4/10/18. Faculty. Disclosures. Confronting Psoriatic Disease: Putting New Tools to Work

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1 Confronting Psoriatic Disease: Putting New Tools to Work Faculty Brad P. Glick, DO, MPH, FAOCD Glick Skin Institute Skin and Cancer Associates Program Director Dermatology Residency Larkin Hospital - Palm Springs Campus Clinical Assistant Professor of Dermatology FIU Herbert Wertheim College of Medicine Miami, Florida Paul S. Yamauchi, MD, PhD Dermatology Institute & Skin Care Center Clinical Science Institute Clinical Assistant Professor of Dermatology David Geffen School of Medicine at UCLA Adjunct Associate Professor of Dermatology John Wayne Cancer Institute Santa Monica, CA 2 Disclosures Dr. Glick serves on the speakers bureau for SunPharma/Ranbaxy, Merz, LEO, Abbvie, Janssen, Celgene, Galderma, Lilly, and Novartis Pharmaceuticals Corporation. Dr. Glick is also a member of the advisory board for Lilly and TopMD stockholder. Dr. Yamauchi serves as a consultant for AbbVie, Amgen, Celgene Corporation, Janssen-Ortho Inc., LEO Pharma, US, Novartis Pharmaceuticals Corporation, Pfizer Inc., and Regeneron. He serves as a speaker for AbbVie, Amgen, Celgene Corporation, Galderma USA, Janssen-Ortho Inc., LEO Pharma Inc., and Novartis Pharmaceuticals Corporation. Dr. Yamauchi is also a principal investigator for Amgen, Celgene Corporation, Dermira, Galderma USA, Janssen-Ortho Inc., LEO Pharma Inc., Lilly ICOS LLC, Medimmune, Novartis Pharmaceuticals Corporation, Pfizer Inc., Regeneron, and Sandoz, a Novartis company. He also serves on the advisory boards of Amgen, Dermira, and Lilly ICOS LLC. 3 1

2 Learning Objectives 1. Identify and describe the clinical features of psoriatic skin and joint disease 2. Review and discuss associated comorbidities and emerging bio factors and their significance in the management of psoriatic disease 3. Discuss the expanding and dynamically changing treatment paradigm for psoriasis and its related disorders 4. Review and interpret up to date evidence-based clinical trial data and the latest treatments available for the management of psoriatic disease 4 PRE-TEST QUESTIONS 5 Pre-test ARS Question 1 Which of the following are among the most common symptoms of psoriatic disease? 1. Enthesitis 2. Depressed mood 3. Pruritic skin lesions 4. Symmetric joint pain and swelling 6 2

3 Pre-test ARS Question 2 According to a population-based study, the relative risk for myocardial infarction is highest in which of the following patients with psoriatic disease? 1. Older patients with severe psoriasis 2. Older patients, regardless of severity 3. Younger patients with severe psoriasis 4. Younger patients with longer duration of disease 7 Pre-test ARS Question 3 A 63-year-old obese man with a 12-year history of psoriasis and 2-year history of psoriatic arthritis presents reporting increased disease activity (5% BSA, moderate joint disease activity). Current medications include topical steroids and NSAIDs. He recently underwent PCI for management of unstable angina. Which of the following might be appropriate based on this history? 1. Avoid methotrexate based on cardiovascular risk 2. Avoid TNF inhibitors based on cardiovascular risk 3. Consider biologic therapy or PDE4 inhibitor despite his cardiovascular risk 4. Consider phototherapy and switch from NSAID to acetaminophen 8 Pre-test ARS Question 4 For a patient with moderate-severe psoriasis and a recent history of major depression, clinicians should consider avoiding which of the following agents? 1. Brodalumab 2. Methotrexate 3. Secukinumab 4. Any TNF inhibitor 9 3

4 Pre-test ARS Question 5 How confident are you in your ability to recognize co-morbidities associated with psoriatic disease? 1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident 10 Pre-test ARS Question 6 How confident are you in your ability to integrate the latest treatment data into the management of patients with psoriatic disease? 1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident 11 Part

