REVIEWS

Management of psoriasis in patients

with inflammatory bowel disease: From
the Medical Board of the National
Psoriasis Foundation
Scott M. Whitlock, MD,a Clinton W. Enos, MD,a April W. Armstrong, MD, MPH,b Alice Gottlieb, MD,c
Richard G. Langley, MD,d Mark Lebwohl, MD,e Joseph F. Merola, MD, MMSc,f Caitriona Ryan, MD,g
Michael P. Siegel, PhD,h Jeffrey M. Weinberg, MD,e Jashin J. Wu, MD,i and Abby S. Van Voorhees, MDa
Norfolk, Virginia; Los Angeles, California; Valhalla and New York, New York; Halifax, Nova Scotia,
Canada; Boston, Massachusetts; Dallas, Texas; and Portland, Oregon

Background: There is a significant association between psoriasis and inflammatory bowel disease (IBD).
Many treatments for psoriasis and psoriatic arthritis are also used for IBD.

Objective: To assess therapeutic options for patients with psoriasis and concurrent IBD.

Methods: A systematic literature search was performed for clinical studies of biologic and systemic
psoriasis medications in psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s disease, for the period
from January 1, 1947, to February 14, 2017. Randomized, controlled, double-blinded studies were selected
if available. If not, the next highest level of available evidence was selected.

Results: Of the 2282 articles identified, 132 were selected. Infliximab and adalimumab have demonstrated
efficacy in psoriasis, psoriatic arthritis, ulcerative; colitis, and Crohn’s disease. Ustekinumab has
demonstrated efficacy in psoriasis, psoriatic arthritis, and Crohn’s disease. Certolizumab has demonstrated
efficacy in psoriatic arthritis and Crohn’s disease. Etanercept, secukinumab, brodalumab, and ixekizumab
have demonstrated efficacy in psoriasis and psoriatic arthritis but may exacerbate or induce IBD.
Guselkumab has demonstrated efficacy in psoriasis.

From the Department of Dermatology, Eastern Virginia Medical
School, Norfolka; Department of Dermatology, University of
Southern California, Los Angelesb; Department of Medicine,
New York Medical College, Valhallac; Division of Clinical
Dermatology and Cutaneous Science, Dalhousie University,
Halifaxd; Department of Dermatology, Icahn School of Medicine
at Mount Sinai, New Yorke; Department of Dermatology,
Harvard Medical School, Brigham and Women’s Hospital,
Bostonf; Division of Dermatology, Baylor University Medical
Center, Dallasg; National Psoriasis Foundation, Portlandh; and
Department of Dermatology, Kaiser Permanente Los Angeles
Medical Center, Los Angeles.i
Funding sources: None.
Disclosure: Dr Whitlock’s mother has been an advisor for Ranbaxy,
Galderma, Valeant, Medicis, and Allergan. Dr Armstrong has
been a consultant or investigator for Abbvie, Amgen, Celgene,
Janssen, Lilly, Novartis, Pfizer, and Merck. Dr Gottlieb has been
an advisor for Amgen, Astellas, Akros, Janssen, Celgene,
Bristol-Meyers Squibb, Beiersdorf, Abbvie, TEVA, Actelion,
UCB, Novo Nordisk, Novartis, Dermipsor, Incyte, Pfizer, Canfite,
Lilly, Coronado, Vertex, Karyopharm, CSL Behring, GSK,
Xenoport, Catabasis, Meiji Seika, Takeda, Mitsubishi, Tanabe,
Genentech, Baxalta, Kineta, KPI, Crescendo, Aclaris, Amicus, and
Reddys, and she has received grants paid to Tufts from Janssen,
Amgen, Abbvie, Novartis, Celgene, Pfizer, Lilly, Levia, Merck,
Xenoport, Dermira, and Baxalta. Dr Langley has been an
investigator, speaker, or advisor for Amgen, Abbvie, Janssen,
Celgene, Lilly, Novartis, and Pfizer. Dr Lebwohl is employed by
Mount Sinai, which receives research funds from Abbvie,
Amgen, Boehringer Ingelheim, Celgene, Lilly, Janssen, Kadmon,
AstraZeneca, Novartis, Pfizer, and ViDac. Dr Merola has been a
consultant, advisor, speaker, or investigator for Biogen, UCB,
Novartis, Momenta, Abbvie, Amgen, Lilly, UCB, Pfizer, Janssen,
Kiniksa, Mallinckrodt, and Boehringer. Dr Ryan has been an
advisor, consultant, or speaker for Abbvie, Aqua, Reddys, Lilly,
Medimetriks, Novartis, UCB, and Regeneron. Dr Siegel is
employed by the National Psoriasis Foundation, which receives
unrestricted financial support from AbbVie, Amgen, Celgene,
Lilly, Janssen, LEO, Mallinckrodt, Novartis, Pfizer, and Valeant.
Dr Weinberg has been a speaker or investigator for Abbvie,
Amgen, Celgene, Lilly, and Novartis. Dr Wu is an investigator for
AbbVie, Amgen, Eli Lilly, Janssen, Novartis, and Regeneron. Dr
Van Voorhees has been an advisor or consultant for Celgene,
Pfizer, Abbvie, Novartis, Aqua, Dermira, AstraZeneca, Janssen,
LEO, Novartis, and Amgen.
Accepted for publication June 20, 2017.
Reprint requests: Abby S. Van Voorhees, MD, Dermatology, Eastern
Virginia Medical School, 721 Fairfax Ave, 255 Andrews Hall,
Norfolk, VA 23507. E-mail: vanvooas@evms.edu.
0190-9622/$36.00
Ó 2017 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2017.06.043

