Transcript J Am Acad Dermatol

Applying Science to Improve the
Individualized Treatment of Patients with
Psoriasis
Abrar Qureshi, MD, MPH
Chief of the Department of Dermatology
Rhode Island Hospital
Chair, Department of Dermatology
The Warren Alpert Medical School of Brown University
PATIENT CASE STUDIES
History and Clinical Presentation
Case #1: History
 A 25-year-old female presents to her primary care provider with a
history of an itchy, red rash on her arms and legs for 3 months and
the rash is spreading gradually. She has had a long-standing history
of scalp “dandruff” and uses anti-dandruff shampoos frequently.
The patient denies fever, recent illness, new exposures, or travel,
and otherwise feels well. She reports that she has had a similar rash
on her elbows and knees over the last couple of years that resolved
in the summer months; but this time the rash has persisted.
– Past medical history: no previous illnesses or surgeries
– Family history: mother has spinal arthritis; father and siblings are
healthy
– Social history: no tobacco use; 1-2 alcoholic drinks per week; married
6 months ago; works full time as a receptionist; has been avoiding
social situations because she feels self-conscious
– Medications: oral contraceptive pills; over-the-counter hydrocortisone
cream (0.5%)
– Allergies: No known drug allergies
Case #1: Clinical Presentation
 Physical exam reveals small plaques with whitish
or silvery scale, involving approximately 9% body
surface area (BSA)
 Lesions are mainly on the arms and legs with
some buttock involvement, but the trunk is
relatively spared
 There are no visible nail changes, but scalp
involvement is severe with thick plaques covered
with a thick plate of scale
 There are several bleeding points where she had
been scratching her scalp
Scalp Psoriasis
Photos courtesy of Abrar Qureshi, MD, MPH.
Case #2: History
 A 54-year-old obese male diagnosed with chronic plaque psoriasis more
than 15 years ago is seeking a consultation with a dermatologist because
he recently heard of the availability of new treatments. He has been
applying clobetasol ointment, which he has used intermittently over the
years. The patient had been treated briefly with SC methotrexate several
years ago but discontinued it because of nausea. He did get some relief
from phototherapy, but he had to stop because he is not able to get
away from work during the day to attend the treatment sessions. The
patient denies joint pain or swelling.
– Past medical history: hypertension, elevated cholesterol and triglycerides;
recently diagnosed with metabolic syndrome
– Family history: mother had colon cancer; father had coronary artery
disease; no siblings
– Social history: current cigarette smoker (1.5 packs per day for 35 years); 1
alcoholic drink/day; married with 2 teenage children; works as an attorney
in a busy firm
– Medications: lisinopril; atorvastatin, clobetasol ointment
– Allergies: penicillin
SC=subcutaneous
Case #2: Clinical Presentation
 Physical exam reveals moderately thick
plaques covering approximately 40% BSA, with
pityriasiform scale above the waist and more
thick ostraceous scale below the waist
 There are several excoriations with
hemorrhagic crusting; fingernails demonstrate
distal onycholysis
 He sheds scale all over the exam table and
surrounding floor during the visit
Severe Plaque Psoriasis
Photos courtesy of Abrar Qureshi, MD, MPH.
Excoriated Plaque Psoriasis
Photos courtesy of Abrar Qureshi, MD, MPH.
Onycholysis
Photo courtesy of Abrar Qureshi, MD, MPH.
Interactive Question
Please rate your confidence in distinguishing
plaque psoriasis from other types of psoriasis.
A. Not at all confident
B. Somewhat confident
C. Very confident
D. Completely confident
Overview of Psoriasis
 Chronic systemic inflammatory disorder affecting 2% of the
population
 Manifests primarily in skin and joints
– Up to 30% of patients with skin disease develop psoriatic arthritis
 Most common form is plaque psoriasis (80% to 90% of
patients)
– Well-demarcated erythematous patches, papules, and plaques
covered by silvery scales
– Typically symmetric and often pruritic
– Most commonly involves the scalp, sacral area, extensor surfaces
of elbows and knees
 Other types include guttate, inverse, erythrodermic, and
pustular
Menter A et al. J Am Acad Dermatol. 2008;58:826-850; Reich A, Szepietowski JC. Clinical aspects of itch: psoriasis. In:
Carstens E, Akiyama T, editors. Itch: Mechanisms and Treatment. Boca Raton, FL: CRC Press/Taylor & Francis; 2014.
