A virtual reality tour - LIVE VIRTUAL SUMMIT - Med Learning Group
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LIVE VIRTUAL SUMMIT
a virtual reality tour
for Dermatologists, Fellows, and Residents –
Integration of Biologics into the Psoriasis Treatment Plan:
A Focus on Reducing Disease Burden and Improving Quality of Life
Tuesday, July 21, 2020
This activity is provided by Med Learning Group. This activity is supported by an independent educational grant from AbbVie.
This activity is co-provided by Ultimate Medical Academy/Complete Conference Management (CCM).
Agenda
Part 1 – Introduction
• Epidemiology and pathophysiology of psoriasis
o Evolving concepts
o Role in development of targeted treatment
o Perspectives for residents and fellows
Part 2 – Patient-Facing Goals in Psoriasis
• Psoriasis: the patient burden
• Quality of life and work productivity
• The pursuit of complete skin clearance
• Improved physical function, sustained reduction of pain, and structural damage
Part 3 – Optimizing Psoriasis Management in the Context of Associated Comorbidities, Special
Populations, and Communities of Color
• Comorbidities associated with psoriasis: a VIRTUAL view
• Considerations in varied populations
o People of color
o Elderly
o Pregnancy
o Obesity
Part 4 – Integrating Biologics in Long-Term Management of Psoriasis
• Overview of conventional therapies
• Biologics therapies: a VIRTUAL view
o Agents targeting TNF-α, IL-23, IL-17, and other pathways
o Efficacy, safety, tolerability, and other considerations
o PASI75 vs PASI90 and PASI100
Conclusions
Questions & Answers
A Virtual Reality Tour for Dermatologists, Fellows, and Residents —
Integration of Biologics into the Psoriasis Treatment Plan: A Focus on
Reducing Disease Burden and Improving Quality of Life
FACULTY
Crystal Aguh, MD
Director, Ethnic Skin Program
Assistant Professor, Department of Dermatology
Johns Hopkins School of Medicine
Baltimore, Maryland
Junko Takeshita, MD, PhD, MSCE
Assistant Professor of Dermatology
Assistant Professor of Epidemiology
University of Pennsylvania Perelman School of Medicine
Philadelphia, Pennsylvania
PROGRAM OVERVIEW
This live activity will cover the management of patients with psoriasis.
TARGET AUDIENCE
This activity is intended for a primary audience of dermatologists, dermatology fellows and
residents, and other healthcare professionals involved in the management of patients with
psoriasis.
LEARNING OBJECTIVES
Upon completion of the program, attendees should be able to:
• Review the pathophysiology of psoriasis, including genetic and cellular mechanisms,
cytokines, and inflammatory process
• Describe the mechanisms of action, efficacy, and safety of approved and emerging
biologics, along with their use in populations where psoriasis is difficult-to-treat
• Evaluate differences in presentation and treatment of special populations with
psoriasis, such as children, the elderly, and pregnant women
ACCREDITATION STATEMENT
Med Learning Group is accredited by the Accreditation Council for Continuing Medical
Education to provide continuing medical education for physicians.
This CME activity was planned and produced in accordance with the ACCME Essentials.
CREDIT DESIGNATION STATEMENT
Med Learning Group designates this live activity for a maximum of 1.5 AMA Category 1
CreditTM. Physicians should claim only the credit commensurate with the extent of their
participation in the live activity.
NURSING CREDIT INFORMATION
Purpose:
This program would be beneficial for nurses involved in the management of patients with
psoriasis.
CNE Credits:
1.5 ANCC Contact Hours
CNE Accreditation Statement:
Ultimate Medical Academy/CCM is accredited as a provider of continuing nursing education
by the American Nurses Credentialing Center’s Commission on Accreditation.
Awarded 1.5 contact hours of continuing nursing education of RNs and APNs.
DISCLOSURE POLICY STATEMENT
In accordance with the Accreditation Council for Continuing Medical Education (ACCME)
Standards for Commercial Support, educational programs sponsored by Med Learning Group
must demonstrate balance, independence, objectivity, and scientific rigor. All faculty, authors,
editors, staff, and planning committee members participating in a MLG-sponsored activity are
required to disclose any relevant financial interest or other relationship with the
manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services that
are discussed in an educational activity.
DISCLOSURE OF CONFLICTS OF INTEREST
Dr. Crystal Aguh has received royalty fees as an author and from UptoDate Inc. as well as
consultant fees from L’Oreal and Leo Pharma.
Dr. Junko Takeshita has received a grant from Pfizer (to the Trustees of the University of
Pennsylvania.
CME Content Review
The content of this activity was independently peer reviewed.
The reviewer of this activity has nothing to disclose.
CNE Content Review
The content of this activity was independently peer reviewed.
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The staff, planners, and managers reported the following financial relationships or
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During the course of this lecture, the faculty may mention the use of medications for both
FDA-approved and non-approved indications.
METHOD OF PARTICIPATION
There are no fees for participating and receiving CME credit for this live activity. To receive
CME/CNE credit participants must:
1. Read the CME/CNE information and faculty disclosures.
2. Participate in the live activity.
3. Complete the online evaluation form.
You will receive your certificate as a downloadable file.
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Med Learning Group makes every effort to develop CME activities that are scientifically based.
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Staff will be glad to assist you with any special needs. Please contact Med Learning Group
prior to participating at info@medlearninggroup.com
Provided by Med Learning Group
Co-provided by Ultimate Medical Academy/Complete Conference Management (CCM).
This activity is supported by an independent educational grant from AbbVie
Copyright © 2020 Med Learning Group. All rights reserved. These materials may be used for
personal use only. Any rebroadcast, distribution, or reuse of this presentation or any part of it
in any form for other than personal use without the express written permission of Med
Learning Group is prohibited.
7/15/2020
A Virtual Reality Tour for
Dermatologists, Fellows, and Residents —
Integration of Biologics into the Psoriasis Treatment Plan:
A Focus on Reducing Disease Burden and Improving Quality of Life
Crystal Aguh, MD Junko Takeshita, MD, PhD, MSCE
Assistant Professor, Department of Dermatology Assistant Professor of Dermatology
Director, Ethnic Skin Program Assistant Professor of Epidemiology
The Johns Hopkins School of Medicine University of Pennsylvania Perelman School of
Baltimore, Maryland Medicine
Philadelphia, Pennsylvania
Disclosures
• In the past 12 months, Dr. Aguh reports:
– Royalty fees as an author and from UptoDate Inc.
– Consultant fees from L’Oreal and Leo Pharma
• In the past 12 months, Dr. Takeshita reports:
– Grant/Research Support: Pfizer Inc. (to the Trustees of the University of
Pennsylvania)
• During this lecture, Drs. Aguh and Takeshita may mention the use of medications for
both FDA‐approved and nonapproved indications.
This activity is supported by an educational grant from AbbVie.
