New Treatment Paradigms in Psoriasis: Understanding and Incorporating Recent and Emerging Trends - Global Academy for Medical ...

 
New Treatment Paradigms in Psoriasis: Understanding and Incorporating Recent and Emerging Trends - Global Academy for Medical ...
A CME/CE CERTIFIED SUPPLEMENT TO

                                                           SUPPLEMENT 2
                                                           VOL. 37, NO. 2S
                                                           MARCH 2018

                                                           EDITORS

                                                           Kenneth A. Arndt, MD
                                                           Philip E. LeBoit, MD
                                                           Bruce U. Wintroub, MD

     New Treatment Paradigms
    in Psoriasis: Understanding
     and Incorporating Recent
          and Emerging Trends
                                           GUEST EDITORS

                         M. Alan Menter, MD, Chair
                      April W. Armstrong, MD, MPH
                             Kenneth B. Gordon, MD
                                   Jashin J. Wu, MD

                                    Introduction    S39

 The Evolving Landscape of Psoriasis Treatment      S40

Treating to Target—A Realistic Goal in Psoriasis?   S45

                 Common and Not-So-Common           S49
                    Comorbidities of Psoriasis

              Practical Strategies for Optimizing   S53
                      Management of Psoriasis

         CME/CE Post-Test and Evaluation Form       S57
New Treatment Paradigms in Psoriasis: Understanding and Incorporating Recent and Emerging Trends - Global Academy for Medical ...
New Treatment Paradigms in Psoriasis: Understanding and Incorporating Recent and Emerging Trends
Original Release Date: March 2018                                                    Learning Objectives
Expiration Date: April 30, 2019                                                      By reading and studying this supplement, participants should be better able to:
Estimated Time to Complete Activity: 2.0 hours                                       • Explain the etiology and pathophysiology of psoriasis and its common
                                                                                        comorbidities
Participants should read the activity information, review the activity in its
entirety, and complete the online post-test and evaluation. Upon completing          • Diagnose and treat patients with psoriasis using treat-to-target guidelines
this activity as designed and achieving a passing score on the post-test, you        • Select appropriate biologic therapies for patients with psoriasis
will be directed to a Web page that will allow you to receive your certificate of    Disclosure Declarations
credit via e-mail or you may print it out at that time. The online post-test and     Individuals in a position to control the content of this educational activity are
evaluation can be accessed at https://tinyurl.com/Psoriasis2018.                     required to disclose: 1) the existence of any relevant financial relationship
Inquiries about CME accreditation may be directed to the University of               with any entity producing, marketing, re-selling, or distributing health care
Louisville Office of Continuing Medical Education & Professional Development         goods or services consumed by, or used on, patients with the exemption of
(CME & PD) at cmepd@louisville.edu or 502-852-5329.                                  non-profit or government organizations and non-health care related compa-
CME/CE Accreditation Statements                                                      nies, within the past 12 months; and 2) the identification of a commercial
Physicians: This activity has been planned and implemented in accordance             product/device that is unlabeled for use or an investigational use of a product/
                                                                                     device not yet approved.
with the accreditation requirements and policies of the Accreditation Council
for Continuing Medical Education (ACCME) through the joint providership of           April W. Armstrong, MD, MPH, Consultant: AbbVie Inc., Amgen Inc., Eli
the University of Louisville and Global Academy for Medical Education, LLC.          Lilly and Company, Janssen Biotech, Inc., Modernizing Medicine, Novartis
The University of Louisville is accredited by the ACCME to provide continuing        Pharmaceuticals Corporation, Regeneron, Sanofi. Speakers Bureau: AbbVie
education for physicians.                                                            Inc., Eli Lilly and Company, Janssen Biotech, Inc.
The University of Louisville Office of Continuing Medical Education &                Kenneth B. Gordon, MD, Consultant: AbbVie Inc., Amgen Inc., Almirall, S.A.,
Professional Development designates this enduring activity for a maximum             Boehringer Ingelheim, Bristol Myers-Squibb Company, Celgene Corporation,
of 2.0 AMA PRA Category 1 Credits™. Physicians should only claim credit              Dermira, Inc., Eli Lilly and Company, LEO Pharma Inc., Novartis Pharmaceuticals
commensurate with the extent of their participation in the activity.                 Corporation, Pfizer Inc., Sun Pharmaceutical Industries Ltd., UCB, Inc.
                                                                                     Investigator: AbbVie Inc., Boehringer Ingelheim, Celgene Corporation, Novartis
                  Joint Accreditation Statement                                      Pharmaceuticals Corporation.
                  In support of improving patient care, this activity has been       M. Alan Menter, MD, Advisory Board: AbbVie Inc., Afecta Pharmaceuticals, Inc.,
                  planned and implemented by Postgraduate Institute for              Amgen Inc., Boehringer Ingelheim, Eli Lilly and Company, Janssen Biotech,
                  Medicine and Global Academy for Medical Education.                 Inc., LEO Pharma Inc., Ortho Dermatologics, Promius Pharma, LLC. Consultant:
Postgraduate Institute for Medicine is jointly accredited by the American            AbbVie Inc., Afecta Pharmaceuticals, Inc., Amgen Inc., Avillion LLP, Boehringer
Council for Continuing Medical Education (ACCME), the Accreditation Council          Ingelheim, Eli Lilly and Company, Galderma S.A., Janssen Biotech, Inc., LEO
for Pharmacy Education (ACPE), and the American Nurses Credentialing                 Pharma Inc., Menlo Therapeutics Inc., Novartis Pharmaceuticals Corporation,
Center (ANCC) to provide continuing education for the healthcare team.               Ortho Dermatologics, Pfizer Inc., Promius Pharma, LLC. Investigator: AbbVie
Continuing Nursing Education                                                         Inc., Amgen Inc., Boehringer Ingelheim, Celgene Corporation, Dermira, Inc.,
The maximum number of hours awarded for this Continuing Nursing                      Eli Lilly and Company, Janssen Biotech, Inc., LEO Pharma Inc., Novartis
Education activity is 2.0 contact hours. Designated for 0.8 contact hours of         Pharmaceuticals Corporation, Pfizer Inc., Regeneron. Speakers Bureau: AbbVie
pharmacotherapy credit for Advance Practice Nurses.                                  Inc., Amgen Inc., Janssen Biotech, Inc., LEO Pharma Inc., Ortho Dermatologics,
                                                                                     Promius Pharma, LLC.
Target Audience
This journal supplement is intended for dermatologists, residents, internists,       Jashin J. Wu, MD, Contracted Research: AbbVie Inc., Amgen Inc., Eli
primary care practitioners, registered nurses, nurse practitioners, and physi-       Lilly and Company, Janssen Biotech, Inc., Novartis Pharmaceuticals
cian assistants who treat patients with psoriasis.                                   Corporation, Regeneron.
                                                                                     University of Louisville CME & PD Advisory Board and Staff Disclosures:
Educational Needs
                                                                                     The CME & PD Advisory Board and Staff have nothing to disclose.
Psoriasis—a chronic, inflammatory, immune-system disease that affects
approximately 8 million Americans—is often underdiagnosed. Many clinicians           CME/CE Reviewers: Timothy S. Brown, MD, Clinical Associate Professor,
do not approach psoriasis as a systemic, immune-mediated disease with                Division of Dermatology, Department of Medicine, University of Louisville
multiple comorbidities, including obesity, metabolic syndrome, cardiovascular        School of Medicine. The Postgraduate Institute of Medicine planners and
disease, and psoriatic arthritis. Even though half of patients with psoriasis        managers Trace Hutchison, PharmD; Samantha Mattiucci, PharmD, CHCP;
complain of arthritic pain, for example, more than two-thirds of dermatolo-          Judi Smelker-Mitchek, MBA, MSN, RN; and Jan Schultz, MSN, RN, CHCP,
gists lack confidence in screening for arthritic comorbidities. Clinicians also      have nothing to disclose.
frequently fail to screen patients with psoriasis for cardiovascular risk factors,   Global Academy for Medical Education Staff: Suzanne Bujara; Tristan
in part because they are unaware that the presence of psoriasis is associated        M. Nelsen, MNM, CMP, HMCC; Sylvia H. Reitman, MBA, DipEd; and Ron
with poor CV outcomes.                                                               Schaumburg have nothing to disclose.
Psoriasis is often undertreated. One recent survey found that two-thirds of          Off-Label/Investigational Use Disclosure
patients with psoriasis reported being dissatisfied with their treatment; many       This CME/CE activity discusses the off-label use of certain approved medi-
discontinue treatment due to a lack of efficacy or because of adverse effects.       cations as well as data from clinical trials on investigational agents. Such
Many clinicians fail to select a therapeutic option that addresses the needs of      material is identified within the text of the articles.
individual patients, and many neglect the importance of counseling patients
adequately about the optimal use of medications or about what to expect                This continuing medical education (CME/CE) supplement was devel-
from treatment. Complicating the situation is the fact that many clinicians do         oped from interviews with the faculty. The Guest Editors acknowledge
not adopt a treat-to-target strategy that establishes clear therapeutic goals          the editorial assistance of Global Academy for Medical Education and
based on treatment severity (including addressing quality-of-life issues) and          Suzanne Bujara, medical writer, in the development of this supplement.
that calls for adjusting the regimen as needed.                                        The manuscript was reviewed and approved by the guest editors as well
Clinicians would benefit from education that describes the growing armamen-            as the Editors of Seminars in Cutaneous Medicine and Surgery. The ideas
tarium of available agents for the treatment of psoriasis, explains the importance     and opinions expressed in this supplement are those of the Guest Editors
of identifying and managing common comorbidities of psoriasis, and presents            and do not necessarily reflect the views of the supporter, Global Academy
current data on designing and deploying a treat-to-target strategy, including the      for Medical Education, University of Louisville, Postgraduate Institute for
use of topical agents and biologics, alone or in combination.                          Medicine, or the publisher.