Available at: www.ncbi.nlm.nih.gov/books/NBK200930/. Accessed May 12, 2016.
Guttate Psoriasis
Photo courtesy of Abrar Qureshi, MD, MPH.
Inverse Psoriasis
Photos courtesy of Abrar Qureshi,
MD, MPH.
Erythrodermic Psoriasis
Photos courtesy of Abrar Qureshi, MD, MPH.
Pustular Psoriasis
Photo courtesy of Abrar Qureshi, MD, MPH.
Immunopathogenesis of Plaque
Psoriasis
Disease initiation
Disease maintenance
Psoriatic plaque
Keratinocyte
activation and
proliferation
Environmental trigger
Stress
Microorganisms
Drugs
Trauma
Smoking
PSORS1
IL-23R
IL-12B
Stressed
keratinocytes
Angiogenesis
Neutrophils
IL-17A
IL-17F
IL-22
TNF-α
IL-2
IFN-γ
TNF-α
IL-6
IL-1β
Tc17
Naïve
T cell
Dermal DC
Activation
IL-12
Genetic predisposition
Th17
Th1
Tc1
IL-17A
IL-17F
IL-22
IL-23
Th1
7
Th2
Lymph
node
TNF-α
IL-6
IL-1β
Th17
Macrophage
DC=dendritic cell; PSORS1=psoriasis susceptibiity 1; IL=interleukin; TNF=tumor necrosis factor. Gaspari AA, Tyring S.
Dermatol Ther. 2015;28:179-193; Nestle FO et al. N Eng J Med. 2009;361:496-509.
Assessment and Classification of
Psoriatic Disease Severity
Classifications of
severity
Assessments
Percentage of BSA involved
Lesion characteristics including
erythema, scaling, induration
Location/distribution of lesions
(eg, hands, feet, face, genitals)
Impact on psychological factors
and quality of life
BSA
Psoriasis Area and Severity Index
(PASI)
Dermatology Life Quality Index
(DLQI)
Mild disease: <3% BSA
Moderate disease: 3%–10% BSA
Severe disease: >10% BSA
Mild disease:
BSA ≤ 10 and PASI ≤ 10
and DLQI ≤ 10
Moderate-to-severe disease:
(BSA >10 or PASI >10)
and DLQI >10
Armstrong AW et al. JAMA Dermatol. 2013;149:1180-1185; Menter A et al. J Am Acad Dermatol. 2008;58:826-250; Spuls
PI et al. J Invest Dermatol. 2010;130:933-943; Both H et al. J Invest Dermatol. 2007;127:2726-2739; Mrowietz U et al. Arch
Dermatol Res. 2011;303:1-10.
Comorbid Conditions Associated with
Psoriasis
 Cardiovascular disease
 Metabolic syndrome and its individual
components (ie, hypertension, obesity, impaired
glucose regulation, and low HDL levels)
 Malignancies including lymphoma, melanoma,
and nonmelanoma skin cancer
 Autoimmune diseases (eg, inflammatory bowel
disease, multiple sclerosis)
 Psychiatric conditions including anxiety and
depression
HDL=high-density lipoprotein.
Menter A et al. J Am Acad Dermatol. 2008;58:826-250.
