Jointly provided by This activity is supported by Held in conjunction with AMCP Managed independent educational grants from Care & Specialty Pharmacy Annual Meeting Novartis Pharmaceutical Corporation 2018 and Celgene Corporation. Psoriasis Clinical Update: Assessing the Latest Trial Data and Treatment Algorithms Paul S. Yamauchi, MD, PhD Clinical Assistant Professor of Medicine Division of Dermatology, David Geffen School of Medicine University of California, Los Angeles Learning Objectives • Assess current and emerging therapies for the treatment of psoriasis and cite their clinical trial data • Examine alignment of managed care psoriasis treatment algorithms with recent clinical trial data Chronic Plaque Psoriasis: A Multisystem Inflammatory Disease • Chronic relapsing immune‐mediated inflammatory disease • Affects >3% of the US population • Affects multiple areas of the body • Up to 30% of patients with psoriasis develop psoriatic arthritis • Accompanied by significant clinical, social, and economic burden Psoriasis Fact Sheet. National Psoriasis Foundation Web site. https://www.psoriasis.org/sites/default/files/publications/PsoriasisFactSheet.pdf. Published February 2015. Accessed March 2018. About Psoriatic Arthritis. National Psoriasis Foundation Web site. https://www.psoriasis.org/about‐psoriatic‐arthritis. Accessed March 2018. Plaque Psoriasis is the Most Common of the Five Recognized Variants Severity of Plaque Psoriasis • Plaque: scaly, erythematous patches, papules, and plaques that are Mild Moderate Severe sometimes pruritic; affects ~80% of patients • Inverse/flexural: lesions are located in the skin folds • Guttate: small papules with fine scale • Erythrodermic: erythema covering nearly the entire body surface area with varying degrees of scaling <3% of BSA 3% ‐10% of BSA >10% of BSA • Pustular: clinically apparent pustules Psoriasis Fact Sheet. National Psoriasis Foundation Web site. https://www.psoriasis.org/sites/default/files/publications/PsoriasisFactSheet.pdf. Published February 2015. Accessed March 2018. Immunopathogenesis of Chronic Plaque Psoriasis Disease Initiation Disease Maintenance Psoriatic plaque Keratinocyte Environmental trigger activation and proliferation Stressed Stress keratinocytes Angiogenesis Neutrophils Microorganisms IL‐17A Drugs IL‐17F Tc17 Trauma TNF‐α IL‐22 Smoking TNF‐α IL‐6 IL‐2 IL‐1β IFN‐γ PSORS1 Naïve T cell IL‐23R Dermal DC Th17 Activation IL‐12 IL‐12B Th1 Tc1 IL‐17A Th17 Genetic predisposition IL‐17F IL‐23 IL‐22 Th2 Lymph node Th17 TNF‐α Macrophage IL‐6 IL‐1β DC=dendritic cell; PSORS1=psoriasis susceptibiity 1; IL=interleukin; TNF=tumor necrosis factor. Gaspari AA, Tyring S. Dermatol Ther. 2015;28(4):179‐93. Nestle FO, Kaplan DH, Barker J. N Engl J Med. 2009;361(5):496‐509. Individuals with Psoriasis are At Risk of Developing Other Chronic Conditions ↑ risk of poor self‐esteem, Depression/Anxiety psychological stress, and anxiety due to their psoriasis 39% ↑ risk of CV mortality Cardiovascular Disease 70% ↑ risk of MI 56% ↑ risk of MI 346% ↑ risk (mild psoriasis) Obesity 123% ↑ risk (severe) Metabolic Syndrome 22% ↑ risk (mild) 98% ↑ risk (severe) 14% ↑ risk (mild) Diabetes 46% ↑ risk (severe) Ni C, Chiu MW. Clin Cosmet Investig Dermatol. 