Jointly provided by                                                                                                               Supported by an independent
                                                                                                                                     educational grant from
                                                                                                                               Ortho Dermatologics
New Treatment Paradigms in Psoriasis: Understanding and Incorporating Recent and Emerging Trends - Global Academy for Medical ...
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New Treatment Paradigms in Psoriasis: Understanding and Incorporating Recent and Emerging Trends - Global Academy for Medical ...
March 2018, Vol. 37, No. 2S

                   TABLE OF CONTENTS

New Treatment Paradigms in Psoriasis:
Understanding and Incorporating Recent
and Emerging Trends
S39   Introduction
      M. Alan Menter, MD

S40   The Evolving Landscape of Psoriasis Treatment
      April W. Armstrong, MD, MPH, Kenneth B. Gordon, MD, M. Alan Menter, MD, and Jashin J. Wu, MD

S45   Treating to Target—A Realistic Goal in Psoriasis?
      Kenneth B. Gordon, MD, April W. Armstrong, MD, MPH, M. Alan Menter, MD, and Jashin J. Wu, MD

S49   Common and Not-So-Common Comorbidities of Psoriasiss
      M. Alan Menter, MD, April W. Armstrong, MD, MPH, Kenneth B. Gordon, MD, and Jashin J. Wu, MD

S53   Practical Strategies for Optimizing Management of Psoriasis
      Jashin J. Wu, MD, April W. Armstrong, MD, MPH, Kenneth B. Gordon, MD, and M. Alan Menter, MD

S57   CME/CE Post-Test and Evaluation Form

GUEST EDITORS

                 M. Alan Menter, MD, Chair                           Kenneth B. Gordon, MD
                 Chairman, Division of Dermatology                   Professor and Chair
                 Baylor University Medical Center                    Department of Dermatology
                 Dallas, Texas                                       Medical College of Wisconsin
                                                                     Milwaukee, Wisconsin

                 April W. Armstrong, MD, MPH                         Jashin J. Wu, MD
                 Associate Professor of Clinical Dermatology         Director of Dermatology Research
                 Associate Dean for Clinical Research                Department of Dermatology
                 Keck School of Medicine of the                      Kaiser Permanente
                  University of Southern California                   Los Angeles Medical Center
                 Los Angeles, California                             Los Angeles, California
New Treatment Paradigms in Psoriasis: Understanding and Incorporating Recent and Emerging Trends - Global Academy for Medical ...
Vol. 37, No. 2S, March 2018

  INTRODUCTION

T
      reating patients with psoriasis offers clinicians the opportunity to get back to their medical roots. Because the disease is multifaceted
      and challenging to manage, clinicians need to look beyond the skin for clues as to how they can best improve and relieve patients’
      symptoms and signs.
   This supplement represents the perspectives of myself and three of my colleagues, all respected and prolific research dermatologists:
   April W. Armstrong, MD, MPH, sets the stage with a primer on the pathophysiology of plaque psoriasis and how drug discovery has
led to breakthrough concepts of inflammation and the systemic nature of the disease. In her thorough walkthrough of the therapeutic
landscape of treatment for patients with plaque psoriasis, Dr Armstrong discusses the benefits of the major therapeutic classes for plaque
psoriasis, from topical agents to biologics.
   Kenneth B. Gordon, MD, discusses the controversial concept of treating to target. The question he poses is: Whose target is it? Although
traditional measures such as the Psoriasis Area and Severity Index and Physician Global Assessment might appear logical to clinicians, he
emphasizes that patients’ individual needs, especially quality-of-life concerns, are equally important and suggests methods that are more
patient-centric. In a case vignette, Dr Gordon illustrates the importance of selecting the right starting therapy—one that balances patients’
needs with appropriate efficacy.
   Jashin J. Wu, MD, offers practical suggestions for helping patients obtain the greatest benefit from treatment. His sensible approach
considers patients’ ages, lifestyles, and concomitant medications for maintaining a therapeutic regimen that sets the stage for success. Dr
Wu also provides tips for mitigating risks with psoriasis treatment.
   In my article, I address one of my favorite topics within the psoriasis spectrum: how comorbidities affect the course of the disease. I
review the common diseases that ride alongside psoriasis, including arthritis/psoriatic arthritis and cardiovascular disease—as well as some
that might not have been considered. I also recommend strategies to avoid flares and suggest therapeutic options that might treat the full
spectrum of psoriasis.
   Our hope is that, even if you do not routinely see patients with psoriasis, you will come away from this supplement with a greater
understanding of this multisystemic disease. We will encourage you to look beyond the skin when treating patients with psoriasis, or at
least to guide these individuals to find the right clinicians to address their needs. If we succeed in this endeavor, we will show that medical
dermatology is still interesting and rewarding intellectually. We hope also to show that dermatologists and dermatologic clinicians need to
be at the forefront in understanding, diagnosing, and treating psoriasis and all its manifestations and comorbidities.

