 (7.9-29.7)
17
VOYAGE 1 (N = 334) 62.6 (57.3-67.6) 47.9 (42.6-53.3) 23.4 (19.1-28.2)
Overall 67.1 (52.9-78.7) 46.2 (38.6-53.9) 24.2 (18.8-30.7)

© 2020 American Medical Association. All rights reserved.

Infliximab 5 mg/kg at week 0, 2, and 6,
then every 8 wk
EXPRESS41 (N = 281) 60.5 (54.7-66.0) 45.2 (39.5-51.1) —
EXPRESS II42 (N = 134) 54.5 (46.0-62.7) 34.3 (26.8-42.7) —
Overall 58.3 (52.5-63.8) 40.1 (30.0-51.1) —
Etanercept 50 mg until week 12, then once weekly
50
FIXTURE (N = 323) 55.5 (50.1-60.9) 33.4 (28.5-38.7) 10.1 (7.3-13.9)
Overall 55.5 (50.1-60.9) 33.4 (28.5-38.7) 10.1 (7.3-13.9)
Apremilast 30 mg twice daily
LIBERATE20 (N = 74) 52.7 (41.4-63.8) 17.6 (10.5-27.9) —
Ohtsuki 201774 (N = 85) 40.0 (30.2-50.7) — —
PSOR-00573/PSOR-005E86 (N = 58) 36.2 (24.9-49.2) 13.8 (7.1-25.2) —
Overall 43.2 (33.8-53.0) 16.0 (10.7-23.3) —
25 50 75 100 0 25 50 75 100 0 25 50 75
Response Rate, % Response Rate, % Response Rate, %
Original Investigation Research

