Treating Psoriasis: A Guide to Understanding Biologics Marlee R. Steele DNP, RN, FNP-BC

Disclosures I have no financial disclosures related to this lecture Brand names as well as generic names are provided in the context of this talk for clarity

Learning Objectives The participant will be able to identify the different classes of biologics The participant will be able to explain the mechanism of action of biologics The participant will be able to recommend appropriate monitoring parameters for patients being treated with a biologic The participant will be able to identify proper administration of biologics The participant will be able to identify potential side effects of specific biologics

Psoriasis: Brief Overview Chronic noninfectious inflammatory disease of the skin Pathologic Process not fully understood Develops as secondary response triggered by T Lymphocytes T-Cell activation leads to cytokine cascade leading to inflammation and proliferation of keratinocytes Resulting in newly formed cells to move rapidly to the surface This occurs every 3-4 days vs normal 26-28 days Causing patches to appear

Types of Psoriasis

Biologic Medications TNF-Alpha (TNF-α) Inhibitors Interleukin-12/23 (IL-12/IL-23) Blockade Agents Interleukin-17A

TNF-Alpha (TNF-α) Inhibitors Cytokine that promotes an inflammatory response At high levels can trigger inflammatory response that leads to excessive keratinocyte proliferation Patients with psoriasis have higher levels of TNF-α TNF inhibitors bind TNF-α to neutralize its pro- inflammatory effects in psoriasis

Adalimumab (Humira) Fully human anti-TNF-α monoclonal antibody that binds to and blocks the activation of TNF-α Approved for treatment of Moderate-to-Severe Psoriasis as well as Moderate-to-Severe Psoriatic Arthritis, Adult and Juvenile Rheumatoid Arthritis, Ankylosing Spondylitis, Crohn’s Disease, and Hidradenitis Suppurativa

(HumiraPro, 2017)

Adalimumab (Humira) Administration Subcutaneous injection Prefilled syringe/pen Dosage and Frequency 80mg day 1 40mg day 8 40mg day 22 Continue 40mg every other week

Adalimumab (Humira) Monitoring Baseline LFT, CBC, Hepatitis Profile, PPD After initiation periodic CBC and LFT Annual PPD Half-Life 10-20 days

Adalimumab (Humira) Drug Interactions Methotrexate Biological Products Anakinra (Kineret) Abatacept (Orencia) Rituximab (Rituxan) Live Vaccines CYP450 Substrates

Adalimumab (Humira) Safety Considerations Safety Considerations Cont. Administered to adults 18 years of age and older Pregnancy Category B Consideration into stopping medication during pregnancy Increased risk for developing serious infections Patients >65 yrs. of age at greater risk of developing infection Live vaccines should not be administered Safety Considerations Cont. Treat latent TB before use Considerations for surgery Adults should be up to date with immunizations History of malignancy Signs or symptoms of infection- patient should be instructed to discontinue medication

Adalimumab (Humira) Adverse Effects Adverse Effects Cont. Injections site pain, erythema, pruritus Upper respiratory tract infection Headache Rash Sinusitis Increased Creatinine Phosphokinase Nausea UTI Adverse Effects Cont. Abdominal pain Flulike symptoms Hyperlipidemia Back pain Hypercholesterolemia Hematuria Hypertension Increased alkaline phosphatase

Adalimimab (Humira) Black Box Warnings: Serious Infection Risk Not to be used with Active TB May cause reactivation of latent TB Treat latent TB infection before use Invasive fungal infections may develop Avoid use in patients with Hepatitis B infection Bacterial infections such as Legionella, Listeria Malignancy Lymphoma (Hepatosplenic T-Cell Lymphoma) Leukemia when being used for RA

Etanercept (Enbrel) Fully human fusion protein consisting of a soluble TNF receptor. Binds to both soluble and membrane bound TNF-α, lowering the amount of available TNF-α, decreasing the pro-inflammatory effects of TNF-α Approved to treat moderate-to-severe psoriasis, moderate-to-severe psoriatic arthritis, juvenile idiopathic arthritis, ankylosing spondylitis,

jpet.aspetjournals.org

Etanercept (Enbrel) Administration Adult: Pediatric: Subcutaneous injection Prefilled syringe/auto injector Adult: Initial: >18 years of age 50mg SC twice weekly for 3 months Maintenance: 50mg SC once weekly Pediatric: Initial: >4 years (<63kg)0.8mg/kg SC weekly not to exceed 50mg weekly Initial: >4 years (>63kg): 50mg SC weekly Dosage and Frequency 50mg SC once weekly