PATIENT CASE STUDIES
Assessment and Plan
Case #1: Assessment and Plan
 Preliminary assessment
– This patient’s presentation is consistent with
moderately severe plaque psoriasis
– The history suggests initial scalp disease with recent
and worsening skin involvement
– Patient is motivated to treat and agrees to be
adherent with topical therapy
 Plan
– Apply topical calcipotriene and betamethasone
dipropionate (solutions to scalp and ointments to the
body) once daily to affected areas; avoid applying to
face or around eyes
– Follow up in 4 weeks
Case #2: Assessment and Plan
 Preliminary assessment
– This patient is presenting with severe
inadequately treated chronic plaque psoriasis for
many years, complicated by comorbid obesity,
hypertension, and dyslipidemia
 Plan
– Follow up in 2 weeks to review results of lab tests
and to discuss treatment options
Psoriasis Treatment Modalities
Topical
Systemic
Corticosteroids
Traditional agents
Vitamin D analogs +/Biologics
Retinoids
Small molecules
Calcineurin inhibitors
Anthralin
Coal tar +/+/-
Photo
UVB
UVA
PUVA
UVB=ultraviolet B; UVA=ultraviolet A; PUVA=psoralen plus ultraviolet A.
Menter A et al. J Am Acad Dermatol. 2011;65:137-174.
Severity of Disease Guides Selection
Among Treatment Modalities
Plaque
psoriasis
diagnosed
Yes
Signs/symptoms of
psoriatic arthritis?
No
Systemic
pharmacotherapy
+/-
Phototherapy
Severity of disease?
Mild
Moderate to severe
No
Topical agents
+/-
Phototherapy
Effective?
Yes
Continue current
therapy
Menter A et al. J Am Acad Dermatol. 2008;58:826-250; Menter A et al. J Am Acad Dermatol. 2009;60:643-659; Menter A
et al. J Am Acad Dermatol. 2010;62:114-135.
Interactive Question
How would you rate your knowledge of the
mechanisms of action of currently available
systemic therapies for psoriasis?
A. Very low
B. Fair, but I need to learn more
C. Sufficient, but I could learn more
D. I think I know all I need to know
SYSTEMIC PHARMACOTHERAPIES
FOR PSORIASIS
Traditional Systemic Treatment
Options
Agent
Description/mechanism
Acitretin
Vitamin A derivative (retinoid); has immunomodulatory
and anti-inflammatory activity and modulates epidermal
proliferation and differentiation
Cyclosporine
Calcineurin inhibitor; blocks inflammatory cytokine
production and T-cell activation
Methotrexate
Competitive inhibitor of dihydrofolate reductase;
interferes with nucleic acid synthesis, thereby inhibiting
lymphoid proliferation
Menter A et al. J Am Acad Dermatol. 2009;61:451-485.
Therapeutic Targets of Current
Biologics and Small Molecules
TNF-α
IL-12/IL-23
IL-17A
PDE-4
Adalimumab
Certolizumab
pegol*
Etanercept
Ustekinumab
Ixekizumab
Secukinumab
Apremilast
Golimumab*
Infliximab
*Approved by FDA for use in psoriatic arthritis; not approved for use in plaque psoriasis. All other agents listed are approved by FDA for use in both plaque
psoriasis and psoriatic arthritis, except for ixekizumab, which is currently FDA-approved for use in plaque psoriasis only. PDE-4=phosphodiesterase 4. Menter
A et al. J Am Acad Dermatol. 2008;58:826-250; Cimzia [package insert]. Smyrna, GA: UCB, Inc., 2015; Simponi [package insert]. Horsham, PA: Janssen
Biotech, Inc.; 2016; Stelara [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2014; Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2016;
Cosentyx [package insert]. East Hanover, NJ: Novartis Pharmaceutical Corp; 2016; Otezla [package insert]. Summit, NJ: Celgene Corp; 2015.
TNF Inhibition in Psoriasis
TNF-α
• Pleotropic,
proinflammatory
cytokine
TNF
inhibitors
• Released from
keratinocytes, T cells,
macrophages, mast
cells, dermal
dendritic cells
• Leads to recruitment,
migration and
activation of T cells
• Causes keratinocyte
hyperproliferation,
vascular changes,
inflammation and
subsequent tissue
damage
Gaspari AA, Tyring S. Dermatol Ther. 2015;28:179-193; Nestle FO et al. N Eng J Med. 2009;361:496-509; Narahari S et al.