383
384 Whitlock et al J AM ACAD DERMATOL
FEBRUARY 2018

Limitations: There are no known clinical trials of treatment specifically for concurrent psoriasis and IBD.

Conclusions: Infliximab and adalimumab have demonstrated efficacy in psoriasis, psoriatic arthritis,
ulcerative colitis, and Crohn’s disease; other agents have demonstrated efficacy for some, but not all, of
these indications. ( J Am Acad Dermatol 2018;78:383-94.)

Key words: Crohn’s disease; IBD; inflammatory bowel disease; psoriasis; psoriatic arthritis; ulcerative
colitis.

There is a significant asso- these interrelated, serious

ciation between psoriasis CAPSULE SUMMARY conditions. This review aims
and inflammatory bowel dis- to provide a summary of
ease (IBD).1-3 Although the dThere is a significant association each medication used in the
exact prevalence of psoriasis between psoriasis and inflammatory care of psoriasis and psoriatic
is unknown, it is estimated to bowel disease. arthritis and briefly discuss
be 9.6% in patients with dInfliximab and adalimumab have the corresponding evidence
Crohn’s disease (compared demonstrated efficacy in psoriasis, in IBD.
with 2.2% in the general psoriatic arthritis, ulcerative colitis, and
population),2 whereas the Crohn’s disease. METHODOLOGY
prevalence of Crohn’s dis- A systematic search of
dBecause of the possible association of
ease is estimated to be 0.5% the PubMed database was
interleukin 17 inhibitors with
in patients with psoriasis performed (Fig 1) for the
inflammatory bowel disease, caution
(compared with 0.2% in the period from January 1,
should be exercised in using these
general population). Similar 1947 to February 14, 2017,
agents in this patient population.
trends occur with ulcerative for the terms infliximab,
colitis.3 In patients with se- adalimumab, golimumab,
vere psoriasis, the relative certolizumab, etanercept, us-
risk for Crohn’s disease is 2.85, and for ulcerative tekinumab, secukinumab, ixekizumab, acitretin,
colitis, 1.96.4 Both psoriasis and IBD are multifacto- cyclosporine, methotrexate, apremilast, mycopheno-
rial, chronic inflammatory diseases of epithelium, late mofetil, sulfasalazine, hydroxyurea, azathio-
involving activated cellular immunity. Overlapping prine, 6-thioguanine, tacrolimus, leflunomide, and
immunologic and genetic features have been fumaric acid esters. With the article type set as
described. Genetic polymorphisms in interleukin clinical trial, these medication terms were searched
23R (IL-23R), which alter signaling in the IL-12/23 in combination with each of the following: psoriasis,
pathway, are found in both psoriasis and IBD.5-7 psoriatic arthritis, inflammatory bowel disease,
There many additional shared psoriasis and Crohn’s Crohn’s disease, and ulcerative colitis. Additional
disease susceptibility loci.8 articles were found through the references of the
Although there are many medications that are articles identified in the initial search.
used in the treatment of both psoriasis and IBD, Only randomized, controlled, double-blind trials
certain psoriasis treatments may potentially worsen were selected for further review, with exclusive
or induce IBD. There have been many cases reported preference given to phase III clinical trials of
in which treatment of IBD with tumor necrosis monotherapy, unless none was available, upon
factor (TNF) inhibitors has induced new-onset which studies of combination therapies, phase II
psoriasiform lesions.9,10 Although systemic cortico- clinical trials, or studies of the next highest level of
steroids are commonly used in the treatment of IBD, evidence were considered. Clinical trials designed
psoriasis guidelines do not recommend their use in primarily to study drug delivery technology
patients with psoriasis, as they have been known to were excluded. Additional meta-analyses covering
cause a rebound psoriasis exacerbation upon each drug and indication were identified by
discontinuation.11,12 When formulating a treatment searching each term in combination with the term
plan for a patient with concurrent psoriasis and IBD, meta-analysis.
it is important to be aware of which drugs may be The highest level of available evidence for each
helpful for improving IBD and which drugs may drug and indication is noted, according to guidelines