2014;7:119‐32. Assessing Psoriasis Severity Assessments Classification of Severity Mild disease: <3% BSA Body Surface Area Percentage of skin area involved Moderate disease: 3%–10% BSA (BSA) Severe disease: >10% BSA Lesion characteristics including erythema, scaling, induration Psoriasis Area and Severity Index (PASI) Mild‐to‐moderate disease: Location/distribution of lesions BSA ≤ 10 and PASI ≤ 10 (eg, hands, feet, face, genitals) and DLQI ≤ 10 Dermatology Life Quality Index Moderate‐to‐severe disease: Impact on psychological factors (DLQI) (BSA >10 or PASI >10) and quality of life Itch Severity Score and DLQI >10 (ISS) Armstrong AW, Robertson AD, Wu J, Schupp C, Lebwohl MG. JAMA Dermatol. 2013;149(10):1180‐5. Menter A, Gottlieb A, Feldman SR, et al. J Am Acad Dermatol. 2008;58(5):826‐50. Spuls PI, Lecluse LL, Poulsen ML, Bos JD, Stern RS, Nijsten. J Invest Dermatol. 2010;130(4):933‐43. Both H, Essink‐bot ML, Busschbach J, Nijsten T. J Invest Dermatol. 2007;127(12):2726‐39. Mrowietz U, Kragballe K, Reich K, et al. Arch Dermatol Res. 2011;303(1):1‐10. Majeski CJ, Johnson JA, Davison SN, Lauzon CJ. Br J Dermatol. 2007;156(4):667‐73. Treatment of Psoriasis: Establish Individualized Treatment Goals • Goals of treatment1 Treatment • Clear the skin AEs • Minimize adverse events • Enhance patient quality of life Tailor • Address comorbidities Therapy Patient Patient Perception • Individualize therapy by involving of Severity the patient in treatment decision‐ making1,2 Disease • Consider patient preferences when Severity selecting therapy1,2 1. Schaarschmidt ML, Schmieder A, Umar N, et al. Arch Dermatol. 2011;147(11):1285‐94. 2. Brezinski EA, Armstrong AW. Semin Cutan Med Surg. 2014;33(2):91‐7. Treatment Approach: Treat‐to‐Target Treatment Goal: Reduce BSA to ≤1% three months after initiating treatment Initiate 3 months 6 months + Treatment post‐initiation post‐initiation Yes No Yes No BSA ≤1% BSA ≤1% Modify therapy Modify therapy Continue • Adjust dose Continue • Adjust dose current • Add another agent current • Add another agent therapy (combination therapy) therapy (combination therapy) • Switch to a new therapy • Switch to a new therapy Armstrong AW, Siegel MP, Bagel J, et al. J Am Acad Dermatol. 2017;76(2):290‐298. Treatment Options for Psoriasis • Topical therapies Mild • Steroid creams • Vitamin D analogues • Vitamin A retinoids • Ultraviolet light/lasers Moderate • UVB • PUVA • Systemic therapies Severe • Traditional/biologic DMARDs Psoriasis Severity Psoriasis Treatments. National Psoriasis Foundation Web site. https://www.psoriasis.org/about‐psoriasis/treatments. Accessed March 2018. Disease Severity Guides Treatment Selection Plaque Signs/symptoms of Yes Systemic psoriasis Phototherapy psoriatic arthritis? pharmacotherapy +/‐ diagnosed No Severity of disease? Mild Moderate‐to‐severe No Topical agents +/‐ Phototherapy Effective? Yes Continue current therapy Menter A, Gottlieb A, Feldman SR, et al. J Am Acad Dermatol. 2008;58(5):826‐50. Menter A, Korman NJ, Elmets CA, et al. J Am Acad Dermatol. 2009;60(4):643‐59. Menter A, Korman NJ, Elmets CA, et al. J Am Acad Dermatol. 