1
7/15/2020
Learning Objectives
• Review the pathophysiology of psoriasis, including genetic and cellular
mechanisms, cytokines, and inflammatory process
• Describe the mechanisms of action, efficacy, and safety of approved and
emerging biologics, along with their use in populations where psoriasis is
difficult‐to‐treat
• Evaluate differences in presentation and treatment of special populations
with psoriasis, such as children, the elderly, and pregnant women
Agenda
• Part 1 – Brief Introduction to Psoriasis (Dr. Aguh)
• Part 2 – Patient‐Facing Goals in Psoriasis (Dr. Takeshita)
• Part 3 – Optimizing Psoriasis Management in the Context of Associated
Comorbidities, Special Populations, and Communities of Color (Dr. Aguh)
– VIRTUAL view of comorbidities associated with psoriasis
• Part 4 – Integrating Biologics in Long‐Term Management of Psoriasis
(Dr. Takeshita)
– VIRTUAL view of biologic therapies for psoriasis
• Conclusions
• Questions & Answers
2
7/15/2020
Brief Introduction to Psoriasis
Dr. Aguh
Psoriasis Is a Multifactorial Disease
Genetics
Modifying
factors/triggers
(skin injury,
Immune infections,
dysfunction medications,
depression,
smoking, alcohol)
Environmental
risk factors
(eg, obesity, smoking)
Slide courtesy of Dr. Junko Takeshita.
Al‐Shobaili HA, Qureshi MG. Pathophysiology of psoriasis: current concepts. In: Lima H, ed. Psoriasis—Types, Causes and Medication. InTech; 2013: 91‐105.
http://cdn.intechopen.com/pdfs‐wm/44201.pdf.
37/15/2020
Genetic Associations With Psoriasis Are Increasingly Identified
>60 genes associated with psoriasis
O’Rielly DD, Rahman P. Nat Rev Rheumatol. 2011;7:718‐732. O’Rielly DD, Rahman P. Rheum Dis Clin N Am. 2015;41:623‐642. Capon F. Int J Mol Sci. 2017;18(12):2526;
doi:10.3390/ijms18122526.
Overlapping Genetic Features of Psoriasis and Other Diseases
Genetic Correlation:
Red/Brown = high
Blue = low
Farh K, et al. Nature. 2015;518:337‐357.
47/15/2020
Immunopathogenesis of Psoriasis: Therapeutic Targets
T cells
(keratinocyte‐derived)
ADAMTSL5 (melanocyte‐derived)
Psoriasis
KC = keratinocyte; DC = dendritic cell; IL = interleukin; IFN = interferon; TNF = tumor necrosis factor; AMP = antimicrobial peptide.
Lowes MA, et al. Annu Rev Immunol. 2014;32:227‐255. Lande R, et al. Nat Commun. 2014;3(5):5621. Arakawa A, et al. J Exp Med. 2015;212(13):2203‐2212.
Psoriasis Competencies for Residents and Fellows
• In‐depth understanding of the pathophysiology of psoriasis
• Understanding of current methodologies for identifying genes/loci
associated with psoriasis
• Recognizing and treating the varied morphologies of psoriasis
– Topical formulations
– Local steroid injections
– Ultraviolet light treatments
– Excimer laser treatments
– Conventional systemic therapies
– Biologic therapies
– Scalp therapies
57/15/2020
Patient‐Facing Goals in Psoriasis
Dr. Takeshita
Psoriasis Impact on Quality of Life Compared With
Other Major Morbidities
HRQoL outcome with SF‐36 physical‐ and mental‐health domains
Mental Physical
Functioning Functioning
Healthy adults 53.43 Healthy adults 55.26
Diabetes type 2 51.90 Depression 44.96
MI 51.67 Arthritis 43.15
CHF 50.43 MI 42.64
Arthritis 48.81 Chronic lung
disease 42.31
Psoriasis 45.69
Chronic lung Diabetes type 2 45.52
disease 44.47 Psoriasis 41.17
Depression 34.84 CHF 34.50
CHF = congestive heart failure; HRQoL = Health‐Related Quality of Life; MI = myocardial infarction; SF‐36 = Short Form‐36 (health survey).
Rapp SR, et al. J Am Acad Dermatol. 1999;41:401‐407.
67/15/2020
Psoriasis Worsening Results in Disproportionately
Negative Impact on HRQoL
• Patients underwent protocol mandated
discontinuation of adalimumab after
achieving PASI 75 response
• An approximately twofold
disproportionately greater degree of
worsening of DLQI score compared with
the degree of worsening of PASI was
observed while patients underwent
discontinuation of therapy
Scatter plot for week 4 and week 52 DLQI vs PASI
DLQI = Dermatology Life Quality Index; PASI = Psoriasis Area and Severity index.
(LOCF; ITT population).
Poulin Y, et al Dermatol Ther (Heidelb). 2014;4(1):33‐42.
Psoriasis Continues to Be a Stigmatizing Disease
• Survey of 198 laypersons and 187 medical students
• Participants viewed pictures of patients with psoriasis
Desire for Social Distance* Endorsing Negative Stereotypes
45% (Lay Persons)
39%
40%
35% 32%
28%
• 27%: PsO “is contagious”
30%
25%
• 34%: PsO “only affects the skin”
20% • 27%: PsO “is not a serious disease”
15% 12%
10%
5% 5%
5%
0%
Shaking hands In my home Marry into my family
*Figures are based on desire to avoid a behavior (eg, avoid
Lay Persons Medical Students shaking hands with someone with psoriasis)
PsO = psoriasis.
Pearl RL, et al. J Am Acad Dermatol. 2019;80(6):1556‐1563.
77/15/2020
Objective Psoriasis Severity and Indications for Treatment
MILD MODERATE SEVERE
Less than 3% of the 3% to 10% of the More than 10% of the
body has psoriasis body has psoriasis body has psoriasis
Topical therapies Phototherapy Systemic therapies
• Orals
• Biologics
Most Psoriasis Patients Are Undertreated
2 1 4
100 1 5 1
4
90 8 5
80
70
Patients (%)
53 55 52 Biologic +/– topical
60 Oral + biologic
50 Oral +/– topical
Topical only
40 No Rx
30 41
20 32 37
10
0 ≤3 palm lesions 4–10 palm lesions >10 palm lesions
(n = 2122) (n = 393) (n = 166)
Body surface area
Lebwohl MG, et al. J Am Acad Dermatol. 2014;70:871‐881.
87/15/2020
Measuring Treatment Efficacy in Clinical Trials: Psoriasis Area and
Severity Index (PASI)
What Does Achieving Higher PASI Outcomes Look Like?
Baseline (25.2) PASI 75 (5.9) PASI 90 (1.2)
PASI
100
Menter AM, et al. J Am Acad Dermatol. 2008;58:106‐115.
Improvements in PASI Achieve Better HRQoL Outcome
Ixekizumab Trial Data (N = 142)
PASI response at week 16
90 84.4
79.3
80 DLQI 0 or 1
DLQI 0
DLQI responders (%)
70
58.6
60 53.1
50
40 33.3
30
20 12.7
10 6.7
1.6
0
PASI7/15/2020
Clinical Practice: Nearly 20% of Almost‐Clear Patients Meet
DLQI Criteria for Treatment Change
DLQI Clear Almost Clear P-value
≥ moderate effect (DLQI
2 (2.1) 85 (19.3) 5), N (%)
Takeshita J et al. J Am Acad Dermatol. 2014;71:633‐641.