(Reprinted) JAMA Dermatology Published online February 5, 2020

E7
 Research Original Investigation
higher PASI 90 rates than ixekizumab and secukinumab;
risankizumab-rzaa, brodalumab, and ixekizumab had signifi-
cantly higher PASI 100 rates than secukinumab, and
risankizumab-rzaa and ixekizumab also had significantly
higher PASI 100 rates than guselkumab (eFigure 2 in the
Supplement).
Sensitivity Analyses: Long-term Efficacy
The estimated long-term response rates for PASI 75, 90, and
100 of each intervention in the sensitivity analyses are
presented in eTable 3 in the Supplement. Among the 22 trials
included in the base-case analysis, the sensitivity analysis
including only global trials excluded 2 country-specific trials
and produced results consistent with the base-case analysis.
A total of 14 trials that reported NRI data at the end of the main-
tenance period (44-60 weeks from baseline) were included in
the sensitivity analysis including only NRI data. The results of
this sensitivity analysis were mostly consistent with the base-
case analysis with the exception of secukinumab, which slightly
increased because only 1 of the 5 trials that were included in
the base case reported NRI values, and this trial had the high-
est PASI responses of the trials considered.13 Three phase 2 trials
were excluded from the sensitivity analysis including only
phase 3 trials; the results of this sensitivity analyses were con-
sistent with the base-case analysis.
To test whether the method of meta-analysis would affect
the results, we conducted an NMA using a fixed-effects bayes-
ian multinomial likelihood model with a probit link for the
long-term PASI outcomes using identified randomized clini-
cal trials that maintained randomization through 52 weeks.
Only 7 randomized clinical trials (AMAGINE 2,87 AMAGINE 3,88
CLEAR,13 FIXTURE,89 IXORA-S,90 UltIMMa1,15 and UltIMMa215)
on 6 treatments (brodalumab, etanercept, ixekizumab,
risankizumab-rzaa, secukinumab, and ustekinumab) were able
to be included into this NMA because of the crossover in the
studies evaluating long-term PASI outcomes (eFigure 3 in the
Supplement). In the NMA, risankizumab-rzaa (81.3%; 95% CrI,
75.7%-86.1%) had the highest estimated PASI 90 rates, fol-
lowed by brodalumab (76.6%; 95% CrI, 71.3%-81.4%), ixeki-
zumab (69.8%; 95% CrI, 60.1%-78.3%), secukinumab (65.2%;
95% CrI, 58.1%-71.6%), ustekinumab (52.5%; 95% CrI, 49.3%-
55.7%), and etanercept (35.9%; 95% CrI, 27.1%-45.6%). As dem-
onstrated by this NMA, risankizumab-rzaa had significantly
higher PASI response rates compared with ixekizumab (PASI
90 OR, 1.89; 95% CrI, 1.12-1.99), secukinumab (OR, 2.33;
95% CrI, 1.54-3.56), ustekinumab (OR, 3.95; 95% CrI, 2.90-
5.45), and etanercept (OR, 7.80; 95% CrI, 4.75-12.94), and bro-
dalumab had significantly higher PASI response rates compared
with secukinumab (OR, 1.76; 95% CrI, 1.22-2.54), ustekinumab
(OR, 2.97; 95% CrI, 2.32-3.83), and etanercept (OR, 5.86;
95% CrI, 3.72-9.36) (eTable 4 and eTable 5 in the Supplement).
Discussion
With increased therapeutic options for psoriasis, it has be-
come increasingly challenging for clinicians to compare across
the available treatments for clinical decision making. Meta-
E8 JAMA Dermatology Published online February 5, 2020 (Reprinted)
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Comparison of Biologics and Oral Treatments for Plaque Psoriasis
analytic approaches have important roles in integrating evi-
dence from multiple studies to determine the relative effi-
cacy of treatments and inform clinical decision making.91 This
study provides a comprehensive assessment of the short-
term and long-term comparative efficacy of biologics and oral
therapies approved by the US Food and Drug Administration
and the European Medicines Agency for the treatment of mod-
erate to severe plaque psoriasis.
Results from this study suggest that brodalumab, gusel-
kumab, ixekizumab, and risankizumab-rzaa had signifi-
cantly higher PASI response rates than adalimumab, apremi-
last, certolizumab pegol, dimethyl fumarate, etanercept,
tildrakizumab-asmn, and ustekinumab at the end of the pri-
mary response period. There were no statistically significant
differences in short-term efficacy among brodalumab, gusel-
kumab, ixekizumab, and risankizumab-rzaa. Over the long-
term, brodalumab, guselkumab, ixekizumab, risankizumab-
rzaa, and secukinumab had significantly higher PASI response
rates than those corresponding to adalimumab, apremilast,
infliximab, etanercept, and ustekinumab.
The short-term results from this study generally align with
published NMAs that compared the efficacy of other biologic
therapies for treatment of moderate to severe plaque psoria-
sis at the end of the primary response period.28,29,92-98 For ex-
ample, a recent NMA study by Sawyer et al95 used similar meth-
ods and a similar list of trials to suggest that brodalumab,
ixekizumab, risankizumab-rzaa, and guselkumab have the
highest short-term PASI response rates.
The Sawyer et al95 NMA also pointed out the lack of a com-
prehensive systematic evaluation of long-term efficacy of sys-
temic treatments in patients with moderate to severe psoria-
sis. Work by Nast et al99 found infliximab, secukinumab, and
ustekinumab to be the most effective long-term treatment op-
tions. However, owing to clinical and methodologic differ-
ences among available studies and a lack of sufficiently long-
term, head-to-head trials, the strength of the ranking of
treatment efficacy was limited beyond 24 to 28 weeks.99 A 2017
NMA of four 52-week randomized clinical trials found that bro-
dalumab achieved significantly higher PASI 100 response rates
compared with secukinumab, ustekinumab, and etanercept.100
Nevertheless, only 4 trials were able to be included in the pri-
mary indirect comparison owing to study design heteroge-
neity and lack of long-term, active-comparator trial data. The
present study overcame these limitations by using tradi-
tional meta-analysis methods.
Despite the differences in methods, the results from the
long-term traditional meta-analysis are consistent with this
NMA, suggesting the robustness of the meta-analysis results.
However, the meta-analysis directly synthesized the PASI re-
sponse rates for patients receiving each active treatment dur-
ing both the induction and maintenance periods, making it pos-
sible to include additional treatments beyond the connected
network.
Strengths and Limitations
The present work analyzes the short-term and long-term ef-
ficacy that included all licensed medications to date (eg, bro-
dalumab, dimethyl fumarate, guselkumab, risankizumab-
jamadermatology.com
 Comparison of Biologics and Oral Treatments for Plaque Psoriasis Original Investigation Research