5 4/10/18 Psoriatic Skin Disease Clinical Features Chronic, relapsing, immune dysregulatory inflammatory disease Erythema (redness) Induration (thickness) Desquamation (scaling) Scaling and itching most common symptoms Epidemiology Bimodal age of onset 2nd-3rd decade of life and after 50 years of age Onset <15 years may indicate more severe disease Genetic component Affected areas of the body Symmetric Extensors (elbows, knees) Scalp Trunk ~33% patients report family history HLA-B13, B17, Bw57, Cw6 PSORS1 gene 6q 21.3 Comorbidities common 13 Assessing Severity of Psoriatic Skin Disease Imagine 1 palm equal to 1% of your body surface area. Mild : 1-3% Moderate: 3-10% Severe: More than 10% Location also determines severity Scalp Hands and feet Groin and skin folds 14 Plaque Psoriasis Most common variant 80% of all psoriasis cases Other variants: guttate, inverse, erythrodermic, scalp, nail, and palmoplantar Differential diagnosis Eczema Drug eruption Tinea corporis 15 5

6 4/10/18 Precipitating Factors Stress Infections Group A beta-hemolytic streptococcus guttate psoriasis Physical trauma (Koebnerization) Drugs Lithium Beta-adenergic blockers Systemic steroids (rebound) Anti-malarials NSAIDS Interferon Gold 16 Psoriatic Arthritis Estimated prevalence 6%-42% of patients with psoriasis Most common between 30 and 50 years of age Increases with disease severity and duration Earlier onset associated with worse prognosis Timing of onset: Psoriasis precedes arthritis in 75% of cases Arthritis onset ~10 years after skin lesions Synchronous onset in 15% of cases Arthritis precedes psoriasis in 10% of cases Findings may include: Asymmetric or symmetric inflammatory joint disease Distal interphalangeal joints (DIP) Spondylitis, enthesitis, dactylitis Gottlieb A et al. J Am Acad Dermatol. 2008;58: Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics Philip J. Mease, MD, Dafna D. Gladman, MD Kim A. Papp, MD, PhD Majed M. Khraishi, MD Diamant Thaçi, MD Frank Behrens, MD Robert Northington, PhD Joanne Fuiman, MS Eustratios Bananis, PhD Robert Boggs, PhD Daniel Alvarez, MD DOI: Background Prompt identification and treatment of psoriatic arthritis (PsA) in patients with psoriasis is critical to reducing the risk of joint damage, disability, and comorbidities. Objective We sought to estimate PsA prevalence in patients with plaque psoriasis in 34 dermatology centers in 7 European and North American countries. Methods Consecutive patients were evaluated by dermatologists for plaque psoriasis and subsequently by rheumatologists for PsA. PsA prevalence was estimated primarily based on rheumatologists' assessment of medical history, physical examination, and laboratory tests. Results Of 949 patients evaluated, 285 (30%) had PsA (95% confidence interval 27-33) based on rheumatologists assessment. PsA diagnosis changed in 1.2% of patients when diagnostic laboratory tests were added to medical history and physical examination. Of 285 patients given the diagnosis of PsA, 117 (41%) had not been previously given the diagnosis

7 4/10/18 Psoriasis Is Caused by Uncontrolled Inflammation1,2 Inflammatory response contributes to increased keratinocyte turnover and joint disease Proinflammatory Anti-inflammatory IFN, interferon; IL, interleukin; TGF, transforming growth factor; Th, T-helper; TNF, tumor necrosis factor; Treg, regulatory T-cell. 1. Goodman et al. Crit Rev Immunol. 2012;32: Lowes et al. Annu Rev Immunol. 2014;32: Psoriasis Is Caused by Uncontrolled Inflammation1,2 Inflammatory response contributes to increased keratinocyte turnover and joint disease Proinflammatory Anti-inflammatory IFN, interferon; IL, interleukin; TGF, transforming growth factor; Th, T-helper; TNF, tumor necrosis factor; Treg, regulatory T-cell. 1. Goodman et al. Crit Rev Immunol. 2012;32: Lowes et al. Annu Rev Immunol. 2014;32: Part