exacerbate it. Collaboration with the patient’s written by Shekelle et al.13 Level IA indicates evi-
internist or gastroenterologist primarily managing dence from meta-analysis of randomized controlled
the IBD will be important to optimize treatment of trials; IB indicates evidence from randomized
J AM ACAD DERMATOL
VOLUME 78, NUMBER 2
Abbreviations used:
IBD: inflammatory bowel disease
IL: interleukin
FDA: US Food and Drug Administration
TNF: tumor necrosis factor
controlled trials; IIA indicates evidence from
controlled studies without randomization; IIB
indicates evidence from other quasi-experimental
study; III indicates evidence from nonexperimental
descriptive studies such as comparative studies,
correlation studies, and case-control studies; and
level IV evidence indicates expert committee reports
and opinions or the clinical experience of respected
authorities. The strength of efficacy is summarized as
strong, moderate, or modest in comparison with
other available treatment options.
RESULTS
A total of 2282 articles were identified during the
search, of which 2164 not meeting inclusion criteria
were excluded. Including 15 meta-analyses, we
examined 132 articles.
FDA-approved biologic medications for
psoriasis and/or psoriatic arthritis
Infliximab. Infliximab (Remicade [Jannsen
Biotech, Horsham, PA] and Inflectra [Pfizer, Inc, New
York, NY]) is a monoclonal anti-TNF antibody that is
US Food and Drug Administration (FDA)eapproved
for psoriasis (2006), psoriatic arthritis (2005),
ulcerative colitis (2006), and Crohn’s disease (1998),
as well as for pediatric Crohn’s disease (2006),
pediatric ulcerative colitis (2011), and other
indications (see Table I).14-47 It has been shown to
be effective in phase III clinical trials for psoriasis14
and psoriatic arthritis.15 Phase III trials have shown
that infliximab is effective for inducing and maintain-
ing remission in patients with Crohn’s disease.16,48,49
Infliximab was also effective in phase III trials for
inducing and maintaining remission of ulcerative
colitis.17
In summary, infliximab has level IA evidence of
strong efficacy for psoriasis50 and psoriatic
arthritis.51 It also has level IA evidence of strong
efficacy for Crohn’s disease52,53 and ulcerative
colitis.54
Adalimumab. Adalimumab (Humira [Abbvie,
North Chicago, IL]) is a monoclonal anti-TNF
antibody that is FDA approved for psoriasis (2008),
psoriatic arthritis (2005), ulcerative colitis (2012), and
Crohn’s disease (2007), as well as for pediatric
Crohn’s disease (2014), pediatric ulcerative colitis
Whitlock et al 385
Fig 1. PubMed search algorithm.
(2011), and other indications.55 It was effective in
phase III clinical trials for psoriasis18,56 and psoriatic
arthritis.19,57 Adalimumab has demonstrated efficacy
in phase III clinical trials for Crohn’s disease.20,58,59 It
was also effective in phase III trials for inducing and
maintaining remission for ulcerative colitis.21,60
In summary, adalimumab has level IA evidence of
strong efficacy for psoriasis50 and psoriatic
arthritis.51 It has level IA evidence of strong efficacy
for Crohn’s disease53 and level IA evidence of
moderate efficacy for ulcerative colitis.54
Golimumab. Golimumab (Simponi [Jannsen
Biotech, Horsham, PA]) is an anti-TNF monoclonal
antibody that is FDA approved for psoriatic arthritis
(2009) and ulcerative colitis (2013), as well as for
other indications, but not for psoriasis or Crohn’s
disease.61 Although there are no published clinical
trials of golimumab specifically for psoriasis, a phase
III clinical trial that demonstrated efficacy for
psoriatic arthritis also noted efficacy for psoriasis.22
Although a noncontrolled, open-label study for
refractory Crohn’s disease reported some efficacy,23
there is no additional evidence for this indication.
Phase III clinical trials indicate efficacy for inducing
and maintaining clinical response in patients with
ulcerative colitis.24,62,63
In summary, golimumab has level IIB evidence of
moderate efficacy for psoriasis61 and level IA
evidence of strong efficacy for psoriatic arthritis.51
It has level III evidence of strong efficacy for Crohn’s
disease23 and level IA evidence of strong efficacy for
ulcerative colitis.54
Certolizumab pegol. Certolizumab pegol
(Cimzia [UCB, Atlanta, GA]) is a PEGylated
monoclonal antibody fragment that inhibits TNF-a.
386 Whitlock et al J AM ACAD DERMATOL
FEBRUARY 2018