rzaa, and tildrakizumab-asmn). This study also has several
other strengths. First, the analytic methods used in the study
are well-established, rigorous, treatment comparison tech-
niques. Meta-analyses are a statistical tool used to synthesize
direct evidence from multiple studies to compare 2 interven-
tions at a time. Network meta-analyses extend traditional meta-
analyses to allow for simultaneous comparison of several dif-
ferent treatments that are regularly used in clinical practice but
have not necessarily been compared head-to-head in a ran-
domized trial. These methods provide useful evidence about
the comparative effectiveness of competing interventions—
which would otherwise be lacking—in a cost-effective and
timely manner. The NMA approach used in the analysis of
short-term efficacy enabled an estimation of comparative ef-
fects among treatments that have not yet been investigated in
head-to-head randomized clinical trials for moderate to se-
vere plaque psoriasis. Adjusting for the reference arm re-
sponse can reduce the outcomes associated with cross-trial
heterogeneity, as the reference arm response rate integrates
the results of other observed and unobserved trial-level fac-
tors likely to affect treatment arm outcomes. The traditional
meta-analysis used to assess the long-term outcomes of treat-
ments allowed for the amalgamation of scientific evidence and
offered an objective appraisal of the available evidence. By
combining data from multiple independent trials of the same
treatment, the meta-analysis increased the sample size and im-
proved statistical precision for the estimation of long-term PASI
responses. In addition, the results from the sensitivity analy-
ses were consistent with the base-case analyses for both short-
term and long-term treatment, which supports the robust-
ness of the primary findings. The comparative analyses of
recently available biologic treatments in the present study fills
an important gap in the current body of literature. Additional
analyses comparing the short-term and long-term safety
outcomes are warranted to provide a complete benefit-risk
assessment of novel psoriasis therapies for health care
stakeholders.101,102
The results of this analysis should be interpreted within
the context of certain limitations. First, as with all meta-
analyses, the presence of cross-trial differences and patient
characteristics that may modify the treatment effect can in-
troduce bias in the comparisons. Although adjusting for the
reference arm response in this NMA can reduce the effects of
cross-trial heterogeneity, there is no guarantee that adjust-
ments will eliminate these effects. In addition, subgroup analy-
ses (eg, by relevant patient characteristics) are generally not
feasible because most published trials do not report detailed
PASI outcomes for subgroups. Second, the findings of this study
are based on clinical trial data, which may not be generaliz-
able to real-world settings. Future research may study the com-
parative efficacy among treatments in real-world settings.
Moreover, a holistic comparison of psoriasis treatments should
include other key aspects, such as safety profile, effect on qual-
ity of life (eg, the Dermatology Life Quality Index), as well as
administration and dosing frequency. Third, the short-term
efficacy analysis only included efficacy data up to week 16, and
any agent’s full efficacy may not have been achieved at this time
point; however, the long-term analyses serve as a comple-
ment to this short-term assessment. Fourth, the long-term
meta-analysis focused on conducting random-effects meta-
analysis within treatments because an anchor-based ap-
proach (eg, NMA) would be limited for all treatments owing
to crossover and rerandomization. Accordingly, the current
meta-analysis using the DerSimonian and Laird27 method can
only account for heterogeneity among trials of the same treat-
ment but not for different treatments. Hence, the long-term
meta-analysis results should be interpreted with caution
beyond the relationships examined in the long-term NMA.
Conclusions
In the absence of head-to-head randomized clinical trials of
treatments for moderate to severe plaque psoriasis, this study
provides what we believe to be a comprehensive assessment
of the comparative short-term and long-term efficacy among
several novel treatments. Over the primary response period and
long-term maintenance period, brodalumab, guselkumab,
ixekizumab, and risankizumab-rzaa were associated with the
highest estimated PASI 75, 90, and 100 response rates.