                                                                                                                                M. Alan Menter, MD
                                                                                                                     Chairman, Division of Dermatology
                                                                                                                       Baylor University Medical Center
Publication of this CME/CE article was jointly provided by University                                                                      Dallas, Texas
of Louisville, Postgraduate Institute for Medicine, and Global Academy
for Medical Education, LLC, and is supported by an educational grant
from Ortho Dermatologics. Dr Menter has received an honorarium for
his participation in this activity. He acknowledges the editorial assistance
of Suzanne Bujara, medical writer, and Global Academy for Medical
Education in the development of this continuing medical education
journal article.
M. Alan Menter, MD, Advisory Board: AbbVie Inc., Afecta Pharmaceuticals,
Inc., Amgen Inc., Boehringer Ingelheim, Eli Lilly and Company, Janssen
Biotech, Inc., LEO Pharma Inc., Ortho Dermatologics, Promius Pharma,
LLC. Consultant: AbbVie Inc., Afecta Pharmaceuticals, Inc., Amgen Inc.,
Avillion LLP, Boehringer Ingelheim, Eli Lilly and Company, Galderma S.A.,
Janssen Biotech, Inc., LEO Pharma Inc., Menlo Therapeutics Inc., Novartis
Pharmaceuticals Corporation, Ortho Dermatologics, Pfizer Inc., Promius
Pharma, LLC. Investigator: AbbVie Inc., Amgen Inc., Boehringer Ingelheim,
Celgene Corporation, Dermira, Inc., Eli Lilly and Company, Janssen Biotech,
Inc., LEO Pharma Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc.,
Regeneron. Speakers Bureau: AbbVie Inc., Amgen Inc., Janssen Biotech, Inc.,
LEO Pharma Inc., Ortho Dermatologics, Promius Pharma, LLC.
Address reprint requests to: M. Alan Menter, MD, 3900 Junius Street,
Suite 145, Dallas, TX 75246; amderm@gmail.com

1085-5629/13/$-see front matter © 2018 Frontline Medical Communications
doi:10.12788/j.sder.2018.008                                                   Vol. 37, No. 2S, March 2018, Seminars in Cutaneous Medicine and Surgery S39
New Treatment Paradigms in Psoriasis: Understanding and Incorporating Recent and Emerging Trends - Global Academy for Medical ...
The Evolving Landscape of Psoriasis Treatment
          April W. Armstrong, MD, MPH,* Kenneth B. Gordon, MD,† M. Alan Menter, MD,‡ and Jashin J. Wu, MD§

                                                                               W
                                                                                         hen researchers discovered in 1979 that the immuno-
  ■ Abstract                                                                             suppressant cyclosporine successfully cleared psoriatic
  The process of discovering new drugs for plaque psoriasis                              plaques, the scientific community began to consider
  has revealed much about the multisystemic nature of the                      psoriasis not “just a skin disease.”1,2 The cause of this chronic,
  disease. Current and emerging biologic agents may reliably                   multisystemic disease is dysregulation of the immune system.1
  achieve a Psoriasis Area and Severity Index (PASI 75) up to                  Approximately 3.2% of the American population has some form
  90. Initially, clinicians select therapies based on the severity
  of the psoriasis. Although mild disease can be treated with
                                                                               of psoriasis. Psoriasis vulgaris, the most common form of plaque
  topical agents, for patients with moderate to severe disease,                psoriasis, affects 80% of people with psoriasis.1,3
  concurrent therapy with oral systemic agents, biologics, and/                   The hallmarks of plaque psoriasis are red-pink plaques with
  or phototherapy needs to be considered. In some instances,                   silvery scales ranging in size from small to medium to large. They
  clinicians may need to combine medications to provide                        are symmetrically distributed on the scalp, elbows, knees, and lower
  patients with rapid relief of symptoms.                                      torso.1 Plaques can also appear on the nails and intertriginous
  Semin Cutan Med Surg 37(supp2):S40-S44
  © 2018 published by Frontline Medical Communications
                                                                               areas, such as the abdominal folds, axillae, inframammary folds,
                                                                               as well as the genitalia.1 Pruritus is among the most prominent and
  ■ Keywords                                                                   bothersome of psoriasis symptoms.1
  Biologics; phototherapy; psoriasis pathophysiology; systemic
  oral therapy; topical therapy                                                Pathogenesis of Psoriasis
                                                                               The inflammation and excess skin growth in psoriasis is the result of
* Associate Professor of Clinical Dermatology, Associate Dean for Clinical
                                                                               the interactions between the innate and adaptive immune systems;
  Research, Keck School of Medicine of the University of Southern              however, the adaptive immune system plays a key role.4 The inflam-
  California, Los Angeles, California                                          matory process involves dendritic cells that secrete the cytokines
† Professor and Chair, Department of Dermatology, Medical College of
                                                                               interleukin (IL)-12 and IL-23, which then stimulate naïve T cells to
  Wisconsin, Milwaukee, Wisconsin
‡ Chairman, Division of Dermatology, Baylor University Medical Center,
                                                                               differentiate into either type 1 or type 17 helper T cell (TH1, TH17)
  Dallas, Texas                                                                pathways (Figure 1).2,4
§ Director of Dermatology Research, Department of Dermatology, Kaiser             Over time it was determined that the TH17 pathways play
  Permanente Los Angeles Medical Center, Los Angeles, California               a larger role in psoriasis than do the TH1 pathways. The TH1
Publication of this CME/CE article was jointly provided by University of       pathways lead to the release of cytokines such as tumor necrosis
Louisville, Postgraduate Institute for Medicine, and Global Academy for        factor (TNF)–alpha and interferon gamma. Activated TH17 cells
Medical Education, LLC, and is supported by an educational grant from
Ortho Dermatologics. The authors have received an honorarium for their         produce inflammatory cytokines including IL-17A, IL-17F, IL-22,
participation in this activity. They acknowledge the editorial assistance of   and TNF-alpha.5 The cytokines in turn cause skin thickening and
Suzanne Bujara, medical writer, and Global Academy for Medical Education       erythema due to vasodilation and angiogenesis.1
in the development of this continuing medical education journal article.
April W. Armstrong, MD, MPH, Consultant: AbbVie Inc., Amgen Inc.,
Eli Lilly and Company, Janssen Biotech, Inc., Modernizing Medicine,                         p40 antibodies                                    IL-19, IL-20, IL-24
Novartis Pharmaceuticals Corporation, Regeneron, Sanofi. Speakers
Bureau: AbbVie Inc., Eli Lilly and Company, Janssen Biotech, Inc.
                                                                                                              TH1                 IFNγ
Kenneth B. Gordon, MD, Consultant: AbbVie Inc., Amgen Inc., Almirall,
S.A., Boehringer Ingelheim, Bristol Myers-Squibb Company, Celgene                               IL-12
Corporation, Dermira, Inc., Eli Lilly and Company, LEO Pharma Inc.,
Novartis Pharmaceuticals Corporation, Pfizer Inc., Sun Pharmaceutical
Industries Ltd., UCB, Inc. Investigator: AbbVie Inc., Boehringer                                IL-23         TH17                TNFα
Ingelheim, Celgene Corporation, Novartis Pharmaceuticals Corporation.
M. Alan Menter, MD, Advisory Board: AbbVie Inc., Afecta Pharmaceuticals,                                                     IL-17
                                                                                Myeloid DC      TNFα                                           Keratinocyte
Inc., Amgen Inc., Boehringer Ingelheim, Eli Lilly and Company, Janssen
                                                                                                        ?
Biotech, Inc., LEO Pharma Inc., Ortho Dermatologics, Promius Pharma,                                          TH22       IL-22               Production of AMPs
LLC. Consultant: AbbVie Inc., Afecta Pharmaceuticals, Inc., Amgen Inc.,                                                                       and chemokines;
                                                                                                                                            epidermal hyperplasia
Avillion LLP, Boehringer Ingelheim, Eli Lilly and Company, Galderma S.A.,                   TNFα inhibitors
Janssen Biotech, Inc., LEO Pharma Inc., Menlo Therapeutics Inc., Novartis
Pharmaceuticals Corporation, Ortho Dermatologics, Pfizer Inc., Promius                                                                   TNFα inhibitors
Pharma, LLC. Investigator: AbbVie Inc., Amgen Inc., Boehringer Ingelheim,                                      IL-22 antibodies
Celgene Corporation, Dermira, Inc., Eli Lilly and Company, Janssen Biotech,
Inc., LEO Pharma Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc.,                                             IL-17 or IL-17R antibodies
Regeneron. Speakers Bureau: AbbVie Inc., Amgen Inc., Janssen Biotech, Inc.,
LEO Pharma Inc., Ortho Dermatologics, Promius Pharma, LLC.
Jashin J. Wu, MD, Contracted Research: AbbVie Inc., Amgen Inc.,                ■ FIGURE 1 Maintenance Phase of Psoriasis With Putative Targets
Eli Lilly and Company, Janssen Biotech, Inc., Novartis Pharmaceuticals
                                                                                             of Current and Emerging Drugs
Corporation, Regeneron.
                                                                               AMP= antimicrobial peptides; DC=dendritic cell; IFN=interferon;
Address reprint requests to: April W. Armstrong, MD, MPH, Office of            IL=interleukin; R=receptor; TH=T helper; TNF=tumor necrosis factor.
the Dean, Keck School of Medicine, University of California, 1975 Zonal        Source: Johnson-Huang LM, et al.2
Avenue, Los Angeles, CA 90089; aprilarmstrong@post.harvard.edu

