2020 Symposia Series 1 Managing the Spectrum of Psoriatic Disease - - PowerPoint PPT Presentation

2020 Symposia Series 1

Managing the Spectrum of Psoriatic Disease in Primary Care

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• Implement screening for CV disease, metabolic syndrome, and psoriatic

arthritis (PsA) in patients with psoriasis

• Identify side effects of drug classes used in the treatment of psoriatic

disease

• Apply long-term management strategies for patients with psoriasis in

coordination with a specialist

Learning Objectives

CV = cardiovascular.

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Clinical Burden of Psoriatic Disease in the United States

• Chronic, multisystem inflammatory disorder
• Affects >8 million individuals

– 10% to 30% develop PsA

• Symptoms usually develop by 15 to 25 years of age but can occur at any time
• ~25% of patients have moderate to severe disease

– Extensive involvement on hands, feet, scalp, or genitals

• Negatively affects QoL, productivity, daily function
• Risk factors include smoking, obesity, stress, genetics

QoL = quality of life. Mayo Clinic. www.mayoclinic.org/diseases-conditions/psoriasis/symptoms-causes/syc-20355840?p=1. Accessed April 21, 2020; Menter A, et al. J Am Acad Dermatol. 2019;80:1029-1072; National Psoriasis Foundation. www.psoriasis.org/content/statistics. Accessed April 21, 2020.

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Plaque Psoriasis: Disease Characteristics

Differential Diagnosis

• Eczema
• Combined

eczema/psoriasis

• Mycosis fungoides
• Plaque-stage cutaneous

T-cell lymphoma

• Tinea corporis
• Bowen disease
• Subacute cutaneous lupus

erythematosus

• 80% to 90% of patients with psoriasis have

plaque psoriasis ‒ Irregularly shaped, dry, thin plaques with silvery-white scaling ‒ Tend to appear symmetrically ‒ Often found on scalp, trunk, buttocks,

• r limbs
• Epidermal hyperproliferation

‒ Clinically evident as raised, inflamed, scaly red skin lesions; cracking, itching ‒ Typically affects elbows, knees, scalp, but can appear anywhere

Crow JM. Nature. 2012;492:S50-S51; Menter A, et al. J Am Acad Dermatol. 2008;58:826-850.

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Plaque Psoriasis: Clinical Photos

Photos courtesy of Kristina Callis Duffin, MD.

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Plaque Psoriasis: Clinical Photos (cont’d)

Photos courtesy of Veronica Richardson, MSN, ANP-BC, DCNP.

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Guttate Psoriasis

Photo used with permission from Visual Dx (2005).

• Primarily affects young adults and children
• Usually triggered by a bacterial infection such as strep

throat

• Small, waterdrop-shaped, scaling lesions on trunk, arms,

legs, and scalp

• Lesions covered by a fine scale (not as thick as typical

plaques)

• Often misdiagnosed as a reaction to penicillin drugs just

given for strep infection

• Often resolves after strep infection resolves
• May portend future development of plaque psoriasis

Mayo Clinic. www.mayoclinic.org/diseases-conditions/psoriasis/symptoms-causes/syc-20355840?p=1. Accessed April 21, 2020.

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AMP = antimicrobial peptide; DC = dendritic cell; IFN = interferon; KC = keratinocyte. Arakawa A, et al. J Exp Med. 2015;212:2203-2212; Lande R, et al. Nat Commun. 2014;5:5621; Lowes MA, et al. Annu Rev Immunol. 2014;32:227-255.

Psoriatic Disease: Immunopathogenesis

Triggers

2 1 Chronic disease Early disease

KCs +RNA TLR7/9 Psoriasis

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Amplification feedback Chemokines AMPs T17 Th1, Tc1 Th22, Tc22 Neutrophils IL-17A IL-17F IL-21 TNF IFN-  TNF IL-22 TNF IL-23 IL-12 IFN- LL37 (keratinocyte-derived) ADAMTSL5 (melanocyte-derived) +DNA/RNA TLR7/8 IFN-/β IL-12 IL-23 Myeloid DCs T cells a β/ CD4/CD8

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TNF Inflammatory myeloid DCs Mature dermal DCs Psoriasis

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Physical and Mental Rankings of Psoriasis and Other Diseases

1 2 3 4 5 6 7 8 9 10 11 1 8 6 11 2 7 4 10 3 9 5 5 10 15 20 Healthy Dermatitis Cancer Depression Hypertension Arthritis Myocardial infarction Chronic lung disease Type 2 diabetes mellitus Psoriasis Heart failure Physical rank Mental rank

Best Functioning (1) to Worst Functioning (11)

Van Voorhees AS, et al. www.psoriasis.org/sites/default/files/npf_pocketguide_2018_0010.pdf. Accessed April 28, 2020.

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NPF Treatment Target for Psoriasis Is ≤1% of BSA During Maintenance

Armstrong AW, et al. J Am Acad Dermatol. 2017;76:290-298.