Table I. FDA-approved biologic medications for psoriasis and/or psoriatic arthritis, and their evidence in
Crohn’s disease and ulcerative colitis
Psoriatic arthritis Crohn’s disease Ulcerative colitis
Medication Plaque psoriasis (PASI 75)* (ACR 20)y (clinical remission rate)z (clinical remission rate)z
Infliximabx FDA approved (80% wk 10)14 FDA approved FDA approved (49% wk 6)16 FDA approved
(58% wk 14)15 (39% wk 8)17
k 18
Adalimumab FDA approved (80% wk 12) FDA approved FDA approved (36% wk 4)20 FDA approved
(58% wk 12)19 (17% wk 8)21
Golimumab Phase III clinical trial for FDA approved Small open-label study FDA approved
psoriatic arthritis suggests (51% wk 14)22 suggests efficacy23 (46% wk 6)24
efficacy in psoriasis (56% wk 12)
(58% wk 14)22
Certolizumab Phase II clinical trial suggests FDA approved FDA approved (48% wk 26)27 Small open-label study
pegol efficacy (83% wk 12)25 (58% wk 12)26 suggests limited
efficacy (10% wk 14)28
Etanercept{ FDA approved (49% wk 12)29 FDA approved Small randomized controlled Potential risk of
(59% wk 12)30 trial suggests lack of exacerbation32
efficacy.31 Potential risk of
exacerbation32
Ustekinumab FDA approved (76% wk 12)33 FDA approved FDA approved (40% wk 8)35 d
(42% wk 12)34
36
Secukinumab FDA approved (82% wk 12) FDA approved Phase II clinical trial suggests Potential risk of
(54% wk 12)37 lack of efficacy. Potential exacerbation38,39
38,39
risk of exacerbation
Ixekizumab FDA approved (89% wk 12)40 Phase III clinical Potential risk of exacerbation40 Potential risk of
trial suggests exacerbation40
efficacy
(60% wk 12)41
Brodalumab FDA approved (83%, 86%, Phase II data Contraindicated based on d
87%)85,86 suggests worsening symptoms90
efficacy87,88
Guselkumab FDA approved (wk 16 91%, Data from d d
83%)92,93 completed
phase II studies
have yet to be
published

Caution must be used when comparing PASI 75, ACR 20, and clinical remission rates among the various medications in this table, because
the rates come from different studies with different trial populations and different placebo rates. Clinical remission rate may be defined
differently in different studies.
ACR, Albumin-to-creatinine ratio; PASI, Psoriasis Area and Severity Index; CDAI, crohn’s Disease Activity Index.
*PASI 75 indicates the fraction of a given population, in a given time period, that experiences a 75% or greater reduction in the PASI.
y
ACR 20 indicates the fraction of a given population, in a given time period, that experiences a 20% or greater improvement in swollen or
tender joints in addition to more than 20% improvement in 3 of 5 other criteria.
z
Clinical remission rate indicates the fraction of a given population, in a given time period, that experiences a remission of symptoms, which
is sometimes defined differently by different studies. For ulcerative colitis, this designation often requires a Mayo score of 2 points or lower
with no individual subscore higher than 1 point.42 For Crohn’s disease, it usually requires a CDAI score lower than 150.43
x
Infliximab-dyyb (Inflectra [Pfizer, New York, NY]) is a biosimilar that is FDA approved (2016) for the same indications as infliximab.44
k
Adalimumab-atto (Amjevita [Amgen, Thousand Oaks, CA]) is a biosimilar that is FDA approved (2016) for the same indications as adalimumab.45
{
Etanercept-szzs (Erelzi [Novartis, Basel, Switzerland]) is a biosimilar that is FDA approved (2016) for the same indications as etanercept.46