                                                                                 © 2018 Frontline Medical Communications 1085-5629/13/$-see front matter
S40 Seminars in Cutaneous Medicine and Surgery, Vol. 37, No. 2S, March 2018                                                    10.12788/j.sder.2018.009
New Treatment Paradigms in Psoriasis: Understanding and Incorporating Recent and Emerging Trends - Global Academy for Medical ...
April W. Armstrong, MD, MPH, Kenneth B. Gordon, MD, M. Alan Menter, MD, and Jashin J. Wu, MD

   IL-17 and IL-23 and their receptors play a crucial role in psori-             The advantage of phototherapy is that it does not create adverse
asis because they respond to dendritic and T-cell cytokines.5 The             immunosuppressive effects that potentially result from use of
three approved IL-17 inhibitors exert a slightly different effect             topical and systemic therapies.1 In short-term data, UVB therapy
on the IL-17 signaling pathway.6 The first two agents approved,               has not been definitively linked to skin cancer; however, the poten-
secukinumab and ixekizumab, neutralize IL-17A, whereas broda-                 tial risk of skin cancer with cumulative long-term UVB therapy is
lumab blocks the IL-17A receptor.6                                            an ongoing concern.
   IL-23 is one of the key cytokines that affect the production                  Targeted light therapy treatments using an excimer laser can
of IL-17.6 Ustekinumab, an IL-23 inhibitor, targets the shared                deliver higher-dose UVB therapy to focused, sensitive areas such
p40 subunit of the IL-12 and IL-23 cytokines.2 Guselkumab and                 as the scalp.12 This therapy is not available in most offices.
tildrakizumab, and the investigational agent, risankizumab, bind
to the p19 subunit of the IL-23 cytokine.7                                    Oral Systemic Therapy
   Our understanding of the inflammatory cascade that results                 Patients with moderate to severe psoriasis benefit most from
in psoriasis continues to evolve. For example, the enzyme phos-               systemic therapies.1 Traditional oral therapies used for psoriasis
phodiesterase-4 (PDE-4) has been found in many inflammatory                   include methotrexate, cyclosporine, and acitretin. A newer oral
cells, and its role is being elucidated in psoriasis.8 In preclinical         therapy for psoriasis is apremilast.
studies, the small molecule apremilast, a PDE-4 inhibitor, blocked               Methotrexate. The oral and injectable antimetabolite metho-
proinflammatory cytokines responsible for chronic inflammatory                trexate increases extra-cellular adenosine with its anti-inflammatory
diseases such as psoriasis and psoriatic arthritis (PsA) in humans.8          properties.1 Methotrexate is the mainstay of systemic treatment for
By blunting the expression of the cytokines TNF-alpha, IL-12, and             psoriasis in the US and Europe, despite its significant adverse effects
IL-23, apremilast reduced keratinocytes and skin thickness.8                  on major organs—liver function enzyme elevation, bone marrow
                                                                              suppression, and pulmonary fibrosis—which limit its long-term
Landscape of Psoriasis Treatment
                                                                              use.1 Methotrexate is contraindicated in women who are actively
Prior American Academy of Dermatology (AAD) guidelines,
which are currently being updated, recommend that clinicians first            conceiving, pregnant, or lactating.1 Warren and colleagues found
ascertain whether a patient with psoriasis also has PsA.3 Patients            that at week 16, 41% of patients who received subcutaneous MTX
who have PsA require systemic medications that treat both psori-              achieved PASI 75 vs 10% of those in the placebo group.13
asis and PsA.3                                                                   Cyclosporine. Although the calcineurin inhibitor cyclosporine is
   If a patient does not have concurrent PsA, the AAD treatment algo-         effective, it is reserved for short-term interventional use in patients
rithm recommends using topical therapies for mild disease (Figure 2).9        with psoriasis who are experiencing flares.1 Because long-term use
For patients with moderate to severe psoriasis, the use of biologics, oral    of cyclosporine is associated with hypertension and irreversible
systemic medications, and phototherapy is required.3                          renal damage, it is typically used for no more than 3 to 6 months
                                                                              and then discontinued.
Topical Therapies                                                                Acitretin. The oral retinoid acitretin has been used with variable
Topical therapies for psoriasis include topical corticosteroids,              success for pustular psoriasis and palmoplantar psoriasis. It has
topical vitamin D analogues, and keratolytic agents.1
                                                                              a synergistic effect when combined with UV therapy. 1 Patients
   The most commonly used topical agents in psoriasis are corti-
                                                                              using a combination of acitretin and UV therapy can reduce the
costeroids, which reduce swelling and redness through their
                                                                              UV dose. Acitretin has modest efficacy in patients with moderate
anti-inflammatory effects.1 Examples of topical steroids include
                                                                              to severe psoriasis. Significant potential adverse effects include
betamethasone dipropionate, clobetasol propionate, desox-
                                                                              dyslipidemia and less frequently liver function test abnormalities.1
imetasone, fluocinonide, fluticasone propionate cream, and
hydrocortisone.1 Topical steroids, which are applied once or twice
daily, come in a variety of strengths and vehicles: ointments,
creams, foams, lotions, shampoos, sprays, tape, and gels.1                          Psoriasis ± Psoriatic Arthritis
   In the last decade, innovations in topical treatment for psoriasis
have focused on combinations such as topical steroids with vitamin
                                                                                       Yes                    No
D analogues, which reduce skin cell growth and scaling.1 Examples
of this combination are betamethasone, dipropionate, and calcipot-
                                                                                  Anti-TNF
riene (vitamin D3)—which are available in multiple vehicles, with the
                                                                                   ± MTX
current foam vehicle shown to be optimal with only once daily appli-                                Limited            Extensive
cation.1,10,11 These topical medications represent advances in vehicle                              Disease             Disease
technology, whereby different active ingredients can be combined in
an efficacious and safe manner to confer therapeutic effect.1
Phototherapy                                                                            Topicals/Targeted        UVB/PUVA Systemic Biologic
Phototherapy has evolved from using broadband UVB to narrow-                              Phototherapy
band UVB.1 Psoralen plus UVA (PUVA), although frequently more
effective, poses a higher risk of skin cancer. A typical regimen starts
with narrow-band UVB 3 times a week for 3 months. If patients                                Lack of Effect
improve, they can decrease the frequency to weekly UVB therapy.1
   Office-based UVB phototherapy is the predominant type of
administration; an office treatment may take less than 5 minutes.             ■ FIGURE 2 American Academy of Dermatology Psoriasis
Home UVB is an option, but because units intended for home use                                Treatment Algorithm
are calibrated at a lower strength, home treatment can take up to             MTX=methotrexate; PUVA=psoralen-ultraviolet A; TNF=tumor necrosis factor;
                                                                              UVB=ultraviolet B.
an hour, which poses a risk that patients may not adhere to an
                                                                              Source: American Academy of Dermatology.9
effective regimen.

