Psoriasis

Disease definition & pathophysiology

Psoriasis is a chronic, immune-mediated inflammatory skin disorder. It involves rapid proliferation of keratinocytes, dysfunctional epidermal differentiation, and infiltration by immune cells (T-helper cells, dendritic cells, neutrophils). Key inflammatory mediators driving psoriasis include cytokines like TNF-α, IL-17, and IL-23.

Commonly used Pharmacodynamic (PD) Models

• Disease progression models (e.g., turnover models for plaque development and resolution)
• Indirect response models (cytokine-driven inflammatory response)
• Target engagement models (cytokine suppression, receptor occupancy models for biologics)

Typical patient population

• Commonly presents in adults aged 15–35 and 50–60 years
• Equal prevalence among genders
• Worldwide prevalence approximately 2–3%

Risk factors & disease progression indicators

• Family history and genetic predisposition (e.g., HLA-Cw6 allele)
• Environmental triggers: infections, stress, medications, trauma
• Comorbidities: psoriatic arthritis, cardiovascular disease, metabolic syndrome
• Disease progression indicated by extent/severity of skin involvement and responsiveness to initial therapies

Key Clinical Biomarkers

• Clinical evaluation of skin lesions (plaque thickness, erythema, scaling)
• Imaging rarely used, except to evaluate psoriatic arthritis (MRI, X-ray)
• Non-specific inflammation markers (CRP, ESR) sometimes elevated

Disease Severity Classification

• Psoriasis Area and Severity Index (PASI):
  • Mild: PASI < 10
    
  • Moderate-to-severe: PASI ≥ 10
• Body Surface Area (BSA) involvement:
  • Mild: <3%, Moderate: 3–10%, Severe: >10%
• Physician Global Assessment (PGA) commonly used

Treatment aim (PD-targets)

• Suppression of inflammation, reduction of epidermal hyperproliferation, and normalization of immune dysregulation
• Primary targets: TNF-α, IL-17, IL-23, IL-12 pathways

Common Drug Classes & Regimens

Commonly used PK-models

• One- or two-compartment pharmacokinetic models (particularly for biologics)
• Population PK-models incorporating covariates (body weight, immunogenicity, PASI scores)
• Exposure-response models linking drug concentration/exposure to PASI improvement