Tildrakizumab

• Plaque Psoriasis
• Moderate-to-Severe Psoriasis
• Chronic Plaque Psoriasis

Tildrakizumab is a humanized IgG1 kappa monoclonal antibody that selectively blocks interleukin-23 (IL-23) and is used to treat moderate-to-severe plaque psoriasis. By specifically targeting the p19 subunit of IL-23, it interrupts a key inflammatory pathway involved in psoriasis pathogenesis while preserving other immune functions.

Mechanism of Action

Tildrakizumab works through selective cytokine inhibition:

• IL-23 p19 subunit blockade: Binds specifically to the p19 subunit of interleukin-23
• Prevents IL-23 signaling: Blocks interaction with the IL-23 receptor
• Reduces Th17 cell activation: Decreases downstream production of IL-17 and IL-22
• Interrupts inflammatory cascade: Reduces keratinocyte proliferation and inflammation
• Selective targeting: Does not block IL-12 (which shares the p40 subunit with IL-23)

This selectivity for IL-23 over IL-12 may preserve protective immune responses while effectively treating psoriasis.

Available Formulations

Tildrakizumab is available as:

• 100 mg/mL single-dose prefilled syringe (Ilumya)
• For subcutaneous injection only

Medical Uses

FDA-Approved Indication:

• Treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy

Tildrakizumab is typically considered for patients who have not responded to or are intolerant of conventional systemic therapies.

Dosing Guidelines

Adults (Plaque Psoriasis):

• 100 mg subcutaneously at weeks 0 and 4 (loading doses)
• Then 100 mg every 12 weeks (maintenance)

Administration:

• Inject subcutaneously in thigh, abdomen, or upper arm
• Rotate injection sites
• Allow prefilled syringe to reach room temperature before injection
• Do not shake

Important Safety Information

Contraindications:

• Previous serious hypersensitivity reaction to tildrakizumab or any excipients

Warnings and Precautions:

• Infections: May increase risk of infections; evaluate and treat any infections before initiating; avoid in active infections
• Tuberculosis: Evaluate for TB before initiating therapy; do not give to patients with active TB
• Hypersensitivity reactions: Angioedema and urticaria have been reported; discontinue if serious reaction occurs
• Vaccinations: Avoid live vaccines during treatment; can give inactivated vaccines

Drug Interactions

Tildrakizumab has low potential for drug interactions:

• No CYP450 metabolism: As a monoclonal antibody, not metabolized by cytochrome P450 enzymes
• Live vaccines: Avoid during tildrakizumab treatment due to immunomodulation
• Other immunosuppressants: Concomitant use with other biologics not studied; potential for additive immunosuppression

Special Populations

• Hepatic Impairment: No formal studies; monoclonal antibodies not hepatically cleared; no dose adjustment expected
• Renal Impairment: No formal studies; monoclonal antibodies not renally cleared; no dose adjustment expected
• Elderly: Clinical studies included patients 65+; no overall difference in safety or efficacy
• Pregnancy: Limited data; use only if benefit outweighs potential risk to fetus
• Lactation: Unknown if excreted in breast milk; consider benefits of breastfeeding vs treatment
• Pediatric: Safety and efficacy not established in patients <18 years

Efficacy Data

Clinical trials demonstrated significant skin clearance:

• PASI 75 response at week 12: ~64% vs 6% placebo
• PASI 90 response at week 28: ~54%
• PASI 100 (complete clearance) at week 28: ~24%
• Responses maintained through 52+ weeks with continued treatment