It is currently FDA approved for psoriatic arthritis
(2013) and Crohn’s disease (2008), as well as for
other indications, but not for psoriasis or ulcerative
colitis.64 Phase II trials show promise for plaque
psoriasis.25 Certolizumab has demonstrated efficacy
for psoriatic arthritis in phase III clinical trials.26 It has
also been shown effective in phase III trials for
Crohn’s disease.27,65,66 One small, noncontrolled,
open-label study for ulcerative colitis suggests
limited efficacy for this indication.28
In summary, certolizumab pegol has level IB
evidence of strong efficacy for psoriasis25 and level
IA evidence of strong efficacy for psoriatic arthritis.67
It has level IA evidence of strong efficacy for Crohn’s
disease53 and level III evidence of modest efficacy for
ulcerative colitis.28
J AM ACAD DERMATOL
VOLUME 78, NUMBER 2
Etanercept. Etanercept (Enbrel [Amgen, Thousand
Oaks, CA]) is an anti-TNF recombinant fusion protein
that is FDA approved for psoriasis (2004), psoriatic
arthritis (2002), and some other indications, including
pediatric psoriasis (2016), but not ulcerative colitis or
Crohn’s disease.68 Phase III clinical trials demonstrated
efficacy for psoriasis29,69,70 and psoriatic arthritis.30,70
There are no published reports available for ulcerative
colitis, and a small randomized controlled trial for
Crohn’s disease did not demonstrate efficacy.71
IBD is a potential adverse effect of etanercept.68
Although phase III clinical trials did not report
any exacerbations or new-onset IBD, a large
retrospective study suggests that etanercept can
induce or exacerbate IBD in some patients.32
In summary, etanercept has level IA evidence of
moderate efficacy for psoriasis50 and level IA
evidence of strong efficacy for psoriatic arthritis.51
It has level IB evidence of no efficacy for Crohn’s
disease,71 and etanercept has not been formally
studied for ulcerative colitis. Given the potential
risk of IBD exacerbation, caution should be used in
the patient with IBD.
Ustekinumab. Ustekinumab (Stelara [Janssen
Biotech, Horsham, PA]) is an IL-12/23 inhibitor that
is FDA approved for psoriasis (2009), psoriatic
arthritis (2013), and Crohn’s disease (2016) but not
for ulcerative colitis.72 It has been effective in
phase III clinical trials for moderate-to-severe plaque
psoriasis33,73 and psoriatic arthritis.31,34 Ustekinumab
has demonstrated efficacy in phase III trials for
induction of remission and maintenance for patients
with Crohn’s disease.35,74-76 There are no published
studies of ustekinumab for ulcerative colitis.
In summary, ustekinumab has level IA evidence of
strong efficacy for psoriasis50 and level IA evidence of
moderate efficacy for psoriatic arthritis.67
Ustekinumab has level IB evidence of strong efficacy
for Crohn’s disease74 and has not been formally
studied for ulcerative colitis.
Secukinumab. Secukinumab (Cosentyx
[Novartis, Basel, Switzerland]) is an IL-17A inhibitor
that is FDA approved for psoriasis (2015) and
psoriatic arthritis (2016), as well as for other
indications.77 It is has been shown effective in phase
III clinical trials for psoriasis36,78,79 and psoriatic
arthritis.37,79 It has not been studied for ulcerative
colitis. A phase II clinical trial for Crohn’s disease did
not demonstrate efficacy, and there was actually
increased disease activity compared with placebo.38
Caution should be used when prescribing
secukinumab for a patient with IBD.77 In a pooled
analysis of phase II and III clinical trials of
secukinumab for plaque psoriasis, there were 9
new-onset cases or exacerbations of IBD (incidence
Whitlock et al 387
rate of 0.33 per 100 patients per year), compared
with 1 in etanercept control groups (incidence rate of
0.34 per 100 patients per year). The authors’ analysis
concluded that there is no meaningful clinical
relationship between secukinumab and IBD.39
However, because the control (etanercept) may be
associated with IBD, as noted previously, it is
difficult to draw definitive conclusions from these
data. In phase III trials of secukinumab for
ankylosing spondylitis, new-onset IBD and/or
exacerbations occurred in 5 patients receiving
secukinumab (incidence rate of 0.7 per 100 patients
per year) compared with 0 in placebo groups.80
In summary, secukinumab has level IA evidence
of strong efficacy for psoriasis51 and psoriatic
arthritis.67 It has level IB evidence of no efficacy in
Crohn’s disease. Secukinumab has not been formally
studied for ulcerative colitis.38 Given the potential
risk for IBD exacerbation, caution should be used in
the patient with IBD.
Ixekizumab. Ixekizumab (Taltz [Eli Lilly and
Company, Indianapolis, IN]) is an IL-17A inhibitor
that is FDA approved for psoriasis (2016).81 It has
been shown to be effective for psoriasis in phase III
clinical trials.40,41 It is not FDA approved for psoriatic
arthritis, although a recent phase III clinical trial
demonstrated efficacy for this indication.82 There are
no published studies of ixekizumab for ulcerative
colitis or Crohn’s disease.
Patients being treated with ixekizumab should be
monitored closely for IBD.81 During the phase III
UNCOVER clinical trials for psoriasis, among patients
exposed to ixekizumab, ulcerative colitis was
reported in 7 (incidence rate of 0.2 per 100 patients
per year) and Crohn’s disease was reported in 4
(incidence rate of 0.1 per 100 patients per year)
compared with 0 patients in the placebo groups.40
However, a causal relationship between ixekizumab
and IBD has not been definitively demonstrated.83
In summary, ixekixumab has IB level evidence of
strong efficacy for psoriasis and psoriatic
arthritis.40,41,82 It has not been formally studied for
use in ulcerative colitis or Crohn’s disease. Given the
potential risk of IBD exacerbation, caution should be
used in the patient with IBD.
Brodalumab. Brodalumab (Siliq [Valeant
Pharmaceuticals North America LLC, Bridgewater,
NJ]) is a human IgG2 monoclonal antibody targeting
the human IL-17 receptor A. It is currently FDA
approved for the treatment of moderate to severe
plaque psoriasis (2017).84 Brodalumab has been
shown to be effective for psoriasis in Phase III
clinical trials, including a head to head trial with
ustekinumab.85-87 It is currently not approved for
psoriatic arthritis, however data from phase II clinical
388 Whitlock et al J AM ACAD DERMATOL
FEBRUARY 2018