2010;62(1):114‐35. Traditional Systemic DMARDS Acitretin Cyclosporine Methotrexate • Vitamin A derivative • Blocks inflammatory • Competitive inhibitor (retinoid) cytokine production of dihydrofolate • Immunomodulatory and T‐cell activation reductase and anti‐inflammatory • Initial approval: 1997 • Interferes with nucleic activity acid synthesis • Modulates epidermal inhibiting lymphoid proliferation and proliferation differentiation • Initial approval: 1972 • Initial approval: 1996 Menter A, Korman NJ, Elmets CA, et al. J Am Acad Dermatol. 2009;61(3):451‐85. Risk‐Benefit Ratios of Traditional DMARDs Efficacy Toxicity Cyclosporine Methotrexate Acitretin Biologics and Small Molecules Approved for the Treatment of Moderate‐to‐Severe Psoriasis Therapeutic Target IL‐17 TNF‐ IL‐17A IL‐23 IL‐12/23 PDE‐4 Receptor Adalimumab Brodalumab Secukinumab Guselkumab Ustekinumab Apremilast Certolizumab Ixekizumab Tildrakizumab Pegol Etanercept Golimumab Infliximab Biosimilars TNF=tumor necrosis factor; IL=interleukin; PDE‐4=phosphodiesterase Treatment Comparison. National Psoriasis Foundation Web site. https://www.psoriasis.org/sites/default/files/treatment_comparison_chart_7.pdf. Published December 2017. Accessed March 2018. Biologics Approved for Moderate‐to‐Severe Chronic Plaque Psoriasis: PASI 75, 90, and 100 Scores 100 PASI 75 PASI 90 PASI 100 90% 90 86% 82% 82% PASI 80 76% 71% 71% 73% 70 64% 59% 58% 59% achieving 60 51% 50 45% 44% 41% 40 36% 35% 75/90/100 33% patients 30% 30 26% of 20% 18% 20 14% 14% 10 7% Percent 0 Methotrexate12 Etanercept Adalimumab 34 Infliximab Ustekinumab 5 Secukinumab 67 Apremilast Ixekizumab8 Brodalumab91011 Guselkumab Tildrakizumab (Week 16) (Week 24) (Week 16) (Week 24) (Week 12) (Week 12) (Week 16) (Week 12) (Week 12) (Week 12) (Week 12) 1. Saurat JH, Stingl G, Dubertret L, et al. Br J Dermatol. 2008;158(3):558‐66. 2. Leonardi CL, Powers JL, Matheson RT, et al. N Engl J Med. 2003;349(21):2014‐22. 3. Menter A, Tyring SK, Gordon K, et al. J Am Acad Dermatol. 2008;58(1):106‐15. 4. Reich K, Nestle FO, Papp K, et al. Lancet. 2005;366(9494):1367‐74. 5. Papp KA, Langley RG, Lebwohl M, et al. Lancet. 2008;371(9625):1675‐84. 6. Langley RG, Elewski BE, Lebwohl M, et al. N Engl J Med. 2014;371(4):326‐38. 7. Otezla (apremilast) [package insert]. Summit, NJ: Celgene Corp.; 2017. 8. Taltz (ixekizumab) [package insert]. Indianapolis, IN: Eli Lilly and Co.; 2018. 9. Siliq (brodalumab) [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals; 2017. 10. Tremfya (guselkumab) [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2017. 9.Sun Pharma announces U.S. FDA approval of Ilumya (tildrakizumab‐asmn) for the treatment of moderate‐to‐severe plaque psoriasis. [news release]. Princeton, NJ: Sun Pharma; March 21, 2018. Biologics and Small Molecules in Late‐Stage Development Agent Description/Mechanism Status • Humanized IgG1 monoclonal antibody Risankizumab Phase 3 • Selectively binds the p19 subunit of IL‐23 • Highly selective monoclonal antibody Bimekizumab Phase 3 • IL‐17A and IL‐17F inhibitor • Small molecule A3 adenosine receptor antagonist Piclidenoson • Downregulates the nuclear factor‐ĸB signaling Phase 3 pathway • PEGylated anti‐TNF‐α biologic Certolizumab