Etanercept (Enbrel) Monitoring Baseline LFT, CBC, Hepatitis Profile, PPD After initiation periodic CBC and LFT Annual PPD Onset 1-2 weeks Half-Life <5 days

Etanercept (Enbrel) Drug Interactions Orencia Kineret Cyclophosphamide Anti-diabetic medications Live Vaccines

Etanercept (Enbrel) Safety Considerations Safety Considerations Cont. Pregnancy Category B Consideration to stopping medication Increased risk for developing serious infections Patients >65 yrs. of age at greater risk of developing infection Live vaccines should not be administered Treat latent TB before use History of Hepatitis B Safety Considerations Cont. Heart failure Diabetes Allergy to rubber or latex Children and adults should be up to date with immunizations before starting drug History of malignancy Signs or symptoms of infection- patient should be instructed to discontinue medication

Etanercept (Enbrel) Adverse Effects Upper respiratory tract infection Non-upper respiratory tract infection Headache Rhinitis Nausea Adverse Effects Cont. Dizziness Pharyngitis Abdominal pain Vomiting Hematologic disorders

Etanercept (Enbrel) Black Box Warnings Serious Infection Risk Not to be used with Active TB May cause reactivation of latent TB Treat latent TB infection before use Invasive fungal infections may develop Avoid use in patients with Hepatitis B infection Bacterial infections such as Legionella, Listeria Malignancy Lymphoma Leukemia in patient’s with RA

Infliximab (Remicade) Part mouse, part human monoclonal antibody that binds to soluble and membrane bound TNF-α molecules, inhibiting the pro-inflammatory action of TNF-α Approved for treating severe psoriasis, moderate-to- severe psoriatic arthritis, adult rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, and Crohn’s disease

jpet.aspetjournals.org

Infliximab (Remicade) Administration IV infusion over 2 hours Dosage and Frequency 5mg/kg IV at 0,2, and 6 weeks then every 8 weeks

Infliximab (Remicade) Monitoring Baseline LFT, CBC, Hepatitis Profile, PPD After initiation periodic CBC and LFT Annual PPD Onset Rapid onset Half-Life 7-12 days

Infliximab (Remicade) Drug Interactions Live vaccines Biologics Kineret Orencia Actemra Methotrexate Immunosuppressant's CYP450

Infliximab (Remicade) Safety Considerations Pregnancy Category B Consideration to stopping medication Increased risk for developing serious infections Patients >65 yrs. of age at greater risk of developing infection Live vaccines should not be administered Treat latent TB before use Safety Considerations Cont. History of Hepatitis B History of malignancy COPD Immunizations should be current before therapy Signs or symptoms of infection- patient should be instructed to discontinue medication

Infliximab (Remicade) Adverse Effects Development of anti-drug neutralizing antibodies Infection Upper respiratory tract infection Abdominal pain Nausea Adverse Effects Cont. Infusion reaction Headache Diarrhea Hepatoxicity Congestive heart failure

Infliximab (Remicade) Black Box Warnings Serious Infection Risk Not to be used with Active TB May cause reactivation of latent TB Treat latent TB infection before use Invasive fungal infections may develop Avoid use in patients with Hepatitis B infection Bacterial infections such as Legionella, Listeria Malignancy Lymphoma (Hepatosplenic T-Cell Lymphoma)

TNF-α Inhibitor’s Overview All TNF Inhibitors carry potential for increased risk for infection with upper respiratory tract infections being the most common Serious infections are uncommon, with patients with underlying predisposing medical conditions being more at risk In the event of an infection requiring an antibiotic the TNF Inhibitor should be withheld, and more serious infections or opportunistic infections the TNF Inhibitor should be discontinued TNF Inhibitors should be avoided if possible in patient’s with chronic, serious, or recurring infections Reactivation of TB has been associated with TNF Inhibitors