Therapeutic Benefit Time

Initiation Phase Maintenance Phase

Preferred assessment instrument in clinical practice BSA Acceptable response after treatment initiation Either BSA ≤3% or BSA improvement ≥75% from baseline at 3 months after treatment initiation Target response after treatment initiation BSA ≤1% at 3 months after treatment initiation Target response during maintenance therapy BSA ≤1% at every 6-month assessment interval during maintenance therapy

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Case Study: Lori, a 31-Year-Old Music Teacher With Scalp Psoriasis

• 6-year history of psoriasis, primarily on the scalp, for which

she has been applying an OTC anti-dandruff shampoo

• Family history of multiple sclerosis
• Mild depression treated with SSRI
• Currently taking an oral contraceptive
• New concerns

‒ Worsening itching and flaking of scalp behind her ears

• Strategically covers these areas with her hairstyle
• Visits a friend for haircuts; too embarrassed to go to

salon

SSRI = selective serotonin reuptake inhibitor.

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Calculating Extent of Psoriasis

Menter A, et al. J Am Acad Dermatol. 2019;80:1029-1072; Van Voorhees AS, et al. www.psoriasis.org/sites/default/files/npf_pocketguide_2018_0010.pdf. Accessed May 23, 2019.

• May also be considered severe if it:

– Involves the hands, feet, scalp, face,

• r genitals

– Causes intractable pruritus – Has significant impact on QoL

• Such an impact may justify use of

systemic therapy

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• Create a partnership based on trust to foster open dialogue about impact
• f psoriasis and treatment goals
• Treatment selection should reflect patient’s answers to questions such as:

‒ How does psoriasis affect your daily living, including function, sleep, socializing, productivity, intimacy? ‒ What are your symptoms (eg, pain, itching, burning, dry skin), and what are all the areas of your body affected? ‒ What has been your experience with previous treatments? ‒ What do you hope treatment will accomplish?

Assess the Patient’s Experience With Psoriatic Disease

Aldredge LM, Higham RC. J Dermatol Nurses Assoc. 2018;10:189-197; American Academy of Dermatology. www.aad.org/education/basic-derm- curriculum/suggested-order-of-modules/psoriasis. Accessed May 23, 2019; Van Voorhees AS, et al. www.psoriasis.org/sites/default/files/npf_pocketguide_2018_0010.pdf. Accessed April 28, 2020.

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Armstrong AW, et al. Dermatol Ther (Heidelb). 2017;7:97-109.

42% 3% 32% 22% Types of Treatment in Year Prior to September 2012

Topical Phototherapy Traditional oral systemic Biologic

Most Patients With Moderate to Severe Psoriasis Are Undertreated or Untreated

• Data from US National Health and

Wellness Survey and insurance claims, 2007 to 2012 − 1.7 million insured US patients with moderate to severe psoriasis

• 59% had not been treated in

past year

• Of those treated in past year,

50% were no longer being treated

17% of patients taking a biologic were also taking a traditional oral systemic

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Patients With Psoriatic Disease Are Dissatisfied With Their Current Treatment: MAPP Survey

AEs/abnormal laboratory tests Injection anxiety/fear 43.7 50 40 30 20 10

Patients (%)

16.4 7.0 6.3 3.9 17.8 25.6 13.3 10.0 13.3

Conventional Oral Therapy (n = 128) Biologic Therapy (n = 90)

Injection physical preparation Pain/discomfort Inconvenience AEs/abnormal laboratory tests Laboratory monitoring Lifestyle modification Lack/loss of effectiveness Inconvenience AE = adverse event; MAPP = Multinational Assessment of Psoriasis and Psoriatic Arthritis. Lebwohl MG, et al. Am J Clin Dermatol. 2016;17:87-97. 50 40 30 20 10

Patients (%)

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Case Study (cont’d): Lori’s Physical Exam and Lab Findings

A1C = glycated hemoglobin; FPG = fasting plasma glucose; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; TG = triglycerides.

• Physical examination

– Height: 5 ft 4 in – Weight: 179 lb – BMI: 30.7 kg/m2 – Waist circumference: 35.5 in – Blood pressure: 141/91 mm Hg

• Laboratory findings

– FPG: 121 mg/dL – A1C: 6.3% – Lipids:

• TC: 215 mg/dL
• LDL-C: 128 mg/dL
• HDL-C: 47 mg/dL
• TG: 260 mg/dL

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Psoriatic Disease: Comprehensive, Collaborative, Patient-Centered Care

Patient

Dermatologist Topicals, systemic therapy, biologics, refractory disease Primary Care Overall evaluation and management; comorbidities, vaccines, monitoring, education Behavioral Health Counseling Pharmacist Medication management Rheumatologist PsA, imaging

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TNF-α IFN- IFN-α IL-1 IL-6 IL-7

Psoriatic Disease and Atherosclerosis: Shared Inflammatory Mediators

CRP = C-reactive protein; IFN = interferon; MCP-1 = monocyte chemotactic protein-1. Adapted from: Gisondi P, Girolomoni G. Semin Thromb Hemostat. 2009;35:313-324. Hugh J, et al. J Am Acad Dermatol. 2014;70:168-177.