The Dermatologist. 2012;20:38-43.
IL-12/IL-23 Inhibition in Psoriasis
IL-12
• Heterodimeric
pleiotropic cytokine (p40
and p35 subunits)
• Produced by dendritic
cells, macrophages, and
B cells
• Multiple effects on T
cells and natural killer
cells
Ustekinumab*
IL-23
• Heterodimeric
pleiotropic cytokine (p40
and p19 subunits)
• Released by dendritic
cells
• Essential for Th17
lymphocyte
differentiation
*Ustekinumab is a human monoclonal antibody directed against the p40 subunit of IL-12 and IL-23. Gaspari AA, Tyring S. Dermatol Ther.
2015;28:179-193; Nestle FO et al. N Eng J Med. 2009;361:496-509; Kofoed K et al. Acta Derm Venereol. 2015;95:133-139; Elyoussfi S et al.
Rheumatol Int. 2016;36:603-612.
IL-17A Inhibition in Psoriasis
IL-17A
• One of 6 members of
the IL-17 family
• Involved in psoriasis
immunopathogenesis
at the keratinocyte
level
• Produced by Th17 and
Tc17 cells
• Proinflammatory
effects on
keratinocytes,
macrophages, and
endothelial cells
Ixekizumab*
Secukinumab†
• Induces expression of
neutrophil, T-cell, and
dendritic-cell
chemokines
*Ixekizumab is a humanized IgG4 monoclonal antibody against IL-17A; †Secukinumab is a fully human IgG1ĸ monoclonal antibody against IL17A. Gaspari AA, Tyring S. Dermatol Ther. 2015;28:179-193; Nestle FO et al. N Eng J Med. 2009;361:496-509.
PDE-4 Inhibition in Psoriasis
PDE-4
Cytoplasm
Apremilast
cAMP
AMP
 cAMP
 Proinflammatory
cytokines*
 Influx of
inflammatory cells,
including neutrophils
 Antiinflammatory
cytokines
(eg, IL-10)
*Proinflammatory cytokines affected by PDE-4 inhibition are indicated with red text. Gaspari AA, Tyring S. Dermatol Ther. 2015;28:179-193;
Nestle FO et al. N Eng J Med. 2009;361:496-509; Kofoed K et al. Acta Derm Venereol. 2015;95:133-139; Schafer PH et al. Br J Pharmacol.
2010; 159:842-855.
Systemic Biologics and Small Molecules in
Late-Stage Development for Plaque Psoriasis
Agent
Description/Mechanism
Status
Brodalumab
Fully human IgG2 monoclonal antibody targeting the IL-17
receptor subunit shared by IL-17A, IL-17F, and IL-17A/F
heterodimer ligands
Phase 3 completed; submitted to FDA
January 25, 2016
Guselkumab
Fully human IgG1λ monoclonal antibody targeting the
p19 subunit of IL-23
Phase 3 ongoing
Tildrakizumab
Humanized IgG1κ monoclonal antibody targeting the p19
subunit of IL-23
Phase 3 ongoing
Tofacitinib
Small molecule inhibitor of Janus kinase (JAK)1 and JAK3
signaling pathway
Phase 3 completed; submitted to FDA;
FDA provided recommendations in a
response October 14, 2015
BI 655066
High-affinity monoclonal antibody targeting the p19
subunit of IL-23
Phase 3 recruiting
CF101
Small molecule A3 adenosine receptor antagonist that
downregulates the nuclear factor-ĸB signaling pathway
Phase 2/3 completed as of July 1, 2016;
FDA submission status not reported
Campa M et al. Dermatol Ther. 2016;6:1-12; Kofoed K et al. Acta Derm Venereol. 2015;95:133-139; Valeant announces FDA acceptance of BLA submission
for brodalumab in moderate-to-severe plaque psoriasis [news release]. Laval, Quebec. Valeant Pharmaceuticals International, Inc. January 25, 2016.
http://ir.valeant.com/news-releases/2016/01-25-2016-130634702. Accessed July 1, 2016; Pfizer receives complete response letter from FDA for oral
XELJANZ (tofacitinib citrate) supplemental new drug application for moderate to severe chronic plaque psoriasis [news release]. New York, NY. Pfizer Inc.
