Applying Science to Improve the Individualized Treatment of Patients with Psoriasis - PowerPoint Presentation

Slide1

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

Slide2

Patient Case Studies

History and Clinical Presentation

Slide3

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

Slide4

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

Slide5

Scalp Psoriasis

Photos courtesy of

Abrar

Qureshi, MD, MPH.

Slide6

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

ointmentAllergies: penicillin

SC=subcutaneous

Slide7

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

Slide8

Severe Plaque Psoriasis

Photos courtesy of

Abrar

Qureshi, MD, MPH.

Slide9

Excoriated Plaque Psoriasis

Photos courtesy of

Abrar

Qureshi, MD, MPH.

Slide10

Onycholysis

Photo courtesy of

Abrar

Qureshi, MD, MPH.

Slide11

Interactive Question

Please rate your confidence in distinguishing plaque psoriasis from other types of psoriasis.

Not at all confident

Somewhat confident

Very confident

Completely confident

Slide12

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.

Slide13

Guttate Psoriasis

Photo courtesy of

Abrar

Qureshi, MD, MPH.

Slide14

Photos courtesy of

Abrar

Qureshi, MD, MPH.

Inverse Psoriasis

Slide15

Erythrodermic Psoriasis

Photos courtesy of

Abrar

Qureshi, MD, MPH.

Slide16

Pustular Psoriasis

Photo courtesy of

Abrar

Qureshi, MD, MPH.

Slide17

Immunopathogenesis of Plaque Psoriasis

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.

Disease initiation

Environmental trigger

TNF-

α

IL-6

IL-1

β

TNF-

α

IL-6

IL-1

β

Macrophage

Dermal DC

Lymph node

Psoriatic plaque

Stressed keratinocytes

Keratinocyte

activation and proliferation

Th1

Th17

Tc17

Th17

Tc1

IL-17A

IL-17F

IL-22

IL-23

TNF-

α

IL-2

IFN-

γ

Genetic predisposition

Stress

Microorganisms

Drugs

Trauma

Smoking

Disease maintenance

PSORS1

IL-23R

IL-12B

Naïve T cell

Angiogenesis

Neutrophils

Activation

Th17

Th2

IL-17A

IL-17F

IL-22

IL-12

Slide18

Assessment and Classification of Psoriatic Disease Severity

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.

Psoriasis Area and Severity Index (PASI)

Assessments

Classifications of severity

Percentage of BSA involved

Location/distribution of lesions (

eg

, hands, feet, face, genitals)

Impact on psychological factors and quality of life

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

Lesion characteristics including erythema, scaling, induration

Dermatology Life Quality Index (DLQI)

BSA

Slide19

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

.

Slide20

Patient Case Studies

Assessment and Plan

Slide21

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

Slide22

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

Slide23

Psoriasis Treatment Modalities

UVB=ultraviolet B; UVA=ultraviolet A; PUVA=psoralen plus ultraviolet A.

Menter A et al.

J Am Acad Dermatol

. 2011;65:137-174.

Corticosteroids

Vitamin D analogs

Retinoids

Calcineurin

inhibitors

Anthralin

Coal tar

UVB

UVA

PUVA

Traditional agents

Biologics

Small molecules

+/-

+/-

+/-

Slide24

Severity of Disease Guides Selection Among Treatment Modalities

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.

Yes

No

Topical agents

+/-

Yes

No

Plaque

psoriasis diagnosed

Signs/symptoms of psoriatic arthritis?

Severity of disease?

Moderate to severe

Mild

Effective?

Systemic pharmacotherapy

Phototherapy

Continue current therapy

+/-

Phototherapy

Slide25

Interactive Question

How would you rate your knowledge of the mechanisms of action of currently available systemic therapies for psoriasis?

Very low

Fair, but I need to learn more

Sufficient, but I could learn more

I think I know all I need to know

Slide26

Systemic Pharmacotherapies for Psoriasis

Slide27

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.

Slide28

Therapeutic Targets of Current Biologics and Small Molecules

*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.

Slide29

TNF Inhibition in Psoriasis

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.

TNF-

α

Pleotropic,

proinflammatory

cytokine

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

TNF inhibitors

Slide30

IL-12/IL-23 Inhibition in Psoriasis

*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.

Ustekinumab

*

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

IL-23

Heterodimeric pleiotropic cytokine (p40 and p19 subunits)

Released by dendritic cells

Essential for Th17 lymphocyte differentiation

Slide31

IL-17A Inhibition in Psoriasis

*Ixekizumab is a humanized IgG4 monoclonal antibody against IL-17A; †Secukinumab is a fully human IgG1ĸ monoclonal antibody against IL-17A. Gaspari AA, Tyring S.