CRP Fibrinogen LDL-C TG Leptin Resistin MCP-1 Insulin resistance

From endothelial dysfunction to atherosclerosis Psoriatic disease inflammation Common link Increased activity

• f inflammatory

mediators Future research

Therapies for psoriasis associated with fewer CV events among patients with psoriasis; further long-term study needed Liver Skeletal muscle Adipose tissue Skin keratinocytes + Inflammatory cells

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Clinical significance

• Increased risk of MI, stroke, CV death, T2DM, CKD
• 5 years of life lost
• 10-year risk of major CV event attributable to

psoriasis is 6%

• 30x more likely to experience MACE (attributable

to psoriasis) than to develop a melanoma

• ACC/AHA now considers psoriasis to be an

ASCVD risk enhancer

Risk of Cardiometabolic Disease in Patients With Severe Psoriasis

CKD = chronic kidney disease; MACE = major adverse cardiovascular events; MI = myocardial infarction; NS = not significant; PsO = psoriasis; RR = relative risk. Gelfand JM et al. JAMA. 2006;296:1735-1741. Gelfand JM et al. J Invest Dermatol. 2009;129:2411-2418. Mehta NN et al. Eur Heart J. 2010;31:1000-1006. Mehta NN et al. Am J Med. 2011;124:775.e1-6. Azfar RS et al. Arch Dermatol. 2012;148:995-1000. Wan J et al. BMJ. 2013;347:f5961; Arnett DK, et al. Circulation. 2019;140:e596-e646. Slide courtesy of Joel M. Gelfand, MD

Outcome Mild PsO Severe PsO MI 1.05 1.5 Stroke 1.06 1.4 CV Death Not done 1.6 MACE Not done 1.5 Diabetes 1.11 1.5 CKD 0.99 (NS) 1.9

Mortality Curve

Percent of Subjects Age

20 1 2 3 4 40 60 80 100

Psoriasis Controls Adjusted RR

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Even Young Adults With Psoriatic Disease Are at Increased Risk for CV Events

*Hypertension, diabetes, history of myocardial infarction, hyperlipidemia, age, sex, smoking, BMI. Gelfand JM, et al. JAMA. 2006;296:1735-1741; National Psoriasis Foundation. www.psoriasis.org/about-psoriasis/living-well/reducing-your-risk-for-

• comorbidities. Accessed April 28, 2020; Osto E, et al. Atherosclerosis. 2012;221:113-117; Pearson TA, et al. Circulation. 2002;106:388-391.

Age (Years) Mild Psoriasis Severe Psoriasis 30 1.29 3.10 60 1.08 1.36

• Young adults with psoriasis have early microvascular impairments

– Coronary flow reserve lower in young patients with psoriasis than in controls – The lower the coronary flow reserve, the higher the PASI

• Risk factor screening recommended as early as age 20 years

Relative Risk of MI Among Patients With Psoriasis, Adjusted for Major CV Risk Factors*

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Joint AAD-NPF Guidelines 2019: Psoriasis and CV Disease Comorbidity Screening Recommendations

Recommendation SOR 2.1 CV risk assessment (screening for hypertension, diabetes, and hyperlipidemia) with national guidelines is recommended for all patients with psoriasis B 2.2 Clinicians should consider early and more frequent screening for hypertension, diabetes, and hyperlipidemia in psoriasis patients who are candidates for systemic or phototherapy or who have psoriasis involving >10% of BSA B

Recommendation key: A = based on consistent and good quality patient-oriented evidence; B = based on inconsistent or limited-quality patient-

• riented evidence; based on consensus, opinion, case studies, or disease-oriented evidence.

SOR = strength of recommendation Elmets CA, et al. J Am Acad Dermatol. 2019;80:1073-1113.

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Additional Comorbidities of Psoriatic Disease

• In addition to CVD, psoriatic

disease associated with increased risk of a wide array of

• ther comorbidities
• Most recent joint AAD/NPF

guidelines comprise 2 sections: – Treatment with biologics – Management of comorbidities

Depression/anxiety Autoimmune ophthalmic disease Obstructive sleep apnea COPD Hypertension Kidney disease Fatty liver disease IBD Diabetes/metabolic syndrome Osteoporosis

IBD = inflammatory bowel disease. Andersson AM, et al. Curr Derm Rep. 2017;6:129-136; Elmets CA, et al. J Am Acad Dermatol. 2019;80:1073-1113; Menter A, et al. J Am Acad Dermatol. 2019;80:1029-1072; Shah K, et al. J Am Acad Dermatol. 2017;77:287-292.

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Case Study: (cont’d): Next Steps in Lori’s Treatment

• You prescribe a nutritious diet, regular exercise, a statin, and HCTZ for

Lori’s cardiometabolic risk profile

• She believes that her depression is largely related to her worsening scalp

psoriasis and the discomfort and embarrassment it causes

• You recommend she continue her current SSRI and recommend cognitive

behavioral therapy with a psychologist

• You refer Lori to a dermatologist to discuss therapies to help improve her

psoriasis ‒ At her dermatology appointment, Lori says she would rather not take a systemic agent because the potential side effects are concerning to her

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Psoriasis Is Independently Associated With Risk of Depression

Max 20-Year Follow-up 36,299 without psoriasis developed depression ~250,000 matched individuals without psoriasis 247,755 patients with psoriasis >18 years old from Danish registries 220,721 with mild disease (topicals) 24,771 with moderate disease (systemic nonbiologics) 2,263 with severe disease (biologics) HR 1.19 (95% CI 1.17-1.20) HR 1.19 (95% CI 1.15-1.23) 45,641 patients with psoriasis developed depression HR 1.50 (95% CI 1.23-1.84)

CI = confidence interval; HR = hazard ratio. Egeberg A, et al. Br J Dermatol. 2019;180:116-121.