                                                                             Vol. 37, No. 2S, March 2018, Seminars in Cutaneous Medicine and Surgery S41
New Treatment Paradigms in Psoriasis: Understanding and Incorporating Recent and Emerging Trends - Global Academy for Medical ...
■ ■ ■ The Evolving Landscape of Psoriasis Treatment

   Apremilast, an oral PDE-4 inhibitor approved in 2014, is modestly          (P
New Treatment Paradigms in Psoriasis: Understanding and Incorporating Recent and Emerging Trends - Global Academy for Medical ...
April W. Armstrong, MD, MPH, Kenneth B. Gordon, MD, M. Alan Menter, MD, and Jashin J. Wu, MD

   Guselkumab, an IL-23 monoclonal antibody that binds to the
p19 subunit of IL-23, was approved in 2017 for patients with                   What’s Next When a Biologic Fails?
moderate to severe psoriasis.32 Initially, the injectable is adminis-          Lynne is a woman in her early 50s who weighs 160 pounds. Her
tered in one 100-mg/mL injection, followed by another injection                plaque psoriasis had been well controlled on a maintenance dose of
4 weeks later, and thereafter every 8 weeks.32 In a pooled analysis
                                                                               adalimumab for at least 5 years. (She does not have PsA.) However,
of 1,829 patients with moderate to severe psoriasis, guselkumab
was superior to adalimumab in the VOYAGE 1 and 2 pivotal trials,               over the course of a year, she experienced several severe flares.
as measured by the Investigator Global Assessment (IGA 0/1=                    This is not uncommon; some patients lose response to their initial
cleared or minimal psoriasis; IGA 0=cleared).7 At week 24, patients            biologic over time. In the context of this current biologic failure, dose
treated with guselkumab achieved a response rate of 83.8% for IGA              escalation might help.
0/1 and 52.1% for IGA 0 vs those treated with adalimumab, who                     Lynne’s physician increased her usual dosage of 40 mg adali-
achieved rates of 63.1% for IGA 0/1 and 30.2% for IGA 0.7 The                  mumab every other week to the off-label maintenance dosage of
most frequently reported adverse events included upper respiratory             40 mg every week.18 After 6 months, though, her flares did not improve.
infections, headache, injection site reactions, arthralgia, diarrhea,             Her physician added methotrexate 10 mg to Lynne’s weekly dose of
gastroenteritis, tinea, and rare cases of herpes simplex infections.32
                                                                               adalimumab, but after 3 months, she continued to experience flares.
   Tildrakizumab, another IL-23 inhibitor, has completed phase 3
trials (reSURFACE 1 and 2), and in March 2018 was approved by the              Her physician decided to switch Lynne to guselkumab, the newest IL-23
FDA.33 Both injectable dosages of tildrakizumab (100 mg and 200 mg)            blocker, and after 3 months, she reported that her flares subsided.
were superior to etanercept and placebo. At 12 weeks, 66% of patients             Key point: When a biologic fails after a prolonged period, it is
receiving 200 mg tildrakizumab and 61% receiving 100 mg tildraki-              time to consider escalating the dose, using combination therapy, or
zumab achieved PASI 75, vs 6% for the placebo group and 48% in the             switching to a biologic with a different mechanism of action.
etanercept group (P
New Treatment Paradigms in Psoriasis: Understanding and Incorporating Recent and Emerging Trends - Global Academy for Medical ...
■ ■ ■ The Evolving Landscape of Psoriasis Treatment

12. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of
    psoriasis and psoriatic arthritis: Section 5. Guidelines of care for the treatment of psoriasis
    with phototherapy and photochemotherapy. J Am Acad Dermatol. 2010;62:114-135.
13. Warren RB, Mrowietz U, von Kiedrowski R, et al. An intensified dosing schedule of subcu-
    taneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP):
    A 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.
    Lancet. 2017;389:528-537.
14. Otezla (apremilast) [prescribing information]. Summit, NJ: Celgene Corporation; 2017.
15. Enbrel (etanercept) [prescribing information]. Thousand Oaks, CA: Amgen Inc; 2017.
16. Papp KA, Tyring S, Lahfa M, et al; for the Etanercept Psoriasis Study Group. A global
    phase III randomized controlled trial of etanercept in psoriasis: Safety, efficacy, and effect
    of dose reduction. Br J Dermatol. 2005;152:1304-1312.
17. Kimball AB, Rothman KJ, Kricorian G, et al. OBSERVE-5: Observational postmarketing
    safety surveillance registry of etanercept for the treatment of psoriasis final 5-year results.
    J Am Acad Dermatol. 2015;72:115-122.
18. Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moderate to severe psori-
    asis: A randomized, controlled phase III trial. J Am Acad Dermatol. 2008;58:106-115.
19. Humira (adalimumab) [prescribing information]. North Chicago, IL: AbbVie Inc; 2017.
20. Gall JS, Kalb RE. Infliximab for the treatment of plaque psoriasis. Biologics. 2008;2:
    115-124.
21. Menter A, Feldman SR, Weinstein GD, et al. A randomized comparison of continuous vs.
    intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-
    severe plaque psoriasis. J Am Acad Dermatol. 2007;56(1):31.e1-15.
22. Remicade (infliximab) [prescribing information]. Horsham, PA: Janssen Biotech Inc; 2017.
23. Leonardi CL, Kimball AB, Papp KA, et al; PHOENIX 1 Study Investigators. Efficacy
    and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients
    with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial
    (PHOENIX 1). Lancet. 2008;371:1665-1674.
24. Papp KA, Langley RG, Lebwohl M, et al; PHOENIX 2 Study Investigators. Efficacy
    and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients
    with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial
    (PHOENIX 2). Lancet. 2008;371:1675-1684.
25. Stelara (ustekinumab) [prescribing information]. Horsham, PA: Janssen Biotech Inc; 2017.
26. US Food and Drug Administration. FDA approves new psoriasis drug Cosentyx [press
    release]. January 21, 2015. http://wayback.archive-it.org/7993/20171115021420/https://www.
    fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm430969.htm. Accessed February
    15, 2018.
27. Pariser D, Frankel E, Schlessinger J, et al. Efficacy of secukinumab in the treatment of
    moderate to severe plaque psoriasis in the North American subgroup of patients: Pooled
    analysis of four phase 3 studies. Dermatol Ther (Heidelb). 2008;8:17-32.
28. Taltz (ixekizumab) [prescribing information]. Indianapolis, IN: Eli Lilly and Company; 2017.
29. Papp KA, Leonardi CL, Blauvelt A, et al. Ixekizumab treatment for psoriasis: Integrated
    efficacy analysis of three double-blinded, controlled studies (UNCOVER-1, UNCOVER-2,
    UNCOVER-3) [published online October 9, 2017]. Br J Dermatol. doi:10.1111/bjd.16050.
30. Siliq (brodalumab) [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals
    North America LLC; 2017.
31. Farahnik B, Beroukhim K, Abrouk M, et al. Brodalumab for the treatment of psoriasis:
    A review of phase III trials. Dermatol Ther (Heidelb). 2016;6:111-124.
32. Tremfya (guselkumab) [prescribing information]. Horsham, PA: Janssen Biotech Inc; 2017.
33. Reich K, Papp KA, Blauvelt A, et al. Tildrakizumab versus placebo or etanercept
    for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): Results from two
    randomised controlled, phase 3 trials. Lancet. 2017;390:276-288.
34. Papp KA, Blauvelt A, Bukhalo M, et al. Risankizumab versus ustekinumab for moderate-
    to-severe plaque psoriasis. N Engl J Med. 2017;376:1551-1560.
35. Mrowietz U, Kragballe K, Nast A, Reich K. Strategies for improving the quality of care in
    psoriasis with the use of treatment goals—A report on an implementation meeting. J Eur
    Acad Dermatol Venereol. 2011;25(suppl 3):1-13.
36. Davison NJ, Warren RB, Mason KJ, et al. Identification of factors that may influence the
    selection of first-line biological therapy for people with psoriasis: A prospective, multicentre
    cohort study. Br J Dermatol. 2017;177:828-836.
37. Armstrong AW, Siegel MP, Bagel J, et al. From the Medical Board of the National Psoriasis
    Foundation: Treatment targets for plaque psoriasis. J Am Acad Dermatol. 2017;76:290-298.