ΔPASI7/15/2020
MIPS (PQRS) 410 Psoriasis: Clinical Response to Oral Systemic or
Biologic Medications
• Only dermatology • 2015 PQRS reporting data
outcome measure – 1269 individuals reported
in MIPS – 69.7% performance rate
• Outcome targets
– PGA ≤2
MIPS
– BSA7/15/2020
Comorbidities associated with psoriasis:
a VIRTUAL view
https://youtu.be/Kc9a7NddLsQ
Psoriasis and Ethnicity
• Large population‐based studies suggest that rates of psoriasis are highest in people of
European ancestry (~3.7%), followed by black (~2.7%) and Hispanic (1.0%) people in
the US
• True prevalence of psoriasis in nonwhite people is likely underestimated
• Plaque psoriasis is the most common type of psoriasis in all populations
• Despite similarities in psoriasis between ethnic groups, there are notable differences
in the presentation, impact on quality of life, and treatment of psoriasis that have
important implications for its management in nonwhite people
– Differences may be explained by heterogeneity in psoriasis susceptibility alleles in combination
with cultural and socioeconomic factors
Kaufman BP, Alexis AF. Am J Clin Dermatol. 2018;19:405–423.
127/15/2020
Impact of Psoriasis in Communities of Color
• Several studies suggest that erythema is more challenging to detect in skin of color
– Inflammation that typically manifests as pink or red lesions in lighter skin may
appear violaceous or hyperpigmented in darker skin types
• Several studies in the US have shown that psoriasis is associated with greater
psychological impact and worse QoL in nonwhite individuals with psoriasis compared
with white individuals
• Compared with white individuals, higher scores on the DLQI are consistently observed
in black and Hispanic individuals, even when controlling for BSA affected and severity
of disease
BSA = body surface area.
Kaufman BP, Alexis AF. Am J Clin Dermatol. 2018;19:405–423.
Presentation Differences in Communities of Color
• In comparison with white individuals,
psoriasis in darker‐skinned patients is
often characterized by
– Less distinguishable erythema
– Increased risk of pigmentation
– Thicker plaques
– More scaling
– Greater body involvement
Kaufman BP, Alexis AF. Am J Clin Dermatol. 2018;19:405–423.
137/15/2020
Disparities in Treatment Among Persons of Color with Psoriasis
• In comparison to non‐Hispanic whites, Hispanics and blacks were roughly
half as likely to receive outpatient dermatology care1
• Based on health care utilization outcomes, including the number of
ambulatory visits, the number of prescriptions, and any dermatology visits
for psoriasis:2
– Non‐Hispanic racial minorities reported fewer ambulatory visits for psoriasis
compared with non‐Hispanic whites
• Absolute difference of 1.24 fewer visits per person per year and more than 3 million fewer
visits per year
– The likelihood of seeing a dermatologist for psoriasis was found to be lower among
non‐Hispanic minorities than non‐Hispanic whites
1. Tripathi R, et al. JAMA Dermatol. 2018;154(11):1286‐1291. 2. Fischer AH, et al. J Am Acad Dermatol. 2018;78(1):200‐203.
Disparities in Treatment Among Persons of Color with Psoriasis
(continued)
• Nonwhite individuals are more likely to have undiagnosed psoriasis than
white individuals1
– Related to barriers to care and decreased health care utilization in these groups
• In the US, black patients are less likely than white patients to receive
biologic treatment for their psoriasis2
• Black patients with psoriasis are more likely to be “unfamiliar” with
biologics and report that they “dislike needles” compared to white patients
with psoriasis3
1. Kaufman BP, Alexis AF. Am J Clin Dermatol. 2018;19:405–423. 2. Takeshita J, et al. J Invest Dermatol. 2019;139(8):1672‐1679.e1. 3. Takeshita J, et al. J Invest Dermatol.
2015;135(12):2955‐2963.
147/15/2020
Special Treatment Considerations For Ethnic Patients with
Moderate to Severe Psoriasis
• Psychosocial barriers
– Insurance coverage (uninsured or underinsured)
– Cultural implications of skin darkening from phototherapy
– Transportation issues
– Implications of prior discrimination from health care system (distrust of medical
professionals and “emerging” therapies)
• Personal preferences regarding route of administration
– Area(s) affected (eg, scalp and hair washing, face)
– Topical vs oral vs subcutaneous
– Frequency of treatments
Well‐Established Comorbidities of Psoriasis
• MI, stroke, CV death
• Metabolic syndrome (obesity, insulin resistance, cholesterol abnormalities, and
hypertension)
• Diabetes
• Psoriatic arthritis
• Mood disorders (anxiety, depression, and suicide)
• Crohn’s disease
• T‐cell lymphoma (rare)
CV = cardiovascular; MI = myocardial infarction.
National Psoriasis Foundation Fact Sheet ‐ Comorbidities. https://www.psoriasis.org/sites/default/files/comorbidities_fs.pdf. Gelfand JM, et al. JAMA. 2006;296:1735‐1741.
Gelfand JM, et al. J Invest Dermatol. 2006;126:2194‐2201. Langan SM, et al. J Invest Dermatol. 2012; 132:556‐562. Kurd SK, et al. Arch Dermatol. 2010;146:891‐895.
Armstrong AW, et al. J Hypertens. 2013;31:433‐442. Ma C, et al. Br J Dermatol. 2013;168:486‐495. Azfar RS, et al. Arch Dermatol. 2012;148:995‐1000. Yeung H, et al. JAMA
Dermatol. 2013;149:1173‐1179. Mehta NN, et al. Eur Heart J. 2010;31:1000‐1006. Najarian DJ, Gottlieb AB. J Am Acad Dermatol. 2003;48:805‐821.
157/15/2020
Risk of Cardiometabolic Disease in Patients with More Severe Psoriasis
4 Mortality curve1 • Clinical significance
Percent of subjects
3
2
Psoriasis • Increased risk of MI, stroke, CV death, diabetes,
Controls
1
and CKD
0
20 40 60 80 100
• 5 years of life lost
Age
Adjusted RR
• Patients with >10% BSA affected have a higher
Outcome
Mild Severe risk of death after controlling for standard
MI2 1.05 1.5 mortality risk factors8
Stroke3 1.06 1.4
CV Death4 Not done 1.6
• Patients treated for severe psoriasis are 30 times
MACE5 Not done 1.5 more likely to experience MACE (attributable to
Diabetes6 1.11 1.5 psoriasis) than to develop a melanoma
CKD7 0.99 (NS) 1.9
RR = relative risk; MI = myocardial infarction; MACE = major adverse cardiovascular events; CKD = chronic kidney disease; NS = not significant.
1. Abuabara K, et al. Br J Dermatol. 2010;163(3):586‐592. 2. Gelfand JM, et al. JAMA. 2006;296:1735‐1741. 3. Gelfand JM, et al. J Invest Dermatol. 2009;129:2411‐2418. 4.