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• Solutions, foams, and sprays are preferred vehicles for corticosteroids to treat

scalp psoriasis

• Keratolytic agents (eg, coal tar, salicylic acid) available as shampoos, gel- or
• il-based compounded formulas
• Significant burning and erythema can occur with topical calcineurin inhibitor use

‒ Often used in sensitive areas (genitals, skin folds, face) ‒ Warning patients in advance can reduce premature cessation of treatment ‒ Treat patients with topical steroids for 5 days to “cool down” region before introducing the calcineurin inhibitor

Topical Therapy for Scalp Psoriasis

Chan CS, et al. J Am Acad Derm. 2009; 60:962-971; Veronica Richardson. Personal communication.

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Topical Nonsteroidal Agents for Psoriasis

Khosravi et.al. J Drugs Dermatol. 2017;16:760-766; Menter et. al. J Am Acad Dermatol.. 2009;60:643-59.

Calcineurin Inhibitors Vitamin D Analogs Keratolytics

• Tacrolimus 0.03%, 0.1% ointment
• Pimecrolimus 1% cream
• Calcipotriene 0.005%
• Calcitriol
• Salicylic acid
• Coal tar
• Retinoids
• Ammonium lactate
• Urea

Face/Genitals: burning and erythema can occur. Consider pretreating for 3-5 days with topical steroids Rotational therapy/combine with topical corticosteroids Scalp: 10% Liquor Carbonis Detergens with 2% salicylic acid in

• il, compounded for scalp

debridement therapy

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Topical Corticosteroids for Psoriasis

Potency Examples Body Locations

• Class I super potent
• Clobetasol/Halobetasol
• Palms/soles, scalp,

elbows/knees

• Class II potent
• Fluocinonide 0.05%
• Class III-V
• Triamicinolone 0.1%
• Extremities, torso
• Class VI-VII
• Hydrocortisone 2.5%
• Desonide 0.05%
• Face, genitals, inverse

Considerations

• Body location
• Vehicle

Corticosteroids

Ference JD. Am Fam Physician. 2009;79:135.

• Cost/Coverage
• Quantity

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Phototherapy for Psoriasis

• Decreased keratinocyte proliferation; anti-inflammatory

properties

• Narrowband UVB preferred over broadband UVB light
• Generally administered 3 times/week for ≥3 months; large

time commitment

• Side effect: With narrowband UVB, burns are more

severe, longer lasting than those with broadband UVB

• PUVA useful for palmoplantar psoriasis

PUVA = psoralen and ultraviolet A; UVB = ultraviolet B. Kupetsky EA, Keller M. J Am Board Fam Med. 2013;26:787-801.

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Phototherapy With Excimer Laser Therapy

• 308 nm excimer laser
• Can be helpful for:

‒ Peripheral scalp involvement ‒ Limited disease/individual plaques

• Handheld lasers emit a focused

wavelength of light; spot size 2 cm

• 2-3 times per week for 4-12 weeks
• May not be widely available, but

efficacious way to treat localized psoriasis without use of biologics

• Well tolerated with low risk

Photos courtesy of Veronica Richardson, MSN, ANP-BC, DCNP. Gattu S, et al. J Eur Acad Dermmatol Venereol. 2009;23:36-41.

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Case Study (cont’d): Lori Returns to Her Dermatologist for Follow-up 6 Months Later

• Even with aggressive scalp debridement, Lori’s scalp psoriasis is

recalcitrant and continues to cause her distress

• She reports her depression/anxiety is better controlled but notes:

‒ Recent plaque involvement of elbows and knees ‒ Hands a little stiff when she wakes up

• Lori considers phototherapy, but her schedule does not allow for the

frequent visits required, and her rural town has limited access to it

• She agrees to systemic therapy for her psoriasis
• She and her dermatologist select an IL-12/23 inhibitor because of its

efficacy, safety profile, and weight-based dosing

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• UVB phototherapy (narrowband more effective

than broadband) − UVB phototherapy alone − UVB phototherapy + systemic retinoids − UVB phototherapy + adjuvant topical agents − UVB phototherapy + short-term isotretinoin, if necessary − Goeckerman therapy If UVB phototherapy available, feasible, practical, and suitable: FIRST LINE If UVB phototherapy unavailable, contraindicated, or ineffective or patient unable to comply: FIRST LINE

CsA = cyclosporine A; MTX = methotrexate. Note: Risankizumab, a newer IL-23 inhibitor, was approved by the FDA after publication of this algorithm. Skyrizi [prescribing information]. AbbVie; 2019; Van Voorhees AS, et al. www.psoriasis.org/sites/default/files/npf_pocketguide_2018_0010.pdf. Accessed April 28, 2020.