S44 Seminars in Cutaneous Medicine and Surgery, Vol. 37, No. 2S, March 2018
Treating to Target—A Realistic Goal in Psoriasis?
          Kenneth B. Gordon, MD,* April W. Armstrong, MD, MPH,† M. Alan Menter, MD,‡ and Jashin J. Wu, MD§

                                                                               P
                                                                                    soriasis and its comorbidities can significantly affect patients’
  ■ Abstract                                                                        overall health and their quality of life. To achieve optimal
  For many patients, the new biologic therapies for psoriasis                       results from therapy, clinicians need to collaborate with patients
  can improve Psoriasis Area and Severity Index (PASI) scores in               to set long- and short-term goals: Is there a level of clearance or
  a relatively short time. But when results are less than optimal,
  patients often become frustrated. By providing effective                     improvement that most patients find acceptable? Is there a target
  medical treatment using a treat-to-target strategy, clinicians               or number that accurately conveys response to therapy and that
  can relieve symptoms and halt disease progression. Although                  represents a realistic goal? Most important, in clinical care, are
  body surface area (BSA) and PASI scores are appropriate for                  these targets—identified by analysis of populations—relevant to
  analyzing results of clinical trials, clinicians need to use more
  patient-centered assessments of patients’ progress such                      the patient in the office?
  as the Dermatology Life Quality Index (DLQI) and Psoriasis                     In psoriasis, there is a limited sense of what those endpoints
  Symptom Inventory (PSI), as well as other validated patient-                 are. However, the recent IHOPE study of >90,000 patients in the
  reported outcomes, which can enable them to set realistic
  and achievable goals for individual patients.                                United Kingdom guides clinicians to reduce psoriasis so that it
  Semin Cutan Med Surg 37(supp2):S45-S48                                       involves 10% was higher than that of people without psoriasis (Hazard
  Severity Index (PASI); quality of life (QOL); treat to target                Ratio [HR], 1.79; 95% confidence interval [CI], 1.23-2.59).1 These
                                                                               data suggest an initial goal of
■ ■ ■ Treating to Target—A Realistic Goal in Psoriasis?

                                                                                 The phase 3 NAVIGATE trial, in which guselkumab was intro-
  Choosing Initial Therapy:                                                   duced after patients had not responded to ustekinumab therapy,
  Patient Preferences vs Medical Need                                         provides a clear example of why it is important to wait until the
                                                                              third dose is administered. Approximately 30% of patients who
  Jared is a 30-year-old man who presents with psoriasis and psoriatic
                                                                              had not responded fully at week 16 (when the third dose would be
  arthritis, which require treatment with a biologic. His plaque psoriasis
                                                                              administered) eventually did respond when they received their third
  covers 25% of his body, and his axial psoriatic arthritis stiffens his      injection.9 However, patients treated with guselkumab fared better
  lower back and hips in the morning. Jared is otherwise healthy, with        overall at week 52 than did patients treated with ustekinumab, with
  no history of multiple sclerosis or inflammatory bowel disease (IBD).       50% and 24% achieving PASI 90, respectively.9
     An anti-TNF or an anti–IL-17agent would be sensible choices                 The National Psoriasis Foundation treat-to-target consensus
  because both classes are efficacious in psoriatic arthritis. Due to         recommends allowing 3 months for patients to respond to therapy.2
  formulary restrictions, the likely choice will be the anti-TNF agent        Ideally, 3 months after initiating treatment, the target BSA should
  adalimumab. Contraindications to anti-TNF medications include               be ≤3% or there should a BSA improvement of 75% or more from
  multiple sclerosis, because these drugs can cause or exacerbate             baseline.2 If a patient is not achieving any response, clinicians
  demyelinating disease.23                                                    should discontinue treatment with the initial agent (Table).2
     If Jared had painful axial psoriatic arthritis, an anti–IL-17 might be      Efficacy is among the leading drivers in drug selection—and
  faster-acting. The anti–IL-17 agents secukinumab, ixekizumab, and           the lack of efficacy is the chief reason for therapeutic attrition.
  brodalumab provide a more predictable and rapid response than               Systemic agents, and biologics specifically, are considered the go-to
  anti-TNF agents.5,24 If he had IBD, anti–IL-17 agents would not be          therapy because they treat moderate to severe plaque psoriasis as
  advisable because, in clinical trials, occasional new cases of IBD          well as the common comorbidities. In systematic reviews, biologics
  developed among patients with psoriasis.                                    in the aggregate can help up to 80% of patients achieve PASI 75.10
                                                                              However, PASI scores do not reflect the whole clinical outcome
                                                                              because the trials often focus on short-term efficacy and may not
Which Measure Is Best?                                                        incorporate health-related QOL concerns.10
Despite its limitations, BSA for plaque psoriasis is likely the best             One such QOL study compared the efficacy of three biologics—
measure of physical disease burden that currently exists. It is quick,        adalimumab, etanercept, and ustekinumab—for 1 year as measured
easily estimated and recorded, and is used in almost all dermatology          by the DLQI and European Quality of Life score-5D (EQ-5D).10
offices. But trying to decrease the BSA as a treatment target can be          Although there was no significant difference in the percentage
daunting. It is possible for clinicians to get to a point where they          of patients who received ustekinumab and adalimumab and
have cleared a substantial proportion of plaques, yet the patient             who achieved a DLQI score of 0/1, adalimumab-treated patients
is still bothered by itching, pain, or unsightliness. These lingering         were more likely than etanercept-treated patients to achieve a
annoyances diminish a patient’s QOL, and clinicians should                    0/1 DLQI score. Among the three biologics, there was no differ-
acknowledge that at this juncture it is the patient who should set
                                                                              ence in the EQ-5D score. Factors most frequently associated with
the treatment goals.
                                                                              poor response to treatment included being female, being a current
   In a busy dermatology office, clinicians need a data point that
is going to help them with decision making. The BSA, while not                smoker, having any comorbidity, and having a higher baseline
perfect, provides a quick and reproducible piece of information.              DLQI score.10 For the EQ-5D score, each 10-year increase in age
If the patient is undressed, clinicians can derive a BSA score in a           was associated with a lower EQ-5D score.10
few seconds.2,6
   Performing long, comprehensive QOL measures in the office may
be more difficult. European dermatologists often use the DLQI, but            ■ TABLE Summary of National Psoriasis
in the United States few offices use it routinely because of time and                      Foundation Consensus Targets for
logistical constraints.                                                                    Plaque Psoriasisa
Drug Selection                                                                 Preferred assessment instrument          BSA
A common misconception is that certain psoriasis therapies, such               in clinical practice
as methotrexate, take longer to work, but mistakenly adhering to
such myths can interfere with successful treatment. The multicenter            Acceptable response after                Either BSA ≤3% or BSA
METOP trial from the United Kingdom showed that subcuta-                       treatment initiation                     improvement of ≥75% from
neous methotrexate does not become more effective after each                                                            baseline after 3 months
successive dose.7 At week 16, 41% of methotrexate-treated patients                                                      of treatment
achieved a PASI 75 response vs 10% of the placebo group (rela-                 Target response after                    BSA ≤1% at 3 months after
tive risk [RR], 3.93; 95% CI, 1.31-11.81; P=0.0026).7 If patients              treatment initiation                     treatment initiation
did not achieve a PASI 50 score at week 8, they received a higher
dose of methotrexate, from 17.5 mg/week for the first 16 weeks, to             Target response during                   BSA ≤1% at every-6-month
22.5 mg/week. However, methotrexate appeared to reach peak effi-               maintenance therapy                      assessment intervals during
cacy around week 24 in the 52-week trial.7                                                                              maintenance therapy
   A recent study with methotrexate found that it takes as little as           BSA=body surface area.
4 weeks to determine whether patients with psoriasis will respond to           a Treatment targets apply to plaque psoriasis, and they are to be

the systemic therapy.8 Methotrexate-treated patients who achieved                discussed in the context of individualized evaluation of benefit-risk
PASI 25 at week 4 were more likely to respond at week 16. In contrast,           assessment and elicitation of patient preferences. They are not to
in cases where patients have a
Kenneth B. Gordon, MD, April W. Armstrong, MD, MPH, M. Alan Menter, MD, and Jashin J. Wu, MD