October 14, 2015. http://www.pfizer.com/news/press-release/press-release-detail/pfizer_receives_complete_response_letter_from_fda_for_
oral_xeljanz_tofacitinib_citrate_supplemental_new_drug_application_for_moderate_to_severe_chronic_plaque_psoriasis. Accessed July 1, 2016;
Clincaltrials.gov; accessed July 1, 2016.
PATIENT CASE STUDIES
Follow-up Visit #1
Case #1: Follow-up Visit
4 Weeks Later
 Since her last visit, the patient has been using her
topical treatments as prescribed
 After some initial improvement, her rash has
become more extensive and now involves her
back and abdomen
 She is becoming increasingly concerned about
the appearance of her skin because she is
planning a tropical vacation to celebrate her first
wedding anniversary in a couple of months
 On exam, the plaques are somewhat thinner and
the scales have improved
 The scalp is unchanged and new plaques have
developed on the patient’s back
Interactive Question
From the options provided below, please select an
appropriate systemic treatment for this patient (choose
only one):
A. Retinoid (acitretin)
B. Immunosuppressant (cyclosporine or methotrexate)
C. TNF inhibitor (adalimumab, etanercept, or infliximab)
D. IL-12/IL-23 inhibitor (ustekinumab)
E. IL-17A inhibitor (ixekizumab or secukinumab)
F. PDE-4 inhibitor (apremilast)
G. Other (including combination therapy)
_________________
Case #2: Follow-up Visit
2 Weeks Later
 The patient returns to discuss his treatment options
 There have been no interval changes
 The results of the laboratory tests that were
ordered at the last visit are as follows:
–
–
–
–
–
–
CBC normal
BUN/creatinine ratio slightly elevated
ALT: 72
AST normal
Hepatitis B and C serologies normal
Interferon-gamma release assay positive
ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea nitrogen; CBC=complete blood count.
Interactive Question
From the options provided below, please select an
appropriate systemic treatment for this patient (choose
only one):
A. Retinoid (acitretin)
B. Immunosuppressant (cyclosporine or methotrexate)
C. TNF inhibitor (adalimumab, etanercept, or infliximab)
D. IL-12/IL-23 inhibitor (ustekinumab)
E. IL-17A inhibitor (ixekizumab or secukinumab)
F. PDE-4 inhibitor (apremilast)
G. Other (including combination therapy)
_________________
Patient-Related Considerations For
Individualized Treatment of Psoriasis




Disease severity and impact on quality of life
Lifestyle and personal preferences
Comorbid conditions
Risk factors for adverse effects of therapy
(eg, active or latent infection)
 Response to previous therapy
Menter A et al. J Am Acad Dermatol. 2008;58:826-850.
Considerations For Individualized Treatment of
Psoriasis with Traditional Systemic Therapies
Agent
Administration
(route;
frequency)
Comments
Acitretin
Oral; once
daily
• Major side effects: mucocutaneous changes; hypertriglyceridemia,
elevated liver enzymes
• Enhanced efficacy and reduced dose possible when combined with
UVB or PUVA therapy
• FDA pregnancy category X
Cyclosporine
Oral; twice
daily
•
•
•
•
•
•
Major toxicities: nephrotoxicity, hypertension
Limited duration of continuous treatment (1 year in US)
Increased risk of skin cancer if history of PUVA
Reversible changes in serum lipids may occur
Caution with major infection and poorly controlled diabetes
FDA pregnancy category C
•
•
•
•
Major toxicities: myelosuppression, hepatotoxicity, pulmonary fibrosis
Parenteral administration may minimize GI side effects
Folate supplementation may be recommended
FDA pregnancy category X
Methotrexate Oral, SC, or IM;
once weekly
GI=gastrointestinal; IM=intramuscular. Menter A et al. J Am Acad Dermatol. 2009;61:451-485.