• Adalimumab
• Apremilast
• Brodalumab
• Certolizumab pegol
• Cyclosporine
• Etanercept
• Guselkumab
• Infliximab
• Ixekizumab
• Methotrexate (MTX)
• PUVA
• Secukinumab
• Systemic retinoids
• Tildrakizumab
• Ustekinumab

SECOND LINE (Combination Therapies)

• MTX + CsA
• MTX + biologic
• Isotretinoin (short term, if necessary;

in conjunction with phototherapy)

• Systemic retinoid + biologic
• UVB + biologic
• Apremilast + UVB

NPF Algorithm for Women of Childbearing Potential Using Appropriate Contraception With Chronic Plaque Psoriasis (>5% BSA), Without PsA

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• UVB phototherapy (narrowband more effective

than broadband) − UVB phototherapy alone − UVB phototherapy + systemic retinoids − UVB phototherapy + adjuvant topical agents − UVB phototherapy + short-term isotretinoin, if necessary − Goeckerman therapy If UVB phototherapy available, feasible, practical, and suitable: FIRST LINE If UVB phototherapy unavailable, contraindicated or ineffective or patient unable to comply: FIRST LINE

CsA = cyclosporine A; MTX = methotrexate. Note: Risankizumab, a newer IL-23 inhibitor, was approved by the FDA after publication of this algorithm. Skyrizi [prescribing information]. AbbVie; 2019; Van Voorhees AS, et al. www.psoriasis.org/sites/default/files/npf_pocketguide_2018_0010.pdf. Accessed April 28, 2020.

• Adalimumab
• Apremilast
• Brodalumab
• Certolizumab pegol
• Cyclosporine
• Etanercept
• Guselkumab
• Infliximab
• Ixekizumab
• Methotrexate (MTX)
• PUVA
• Secukinumab
• Systemic retinoids
• Tildrakizumab
• Ustekinumab

SECOND LINE (Combination Therapies)

• MTX + CsA
• MTX + biologic
• Isotretinoin (short term, if necessary;

in conjunction with phototherapy)

• Systemic retinoid + biologic
• UVB + biologic
• Apremilast + UVB

NPF Algorithm for Women of Childbearing Potential Using Appropriate Contraception With Chronic Plaque Psoriasis (>5% BSA), Without PsA

WOMEN OF CHILDBEARING POTENTIAL SHOULD BE INFORMED ABOUT THE NEED TO ABSTAIN FROM BECOMING PREGNANT AND REMAIN ON APPROPRIATE CONTRACEPTION FOR THE RECOMMENDED INTERVAL AFTER THE DISCONTINUATION OF THESE MEDICATIONS.

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Conventional Systemic Oral Therapies for Moderate to Severe Psoriatic Disease

Kupetsky EA, Keller M. J Am Board Fam Med. 2013;26:787-801; Menter A, et al. J Am Acad Dermatol. 2009;61:451-485; Pang ML, et al. Expert Opin Drug Metab Toxicol. 2008;4:953-964.

MTX Cyclosporine Acitretin Widely prescribed for PsO; not FDA approved for PsA but often used Reserved for rescue therapy Often used with UV light; least effective as monotherapy PASI 75 achieved by 36% to 60% of patients after 16 weeks PASI 75 achieved by 50% to 70% of patients after 8 to 16 weeks Response takes 3 to 6 months; PASI 75 highly variable For moderate or severe PsO; can be used in combination with biologics Use limited to 1 year; initial dosage: 3 mg/kg/day; usually divided in 2 doses Dose-dependent efficacy; can be used with biologics Single weekly dose: 15 mg; if needed, titrate up to 25 mg; divided-dose schedule: 2.5 mg q12h x 3 doses Retinoid; starting dosage 10-25 mg/d, increase q2wk until xerosis appears Key safety issues: hepatotoxicity, bone marrow suppression, pneumonitis, contraindicated in pregnancy (category X) Key safety issues: renal insufficiency, hypertension Key safety issues: mucous membrane dryness, ↑ TG and liver function tests, contraindicated in pregnancy (category X)

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Newer Oral Therapies: Moderate to Severe Psoriatic Disease

PDE = phosphodiesterase. Otezla [prescribing information]. Celgene; 2019; Xeljanz [prescribing information]. Pfizer; 2019.

*No boxed warning for apremilast, but warnings and precautions for diarrhea (especially in patients ≥65 years of age), nausea, vomiting, weight loss, and depression.

Indication(s) Recommended Dosage (adults) Boxed Warning PDE-4 enzyme inhibitor Apremilast PsO, PsA 5-day titration (10-30 mg), then 30 mg PO twice/day No* Janus kinase (JAK) inhibitor Tofacitinib PsA only 5 mg/day Extended release: 11 mg/d Serious infections, mortality, malignancy, thrombosis

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“Biologic agents, as monotherapy or combined with other topical or systemic medications, have a high benefit-to-risk ratio, and because of that, they are a welcome addition to the armamentarium of psoriasis management.” – AAD/NPF Guidelines

Jabbar-Lopez ZK, et al. J Invest Dermatol. 2017;137:1646-1654; Menter A, et al. J Am Acad Dermatol. 2019;80:1029-1072; Sbidian E, et al. Cochrane Database Syst Rev. 2017;12:Art. No. CD011535.