Mehta NN, et al. Eur Heart J. 2010;31:1000‐1006. 5. Mehta NN, et al. Am J Med. 2011;124:775.e1‐6. 6. Azfar RS, et al. Arch Dermatol. 2012;148:995‐1000. 7. Wan J, et al.
BMJ. 2013;347:f5961. 8. Noe MH, et al. J Invest Dermatol. 2018;138(1):228‐230.
BSA Affected by Psoriasis Predicts Diabetes
• N = 8124
Kaplan‐Meier Survival Estimates
• BSA ≤2%: HR 1.2 1.00
– 199 extra cases of DM per year 0.98
per 100,000
0.96
• BSA >10%: 1.6
0.94
– 625 extra cases of DM per year
0.92
per 100,000
0.90
• For each 10% increase in BSA above 0 2 4 6
10% there is a 20% increase in risk Analysis Time
Non‐Psoriasis BSA ≥2%
• 125,650 new cases of DM each year BSA 3‐10% BSA >10%
worldwide attributable to psoriasis
DM = diabetes mellitus; HR = hazard ratio.
Wan MT, et al. J Am Acad Dermatol. 2018;78:315‐322.
167/15/2020
Comparison of Cardiometabolic Outcomes:
Psoriasis vs Rheumatoid Arthritis
Included in
CVD risk score
CVD
RA
Severe
risk psoriasis ()
Psoriasis, PsA ?
IBD ?
Kristensen SL et al. Ann Rheum Dis. 2015;74:321‐322.
DMARD = disease‐modifying antirheumatic drug; RA = rheumatoid arthritis; IBD = inflammatory bowel disease.
Ogdie A, et al. Ann Rheum Dis. 2014;73:149‐153. Ogdie A, et al. Ann Rheum Dis. 2015;74: 326‐332. Dubreuil M, et al. Rheumatology (Oxford). 2014;53:346‐352.
Clinical Care Recommendations:
Educate and Screen for CV Risk Factors
Friedewald VE, et al. Am J Cardiol. 2008;102:1631‐1643. Kimball AB, et al. J Am Acad Dermatol. 2008;58:1031‐1042. Elmets CA, et al. J Am Acad Dermatol. 2019;80(4):1073‐
1113.
177/15/2020
Standard Screening Recommendations*
• Hypertension1
– Age 18–39 years, no risk factors and BP7/15/2020
Proof of Principle: The CANTOS Trial
Biologic Inhibition of IL‐1 Lowers MACE
• Prior MI, CRP ≥2 mg/L • Canakinumab* q12 weeks IL‐1
• N= 6717; median follow up 3.7 years (50, 150, or 300 mg)
High‐Sensitivity C‐Reactive Protein Level
10
0
Primary End Point with
‐10 Canakinumab, 150 mg vs Placebo
‐20
Baseline
25
Change
Percent
Hazard ratio, 0.85 (95% CI, 0.74‐0.98)
from
‐30
‐40 100 P=0.021
‐50 20
Cumulative Incidence of
‐60
Primary End Point (%)
‐70 Placebo 80 15
Placebo
0 3 6 9 12 24 36 48
Months
Canakinumab
LDL Cholesterol Level 10
50 mg 60
Canakinumab 150 mg
Baseline
10
Change
Percent
5
from
0 Canakinumab
‐10
0 3 6 9 12 24 36 48 150 mg 40
Months 0
0 1 2 3 4 5
HDL Cholesterol Level Canakinumab
20
10 300 mg
Baseline
Change
Percent
0
from
‐10
0 3 6 9 12 24
Months
36 48 0
0 1 2 3 4 5
Triglyceride Level Years
10 No. at Risk
Baseline
Change
Percent
from
0
‐10
Placebo 3344 3141 2973 2632 1266 210
0 3 6 9 12 24 36 48
Months Canakinumab 2284 2151 2057 1849 907 207
Ridker PM, et al. N Engl J Med. 2017;377:1119‐1131. *Canakinumab is not FDA‐approved for psoriasis.
Psoriatic Arthritis and Psoriasis
• >10% of psoriasis patients seen by Strata Prevalence
dermatologists had undiagnosed PsA1 % (95% CI)2
• PsA generally occurs after onset of All psoriasis 11% (9, 14)
psoriasis
No or little psoriasis 6% (4, 10)
• PsA may be progressive and can cause
permanent joint damage 1%‐2% BSA 14% (9, 21)
• CRP and number of joints involved are
markers of progression 3%‐10% BSA 18% (10, 28)
10+% BSA 56% (34, 76)
PsA = psoriatic arthritis.
1. Mease PJ, et al. J Am Acad Dermatol. 2013;69:729‐735. 2. Gelfand JM, et al. J Am Acad Dermatol. 2005;53:573.e1–573.e13.
197/15/2020
Screening for Psoriatic Arthritis in Clinical Practice
• Identify symptoms/signs of PsA PEST
Questionnaire
– Morning‐joint stiffness
– Joint pain that improves with activity
– Swollen, tender joints, dactylitis, and enthesitis
– Check X‐rays of affected joints and CRP, RF, CCP
Ibrahim GH, et al. Clin Exp Rheumatol. 2009;27(3):469‐474.
Score 1 point for each question answered ‘yes’. A total score of 3 or
more is indicative of psoriatic arthritis.
Images courtesy of Dr. Joel Gelfand.
CRP = C‐reactive protein; RF = rheumatoid factor; CCP = cyclic citrullinated peptide; PsA = psoriatic arthritis.
Coates LC, et al. Clin Med (Lond). 2017;17(1):65–70. Gisondi P, et al. J Eur Acad Dermatol Venereol. 2017;31,774–790.
Clinical Implications: Psoriasis and Infection
• Patients with severe psoriasis are 65% more likely to die of infection (2nd
highest excess risk)1
• Screen for streptococcal infection with guttate flares
• Screen for HIV in severe psoriasis
• Vaccination for2,3
– Influenza (annually)
– Pneumonia (PCV13 and PPSV23)
• Refer to CDC website for specific ages/schedules
– Zoster (age ≥50 years)
• Shingrix® vaccination recommended for adults 50 or older4
– Hepatitis B
– HPV (ages 9–45 years)
• Gardasil‐9® vaccination; can be started at age 9
HIV = human immunodeficiency virus; PCV = pneumococcal conjugate vaccine; PPSV = pneumococcal polysaccharide vaccine; HPV = human papillomavirus.
1. Abuabara K, et al. Br J Dermatol. 2010;163(3):586‐592. 2. Wine‐Lee L, et al. J Am Acad Dermatol. 2013;69:1003‐1013. 3. CDC. Recommended Adult Immunization Schedule
for ages 19 years or older, United States, 2019. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html. 4. CDC – Shingles Vaccination.
https://www.cdc.gov/shingles/vaccination.html.