8 Psoriasis is a Systemic Inflammatory Disease Increased signal indicative of systemic inflammation 1 : Knee and Ankle Liver Aorta and Femoral Arteries Psoriatic Plaques Chronic, widespread inflammation may contribute to psoriasisassociated comorbidities 2 Person without Psoriasis Person with Psoriasis Positron emission tomography (PET) scan 1. Mehta NN, et al. Arch Dermatol. 2011;147(9): Gottlieb AB, et al. Am J Med. 2009;122(12):1150 e Psoriasis PET Scan Images Copyright 2011 American Medical Association. All rights reserved. 22 Established Psoriatic arthritis IBD Psychological and psychiatric disorders Metabolic syndrome Cardiovascular disease Oliveira MF et al. Psoriasis: classical and emerging comorbidities. An Bras Dermatol. 2015;90(1):9-20. Comorbidities Emerging NAFLD Lymphomas Sleep apnea COPD Osteoporosis Parkinson s disease Celiac disease Connective tissue disease Erectile dysfunction Uveitis Aortic aneurysm Fractures 23 Metabolic Comorbidities Obesity Doubles risk for psoriasis BMI correlates with psoriasis severity Diabetes More common in psoriasis Role of TNF-α in insulin resistance Significant correlation of blood resistin levels with psoriasis activity Hammings EA et al. Med Hypoth. 2006;67:76; Johnson A et al. Br J Dermatol. 2008; 159:342; Cohen A et al. J Am Acad Dermatol. 2007;56:

9 Risk of myocardial infarction in patients with psoriasis Incidences per 1000 pt-y for: Control 3.58 (95% CI, ) Mild psoriasis: 4.04 ( ) Severe psoriasis 5.13 ( ) Conclusions: Psoriasis may confer an independent risk of MI The RR was greatest in young patients with severe psoriasis RR (95% CI) Adjusted RR of MI in patients with psoriasis based on patient age Severe psoriasis Mild psoriasis Gelfand J et al. JAMA 2006;296: Age (y) 25 Comparing Comorbidities Risk for diabetes higher in psoriasis than rheumatoid arthritis (hazard ratio) Psoriasis RA Diabetes (all patients) CV death (DMARD) All-cause death (DMARD) Severe psoriatic disease linked to higher rate of atherosclerotic outcomes (hazard ratio) Atherosclerotic outcomes Severity of Psoriatic Disease Mild Moderate Severe Dubreuil et al. Rhematology. 2014;53: ; Ogdie A et al. Ann Rheum Dis. 2014;73: ; Yeung H et al. JAMA Derm. 2013;149: Risk of Lymphoma in Psoriasis Lymphoma Adjusted relative risk (RR, 95% CI) Mild Psoriasis Population-based cohort study of UK General Practice Research Database ( ). 153,197 psoriasis patients and 765,950 controls. Severity determined by use of systemic treatment for extensive disease (3,994 yes, 149,203 no). *RR = relative risk (confidence interval), adjusted for gender and age; P<.001; P =.1; P =.5; **P =.05. Excludes cutaneous T-cell lymphoma; Gelfand M, et al. J Invest Dermatol. 2006;126: Severe Psoriasis All lymphoma 1.34 ( ) 1.59 ( ) Non-Hodgkin s lymphoma 1.15 ( ) 1.34 ( ) Hodgkin s lymphoma 1.42 ( )** 3.18 ( )** T-cell lymphoma 4.10 ( ) ( ) 27 9

10 Psoriasis Affects Employment Adults with severe psoriasis reported that their health negatively impacted their work Adults with severe psoriasis reported that they have lost a job because of their health condition Percentage of Subjects Adults without psoriasis (n=837) P< Adults with self-reported severe psoriasis (n=81) Percentage of Subjects Adults without psoriasis (n=837) P< Adults with self-reported severe psoriasis (n=81) Krueger GG, et al. Presented at: 63rd Annual Meeting of AAD; February 18-22, 2005; New Orleans, La. 28 Clinical and Psychological Burden of Psoriasis Psoriasis patients are more likely to suffer from depression, to use an SSRI, and have CV risk factors compared with control* Increased likelihood (%) n= 24,256 * After adjusting for age, gender, and Deyo-Charlson comorbiditiy. Dabbous O, et al. AAD 2007: P2743. Kimball, AB, et al. Am J Clin Dermatol. 2005;6(6): Part

