Psoriasis What’s New Dr. Vincent P Beltrani Clinical Instructor of Dermatology Columbia University College of Physicians and Surgeons

Old concepts Psoriasis is just a skin disease --minimal impact on quality of life --no association with other comorbidities Effective drugs are often discovered accidentally

New concepts Psoriasis is an inflammatory disease of the skin and joints that is often a reflection of more pervasive systemic inflammation. Moderate to severe psoriasis is associated with numerous common comorbidities. Modern treatments are specifically designed to target proinflammatory cytokines implicated in the pathogenesis of psoriasis

Psoriasis Comorbities Obesity Cardiovascular disease including myocardial infarction, stroke, hypertension Diabetes Hyperlipidemia Psoriatic arthritis Crohn’s disease Lymphoma Psychiatric disease Increase risk mortality

Treatment of moderate to severe psoriasis reduces risks of comorbities In one meta-analysis, standardized mortality rates in treated patients was less than 1 (less than expected in the general population)

Old Systemic Drugs Methotrexate Cyclosporine Acetretin Mycophenolic acid and other immunosuppressive agents (phototherapy)

Methotrexate First used 1947 for childhood leukemia 1951 noted to have positive effects on psoriasis and RA 1971 approved for psoriasis 1988 approved for RA Adverse effects and toxicity-patient selection Drug interactions Contraindications PASI 75 approx 35%

Cyclosporine 1983 approved for organ transplantation 1997 approved for psoriasis Adverse effects and toxicity Drug interactions Contraindications PASI 75 approx 50-70%

Etretinate/Acetretin 1986/1997 approved for psoriasis Adverse effects and toxicity Drug interactions Contraindications PASI 75 approx 34-52%

New Systemic drugs Etanercept (Enbrel) Infliximab (Remicaide) Adalimumab (Humira) Ustekinumab (Stelara) Secukinumab (Cosentyx) Ixekizumab (Taltz) Apremilast (Otezla)

Psoriasis cytokines

Psoriasis cytokines

etanercept/Enbrel 1998 approved for RA 2004 approved for psoriasis Nov 2016 approved for childhood psoriasis to age 4 Soluble TNF receptor PASI 75 approx 44%

infliximab/Remiciade 1998 approved for Crohn’s disease 1999 approved for RA 2006 approved for psoriasis IV chimeric monoclonal antibody to TNF PASI 75 approx 80%

adalimumab/Humira 2002 approved for RA 2008 approved for psoriasis (at that time, the 5th indication for adalimumab) Now approved for 10 indications Human monoclonal antibody to TNF PASI 75 approx 71%

Monitoring of TNF inhibitors Baseline TB test and HBV screening Periodic CBC/CMP ? Pregnancy category B

ustekinumab/Stelara 2009 approved for psoriasis 2013 approved for PsA 2016 approved for Crohn’s disease Human monoclonal antibody to IL-12 and IL-23 PASI 70 approx 75% Monitoring-baseline TB test Pregnancy category B

secukinumab/Cosentyx 2015 approved for psoriasis 2016 approved for PsA and AS Human monoclonal IgG1 antibody to IL-17 PASI 75 approx 82% at week 12 Monitoring-baseline TB test Pregnancy category B

ixekizumab/Taltz March 2016 approved for psoriasis Humanized monoclonal IgG4 antibody to IL-17 PASI 75 approx 89% Monitoring-baseline TB test Pregnancy category B

apremilast/Otezla 2014 approved for Psoriasis and PsA Orally administered “small molecule” inhibitor of PDE4. PDE4 breaks down cAMP. Increased cAMP down regulates TNF, IL-17 and 23. PASI 75 approx 33%. Higher over time? Monitoring-none Pregnancy category C