Table II. FDA-approved, nonbiologic systemic medications for psoriasis, and evidence on their use in psoriatic
arthritis, Crohn’s disease, and ulcerative colitis
Plaque psoriasis Psoriatic arthritis Crohn’s disease Ulcerative colitis
Medication (PASI 75)* (ACR 20)y (clinical remission rate)z (clinical remission rate)z
Acitretin FDA approved d d d
(69% wk 12)94
Cyclosporine FDA approved Randomized controlled Randomized controlled Small randomized controlled
(71% wk 16)95 trials of combination trials suggest variable trials suggest efficacy99-101
97,98
therapies suggest efficacy (Not reported) (Not reported)
efficacy (44% wk 24)96
Methotrexate FDA approved Randomized controlled Randomized controlled Randomized controlled trials
(36%-60% trial and open-label trials suggest efficacy suggest questionable
wk 16)95,102 studies suggest (39% wk 16)107 efficacy (42% wk 16)108
103-105
variable efficacy
(41% wk 12)106
Apremilast FDA approved FDA approved d d
(33% wk 16)109 (40% wk 16)110

Caution must be used when comparing PASI 75, ACR 20, and clinical remission rates among the various medications in this table, because
the rates come from different studies with different trial populations and different placebo rates. Clinical remission rate may be defined
differently in different studies.
ACR, Albumin-to-creatinine ratio; PASI, Psoriasis Area and Severity Index; CDAI, crohn’s Disease Activity Index.
*PASI 75 indicates the fraction of a given population, in a given time period, that experiences a 75% or greater reduction in the PASI.
y
ACR 20 indicates the fraction of a given population, in a given time period, that experiences a 20% or greater improvement in swollen or
tender joints, in addition to more than 20% improvement in 3 of 5 other criteria
z
Clinical remission rate indicates the fraction of a given population, in a given time period, that experiences a remission of symptoms, which
is sometimes defined differently by different studies. For ulcerative colitis, this designation often requires a Mayo score of 2 points or lower
with no individual subscore higher than 1 point.42 For Crohn’s disease, it usually requires a CDAI score lower than 150.43