207/15/2020
Cancer and Psoriasis
Cancer Type by Study Group, HR (95% CI) aHR Overall Psoriasis group
Overall Psoriasis Mild Psoriasis Moderate to Severe Adjusted Hazard Ratio (aHR, 95% CI) for aHR Mild Psoriasis group
Source Psoriasis cancer by study group aHR Moderate to severe
1.06 1.06 1.08 Psoriasis group
Any cancer except NMSC
(1.02‐1.09) (1.02‐1.09) (0.96‐1.22)
1.34 1.33 1.86
Any lymphoma
• Common solid
(1.18‐1.51) (1.17‐1.51) (1.23‐2.80)
Any lymphoma excluding 1.25 1.24 1.62
CTCL (1.10‐1.43) (1.08‐1.41) (1.16‐2.28)
CTCL
3.82 3.51 9.25 cancer
(2.50‐5.85) (2.20‐5.47) (3.69‐23.22)
Leukemia
1.09 1.10 1.05 (colon, breast,
(0.98‐1.23) (0.98‐1.23) (0.67‐1.65)
1.15 1.13 1.60 prostate) NOT
Lung
(1.03‐1.27) (1.01‐1.25) (1.14‐2.24)
1.06 1.05 1.16
associated with
Prostate
(0.99‐1.13)
1.25
(0.99‐1.12)
1.25
(0.90‐1.50)
1.29
psoriasis
Pancreas
(1.04‐1.51) (1.03‐1.51) (0.64‐2.61)
Breast
1.04 1.04 0.96 • Lymphoma
(0.97‐1.12) (0.97‐1.13) (0.71‐1.28)
Colon
1.08 1.07 1.20 (especially CTCL)
(0.98‐1.30) (0.97‐1.19) (0.82‐1.99)
Melanoma
1.15 1.14 1.28 is increased
(1.02‐1.30) (1.01‐1.29) (0.82‐1.99)
1.12 1.09 1.61
NMSC
(1.07‐1.16) (1.05‐1.13) (1.42‐1.84)
0 1 10
CTCL, Cutaneous T‐Cell Lymphoma; NMSC, nonmelanoma skin cancer. aHR (95% CI)
Chiesa Fuxench ZC, et al. JAMA Dermatol. 2016;152:282‐290.
Clinical Implications: Psoriasis and Cancer
• Biopsy patients with atypical features of psoriasis and/or those not
responding to treatment
• Encourage patients to stay up to date on age‐appropriate cancer screening
– Cervical cancer:1
• Age 21‐29: q 3 yrs w/ cervical cytology
• Age 30‐65: q 3 yrs w/ cervical cytology; or every 5 yrs with hrHPV with or without cytology
– Breast cancer: mammography (ages 50–74 years, q 2 years)2
– Colon cancer: (ages 50–75 years) FOBT q year, flex sig q 5 yrs + FOBT q 3 years,
colonoscopy q 10 yrs3
– Lung cancer: Annual low‐dose CT screening for ages 55–80 years with ≥30
pack/year history and current smoker or quit within 15 years4
q = every; FOBT = fecal occult blood testing; CT = computed tomography; hrHPV = high‐risk HPV.
1. USPSTF. https://jamanetwork.com/journals/jama/fullarticle/2697704?resultClick=1. 2. USPSTF. Nov 2016.
https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/breast‐cancer‐screening1. 3. USPSTF. Ann Intern Med. 2008;149:627‐637.
4. Moyer VA; USPSTF. Ann Intern Med. 2014;160:330‐338.
217/15/2020
Clinical Implications: Psoriasis and Cancer (continued)
• Earlier/more frequent screening may be recommended for those with
personal/family history that places them at higher risk1,2
• Large, long‐term follow‐up studies are necessary to determine risk of
cancer with psoriasis treatments
FOBT = fecal occult blood testing; CT = computed tomography; hrHPV = high‐risk HPV.
1. Oeffinger K. JAMA. 2015;314(15):1599‐1614. 2. https://www.cancer.org/healthy/find‐cancer‐early/cancer‐screening‐guidelines/american‐cancer‐society‐guidelines‐for‐
the‐early‐detection‐of‐cancer.html.
Obesity and Psoriasis
• Obesity appears to be associated with an increased risk of psoriasis
• Metabolic comorbidities associated with psoriasis may also explain
variations in obesity prevalence among psoriasis populations
Kaufman BP, Alexis AF. Am J Clin Dermatol. 2018;19:405–423.
227/15/2020
Meta‐Analysis of RCTs of Weight Loss Intervention Effects
on Psoriasis Severity
Forest Plot for Comparing Change in PASI Score After Weight Loss Intervention vs Control
Study or Intervention Control Mean Difference Mean Difference
Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Gisondi 2008 ‐12.6 6.3 30 ‐6 7.2 31 12.2% ‐6.60 (‐9.99, ‐3.21)
Guida 2014 ‐5.1 4.7 18 ‐1.1 4.2 18 14.9% ‐4.00 (‐6.91, ‐1.09)
Jensen 2013 ‐2.3 0.7 30 ‐0.3 0.7 30 39.5% ‐2.00 (‐2.35, ‐1.65)
Naldi 2014 ‐1.92 4.12 151 ‐1.02 4.9 152 33.5% ‐0.90 (‐3.90, ‐1.08)
Total (95% CI) 229 231 100.0% ‐2.49 (‐3.90, ‐1.08)
Heterogeneity: Tau2=1.28; Chi2=13.28; df=3 (P = .0004); I2=77%
Test for overall effect: Z=3.45 (P = .0006)
‐10 ‐5 0 5 10
Favors intervention Favors control
Upala S, Sanguankeo A. Int J Obes (Lond). 2015; 39:1197‐1202.
Psoriasis in Pregnancy
• Treatment of psoriasis in pregnant women and during breast‐feeding
should be approached with caution in all cases, particularly with regard to
drug recommendations
– Methotrexate and acitretin are contraindicated in pregnancy and are not
recommended during breast‐feeding
– Biologics have varying recommendations in pregnant women which need to be
considered when choosing therapy
Ferreira C, et al. Drugs Context. 2020;9:2019‐11‐6. 2.
237/15/2020
Psoriasis in Elderly Persons
• Treatment of moderate‐to‐severe psoriasis in the older population is
difficult due to associated comorbidities, potential drug interactions, and
possible dose adjustments
– Few studies have evaluated the treatment of psoriasis in older persons
– Systemic therapies tend to be overlooked in favor of topical therapies due to
concerns and lack of knowledge on their safety
• This can result in inadequate or insufficient treatment
Balato N, et al. Drugs Aging. 2014;31:233–238.
Psoriasis in Children
• Data on psoriasis treatment in the pediatric population are limited
– Children with psoriasis should undergo obesity, cardiovascular, metabolic, and
mental health screenings
– The decision to treat with systemic therapy is based on:
• Baseline severity of disease
• Subtype of psoriasis
• Speed of disease progression
• Lack of response to more conservative therapies such as topical agents and phototherapy
• Impaired physical or psychological functioning or QOL due to disease extent
• Presence of comorbidities
Menter A, et al. [published correction appears in J Am Acad Dermatol. 2020;82(3):574]. J Am Acad Dermatol. 2020;82(1):161‐201.