Considerations For Individualized Treatment of
Psoriasis with Biologics and Small Molecules
Class
Agent(s)
Administration
(route; frequency)
TNF
inhibitors
Adalimumab
Certolizumab
pegol*
Etanercept
Golimumab*
Infliximab
SC or IV, depending on
agent; variable loading
doses followed by
maintenance doses
every week to every 8
weeks
•
•
•
•
•
Ustekinumab
SC; every 4 weeks x 2
doses, then every 12
weeks
• Most common adverse reactions: nasopharyngitis, URTI, headache, and
fatigue
• Greater effectiveness compared with TNF inhibitors in recent real-world study
• Pregnancy risk category B
Ixekizumab
SC; every 2 weeks x 7
doses, then every 4
weeks
• Most common adverse reactions: injection-site reactions, URTI, nausea, and
tinea infections
• Pregnancy risk category not yet assigned
Secukinumab
SC; weekly x 5 doses,
then every 4 weeks
• Most common adverse reactions: nasopharyngitis, diarrhea, and URTI
• Greater efficacy compared with ustekinumab in recent randomized trial
• Pregnancy risk category B
Apremilast
Oral; twice daily
• Most common adverse reactions: diarrhea, nausea, URTI, and headache
• Associated with new or worsening depression and weight loss
• Pregnancy risk category C
IL-12/IL-23
inhibitor
IL-17A
inhibitors
PDE-4
inhibitor
Comments
Efficacy and safety profiles well established
Associated with increased risk of infection; URTI most common
Associated with demyelinating diseases
Caution recommended in patients with congestive heart failure
Pregnancy risk category B
*Approved by FDA for use in psoriatic arthritis; not approved for use in plaque psoriasis. All other agents listed are approved by FDA for use in both plaque psoriasis and psoriatic arthritis,
except for ixekizumab, which is currently FDA-approved for use in plaque psoriasis only. IV=intravenous; URTI: upper respiratory infection. Menter A et al. J Am Acad Dermatol. 2008;58:826250; Strober BE et al. J Am Acad Dermatol. 2016 Feb 4 [Epub ahead of print]. Thaci E et al. J Am Acad Dermatol. 2015;400-409; Cimzia [package insert]. Smyrna, GA: UCB, Inc., 2015;
Simponi [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2016; Stelara [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2014; Taltz [package insert]. Indianapolis, IN: Eli Lilly and
Company; 2016; Cosentyx [package insert]. East Hanover, NJ: Novartis Pharmaceutical Corp; 2016; Otezla [package insert]. Summit, NJ: Celgene Corp; 2015.
Case #1: Assessment and Treatment
Considerations
 Worsening plaque psoriasis despite combination topical therapy
 Psychological distress/impaired quality of life
– Up to 79% of patients report psoriasis has an overall negative impact on
their lives
 Scalp involvement
– Scalp is involved in up to 80% of patients with psoriasis
– Topical therapy is most commonly used and is often effective
– Systemic therapies are used for recalcitrant cases
• The scalp is considered equivalent to the rest of the integument; modifications in the
therapeutic regimen are generally not necessary for scalp-specific treatment
 Pregnancy potential
– Discuss contraception
– Consider pregnancy risk category
 Consider referral to dermatologist
Krueger G et al. Arch Dermatol. 2001;137:280-284; Guenther L. Skin Therapy Lett. 2015;20:5-7; Nguyen CM et al. J Drugs Dermatol.