trials suggest efficacy for this indication.88,89 Per our
search criteria, there were no clinical trials of
brodalumab for ulcerative colitis. Data from a phase
II clinical trial of brodalumab for the treatment of
moderate to severe Crohn’s disease indicated
worsening clinical disease, resulting in early
termination of the study.90
Brodalumab carries a black box warning for sui-
cidal ideation and behavior, and is available only
through a restricted program under a Risk Evaluation
and Mitigation Strategy. Two of the four fatal adverse
events were reported as suicide in one phase III
clinical trial.86 Further, patients taking brodalumab
should be monitored for inflammatory bowel disease.
In addition to the data from the phase II study
mentioned above, one patient was reported to
develop Crohn’s disease during one phase III trial.85
In summary, brodalumab has IA level evidence of
strong efficacy for the treatment of psoriasis and IB
evidence for psoriatic arthritis.
Guselkumab. Guselkumab (Tremfya [Janssen
Biotech, Horsham, PA]) is a human IgG1 monoclonal
antibody targeting the p19 subunit of IL-23 that is FDA
approved for the treatment of moderate to severe
psoriasis.91 It has been shown to be well tolerated and
efficacious in phase III clinical trials.92,93 Per our
search criteria, there are no published studies on the
use of guselkumab for psoriatic arthritis, however
searching clinicaltrials.gov for guselkumab and
psoriatic arthritis indicates a completed phase II trial
and phase III studies in progress. There are no
published studies of guselkumab for Crohn’s disease
or ulcerative colitis.
In summary, guselkumab has level IB evidence of
strong efficacy for the treatment of psoriasis.92,93
Data from completed clinical trials for psoriatic
arthritis have yet to be published at the time of
writing this manuscript. Guselkumab has not been
formally studied in ulcerative colitis or Crohn’s
disease.
FDA-approved nonbiologic systemic
medications for psoriasis
Acitretin. Acitretin is an oral retinoid that is
FDA approved for psoriasis (1997) but not for
psoriatic arthritis, Crohn’s disease, or ulcerative
colitis (Table II).94-105,107-111 Randomized, controlled
trials have shown efficacy for psoriasis,94,112
although acitretin is generally not as clinically useful
as other traditional systemic agents because of
dose-limiting toxicities. Acitretin is considered
ineffective for psoriatic arthritis, and there are no
clinical trials available for this indication. It has not
been studied for the treatment of IBD.
In summary, acitretin has IA level evidence of
strong efficacy for psoriasis.113 It has not been
formally studied for psoriatic arthritis, Crohn’s
disease, or ulcerative colitis.
J AM ACAD DERMATOL Whitlock et al 389
VOLUME 78, NUMBER 2

Table III. Off-label systemic medications for psoriasis and evidence on their use in psoriatic arthritis, Crohn’s
disease, and ulcerative colitis
Crohn’s disease (clinical Ulcerative colitis
Medication Plaque psoriasis (PASI 75)* Psoriatic arthritis (ACR 20)y remission rate)z (clinical remission rate)z
Mycophenolate Small randomized Case series suggests Small randomized Case series and small
mofitil controlled trial efficacy128 (not controlled trial comparative trial
suggests efficacy reported) suggests efficacy129 suggest efficacy130,131
(59% wk 12)127 (67% wk 8)130 (80% wk 8)130
Sulfasalazine Small randomized Randomized controlled Small randomized FDA approved (not
controlled trial trial suggests controlled trials reported)
suggests efficacy131 efficacy132 (44% wk suggest efficacy for
(not reported) 24)96 subset of
patients133,134 (not
reported)
Hydroxyurea Comparative studies and d d d
open-label trials
suggest efficacy135-137
(Not reported)
Azathioprine Small open-label studies Open-label study Small randomized Small randomized
suggest efficacy138,139 suggests efficacy140 controlled trials controlled trials
(not reported) (not reported) suggest efficacy141-143 suggest efficacy144-146
16
(30% wk 26) (not reported)
6-Thioguanine Small open-label and d Small open-label study, Small open-label study
retrospective studies and retrospective suggests efficacy
suggest efficacy147-149 study, suggest efficacy (36% wk 12)152
150,151
(not reported) (38% wk 44)
Tacrolimus Small randomized Case report suggests Small open-label studies Small randomized
controlled trial efficacy154 (not suggest efficacy (64% controlled trial
suggests efficacy153 reported) overall)155 suggests efficacy
(not reported) (20% wk 2)156
Leflunomide Randomized controlled Randomized controlled Small open-label phase I d
trial suggests efficacy trial suggests efficacy trial suggests efficacy
(17% wk 24)157 (36% wk 24)157 (42% wk 16)158
Fumaric acid Randomized controlled Small clinical trial d d
esters trials suggest suggests minimal
efficacy159,160 (Not efficacy161 (Not
reported) reported)

Caution must be used when comparing PASI 75, ACR 20, and clinical remission rates among the various medications in this table, because
the rates come from different studies with different trial populations and different placebo rates. Clinical remission rate may be defined
differently in different studies.
ACR, Albumin-to-creatinine ratio; PASI, Psoriasis Area and Severity Index; CDAI, crohn’s disease activity index.
*PASI 75 indicates the fraction of a given population, in a given time period, that experiences 75% or greater reduction in the PASI.
y
ACR 20 indicates the fraction of a given population, in a given time period, that experiences a 20% or greater improvement in swollen or
tender joints, in addition to more than 20% improvement in 3 of 5 other criteria
z
Clinical remission rate indicates the fraction of a given population, in a given time period, that experiences a remission of symptoms, which
is sometimes defined differently by different studies. For ulcerative colitis, this designation often requires a Mayo score of 2 points or lower
with no individual subscore higher than 1 point.42 For Crohn’s disease, it usually requires a CDAI score lower than 150.43