Interleukin 12/23 Blockade Agents IL-12 promotes T-cell differentiation into Th1 cells and production of IFN-ϒ IL-23 induces differentiation of the TH17 T-cell that leads to inflammation and autoimmunity IL-12 and IL-23 contain a p40 subunit that is over- expressed in psoriasis patients causing elevated levels of IL-12/23 Drugs in this class are injected antibodies that bind to this shared p40 protein subunit and consequently modulate the levels of IL-12/23. Due to their role in the formation of psoriatic lesions, IL-12/23 have become the focus for biologic medications. Currently there is only one medication in this class for the management of moderate to severe psoriasis.

www.nature.com

Ustekinumab (Stelara) Monoclonal human antibody that targets IL-12/IL-23 chemical messengers Approved to treat moderate-to-severe plaque psoriasis, psoriatic arthritis, and crohn’s disease in patients 18 years of age and older

Ustekinumab (Stelara) Administration Subcutaneous Injection (pre-filled syringes) IV Infusion Dosage and Frequency ≤100kg: 45mg SC initially, then 4 weeks later 45mg SC, and then every 12weeks 45mg SC >100kg: 90mg SC initially, then 4 weeks later give 90mg SC, and then every 12 weeks 90mg SC

Ustekinumab (Stelara) Monitoring Baseline LFT, CBC, Hepatitis Profile, PPD After initiation periodic CBC and LFT Annual PPD Half-Life 10-126 days

Ustekinumab (Stelara) Drug Interactions Live Vaccines CYP450 Substrates Concomitant Therapies Allergen Immunotherapy

Ustekinumab (Stelara) Safety Considerations Pregnancy Category B Pregnancy should be avoided while on medication Increased risk for developing serious infections Patients >65 yrs. of age at greater risk of developing infection Live vaccines should not be administered Treat latent TB before use History of malignancy Immunizations should be current before therapy Signs or symptoms of infection- patient should be instructed to discontinue medication

Ustekinumab (Stelara) Adverse Effects Upper respiratory infection Nasopharyngitis Back pain Cellulitis Depression Diarrhea Fatigue Adverse Effects Cont. Headache Injection site erythema Myalgia Nasal Congestion Urticaria Rash

Ustekinumab (Stelara) Warnings May increase risk of infections and/or reactivation of latent infections Increased risk of malignancy Non-melanoma skin cancers May decrease the protective effect of allergen immunotherapy One reported case of Reversible Posterior Leukoencephalopathy Syndrome Avoid pregnancy No black box warnings are noted at this point in time

Interleukin 12/23 Blockade Agents Overview Serious infections may occur from mycobacteria, salmonella, and BCG vaccinations in patients genetically deficient in IL-12/IL-23 Evaluate patients for TB May increase the risk of malignancy Hypersensitivity reactions Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

Interleukin-17A (IL-17A) Monoclonal antibodies that that target and block the actions of IL-17A Used in the treatment of moderate-to-severe plaque psoriasis, psoriatic arthritis, ankylosing spondylitis IL-17A is elevated in lesions of psoriasis. Th17 cells are main producers of IL-17A. IL-17A has many functions relevant to psoriasis including the enhancement of angiogenesis, the promotion of the release of other inflammatory cytokines such as TNF-α and the activation of keratinocytes leading to increased production of chemokines.

Secukinumab (Cosentyx) Administration 150mg prefilled syringe or sensoready pen Subcutaneous Injections Adults >18 years of age Dosage/Frequency 300mg SC at weeks 0,1,2,3, and 4 Monthly maintenance beginning at week 8, 300mg SC once monthly

www.cosentyx.com

Secukinumab (Cosentyx) Monitoring Baseline LFT, CBC, Hepatitis Profile, PPD After initiation periodic CBC and LFT Annual PPD Half-Life 22-31 days

Secukinumab (Cosentyx) Safety Considerations Pregnancy Category B While Category B it is recommended to stop medication Live vaccines should not be administered Caution in considering use in patients with chronic infection or history of recurrent infection Immunizations should be current before therapy Treat latent TB before use May exacerbate Crohn’s Disease

