Psoriasis Biologics and Beyond

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PsoriasisBiologics and Beyond

• Clive M. Liu, M.D.
• Dermatology Associates
• Clinical Instructor
• University of Washington

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Psoriasis

• Each morning, I vacuum my bed. My torture is skin
  deep there is no pain, not even itching we
  lepers live a long time, and are ironically
  healthy in other respects. Lusty though we are
  loathsome to love. Keen-sighted though we hate
  to look upon ourselves. The name of the disease,
  spiritually speaking, is Humiliation
• John Updike. The New Yorker, July 19, 1986

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Question 1Can you cure psoriasis?Answer Well
Yes!!!!

• Human bone marrow transplant experiment
• Treatment for various leukemias and lymphomas
• Risk
• Mortality 10-40
• Serious Infections.

BMTx from non affected
BMTx from affected
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What does this mean? Psoriasis is an autoimmune
disease
Concept from Grabbe S, Schwarz T. Immunol Today.
19981937-43.
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Question 2Is there is a genetic influence
35-70
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Question 3Is there a highly effective and very
safe treatment for psoriasis?

• Yes Geockerman therapy

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Types of Psoriasis

• Plaque
• Most common, 80 of all cases
• Raised, red scaly lesions
• Guttate
• Small, dot-like lesions
• Erythrodermic
• Intense redness, inflammation, some scaling
• Pustular
• Pus-filled lesions, some scaling
• often localized to palms and soles

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Psoriatic Arthritis

• Affect between 15-40 of patients with psoriasis
• Average age mid thirties
• 70 develop after appearance of psoriasis
• 15 with the appearance of psoriasis
• 15 before the development of psoriasis
• Diagnosis of exclusion

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New Kids on the Block

• Anti CD2
• Alefacept
• TNF- Inhibitor
• Etanercpet
• Adalimumab
• Infliximab
• Anti IL12/23
• Ustekinumab

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Alefacept

• First biologic for psoriasis
• Rarely used
• Blocks CD2 found in Memory T-cells
• Injected at 12 week intervals at the doctors
  office. Interspaced with at least 12 weeks
  without therapy.
• Pros Intermittent treatment considered
  relatively safe
• Con 20 30 clearance rate. Need to monitor CD4
  levels. Slow rate of improvement

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Inhibitors of Tumor Necrosis Factor -alpha

• Used for multiple indications
• Rheumatoid arthritis
• Juvenile idiopathic arthritis
• Ankylosing spondylitits
• Psoriasis
• Psoriatic Arthritis
• Crohns disease (not etanercept)

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Etanercept

• Rheumatoid arthritis indication
• Psoriasis indication
• Soluable receptor for pro-inflammatory molecule
  (TNF)
• Inject under the skin 50 mg twice a week for 3
  months than 25 mg twice a week

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Adalimumab

• Rheumatoid arthritis indication
• Psoriasis indication
• Humanized monoclonal antibody against TNF
• Inject under the skin 80 mg once followed by 40
  mg every two weeks (starts one week after loading
  dose)

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Infliximab

• Rheumatoid Arthritis indication
• Psoriasis indication
• Chimeric antibody against TNF
• Intravenous injection at weeks 0, 2, 6 and then
  every 8 weeks

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Safety Concerns

• Infections
• Tuberculosis
• Case of Disseminated TB
• Get a PPD
• Consider positive if PPD is GREATER THAN 5mm
• or
• Quantiferon Gold blood test
• Positive Get CXR and start treatment for latent
  TB
• When to start treatment????
• Completion of therapy
• After one to three months of therapy

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Infections

• Atypical fungal infections
• Hepatitis B
• HIV
• Most common side effects
• Upper respiratory infection
• Injection Site Reactions

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Other Concerns

• Congestive Heart Failure
• Demyelinating disorders
• Lymphoma
• Non-melanoma skin cancer
• Lupus like disorder

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New Neighbors

• Ustekinumab
• Humanized monoclonal antibody IL-12/23
• Dosing
• Under 100kg 45 mg
• Above 100kg 90 mg
• Week 0, 4 and every 12 week

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Safety Concerns

• Infections
• No signal yet for Tuberculosis
• Major adverse cardiac events?

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Take with a grain of saltPASI 75 response 12-16
weeks
Percent of patients achieving PASI 75
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Future

• Briakinumab
• Antibody against IL-12/23
• Monthly injections
• On hold due to concerns of major adverse
  cardiac events.

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90
93
93
90
63
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In Phase II and III Trials

• Anti Il-17
• Jak3 Kinase inhibitor
• Protein Kinase C inhibitor