   Discontinuing a biologic regardless of the reason is also associ-
ated with lower health-related QOL scores.10 Because biologics are                                       60
immunomodulators, clinicians need to be alert for any infections                                                               49.9

                                                                            % Among Treatment Failures
that may arise.11 Occasionally, patients experience side effects, the                                    50

most common being an infection while on a biologic. Although
                                                                                                         40
patients are at an increased risk of infection with biologics, some
still get infections even without being on the medications. The                                          30                                                    25.6
dosages used in clinical trials become the required dosages in                                                  22.4
clinical practice, and third party payers frequently will not allow a                                    20
change in dosing in clinical practice.
                                                                                                         10                                      4.4
Dosing Strategies
                                                                                                          0
There is a dearth of evidence in prospective studies to guide clini-
                                                                                                              Switching   Discontinuation   Dose Increase   Augmented
cians on adjusting the dose of psoriasis medications.12 A 3-year                                               n=200          n=445             n=39          n=228
retrospective observational study found that clinicians increased                                              N=891          N=891            N=891          N=891
the dose for 28.6% of patients and decreased the dose for 71.4%.
The reason given for the increase was inadequate response in 60%           ■ FIGURE Causes of Treatment Regimen Failures
of patients with plaque psoriasis and 40% of those with psoriatic          Percentages do not add up to 100% because some patients were
arthritis. More than half of clinicians reduced the dose because of        included in more than 1 category.
disease remission, 14% did so at the patients’ request, and 18% did        Source: Foster SA, et al.22
so for unspecified reasons.12
   Labeling for many antipsoriatic medicines includes step-down
                                                                           (IL)-17 medication works well—yet needs a more potent regimen—
dosing—starting with a bolus dose and then gradually decreasing
                                                                           should probably be switched to another anti–IL-17 agent because
it. But some patients may fare worse when the dose is reduced.13
                                                                           it is mechanistically sound for the patient.17 Finding the right drug
If there is some response, clinicians may obtain better results by
                                                                           that gets the right levels for the patient is critical. If a patient is on
increasing the dose or shortening the intervals between doses rather
                                                                           secukinumab and does not respond, switching to another class of
than switching to another agent.14
   A systematic review of 23 studies that included 12,617 patients         agent would be prudent. Clinicians can apply the same paradigm
with psoriasis demonstrated that increasing the dose helps                 when prescribing either the anti–tumor necrosis factor (TNF) or
patients fare better overall than does decreasing the dose or              the anti–IL-23 classes.
switching to another agent.14 Patient nonresponders have better            Adjusting Therapy: Dosing, Switching
outcomes with continuous vs interrupted therapy for moderate               For patients with moderate to severe psoriasis, clinicians change
to severe plaque psoriasis.14 Even with higher doses that are off-         treatments due to inadequate disease control.18 In a 5-year analysis
label, the benefits of dose escalation outweighed any adverse effects,     of insurance claims, Armstrong and colleagues reported that there
which were mostly infections.14 However, more and larger studies
                                                                           were frequent changes among topical agents, oral systemic medi-
are needed to examine the effect of off-label dosing on patients
                                                                           cations, biologics, and phototherapy. Of the biologics studied,
with psoriasis, so as to determine a more realistic risk-benefit ratio
                                                                           infliximab had the longest persistence, with a median 19 months
of dose escalation.
                                                                           of use.18 Overall, more patients stopped topical agents (15.9%) or
Follow-Up Assessments                                                      phototherapy compared with those who stopped biologic or tradi-
Although there is no firm, established timeline for follow-up visits,      tional oral therapy (7.8%).18
patients taking older systemic agents, such as methotrexate and               The concept of changing to a therapy with a different mecha-
cyclosporine, should be followed closely because they require              nism of action was the focus of two papers in which the anti–IL-17
routine laboratory tests, including complete blood count serum             ixekizumab improved the signs and symptoms of psoriasis and
creatinine, blood urea nitrogen, uric acid, aspartate aminotrans-          psoriatic arthritis in patients who had originally failed on a TNF
ferase, alanine aminotransferase, tests for hepatitis B and C viruses,     inhibitor.19 In the SPIRIT studies, at both the 2- and 4-week dosing
and urinalysis.15 Indeed, long-term use of cyclosporine is not recom-      intervals, ixekizumab reduced symptoms in 363 patients who were
mended because of the risk for nephrotoxicity and hypertension.15          nonresponders to TNF inhibitors. The safety profile was similar to
   When to follow up on patients taking the newer biologics is a           that seen in previous ixekizumab studies. In the UNCOVER-2 and
subject of ongoing discussion. A consensus panel of the National
                                                                           UNCOVER-3 studies, both the every-2-week and every-4-week
Psoriasis Foundation has suggested that patients should undergo
                                                                           doses of ixekizumab were found to be superior to etanercept and
follow-up at 3 months after initiating a new therapy and again every
                                                                           placebo in the 12-week studies. The safety profile in these studies
6 months during the maintenance phase.2 Experienced clinicians
                                                                           was comparable to that seen in previous ixekizumab and etaner-
say that, for most patients, 8 weeks is sufficient to assess their prog-
ress. What may also be important, especially to the patient, is the        cept studies.20
speed with which the agent works.                                             Likewise, the IL-23 inhibitor guselkumab was found to be
   The follow-up for a certain medication may depend on the                superior to the TNF inhibitor adalimumab when tested in subpop-
loading dose, subsequent doses, and the interval between dosing.           ulations of patients with moderate to severe psoriasis (N=1,829).21
A classic example is a patient who is on secukinumab and who does          The subpopulations included more ethnically diverse patients,
well in the first 5 weeks but who returns with flares 2 months later.      overweight and obese patients, and patients whose psoriasis had
Because the loading dosage (300 mg per week in weeks 1-4) is much          been present for a mean of 17 years. Previous studies of biologics,
higher than the follow-up dosage (300 mg every 4 weeks), some              systemic agents, and phototherapy with these populations had
patients may be undermedicated if they receive the less-frequent           lower efficacy. Among the subpopulations, guselkumab achieved
maintenance dosage.16 Such a patient for whom the anti–interleukin         an Investigator Global Assessment (IGA) score of 0/1 at week 16

                                                                           Vol. 37, No. 2S, March 2018, Seminars in Cutaneous Medicine and Surgery S47
■ ■ ■ Treating to Target—A Realistic Goal in Psoriasis?

vs placebo and at week 24 vs adalimumab. The VOYAGE 1 and                                          15. Choi CW, Kim BR, Ohn J, Youn SW. The advantage of cyclosporine A and methotrexate
                                                                                                       rotational therapy in long-term systemic treatment for chronic plaque psoriasis in a real
VOYAGE 2 studies suggest that dosing based on patient character-                                       world practice. Ann Dermatol. 2017;29:55-60.
istics such as weight and previous therapy can be effective.                                       16. Cosentyx (secukinumab) [prescribing information]. East Hanover, NJ: Novartis
                                                                                                       Pharmaceuticals Corporation; 2018.
   No clear biomarkers exist that would enable clinicians to predict                               17. Kerdel F, Zaiac M. An evolution in switching therapy for psoriasis patients who fail to meet
failure with biologic therapy (Figure).22 One study found that those                                   treatment goals. Dermatol Ther. 2015;28:390-403.
more likely to fail biologic treatment include women and those                                     18. Armstrong AW, Koning JW, Rowse S, Tan H, Mamolo C, Kaur M. Initiation, switching,
                                                                                                       and cessation of psoriasis treatments among patients with moderate to severe psoriasis in
taking concomitant medications such as topical agents (67.0%                                           the United States. Clin Drug Investig. 2017;37:493-501.
vs 58.4%; P
Common and Not-So-Common
           Comorbidities of Psoriasis
           M. Alan Menter, MD,* April W. Armstrong, MD, MPH,† Kenneth B. Gordon, MD,‡ and Jashin J. Wu, MD§