ARTICLE INFORMATION
Accepted for Publication: October 25, 2019.
Published Online: February 5, 2020.
doi:10.1001/jamadermatol.2019.4029
Author Contributions: Drs Li and Betts had full
access to all of the data in the study and take
responsibility for the integrity of the data and the
accuracy of the data analysis.
Concept and design: Armstrong, Joshi, Skup, Li,
Betts, Augustin.
Acquisition, analysis, or interpretation of data:
All authors.
Drafting of the manuscript: Armstrong, Joshi, Skup,
Williams, Li, Betts.
Critical revision of the manuscript for important
intellectual content: All authors.
Statistical analysis: Armstrong, Puig, Joshi, Li, Betts.
Administrative, technical, or material support: Joshi,
Williams.
Supervision: Armstrong, Puig, Joshi, Skup, Williams,
Betts, Augustin.
Conflict of Interest Disclosures: Dr Armstrong
reported receiving grants and personal fees from
AbbVie, Eli Lilly, Leo Pharma, and Novartis
Pharmaceuticals Corp; personal fees from
Boehringer Ingelheim/Parexel, Bristol-Myers
Squibb, Celgene, Dermavant, Janssen
Pharmaceuticals Inc, Merck, Modernizing Medicine,
Ortho Dermatologics, Pfizer Inc, Regeneron
Pharmaceuticals, Sanofi Genzyme, Science 37 Inc,
Genentech, GlaxoSmithKline, and Valeant; and
grants from Dermira, Janssen-Ortho Inc, Kyowa
Hakko Kirin, and UCB Pharma outside the
submitted work. Dr Puig reported receiving grants
and personal fees from AbbVie during the conduct
of the study; grants and personal fees from Almirall,
Amgen, Boehringer Ingelheim, Celgene, Janssen,
Leo-Pharma, Lilly, Novartis, Pfizer, Regeneron,
Sanofi, Roche, and UCB outside the submitted
work; and personal fees from Sandoz,
Merck-Serono, MSD, Mylan, and Samsung-Bioepis.
Dr Joshi is an employee AbbVie during the conduct
of the study. Dr Skup is an employee AbbVie.
Dr Williams is an of AbbVie. Dr Li reported receiving
grants from AbbVie during the conduct of the study
outside the submitted work. Dr Betts reported
receiving consultancy fees from AbbVie Inc. during
the conduct of the study. No other disclosures were
reported.
Funding/Support: Design, study conduct, and
financial support for the study were provided by
AbbVie.
Role of the Funder/Sponsor: AbbVie participated
in the interpretation of data, review, and approval
of the abstract; all authors contributed to the
development of the publication and maintained
control over the final content.

jamadermatology.com (Reprinted) JAMA Dermatology Published online February 5, 2020 E9

© 2020 American Medical Association. All rights reserved.

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 Research Original Investigation
Additional Contributions: Yan Wang, ScD, and
Viviana Garcia-Horton, PhD, provided analytical
support and Gloria DeWalt, PhD (Analysis Group Inc),
provided editorial assistance. Analysis Group Inc
received payment from AbbVie for participation in
this research. Palvi Gupta, MPharm, Jatin Gupta,
MPharm, and Rashi Patel, MPharm (DRG Abacus)
provided support with literature search and study
selection.
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