Biologic Therapies: Moderate to Severe Psoriasis

• Cochrane review

− 109 trials, N = 39,882 − Ranking of efficacy

• IL-17, IL-23, IL-12/23, TNF-ɑ inhibitors
• Small molecules
• Conventional systemic drugs
• Meta-analysis

− 41 trials, N = 20,561 − Biologics more effective than placebo or MTX

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*Risankizumab was not included in this review. Sbidian E, et al. Cochrane Database Syst Rev. 2017;12:CD011535.

Cochrane Meta-analysis: Efficacy of Systemic Therapies in Moderate to Severe Psoriasis

5 10 15 20 25 30 35

Relative Effect vs Placebo

Risk Ratio for Achieving PASI 90*

PDE-4 JAK TNF IL 12/23 IL 17 IL 23 Conventional

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Biologic Therapies: Moderate to Severe Psoriatic Disease

Armstrong A, et al. Dermatol Ther (Heidelb); 2017;7:97-109; Cimzia [prescribing information]. UCB Inc; 2018; Enbrel [prescribing information]. Amgen; 2017; Humira [prescribing information]. AbbVie; 2018; Remicade [prescribing information]. Janssen; 2013; Simponi [prescribing information]. Janssen; 2018; Stelara [prescribing information]. Janssen; 2014.

ANA = antinuclear antibody; LFT = liver function tests

Agent/Indication(s) Common (>5%) AEs Boxed Warning Cautions/Considerations

TNF-α Inhibitors Adalimumab PsO, PsA Injection site reaction + ANA; elevated alkaline phosphatase, cholesterol Serious infections, malignancy Demyelinating disease Congestive Heart Failure Inflammatory Bowel Disease (Adalimumab, Infliximab) Pregnancy (Certolizumab) Etanercept PsO, PsA Injection site reaction + ANA Infliximab PsO, PsA Infusion reactions + ANA; elevated LFT; neutralizing antibodies Certolizumab PsO, PsA URIs, rash, UTIs IL-12/23 Inhibitor Ustekinumab PsO, PsA None No  Inflammatory Bowel Disease

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Biologic Therapies: Moderate to Severe Psoriatic Disease (cont’d)

Cosentyx [prescribing information]. Novartis; 2018; Ilumya [prescribing information]. Sun Pharmaceuticals; 2018; Siliq [prescribing information]. Valeant; 2017; Taltz [prescribing information]. Lilly; 2018; Tremfya [prescribing information]. Janssen Immunology; 2018; Skyrizi [prescribing information]. AbbVie; 2019.

Indication(s) Common (>5%) AEs Boxed Warning Cautions/Considerations

IL-17A Inhibitors and Targets of IL-17 Receptor Brodalumab PsO None Suicidal ideation and behavior Inflammatory Bowel Disease Ixekizumab PsO, PsA Nasopharyngitis; injection-site reactions No Secukinumab PsO, PsA Nasopharyngitis IL-23 Inhibitor Guselkumab PsO only Upper respiratory infection No Promising data for treatment of Inflammatory bowel disease Risankizumab Tildrakizumab

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Long-term Efficacy of IL-17 and IL-12/23 Inhibitors: Patients With Moderate to Severe Psoriasis Achieving PASI 90 at Week 52

76% 61% 20 40 60 80 Secukinumab Ustekinumab

Secukinumab vs Ustekinumab (N = 676)

76% 59% 20 40 60 80 Ixekizumab Ustekinumab

Ixekizumab vs Ustekinumab (N = 302) P <0.0001 P <0.01 Patients (%) Patients (%)

Blauvelt A, et al. J Am Acad Dermatol. 2017;76:60-69; Paul C, et al. J Am Acad Dermatol. 2019;80:70-79.

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Impact of Biologics on QoL in Psoriasis

*12 studies; 12,240 participants; various QoL scales used; †Pooled analysis from 4 phase 3 trials; n = 309 secukinumab 300 mg, n = 282 placebo; QoL measured with EuroQol 5-Dimensions (EQ-5D-3L) questionnaire. Sbidian E, et al. Cochrane Database Systematic Rev. 2017;12. doi: 10.1002/14651858.CD011535.pub.2; Feldman SR, et al. Abstract presented at Maui Derm for Dermatologists 2019; January 26-30, 2019, Maui, Hawaii.