                                                                                S
                                                                                      cientific research continues to reveal the inflammatory process
  ■ Abstract                                                                          that is the basis of many chronic conditions, including psori-
  Plaque psoriasis is increasingly recognized as a multisystemic                      asis and its many associated comorbidities (Table).
  disease whose most common comorbidities include psoriatic                        Psoriatic arthritis (PsA) is among the most frequent of these
  arthritis, cardiovascular disease, metabolic syndrome,                        comorbidities. Approximately 30% of patients with psoriasis have
  overweight/obesity, inflammatory bowel disease, and                           comorbid PsA. PsA onset typically occurs 5 to 10 years after the
  depression. The presence of such comorbidities affects                        onset of psoriasis, ie, in the third to fifth decade of life; in children,
  the therapeutic choices for clinicians. Patients often visit                  the age of onset peaks between 11 and 12 years.1
  dermatologists more frequently than they do other clinicians,                    Positioned on the frontlines for identifying PsA, dermatologists
  so it is incumbent upon dermatologists to recognize and
                                                                                should be aware of the importance of evaluating patients for joint
  address early signs of psoriatic comorbidities to prevent further
                                                                                stiffness and pain. Physical examinations should include the fingers
  deterioration and improve their patients’ quality of life.
  Semin Cutan Med Surg 37(supp2):S49-S52
                                                                                (dactylitis) and toes, Achilles tendon (enthesitis), sacroiliac, axial
  © 2018 published by Frontline Medical Communications                          skeleton, and the large joints to identify evidence of swelling, inflam-
                                                                                mation, and nail disease (Figure). When examining patients who
  ■ Keywords                                                                    present with early onset of PsA, consider the following questions:
  Cardiovascular disease; comorbidities; immune-mediated                        • Does early morning stiffness last for ≥30 minutes, eg, hands,
  disorders; overweight/obesity; psoriasis; psoriatic arthritis;                   feet, hips and other large joints, without clinical signs of PsA?
  psychiatric disorders                                                         • When is a rheumatologic consultation indicated?
                                                                                • PsA usually improves more dramatically than psoriasis.
* Chairman, Division of Dermatology, Baylor University Medical Center,
                                                                                   When does the rheumatologist refer to the dermatologist?
  Dallas, Texas                                                                 • Should dermatologists be ordering x-rays for suspected psori-
† Associate Professor of Clinical Dermatology, Associate Dean for Clinical         atic joint disease?
  Research, Keck School of Medicine of the University of Southern               • Can radiologists discern the early signs of PsA?
  California, Los Angeles, California
‡ Professor and Chair, Department of Dermatology, Medical College of
                                                                                There are several self-administered screening tools for PsA:
  Wisconsin, Milwaukee, Wisconsin                                               • The Psoriasis Epidemiology Screening Tool (PEST) is a one-
§ Director of Dermatology Research, Department of Dermatology, Kaiser              page questionnaire with a body diagram allowing patients to
  Permanente Los Angeles Medical Center, Los Angeles, California                   identify painful joints2
Publication of this CME/CE article was jointly provided by University of        • The Toronto Psoriatic Arthritis Screening Tool (TOPAS) is
Louisville, Postgraduate Institute for Medicine, and Global Academy for            meant for the general population to determine whether a
Medical Education, LLC, and is supported by an educational grant from              person might have PsA3
Ortho Dermatologics. The authors have received an honorarium for their          • The Psoriatic Arthritis Screening and Evaluation Tool (PASE)
participation in this activity. They acknowledge the editorial assistance of
Suzanne Bujara, medical writer, and Global Academy for Medical Education           can distinguish between signs and clinical symptoms of PsA
in the development of this continuing medical education journal article.           and those of osteoarthritis4
M. Alan Menter, MD, Advisory Board: AbbVie Inc., Afecta Pharmaceuticals,
Inc., Amgen Inc., Boehringer Ingelheim, Eli Lilly and Company, Janssen
Biotech, Inc., LEO Pharma Inc., Ortho Dermatologics, Promius Pharma,            ■ TABLE Comorbidities Associated With Psoriasis
LLC. Consultant: AbbVie Inc., Afecta Pharmaceuticals, Inc., Amgen Inc.,
Avillion LLP, Boehringer Ingelheim, Eli Lilly and Company, Galderma S.A.,
Janssen Biotech, Inc., LEO Pharma Inc., Menlo Therapeutics Inc., Novartis        Related to systemic              •   Psoriatic arthritis
Pharmaceuticals Corporation, Ortho Dermatologics, Pfizer Inc., Promius           inflammation                     •   Atherosclerosis
Pharma, LLC. Investigator: AbbVie Inc., Amgen Inc., Boehringer Ingelheim,
Celgene Corporation, Dermira, Inc., Eli Lilly and Company, Janssen Biotech,                                       •   Diabetes and insulin resistance
Inc., LEO Pharma Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc.,                                         •   Hypertension
Regeneron. Speakers Bureau: AbbVie Inc., Amgen Inc., Janssen Biotech, Inc.,                                       •   Metabolic syndrome
LEO Pharma Inc., Ortho Dermatologics, Promius Pharma, LLC.
                                                                                                                  •   Myocardial infarction
April W. Armstrong, MD, MPH, Consultant: AbbVie Inc., Amgen Inc.,
Eli Lilly and Company, Janssen Biotech, Inc., Modernizing Medicine,                                               •   Obesity
Novartis Pharmaceuticals Corporation, Regeneron, Sanofi. Speakers
Bureau: AbbVie Inc., Eli Lilly and Company, Janssen Biotech, Inc.                Related to lifestyle risk        •   Alcohol abuse
Kenneth B. Gordon, MD, Consultant: AbbVie Inc., Amgen Inc., Almirall,            factors or to impaired           •   Anxiety
S.A., Boehringer Ingelheim, Bristol Myers-Squibb Company, Celgene                quality of life                  •   Depression
Corporation, Dermira, Inc., Eli Lilly and Company, LEO Pharma Inc.,
Novartis Pharmaceuticals Corporation, Pfizer Inc., Sun Pharmaceutical                                             •   Smoking
Industries Ltd., UCB, Inc. Investigator: AbbVie Inc., Boehringer                                                  •   Suicidal ideation
Ingelheim, Celgene Corporation, Novartis Pharmaceuticals Corporation.
Jashin J. Wu, MD, Contracted Research: AbbVie Inc., Amgen Inc.,                  Related to treatment             • Hepatotoxicity
Eli Lilly and Company, Janssen Biotech, Inc., Novartis Pharmaceuticals           (eg, systemic agents,            • Nephrotoxicity
Corporation, Regeneron.                                                          TNF-alpha inhibitors)
                                                                                                                  • Nonmelanoma skin cancer
Address reprint requests to: Address reprint requests to: M. Alan Menter, MD,    TNF=tumor necrosis factor. Source: Gulliver W.9
3900 Junius Street, Suite 145, Dallas, TX 75246; amderm@gmail.com

1085-5629/13/$-see front matter © 2018 Frontline Medical Communications
doi:10.12788/j.sder.2018.011                                                    Vol. 37, No. 2S, March 2018, Seminars in Cutaneous Medicine and Surgery S49
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