11 31 Hospitalized Moderate-Severe Psoriasis Patients Condition OR Type 2 Diabetes 2.48 Hypertension 3.27 Hyperlipidemia 2.09 Coronary Heart Disease 1.95 Metabolic Syndrome 5.29 Smoking 2.96 Regular alcohol consumption 3.33 Heavy alcohol consumption 3.61 Sommer DM et al. Arch Dermato res. 2006; 298: Clinical Significance Increased risks for MI, stroke, cardiovascular death, diabetes, chronic kidney disease 5 years of life lost 10-year risk for major CV event attributable to psoriasis = 6% Risk for cardiovascular disease in patients with severe psoriasis similar to risk conferred by diabetes Patients treated for severe psoriasis are 30x more likely to experience MACE (attributable to psoriasis) than melanoma Abuabara, K, et al. Br J Dermatol. 2010;163:

12 Screening Recommendations Hypertension Diabetes (fasting plasma glucose, HbA1c, or oral glucose tolerance test) Cardiovascular Risk Assessment Annual skin cancer exam 34 Talk With Your Patients About Comorbidities How does your disease affect you on a daily basis? Lifestyle modification recommended for things you can control (weight, smoking, alcohol consumption)

13 37 Part 4 38 Topical therapy Moisturizers Cortisone and steroid creams Calcipotriene Vitamin A retinoids Ultraviolet light/lasers UVB PUVA Excimer laser Systemic Therapy Methotrexate Cyclosporine Acitretin (Soriatane) Apremilast (Otezla) Biologics Etanercept (Enbrel) Infliximab (Remicade) Adalimumab (Humira, Exemptia) Ustekinumab (Stelara) Golimumab * (Simponi) Certolizumab * (Cimzia) Secukinumab (Cosentyx) Ixekizumab (Taltz) Guselkumab (Tremfya) Brodalumab (Siliq) Treating Psoriatic Disease: A Focus on Systemic Therapy * FDA approved or psoriatic arthritis and not psoriasis Mild Psoriasis Moderate to Severe Psoriasis 39 13

14 4/10/18 Adverse Events Topical Steroids Tachyphylaxis Skin atrophy Telangiectasias Striae Discoloration HPA axis suppression 40 Conventional Oral Agents Drug Lab Tests Preg. Cat. Methotrexate Hepatotoxicity GI (nausea/vomiting) Malaise Reactivation of phototoxic reactions Ulcerative stomatitis Myelosuppression/anemia Pulmonary fibrosis Induction of lymphomas Adverse Effects LFTs CBC with platelets Liver biopsy when 1.5 g methotrexate reached Cyclosporine Renal toxicity Hypertension GI (nausea/vomiting) Flu-like symptoms Hypertrichosis Gingival hypertrophy Skin malignancies Renal function tests CBC with platelets Magnesium Potassium Blood pressure monitoring C Acitretin Teratogenicity Alopecia Hepatotoxicity Hyperlipidemia Mucocutaneous Pseudotumor cerebri Hyperostosis Pregnancy Lipid panel LFTs CVC with platelets Creatine phosphokinase 41 TNF Inhibitors and Comorbidities Drug PsO PsA All TNF inhibitors Comorbidity Concerns Untreated/latent TB, MS/ demyelinating disease, HF NYHA class III/IV, active/chronic HBV or other active infections Adalimumab Infliximab Etanercept Golimumab Certolizumab Also: infusion reactions, dose creep Humira [prescribing information]. North Chicago, IL: Abbvie; 2017; Remicade [prescribing information]. Horsham, PA: Janssen Biotech, Inc.; 2013; Enbrel [prescribing information]. Thousand Oaks, CA: Amgen; 2017; Simponi [prescribing information]. Horsham, PA: Janssen Biotech, Inc.; 2011; Cimzia [prescribing information]. Smyrna, GA: UCB, Inc.;