Favors drug Favors placebo

Cochrane Database 2017 Meta-analysis* 2019 analysis: % patients reporting no problem with domains below, secukinumab vs placebo, week 12†

Drug Ixekizumab Guselkumab Tildrakizumab Ustekinumab Etanercept Tofacitinib Adalimumab Brodalumab MTX Apremilast

• 2
• 1

1

QoL

71% 87% 83% 47% 43% 43% 0% 20% 40% 60% 80% 100% Mobility Self care Usual Activities Secukinumab Placebo

% Patients

Favors drug Favors placebo

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Summary: Long-term Safety of Biologic Agents for Psoriatic Disease

• TNF inhibitors

‒ No long-term AEs noted beyond those identified in clinical trials

• IL-12/23 inhibitors

– No dose-related or cumulative toxicity with increasing duration of exposure

• IL-17A inhibitors

– No new safety signals with increasing duration of exposure – IL-23 inhibitors (guselkumab, tildrakizumab-asmn, risankizumab-rzaa) – Open-label extensions of phase 3 trials showed no new safety signals

Bilal J, et al. J Dermatolog Treat. 2018;29:569-578; Fagerli KM, et al. RMD Open. 2018;4:e000596; Griffiths CEM, et al. J Drugs Dermatol. 2018;17:826- 832; Reich K, et al. Lancet. 2017;390:276-288. Reich K, et al. Lancet. 2019;394:576-586.

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Screening Before Starting a Biologic

HBV = hepatitis B virus; HCV = hepatitis C virus. Lebwohl M, et al. J Am Acad Dermatol. 2008;58:94-105; Stelara [prescribing information]. Janssen; 2018; Taltz [prescribing information]. Lilly; 2018; Wine-Lee L, et al. J Am Acad Dermatol. 2013;69:1003-1013.

• Assess immunization status or disease

history ‒ Haemophilus influenzae ‒ HBV, HCV, HIV ‒ Human papillomavirus ‒ Pertussis ‒ Tetanus ‒ Streptococcus pneumoniae ‒ Varicella zoster

• TB test

– Baseline – Periodically

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Live Vaccines to Be Avoided When Using Biologics

*Shingrix is an inactivated recombinant, adjuvanted (non-live) vaccine for herpes zoster. Centers for Disease Control and Prevention. www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/B/us-vaccines.pdf. Accessed April 28, 2020.

• Adenovirus
• Cholera
• Herpes zoster (shingles) – Zostavax only*
• Live attenuated viral/intranasal spray for

influenza

• Measles, mumps, rubella or measles,

mumps, rubella, varicella

• Rotavirus
• Typhoid (live attenuated

bacterial oral)

• Varicella
• Vaccinia (smallpox)
• Yellow fever

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Vaccinations for Patients Taking Biologic Therapy for Psoriatic Disease

• Assess vaccination status before starting any biologic agent
• Live attenuated vaccines should be avoided for patients who are receiving

biologics

• Inactivated influenza and pneumococcal vaccines are strongly

recommended and are safe, but therapeutic response may be reduced

• If live vaccine is indicated, administer 4 weeks before starting therapy for

psoriatic disease

• Routine immunizations should be up to date before travel

Wine-Lee L, et al. J Am Acad Dermatol. 2013;69:1003-1013.

46

Case Study (cont’d): Lori Is Diagnosed With PsA

• At a follow-up visit, Lori has noticed improvement in her skin, but the

stiffness in her joints continues to bother her, especially when she is giving piano lessons to students

• She is referred to a rheumatologist for further evaluation
• At Lori’s visit to the rheumatologist, she is diagnosed with concomitant PsA

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Psoriatic Arthritis

• Seronegative spondyloarthritis
• Present in 6% to 42% of patients with psoriasis

‒ Greater prevalence among those with more severe psoriasis ‒ ~50% of patients with PsA have progressive, disabling disease

• Missed diagnoses are common

‒ ~15% of psoriasis patients have undiagnosed PsA ‒ 21.5% of patients with moderate to severe PsA are not being treated ‒ Up to 20% of those with severe PsA receive only topical therapy

• Patients with PsA report worse QoL than do those with psoriasis only

Armstrong AW, et al. JAMA Dermatol. 2013;149:1180-1185; Gottlieb A, et al. J Am Acad Dermatol. 2008;58:851-864; Mease PJ, et al. Drugs. 2014;74:423-441; Mease PJ, et al. J Am Acad Dermatol. 2013;69:729-735; Menter A, et al. J Am Acad Dermatol. 2008;58:826-850.

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PsA: Characteristics

• Enthesitis a predominant characteristic
• Asymmetric joint involvement in ~80% of

patients—usually involves 1 to 3 joints

• 80% to 90% of patients with PsA have nail lesions
• Fingers and toes may be enlarged (“sausage digits”)
• Can develop at any time, even before psoriasis

is evident, but usually between ages 30 and 50 years

• Other symptoms: stiffness, pain, swelling
• Severity of PsA may not correlate with severity of psoriasis

Gottlieb A, et al. J Am Acad Dermatol. 2008;58:851-864; Mease PJ, et al. J Rheumatol. 2014;41:1249-1251; National Psoriasis Foundation. www.psoriasis.org/psoriatic-arthritis. Accessed April 28, 2020; Singh JA, et al. Arthritis Care Res (Hoboken). 2019;71:2-29.

49

PsA: Clinical Photos

49

Helliwell PS, et al. Ann Rheum Dis. 2007;66:113-117.

Dactylitis Enthesitis

(photo courtesy Alexis Ogdie, MD)

Nail Dystrophy Associated with PSA

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PsA: Differential Diagnosis

*Premenopausal women. OA = osteoarthritis. Gottlieb A, Merola J. J Dermatolog Treat. 2019; DOI: 10.1080/09546634.2019.1605142; Gottlieb A, et al. J Am Acad Dermatol. 2008;58:851-864; Mease PJ, Armstrong AW. Drugs. 2014;74:423-441.