Secukinumab (Cosentyx) Adverse Effects Infections Nasopharyngitis Diarrhea URT Infection Rhinitis Adverse Effects Cont. Oral Herpes Pharyngitis Urticaria Rhinorrhea Anaphylaxis

Secukinumab (Cosentyx) Drug Interactions CYP450 substrates Live Vaccines Non-Live Vaccines

Ixekizumab (Taltz) Administration Subcutaneous injection Auto injector or Prefilled Syringe Adults >18 years of age Dosage/Frequency Week 0- 160mg SC Week 2,4,6,8,10,& 12 80mg SC Then 80mg SC every 4 weeks

Ixekizumab (Taltz)

Ixekizumab (Taltz) Monitoring Baseline LFT, CBC, Hepatitis Profile, PPD After initiation periodic CBC and LFT Annual PPD Half-Life 13 days

Ixekizumab (Taltz) Drug Interactions Live Vaccines CYP450 Substrates

Ixekizumab (Taltz) Safety Considerations Pregnancy Category B While Category B it is recommended to stop medication Live vaccines should not be administered Caution in considering use in patients with chronic infection or history of recurrent infection Immunizations should be current before therapy Treat latent TB before use May exacerbate Crohn’s Disease

Ixekizumab (Taltz) Adverse Effects Injection site reactions Upper Respiratory Tract Infections Serious Infections Nausea Tinea Infections Hypersensitivity reactions

Ixekizumab (Taltz) Warnings Serious hypersensitivity reactions such as angioedema and urticarial Discontinue use of Taltz while patient is being treated for infection

Interleukin 17-A (IL-17A) Overview In the event of an infection requiring an antibiotic the IL-17A should be withheld, and more serious infections or opportunistic infections the IL-17A should be discontinued May cause inflammatory bowel disease exacerbations, patient’s who have inflammatory bowel disease should be monitored closely Evaluate patient for TB prior to initiating therapy

Guide to Prescribing Biologics Complete history and physical examination Identifying any potential contraindications to therapy Past treatment Topical therapy indicated for patient’s with plaque type psoriasis with less than 5% BSA Systemic therapy- including biologics and phototherapy appropriate for patients with >5% BSA Patient’s with <5% BSA are candidates for systemic therapy if they have failed topical therapy, or difficult-to-treat areas Lab work Therapy for psoriasis must be individualized and take into account multiple factors including extent of disease, response to previous treatments, cost, availability, and the patient’s lifestyle. Difficult to treat areas include scalp, nails, palmo-plantar surfaces, or patients with forms of psoriasis such as guttate, erythodermic, or pustular psoriasis

The End

References Gottlieb, A., Kardos, M., & Yee, M. (2009). Current biologic treatments for psoriasis. Dermatology Nursing, 21,259-272. Herrier, R. (2011). Advances in the treatment of moderate-to-severe plague psoriasis. American Society of Health-System Pharmacists, 68, 795-806. doi:10.2146/ajhp100227 Krueger, J. (2002). The immunologic basis for the treatment of psoriasis with new biologic agents. American Academy of Dermatology, 1-23. doi:10.1067/mjd.2002.120568 Loss L., & Kalb, R. (2009). Psoriasis therapy. Disease Management, 15-20.

References Menter, A., Gottlieb, A., Feldman, S., Voorhees, A., & Leonardi, C. et. al. (2008). Guidelines of care for the management of psoriasis and psoriatic arthritis. American Academy of Dermatology, 826-850. doi:10.1016/j.aad.2008.02.039 Phung, O., White, M., & Coleman, C. (2009). Ustekinumab: A human monoclonal antibody for the treatment of plaque psoriasis, Formulary Journal, 44, 72-76. Roman, M., Madkan, V., & Chiu, M. (2015). Profile of secukinumab in the treatment of psoriasis: current perspectives. Therapeutics and Clinical Risk Management, 11, 1767-1777. doi: 10.2147/TCRM.S79053 Thomas, V., Yang, C., & Kvedar, J. (2005). Biologics in psoriasis: A quick reference guide. American Academy of Dermatology, 53, 346-351. doi:10.1016/j.jaad.2005.04.011