247/15/2020
Psoriasis in Various Treatment Settings
Treatment Setting Available Data
Obesity1 • Obesity appears to be associated with an increased risk of psoriasis
• Metabolic comorbidities associated with psoriasis may also explain variations in obesity prevalence among
psoriasis populations
Pregnancy2 • Treatment of psoriasis in pregnant women and during breast‐feeding should be approached with caution in all
cases, particularly with regard to drug recommendations
– Methotrexate and acitretin are contraindicated in pregnancy and are not recommended during breast‐feeding
– Biologics have varying recommendations in pregnant women which need to be considered when choosing therapy
Elderly3 • Treatment of moderate‐to‐severe psoriasis in the older population is difficult due to associated comorbidities,
potential drug interactions, and possible dose adjustments
– Few studies have evaluated the treatment of psoriasis in older persons
– Systemic therapies tend to be overlooked in favor of topical therapies due to concerns and lack of knowledge on their
safety
• This can result in inadequate or insufficient treatment
Children4 • Data on psoriasis treatment in the pediatric population are limited
– Children with psoriasis should undergo obesity, cardiovascular, metabolic, and mental health screenings
– The decision to treat with systemic therapy is based on:
• Baseline severity of disease
• Subtype of psoriasis
• Speed of disease progression
• Lack of response to more conservative therapies such as topical agents and phototherapy
• Impaired physical or psychological functioning or QOL due to disease extent
• Presence of comorbidities
1. Kaufman BP, Alexis AF. Am J Clin Dermatol. 2018;19:405–423. 2. Ferreira C, et al. Drugs Context. 2020;9:2019‐11‐6. 3. Balato N, et al. Drugs Aging. 2014;31:233–238.
4. Menter A, et al. [published correction appears in J Am Acad Dermatol. 2020;82(3):574]. J Am Acad Dermatol. 2020;82(1):161‐201.
Integrating Biologics in Long‐Term Management
of Psoriasis
Dr. Takeshita
257/15/2020
Biologics therapies:
a VIRTUAL view
https://youtu.be/jApyA9FYa0U
Therapeutic Targets in Treatment of Psoriasis
Etanercept
Infliximab
T cells
Adalimumab
Certolizumab
(keratinocyte‐derived)
ADAMTSL5 (melanocyte‐derived)
Psoriasis
Lowes MA, et al. Annu Rev Immunol. 2014;32:227‐255. Lande R, et al. Nat Commun. 2014;3(5):5621. Arakawa A, et al. J Exp Med. 2015;212(13):2203‐2212.
267/15/2020
Therapeutic Targets in Treatment of Psoriasis
Ustekinumab
T cells
(keratinocyte‐derived)
ADAMTSL5 (melanocyte‐derived)
Psoriasis
Lowes MA, et al. Annu Rev Immunol. 2014;32:227‐255. Lande R, et al. Nat Commun. 2014;3(5):5621. Arakawa A, et al. J Exp Med. 2015;212(13):2203‐2212.
Therapeutic Targets in Treatment of Psoriasis
T cells
(keratinocyte‐derived)
ADAMTSL5 (melanocyte‐derived)
Psoriasis
Guselkumab
Tildrakizumab
Risankizumab
Lowes MA, et al. Annu Rev Immunol. 2014;32:227‐255. Lande R, et al. Nat Commun. 2014;3(5):5621. Arakawa A, et al. J Exp Med. 2015;212(13):2203‐2212.
277/15/2020
Therapeutic Targets in Treatment of Psoriasis
Ixekizumab
Secukinumab
T cells
(keratinocyte‐derived)
ADAMTSL5 (melanocyte‐derived)
Psoriasis
Lowes MA, et al. Annu Rev Immunol. 2014;32:227‐255. Lande R, et al. Nat Commun. 2014;3(5):5621. Arakawa A, et al. J Exp Med. 2015;212(13):2203‐2212.
Therapeutic Targets in Treatment of Psoriasis
Bimekizumab*
T cells
(keratinocyte‐derived)
ADAMTSL5 (melanocyte‐derived)
Psoriasis
*Bimekizumab is investigational and not FDA‐approved for use in psoriasis.
Lowes MA, et al. Annu Rev Immunol. 2014;32:227‐255. Lande R, et al. Nat Commun. 2014;3(5):5621. Arakawa A, et al. J Exp Med. 2015;212(13):2203‐2212.
287/15/2020
Therapeutic Targets in Treatment of Psoriasis
Brodalumab
T cells
(keratinocyte‐derived)
ADAMTSL5 (melanocyte‐derived)
Psoriasis
Lowes MA, et al. Annu Rev Immunol. 2014;32:227‐255. Lande R, et al. Nat Commun. 2014;3(5):5621. Arakawa A, et al. J Exp Med. 2015;212(13):2203‐2212.
Psoriasis Area and Severity Index (PASI) End Points
What Does Achieving Higher PASI Outcomes Look Like?
Baseline (25.2) PASI 75 (5.9) PASI 90 (1.2)
Week 4 Week 16
PASI
100
Menter AM, et al. J Am Acad Dermatol. 2008;58:106‐115.
297/15/2020
Physician (Investigator) Global Assessment (PGA or IGA)
• Increasingly used as psoriasis severity measure in clinical trials
• Several different scales exist
‒ 5‐ and 6‐point scales most common
‒ Single overall score vs average score of components of erythema, induration and
scale
• Clear (PGA=0) or almost clear skin (PGA=1) is common clinical efficacy
measure
CLEAR Study: Secukinumab (IL‐17A Inhibitor)
Has Superior 1‐Year Efficacy vs Ustekinumab
PASI 90 PASI 100
100 100
‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡
Responders (%)
Responders (%)
80 ‡ 80
60 ‡ 60 † ‡ † † ‡ ‡ †
‡ ‡ † *
40 40 ‡
‡
20 ‡ 20
* *
0 0
0 4 8 12 16 20 24 28 32 36 40 44 48 52 0 4 8 12 16 20 24 28 32 36 40 44 48 52
Weeks Weeks
Secukinumab Ustekinumab
*P < .05; †P < .01; ‡P < .001 vs ustekinumab
Blauvelt A, et al. J Am Acad Dermatol. 2017;76(1):60‐69.
307/15/2020
IXORA‐S Trial: Ixekizumab (IL‐17A Inhibitor) Has Superior
24‐Week Efficacy vs Ustekinumab
PASI 75 response rate (NRI) PASI 90 response rate (NRI)
100 *** *** ** * 100
*** 91.2 *** *** ***
80 88.2 81.9 80 *** 83.1
60 60 *** 72.8
*** 68.7 59.0
40 40
*** *** 42.2
20 20
0 0
0 2 4 8 12 16 20 24 0 2 4 8 12 16 20 24
PASI 100 response rate (NRI)
100
80
60 *** *** UST (n = 166)
***
*** 49.3 IXE (n = 136)
40
20 *** 36.0 23.5
***
14.5
0
0 2 4 8 12 16 20 24
NRI = nonresponder imputation; IXE = ixekizumab; UST = ustekinumab
*P < .05; **P < .01; ***P < .001 vs UST
Reich K, et al. Br J Dermatol. 2017:177:1014‐1023.