15 Non-TNF Agents and Comorbidities Drug PsO PsA Comorbidity Concerns IL-12/23 inhibitor Ustekinumab Weight-based dosing and injection frequency not optimized IL-17 inhibitors Secukinumab IBD, Candidiasis, neutropenia, hypercholesterolemia Ixekizumab IBD, Candidiasis, injection site pain, neutropenia Brodalumab IBD, depression/suicidal ideations IL-23 inhibitor Guselkumab URI, Candidiasis, HSV PDE-4 inhibitor Apremilast Depression and suicide 43 PASI Rates for Systemic Psoriasis Therapies Percent of patients achieving PASI 75/90/ PASI 75 PASI 90 PASI Methotrexate Etanercept Adalimumab Infliximab Ustekinumab Secukinumab Apremilast Ixekizumab (Week 16) (Week 24) (Week 16) (Week 24) (Week 12) (Week 12) (Week 16) (Week 12) 1. Saurat JH, et al. Br J Dermatol : ; 2. Leonardi CL, et al. N Engl J Med. 2003;349: ; 3. Menter A, et al. J Am Acad Dermatol. 2008;58: ; 4. Reich K, et al. Lancet. 2005;366: ; 5. Papp K, et al. Lancet. 2008;371: ; 6. Langley RG, et al. N Engl J Med. 2014;371: ; 7. Otezla (apremilast) prescribing information. Celgene Corp. 2015; 8. UNCOVER-2 trial. Presented at the American Academy of Dermatology annual meeting PASI Rates for Systemic Psoriasis Therapies in Development (Week 12; 210 mg; Phase 3) (Week 16; 200 mg; Phase 2) (Week 16; 200 mg) (Week 12; Phase 2) 1. Lebwohl M, et al. N Engl J Med. 2015;373: ; 2. Gordon KB, et al. N Engl J Med. 2015;373: ; 3. Papp K, et al. Br J Dermatol. 2015; 4. Papp K, et al. AAD

16 Monitoring Screen for TB before starting a biologic and on a yearly basis Obtain CBC at baseline and yearly Obtain complete metabolic panel at baseline and yearly HBV and HCV screening at baseline and yearly Optional HIV screen (high-risk patients/geographic areas) While on therapy, use caution when the patient Develops an infection Plans to have major surgery Plans to get a live vaccine (shingles, yellow fever, etc.) PDR.net. Accessed March 6, Summary 48 16

17 Final Thoughts Detail the patient s history Listen and hear their story Focus on comorbidity AND lifestyle management concurrently Discuss goals of therapy Choose treatment options that maximize benefit and minimize risk Spend 5 extra minutes! It may extend a psoriatic patient s life by 5 years 49 POST-TEST QUESTIONS 50 Post-test ARS Question 1 Which of the following are among the most common symptoms of psoriatic disease? 1. Enthesitis 2. Depressed mood 3. Pruritic skin lesions 4. Symmetric joint pain and swelling 51 17

18 Post-test ARS Question 2 According to a population-based study, the relative risk for myocardial infarction is highest in which of the following patients with psoriatic disease? 1. Older patients with severe psoriasis 2. Older patients, regardless of severity 3. Younger patients with severe psoriasis 4. Younger patients with longer duration of disease 52 Post-test ARS Question 3 A 63-year-old obese man with a 12-year history of psoriasis and 2-year history of psoriatic arthritis presents reporting increased disease activity (5% BSA, moderate joint disease activity). Current medications include topical steroids and NSAIDs. He recently underwent PCI for management of unstable angina. Which of the following might be appropriate based on this history? 1. Avoid methotrexate based on cardiovascular risk 2. Avoid TNF inhibitors based on cardiovascular risk 3. Consider biologic therapy or PDE4 inhibitor despite his cardiovascular risk 4. Consider phototherapy and switch from NSAID to acetaminophen 53 Post-test ARS Question 4 For a patient with moderate-severe psoriasis and a recent history of major depression, clinicians should consider avoiding which of the following agents? 1. Brodalumab 2. Methotrexate 3. Secukinumab 4. Any TNF inhibitor 54 18

19 Post-test ARS Question 5 After participating in this program, how confident are you in your ability to recognize co-morbidities associated with psoriatic disease? 1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident 55 Post-test ARS Question 6 After participating in this program, how confident are you in your ability to integrate the latest treatment data into the management of patients with psoriatic disease? 1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident 56 19