2016;15:272-276; Strober BE et al. Dermatol Ther. 2012;2:1; Menter A et al. J Am Acad Dermatol. 2008;58:826-850; Stelara [package
insert]. Horsham, PA: Janssen Biotech, Inc.; 2014; Cosentyx [package insert]. East Hanover, NJ: Novartis Pharmaceutical Corp; 2016; Otezla
[package insert]. Summit, NJ: Celgene Corp; 2015; Weigle N, McBane S. Am Fam Physician. 2013;87:626-633.
Case #2: Assessment and Treatment
Considerations
 Chronic severe plaque psoriasis with nail involvement
– Nail disease (psoriatic onychodystrophy) affects 35%50% of patients
with plaque psoriasis and up to 90% of patients with psoriatic arthritis
– All currently available targeted biologics and small molecules have
been shown to improve psoriatic onychodystrophy in clinical trials
 Multiple comorbidities and risk factors
– Cigarette smoking
– Metabolic syndrome (obesity, high triglycerides, hypertension)
– Elevated liver enzyme
• Non-alcoholic fatty liver disease has been associated with psoriasis,
independently of other risk factors including metabolic syndrome
– Latent TB
• All available biologics are associated with an increased risk of TB infection or
reactivation
TB=tuberculosis. Menter A et al. J Am Acad Dermatol. 2008;58:826-850; Strober BA et al. Dermatol Ther. 2012;2:1; Rich P et al. Br J
Dermatol. 2014;170:398-407; Paul C et al. J Eur Acad Dermatol Venereol. 2014;28:1670-1675. Rich P et al. J Am Acad Dermatol. 2016;74:134142; Langley RG et al. J Eur Acad Dermatol Venereol. 2015;29:1763-1770; Mantovani A et al. Int J Mol Sci. 2016;17(2); Sivamani RK et al.
Clinic Rev Allerg Immunol. 2013;44:121-140.
Recommendations for Screening and Management
of Latent and Active TB Infection in Patients
Requiring Biologic Therapy
BCG-unvaccinated
TST and IGRA
TST negative
and
IGRA negative
IGRA
TST and/or
IGRA
positive
Annual screening with
TST and/or IGRA if at high
risk for TB exposure
IGRA
positive
Preventive therapy for
LBTI
+
TB education
IGRA
negative
Annual screening
with IGRA if at high
risk for TB exposure
CXR
No active TB
BCG-vaccinated
Active
TB
Active TB
management
Start or resume biologic
agent after 1 month of LBTI
therapy or after completion
of treatment for active TB
CXR=chest x-ray; IGRA=interferon gamma release assay; BCG=Bacillus Calmette-Guérin; TST= tuberculin skin test.
Cantini F et al. Autoimmun Rev. 2015;14:503-509.
Psoriasis and Cardiovascular Disease
Psoriasis is associated with an increased risk of major cardiovascular events
Cardiovascular Outcome
Myocardial
infarction
Stroke
Mortality
Mild, RR (95% CI)
1.29 (1.02, 1.63)
1.12 (1.08, 1.16)
NS
Severe, RR (95% CI)
1.70 (1.32, 2.18)
1.56 (1.32, 1.84)
1.39 (1.11, 1.74)
Psoriasis by severity
 Estimated excess of 11,500 (95% CI, 1169 to 24,407) major adverse
cardiovascular events in the United States each year
 Chronic and uncontrolled inflammation from psoriatic disease may be related
to endothelial dysfunction that increases cardiovascular risk
 Systemic therapies for psoriasis (eg, methotrexate and TNF inhibitors) have
been associated with reductions in cardiovascular events
RR=relative risk; CI-confidence interval; NS=not significant
Armstrong EJ et al. J Am Heart Assoc. 2013;2:e000062. Strober BE et al. Dermatol Ther. 2012;2:1. Wu JJ et al. Arch
Dermatol. 2012;148:1244-1250; Ahlehoff O et al. J Eur Acad Dermatol Venereol. 2015;29:1128-1134; Hugh J et al. J Am
Acad Dermatol. 2014;70:168-177.