Dermatol Ther

. 2015;28:179-193; Nestle FO et al.

N Eng J Med

. 2009;361:496-509.

Ixekizumab

*

Secukinumab

†

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

Induces expression of neutrophil, T-cell, and dendritic-cell chemokines

Slide32

PDE-4 Inhibition in Psoriasis

*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.



cAMP



Proinflammatory

cytokines*

 Influx of inflammatory cells, including neutrophils

Antiinflammatory

cytokines

(

eg

, IL-10)

 

cAMP

AMP

PDE-4

Cytoplasm

Apremilast

Slide33

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 IgG1

λ

monoclonal antibody targeting the p19 subunit of IL-23

Phase

3 ongoing

Tildrakizumab

Humanized

IgG1

κ

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 A

3

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.

Slide34

Patient Case Studies

Follow-up Visit #1

Slide35

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

Slide36

Interactive Question

From the options provided below, please select an appropriate systemic treatment for this patient (choose only one):

Retinoid (

acitretin

)

Immunosuppressant (cyclosporine or methotrexate)

TNF inhibitor (adalimumab,

etanercept

, or infliximab)

IL-12/IL-23 inhibitor (

ustekinumab

)IL-17A inhibitor (ixekizumab or secukinumab

)

PDE-4 inhibitor (

apremilast

)

Other (including combination therapy) _________________

Slide37

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 positiveALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea nitrogen; CBC=complete blood count.

Slide38

Interactive Question

From the options provided below, please select an appropriate systemic treatment for this patient (choose only one):

Retinoid (

acitretin

)

Immunosuppressant (cyclosporine or methotrexate)

TNF inhibitor (adalimumab,

etanercept

, or infliximab)

IL-12/IL-23 inhibitor (

ustekinumab

)IL-17A inhibitor (ixekizumab or secukinumab

)

PDE-4 inhibitor (

apremilast

)

Other (including combination therapy) _________________

Slide39

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

.

Slide40

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

Methotrexate

Oral, SC, or IM;

once weekly

Major toxicities: myelosuppression, hepatotoxicity, pulmonary fibrosis

Parenteral

administration may minimize GI side effects

Folate supplementation may be recommended

FDA pregnancy category X

GI=gastrointestinal; IM=intramuscular. Menter A et al.

J Am Acad Dermatol

. 2009;61:451-485.

Slide41

Considerations For Individualized Treatment of Psoriasis with Biologics and Small Molecules

Class

Agent(s)

Administration

(route

;

frequency)

Comments

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

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

IL-12/IL-23 inhibitor

U

stekinumab

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

IL-17A inhibitors

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

PDE-4 inhibitor

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

*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;58:826-250; 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.

Slide42

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 categoryConsider 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.

Slide43

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 enzymeNon-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;74:134-142; 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.

Slide44

Recommendations for Screening and Management of Latent and Active TB Infection in Patients Requiring Biologic Therapy

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

.

BCG-unvaccinated

BCG-vaccinated

TST and IGRA

IGRA

Annual screening with TST and/or IGRA if at high risk for TB exposure

CXR

TST negative and

IGRA negative

Annual screening with IGRA if at high risk for TB exposure

Preventive therapy for LBTI

+

TB education

Active TB management

Start or resume biologic agent after 1 month of LBTI therapy or after completion of treatment for active TB

TST and/or IGRA

positive

No active TB

Active TB

IGRA positive

IGRA negative

Slide45

Psoriasis and Cardiovascular Disease

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.

Psoriasis by severity

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 is associated with an increased risk of major cardiovascular events

Slide46

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)

BSA only

Psoriasis Area and Severity Index (PASI)

Dermatology Life Quality Index (DLQI)

Physician Global Assessment (PGA)

Patient-reported satisfaction

Other _________________

Slide47

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

Mrowietz

U et al.

Arch Dermatol Res

. 2011;303:1-10.

Change in PASI

 75

DLQI > 5

Continue current therapy

Change in PASI < 75 and

 50

Change in PASI

< 50

DLQI ≤ 5

Modify treatment regimen

Adjust dose

Add another therapy (combination therapy)

Transition to another therapy

Slide48

Strategies to Optimize Systemic Therapy: Combination Therapy

Potential Indications for Systemic Combination Therapy

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

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.

Slide49

Patient Case Studies

Follow-up Visit #2

Slide50

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

Slide51

Dactylitis

Photo courtesy of

Abrar

Qureshi, MD.

Slide52

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

.

Slide53

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

   

Slide54

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.

Slide55

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