PsA RA OA Gout Peripheral disease Asymmetric Symmetric Asymmetric — Axial joint/spondylitis Yes — No Less often Stiffness Morning/ immobility Morning/ immobility With activity Yes Enthesitis Yes No No Yes Nail lesions Yes No No No Psoriasis Yes Uncommon Uncommon Uncommon Female:male ratio 1:1 3:1 to 4:1 1:1 to 2:1 1:5 to 1:10*

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Psoriasis Epidemiology Screening Tool (PEST)

5-item questionnaire

(sensitivity = 92%; specificity = 78%; positive likelihood ratio 4:1)

• 1. Have you ever had a swollen joint (or joints)?
• 2. Has a clinician ever told you that you have arthritis?
• 3. Do your fingernails or toenails have holes or pits?
• 4. Have you had pain in your heel?
• 5. Have you had a finger or toe that was completely swollen

and painful for no apparent reason?

Ibrahim GH, et al. Clin Exp Rhematol. 2009;27:469-474.

Answering “yes” to ≥3 questions is suggestive of PsA.

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PsA Treatment Toolbox

Nonpharmacologic csDMARDS Targeted DMARDS Biologics Others Education and counseling Weight loss Physical Therapy/Exercise Bracing, adaptive aids MTX Cyclosporine Sulfasalazine Leflunomide Azathioprine Apremilast Tofacitinib Etanercept Adalimumab Infliximab Certolizumab Golimumab Abatacept Ixekizumab Secukinumab Ustekinumab **several others under investigation NSAIDS Intra-articular/entheseal injections

Avoid TNF inhibitors for Lori due to her family history of MS

csDMARD = conventional synthetic disease-modifying anti-rheumatic drug; DMARD = disease modifying anti-rheumatic drug.

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PsA: Summary

• In patients with psoriasis, clinicians should look for signs and

symptoms of PsA at each visit

• However:

‒ PsA may appear before the diagnosis of psoriasis ‒ If PsA is suspected, refer patient to a rheumatologist

• Treatment goals

‒ Alleviate signs and symptoms of arthritis ‒ Inhibit structural damage ‒ Maximize QoL

.

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Case Conclusion

• Lori has been taking an IL-17 inhibitor for 2 years
• Most of her lesions have resolved; maximum BSA involvement is 1%, and

she occasionally has complete clearance

• Stiffness in her fingers has diminished significantly
• She now visits the hair salon for cuts and styling
• Lori relies on your partnership to ensure her vaccinations remain current

and her cardiometabolic disease and depression are well managed

• You coordinate care with her dermatologist and rheumatologist
• You and Lori are vigilant for any AEs associated with her treatment

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• AAD and NPF released statements on COVID-19 and immunosuppressive

therapies ‒ Stop therapy if patient tests positive or has symptoms consistent with COVID-19; reinitiate once completely recovered ‒ Assess the risk vs benefits in lower-risk patients before initiating immunosuppressive agents on a case-by-case basis ‒ High-risk individuals should have risk/benefit discussion with their healthcare provider ‒ Initiation and cessation of systemic therapy should be discussed with healthcare provider

What if Lori Was Infected With COVID-19?

55

National Psoriasis Foundation. www.psoriasis.org/advance/coronavirus. Accessed April 30, 2020; American Academy of Dermatology. www.aad.org/member/practice/coronavirus/clinical-guidance/biologics. Accessed April 30, 2020.

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• Pregnancy and biologics

‒ No large scale trials

• Extrapolation from IBD and RA literature
• Weigh pros/cons
• Favor TNF use over other classes

‒ Certolizumab >entanercept >adalimumab >infliximab

• Generally deemed safe for first half of pregnancy
• Delayed live vaccination schedule for infant

What if Lori Wanted to Become Pregnant?

56

IBD = inflammatory bowel disease. Porter ML. Int J Womens Dermatol. 2017:3:21-25.

57

Biologics and surgery

• All biologics can be continued through low-risk surgery safely
• For moderate to high-risk surgery: case by case basis

‒ Most conservative approach is to discontinue biologic for a period of 3 to 4 half-lives (but this may not be feasible nor necessary in all cases)

• Informed risk/benefit discussion between patient, dermatology provider,

medical team, and surgery team

• Resume biologic therapy 1 to 2 weeks after surgery assuming no

complications

What if Lori Needed Surgery?

57

Choi YM, et al. J Am Acad Dermatol. 2016;75:798-805.

58

PCE Action Plan

✓ Set a target goal of complete/near-complete skin clearance for patients with moderate to severe psoriasis ✓ Investigate all body areas that may be affected by psoriasis ✓ Consider patient’s perspective in selecting treatment ✓ Optimize care of patients with psoriatic disease by working as part of a collaborative team ✓ Screen patients with psoriatic disease for CVD and other comorbidities ✓ Recommend appropriate vaccinations; HBV, HCV, and HIV screening; and TB testing for patients taking biologic therapies

PCE Promotes Practice Change

2020 Symposia Series 1