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

2. 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

3. 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

4. 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 days
Causing patches to appear

5. Types of Psoriasis

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

7. 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

9. 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

10. (HumiraPro, 2017)

11. 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

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

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

14. 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

15. 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

16. 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

17. 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,

18. jpet.aspetjournals.org

19. 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

20. 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

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

22. 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

23. 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

24. 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

25. 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

26. jpet.aspetjournals.org

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

28. 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

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

30. 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

31. 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

32. 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)

33. 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

34. 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.

36. 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

38. 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

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

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

41. 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

42. 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

43. 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

44. 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)

45. 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.

47. 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

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

50. 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

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

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

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

54. Ixekizumab (Taltz)

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

56. Ixekizumab (Taltz)
Drug Interactions
Live Vaccines
CYP450 Substrates

57. 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

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

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

60. 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

61. 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

62. The End

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

64. 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, doi: /j.aad
Phung, O., White, M., & Coleman, C. (2009). Ustekinumab: A human monoclonal antibody for the treatment of plaque psoriasis, Formulary Journal, 44,
Roman, M., Madkan, V., & Chiu, M. (2015). Profile of secukinumab in the treatment of psoriasis: current perspectives. Therapeutics and Clinical Risk Management, 11, doi: /TCRM.S79053
Thomas, V., Yang, C., & Kvedar, J. (2005). Biologics in psoriasis: A quick reference guide. American Academy of Dermatology, 53, doi: /j.jaad