Cyclosporine. Cyclosporine is a systemic immu-
nosuppressant that is FDA approved for psoriasis
(1997) but not for psoriatic arthritis, Crohn’s
disease, or ulcerative colitis.114 Randomized,
controlled trials have demonstrated efficacy for
psoriasis.95,115 In randomized, controlled trials,
cyclosporine appeared to be efficacious for psoriatic
arthritis.96,116,117 Cyclosporine is sometimes used off
label for Crohn’s disease, for which studies have
shown variable efficacy.97,98 Small, randomized
controlled trials suggest efficacy for induction of
remission in ulcerative colitis.99-101 Cyclosporine has
several serious adverse effects, such as nephro-
toxicity, that limit duration of safe treatment.114
In summary, cyclosporine has level IA evidence of
strong efficacy for psoriasis118 and level IA evidence
of strong efficacy in psoriatic arthritis.119
Cyclosporine has level IA evidence of moderate
efficacy for ulcerative colitis,120 and level IA
evidence of modest efficacy in Crohn’s disease.98
390 Whitlock et al
Methotrexate. Methotrexate is FDA approved for
psoriasis (1972), for which randomized, controlled
trials have demonstrated efficacy.95,102 It is used off
label for psoriatic arthritis, for which randomized,
controlled trials have demonstrated variable
efficacy.103-105 Randomized, controlled trials have
demonstrated the efficacy of methotrexate for
Crohn’s disease.107,121 Randomized, controlled trials
of methotrexate for ulcerative colitis have found
contradictory results.108,122 Methotrexate’s prescribing
information notes that it should be used with extreme
caution in the presence of ulcerative colitis.103
In summary, methotrexate has level IA evidence of
moderate efficacy for psoriasis106 and level IA
evidence of moderate efficacy for psoriatic
arthritis.119 Methotrexate has level IA evidence of
strong efficacy for Crohn’s disease123 and level IA
evidence of modest efficacy in ulcerative colitis.124
Apremilast. Apremilast (Otezla [Celgene,
Summit, NJ]) is an oral phosphodiesterase-4 inhibitor
that is FDA approved for psoriasis (2014) and psoriatic
arthritis (2014).125 It has shown efficacy in phase III
clinical trials for plaque psoriasis109,126 and psoriatic
arthritis.110 There have not been clinical trials of
apremilast for ulcerative colitis or Crohn’s disease.
Nausea and diarrhea are among the most common
side effects, which should be taken into account if
considering this medication in the setting of IBD.
In summary, apremilast has level IA evidence of
moderate efficacy for psoriasis50 and level IA
evidence of strong efficacy for psoriatic arthritis.67
It has not been formally studied for ulcerative colitis
and Crohn’s disease.
Off-label medications
Off-label medications for psoriasis and evidence
of their use for psoriatic arthritis, Crohn’s
disease, and ulcerative colitis are presented in
Table III.16,96,127-161
CONCLUSION
Infliximab and adalimumab have demonstrated
efficacy in plaque psoriasis, psoriatic arthritis,
Crohn’s disease, and ulcerative colitis.
Ustekinumab has demonstrated efficacy in psoriasis
and psoriatic arthritis, as well as in Crohn’s disease.
Certolizumab has demonstrated efficacy for psoriatic
arthritis and Crohn’s disease. Golimumab has
demonstrated efficacy for psoriatic arthritis and
ulcerative colitis. Brodalumab has demonstrated
efficacy for psoriasis and shows promise for psoriatic
arthritis. Guselkumab has demonstrated efficacy for
psoriasis. There are many additional agents with
varying levels of evidence.
J AM ACAD DERMATOL
FEBRUARY 2018
Brodalumab has been shown to worsen
symptoms of Crohn’s disease; and etanercept,
ixekizumab, and secukinumab may possibly do the
same. There are limitations in extrapolating the
existing psoriasis clinical trial data to assess risk for
IBD exacerbation. Some of the clinical trials have not
adjudicated IBD data. Also, a medication’s highest
potential risk for IBD exacerbation is likely to be
seen in a patient with a history of IBD. Thus, using
the risk for IBD in the larger overall psoriasis
population versus in a population consisting only
of patients with a history of IBD may result
in underestimation of the true risk. Rigorous
examination of long-term data will be necessary to
determine the nature of any potential association.
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