Higher Dose Brodalumab (IL‐17 Receptor Inhibitor) Has Superior
Efficacy Compared With Ustekinumab
PASI 75 response rates (NRI) by week in the PASI 100 response rates (NRI) by week in the
induction phase induction phase
100 100
Response rate (%)
Response rate (%)
90 85.1% 90
80 80
70 69.3% 70
60 69.2% 60
50 50
40 40 36.7%
30 30 27.0%
20 20 18.5%
10 6.0% 10
0 0 0.3%
0 2 4 6 8 10 12 0 2 4 6 8 10 12
Week Week
Placebo Ustekinumab Brodalumab 140 mg Brodalumab 210 mg
• Coprimary endpoint: PASI 75 at week 12 brodalumab vs • Primary endpoint: PASI 100 at week 12 brodalumab 210 mg
placebo—adjusted P value < .001 for both dosages Q2W vs ustekinumab—adjusted P value < .001
• Secondary endpoint: brodalumab 210 mg Q2W vs – Weight‐based brodalumab subgroup vs ustekinumab (primary endpoint) was
also significant—adjusted P‐value7/15/2020
ultIMMa‐1/2 Trial: Risankizumab (IL‐23 inhibitor) is Superior to
Ustekinumab up to 52 Weeks
ultIMMa‐1 ultIMMa‐2
100 Part A Part B Part A Part B
85%† 85%† 84%† 87%† 85%†
82%† 82%† 81%†
80 75%*†
80%† 75%*† 82%† 86% 83% 84%† 81%†
Patients with
68%*† 68% 79% 78%
PASI 90 (%)
74% 62%*§ 67% 61%
60 55% 52% 54% 57%
52% 48% 47%
44%*† 45% 47%*† 54%
49% 47% 49% 51%
40 42% 44% 44%
Risankizumab
32% 24%
20 26% Placebo
19%
6%* 3% 2%
Ustekinumab
6%† 5% 5% 3%
5% 3% 2% Placebo Risankizumab
0
0% 0%
100 91% 91%
88%† 87%† 87%† 89%† 89% 87% 89%† 87%† 87%† 89% 87%
82%*** 82%§§
88%† 86%† 87% 88%† 85% 88%†
sPGA 0 or 1 (%)
80 74% ||
81%
86% 86%† 84%† 83%†
Patients with
70% 70%‡‡
65% 64% 65% 64% 64% 67%
62%
60 63% 62% 62% 60% 63%
61% 59%
54% 54% 56% 57% 55%
40 34%¶ 33%††
20 20% 21%
9% 9%
3% 6% 1%
5%
5%
8%
0
0 4 8 12 16 22 28 34 40 46 52 0 4 8 12 16 22 28 34 40 46 52
Time (weeks) Time (weeks)
P7/15/2020
Guselkumab has Superior Long‐Term Efficacy
Compared to Secukinumab
100 100
Patients Achieving
Patients Achieving
80 80
Proportion od
Proportion od
PASI 100 (%)
PASI 90 (%)
60 60
40 40
20 Guselkumab group 20 Guselkumab group
Secukinumab group Secukinumab group
0 0
0 4 8 12 16 20 24 28 32 36 40 44 48 0 4 8 12 16 20 24 28 32 36 40 44 48
Time (weeks) Time (weeks)
100 100
Proportion od Patients
Achieving IGA Score of
Patients Achieving
IGA Score of 0 (%)
80 80
Proportion od
0 or 1 (%)
60 60
40 40
20 Guselkumab group 20 Guselkumab group
Secukinumab group Secukinumab group
0 0
0 4 8 12 16 20 24 28 32 36 40 44 48 0 4 8 12 16 20 24 28 32 36 40 44 48
Time (weeks) Time (weeks)
Reich K, et al. Lancet. 2019;394:831‐839.
Phase 3 reSURFACE 1/2: Tildrakizumab vs Placebo/Etanercept
Proportion of patients achieving PASI 75
reSURFACE 1 reSURFACE 2
100 Part 1 Part 2 Part 1 Part 2
80
* **
%
60
40
20
0
0 4 8 12 16 22 28 0 4 8 12 16 22 28
Week Week
Tildrakizumab 100 mg Placebo Tildrakizumab 100 mg Etanercept
Tildrakizumab 200 mg Placebo Tildrakizumab 200 mg
Reich K, et al. Lancet. 2017;390:276‐288. *P < .0001 vs placebo. **P < .05 vs placebo or etanercept
337/15/2020
BE ABLE 1 (Phase 2b): Bimekizumab* (BKZ; IL17A & F Inhibitor)
PASI75 PASI90
100 100
PASI75 Responses,
PASI90 Responses,
80 80
% patients
% patients
60 60
40 40
20 20
0 0
0 1 1 4 6 8 12 0 1 1 4 6 8 12
Weeks Weeks
PASI100 IGA
100 100
PASI100 Responses,
IGA 0/1 Responses,
80 80
% patients
% patients
60 60
40 40
20 20
0 0
0 1 1 4 6 8 12 0 1 1 4 6 8 12
Weeks Weeks
Placebo; n=42 BKZ 64 mg; n=39 BKZ 160 mg; n=43
BKZ 160 mg (320 mg LD); n=40 BKZ 320 mg; n=43 BKZ 480 mg; n=43
*Not currently FDA
Papp KA, et al. J Am Acad Dermatol. 2018;79:277‐286. approved for psoriasis.
Biologics and Commonly Used Oral Treatments: PASI 90 Response
Anti-IL23
100 Anti-IL17
90
PASI 90 Response Rate (%)
Anti-TNF Anti-
75%
70% 70% 73%
80
IL12/23
70
60 57% 57%
52%
50 45% 45%
40 37%
Orals
30
20%
20
9% 9%
10
0
Treatment Placebo
*400 mg Q2W dose for certolizumab pegol.
Data derived from phase respective product labels. Saurat J, et al. Br J Dermatol. 2008;158:558‐566. Blauvelt A. JAAD. 76(3):405‐417. Reich K. Lancet. 2017;390:276‐288.
Farahnik B. Dermatol Ther. 2016;6:111‐1124. Moul D. J Cut Med Surg. 2007;11(4):132‐136. Woolacott N. Health Technol Assess. 2006;10:1‐233. Reich K. Lancet.
2005;366:1367‐1374. Press Release. 10/26/17. Abbvie PressRoom. https://news.abbvie.com/news/risankizumab‐meets‐all‐co‐primary‐and‐ranked‐secondary‐endpoints‐
achieving‐significantly‐greater‐efficacy‐versus‐standard‐biologic‐therapies‐in‐three‐pivotal‐phase‐3‐psoriasis‐studies.htm. Menter A, et al. J Am Acad Dermatol.
2008;58(1):106‐115.