Interactive Question
Which of the following tools/measures do you use
to assess response to systemic therapy in your
patients with psoriasis? (Please select all that apply)
A. BSA only
B. Psoriasis Area and Severity Index (PASI)
C. Dermatology Life Quality Index (DLQI)
D. Physician Global Assessment (PGA)
E. Patient-reported satisfaction
F. Other _________________
Treatment Goals for
Moderate-to-Severe Psoriasis
 Ultimate goal is to achieve complete skin clearance
 Assess response to systemic therapy after induction
phase (16–24 weeks) and at regular intervals during
maintenance phase
Change in PASI  75
Change in PASI < 75 and  50
DLQI ≤ 5
Continue current
therapy
Mrowietz U et al. Arch Dermatol Res. 2011;303:1-10.
Change in PASI < 50
DLQI > 5
Modify treatment regimen
• Adjust dose
• Add another therapy
(combination therapy)
• Transition to another
therapy
Strategies to Optimize Systemic
Therapy: Combination Therapy
Potential Indications for Systemic
Combination Therapy
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Inadequate efficacy of monotherapies
(potential for additive or synergistic efficacy)
Tolerability concerns (dose of individual
agents may be reduced)
Complications or comorbidities (eg, psoriatic
arthritis, cardiovascular disease)
Bridging treatment in patients switching
between systemic therapies
Potential for intermittent or continuous use
during long-term treatment for relapsing
disease
Tailoring therapy to meet individual patients’
needs
Evidence and Recommendations for
Combination Therapy


Experience with combination therapy is
greater for psoriatic and rheumatoid arthritis
than psoriasis
Methotrexate or acitretin can be added to a
biologic monotherapy
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A TNF inhibitor + methotrexate (5–15 mg/week)
is safe and increases long-term efficacy
Data on combining traditional systemic
therapies with non-TNF biologics are limited
Combined use of cyclosporine and a biologic
raises safety concerns
Optimal safety monitoring for combination
therapy has not been determined
Monitoring interval should be defined by the
agent with the most stringent monitoring
criteria
Cather JC, Crowley JJ. Am J Clin Dermatol. 2014;15:467-478; Mrowietz U et al. J Eur Acad Dermatol Venereol.
2014;28:438-453.
PATIENT CASE STUDIES
Follow-up Visit #2
Case #1: Follow-up Visit
3 Months Later
 The patient returns after 3 months of
treatment
 Her skin is much improved
 However, she has recently noticed some
painful swelling of her toes
Dactylitis
Photo courtesy of Abrar Qureshi, MD.
Case #1: Assessment and
Considerations
 Plaque psoriasis well controlled on current
therapy
 New joint manifestations
– Dactylitis (‘‘sausage digit’’) is a common characteristic
of psoriatic arthritis
• Combination of enthesitis of the tendons and ligaments and
synovitis involving entire digit
• Associated with radiologic findings
 May require modification of treatment regimen
 Consider referral to specialist
Gottlieb A et al. J Am Acad Dermatol. 2008;58:851-864.
Case #2: Follow-up Visit
18 Months Later
 The patient had been doing well on the
prescribed therapy
 However, approximately 18 months later, he
experiences a flare
Case #2: Assessment and
Considerations
 Loss of response/management of chronic
disease
 Development or worsening of psoriasis may
occur during anti-TNF treatment
 Switching to a therapy with a different
mechanism of action may be beneficial
Collamer AN et al. Arthritis Rheum. 2008;59:996-1001; Fagerli KM et al. Ann Rheum Dis. 2013;72:1840-1844.
Summary
 Psoriasis is a multisystem inflammatory disorder
 While local therapy is a mainstay of treatment for
psoriasis, systemic therapy may be required to
achieve treatment goals
 Improved understanding of the dysregulated
immune response characteristic of psoriasis has
allowed for development of a number of systemic
therapies that target specific mediators involved
in the immunopathogenesis of the disease
 Optimal treatment depends on accurate
assessment of disease severity and consideration
of patient-specific factors that may affect
treatment decisions