347/15/2020
Real‐World Effectiveness of Treatments for
Moderate to Severe Psoriasis
PGA: clear/almost clear skin with psoriasis Cumulative survival (time to drug discontinuation)
treatments1–4 for agents5
1.0
RCTs 0.8
Clear or Almost Clear
Survival Probability
(95% CI)(%)
0.6 Ustekinumab
Adalimumab
0.4
Secukinumab
Infliximab
0.2
Etanercept
0.0
MTX ADA ETAN INFX UST UVB
0 25 50 75 100 125
= PGA from trials Time (months)
PGA = Physician Global Assessment; RCT = randomized controlled trial; MTX = methotrexate; UVB = ultraviolet B.
1. Gelfand JM, et al. Arch Dermatol. 2012;148:487‐494. 2. Takeshita J, et al. J Am Acad Dermatol. 2014;71:1167‐1175. 3. Saurat JH, et al. Br J Dermatol. 2008;158:558‐566.
4. Adalimumab, etanercept, and ustekinumab prescribing information. 5. Egeberg A, et al. Br J Dermatol. 2018;178:509‐519.
FDA‐Approved Biologics Dosing Regimens
weekly q2 weeks q4 weeks q8 weeks q12 weeks
Etanercept 50 mg SCa
Adalimumab 40 mg SCb
Infliximab 5 mg/kg IVc
Certolizumab 400 mgd
45 mg (≤100kg)
Ustekinumab
90 mg (>100kg) SCe
Guselkumab 100 mg SCf
Tildrakizumab 100 mg SCg
Risankizumab 150mg SCh
Secukinumab 150 mg or 300 mg
SCi
Ixekizumab 80 mg SCj
Brodalumab 210 mg SCk
aLoading dose for plaque psoriasis: 50 mg SC 2x/week x 3 mo fLoading dose: 100 mg SC at week 0 and 4
bLoading dose: 80 mg SC day 1, 40 mg SC day 8 gLoading dose: 100 mg SC at weeks 0 and 4
cLoading dose: 5 mg/kg IV week 0, week 2, week 6 hLoading dose: 150 mg (two 75 mg injections) SC at 0 and 4 weeks
dReduced dose (body weight < 90kg: 400mg at week 0, 2, and 4, then 200 mg every iLoading dose: 300 mg SC weekly x 5 weeks
other week) jLoading dose: 160 mg SC (in 2 doses) week 0; 80 mg SC at week 2, 4, 6, 8, 10, and 12
eLoading dose: 45/90 mg SC week 0, week 4 kLoading dose: 210 mg SC at 0, 1, and 2 weeks
Adapted from prescribing information for these agents; August 2019.
357/15/2020
Selected Clinically Important Biologic AEs: Anti‐TNF Therapies
Common Uncommon Rare
Biologic (>5%) (0.1%–5%) (5%) (0.1%–5%) (7/15/2020
Scenario TNF IL12/23 IL-23 IL-17
Psoriatic FDA FDA
Biologic Selection Depends
TBD
arthritis approved approved*
FDA approved
on Many Factors
FDA approved
adalimumab, FDA
Crohn’s disease certolizumab, TBD Warning!
approved
infliximab
Associated with
decreased MI Yes TBD TBD TBD
and stroke
CHF No warning No warning No warning = gold standard
Warning! No benefit
Multiple or harm Promising
No warning
sclerosis phase 2 phase 2
Ease of
administration
Infliximab Weight-based *Ixekizumab and secukinumab only
Patient is obese preferred dosing Flexible dosing**
**Flexible dosing relevant for secukinumab
Rapid onset
Long-term
TBD TBD
persistence
Pediatric Etanercept Adolescents Ixekizumab
psoriasis only (≥4yo) only (≥12yo) only (≥6yo) Courtesy of Dr. Joel Gelfand (August 2019).
Psoriasis Management in the Setting of the COVID‐19 Pandemic
• Patients with severe psoriasis are more likely to have comorbidities that are
associated with worse outcomes from COVID‐19
– Hypertension, diabetes, cardiovascular disease, chronic lung disease
• Most treatments for moderate‐to‐severe psoriasis suppress the immune system
Immunomodulatory or
Not Immunosuppressive Tx
Suppressive Tx
Phototherapy Cyclosporine
Acitretin Methotrexate
Apremilast
TNF Inhibitors
IL12/23 Inhibitors
IL23 Inhibitors
IL17 Inhibitors
377/15/2020
Psoriasis Management in the Setting of the COVID‐19 Pandemic
(continued 1)
• Case series reports from New York1 and Northern Italy2
– New York, N = 86 (14 with psoriasis, 21 with psoriatic arthritis) with immune‐
mediated disease and COVID‐19
• No relationship between biologic treatment and worse COVID‐19 outcomes
– Northern Italy, N = 5,206 patients with psoriasis on biologic
• Higher risk of SARS‐CoV‐2 infection and hospitalization for COVID‐19
• No difference in mortality or ventilator use
• Several treatments for psoriatic disease are being evaluated in clinical trials
for COVID‐19
– Adalimumab, ixekizumab, apremilast, JAK inhibitors
1. Haberman R, et al. N Engl J Med. 2020; doi: 10.1056/NEJMc2009567. 2. Gisondi P, et al. Br J Dermatol. 2020; doi:10.1111/bjd.19158.
Psoriasis Management in the Setting of the COVID‐19 Pandemic
(continued 2)
• Goals of treatment:
– Minimize risk of treatment
– Maximize treatment of psoriasis to keep
patients out of the hospital
• Resources:
– American Academy of Dermatology
• https://www.aad.org/member/practice/coronavi
rus/clinical‐guidance/biologics
– International Psoriasis Council
• https://www.psoriasiscouncil.org/blog/Statemen
t‐on‐COVID‐19‐and‐Psoriasis.htm
– National Psoriasis Foundation
• https://www.psoriasis.org/advance/coronavirus
Available at:
https://assets.ctfassets.net/1ny4yoiyrqia/PicgNuD0IpYd9MSOwab47/5e6d85324e7b5aafed45dde0ac4ea21e/Guidance_on_medications_AHTF_approved_April_15.pdf
387/15/2020
Conclusions
Psoriasis—Conclusions
• Moderate‐to‐severe psoriasis is associated with serious impairment in
HRQoL and an approximate 5‐year decrease in life expectancy
• Comorbidities associated with psoriasis include cardiovascular and
metabolic syndromes (obesity, insulin resistance, cholesterol abnormalities,
and hypertension), diabetes, and psoriatic arthritis
• Limited information is available for treating psoriasis in children, the
elderly, and during pregnancy
– Biologics have varying recommendations in pregnant women which need to be
considered when choosing therapy
397/15/2020
Psoriasis—Conclusions
• Current research suggests that available therapies for psoriasis are effective
in patients with skin of color
– Inclusion of diverse ethnic groups in clinical trials and the characterization of
differences in genetic and molecular profiles between groups are needed
• There has been a rapid expansion of treatment alternatives achieving
greater efficacy and possibly improved safety in psoriasis
– Longer‐term data are needed
• Treatment selection remains highly dependent on individual patient
characteristics and preferences
• Management of psoriasis during the COVID‐19 pandemic requires careful
consideration of the risks and benefits of treatment
Thank You!
Questions & Answers
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