What is tildrakizumab (biologic medication) and its indications for treating adult patients with moderate to severe plaque psoriasis?

Tildrakizumab: Mechanism and Indications

Tildrakizumab (ILUMYA®) is a humanized monoclonal antibody that selectively targets the p19 subunit of interleukin-23 (IL-23), and is FDA-approved for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. 1

Mechanism of Action

Tildrakizumab is an IL-23 antagonist that specifically inhibits the p19 subunit of IL-23, thereby blocking the IL-23/IL-17 axis—the signaling pathway primarily implicated in the immunopathogenesis of psoriasis. 2, 3 This targeted mechanism distinguishes it from broader IL-12/IL-23 inhibitors by providing more selective immunomodulation. 2

FDA-Approved Indication

The sole FDA-approved indication for tildrakizumab is the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. 1

Dosing and Administration

The recommended dose is 100 mg administered by subcutaneous injection at weeks 0 and 4, then every 12 weeks thereafter. 4, 1 This dosing schedule is supported by Grade A evidence from the American Academy of Dermatology/National Psoriasis Foundation guidelines. 4

Key Dosing Characteristics:

• Initial loading: 100 mg at week 0 and week 4 4, 1
• Maintenance: 100 mg every 12 weeks 4, 1
• Administration route: Subcutaneous injection 1
• Administration setting: Originally physician-administered in office per guidelines 4, though the FDA label indicates it can be self-administered 1

Clinical Efficacy

Short-Term Efficacy (Week 12-28)

Tildrakizumab demonstrates robust efficacy in moderate-to-severe plaque psoriasis:

• 66% of patients achieved PASI 75 at week 12 with the 200 mg dose in the reSURFACE 2 trial 4
• 61% achieved PASI 75 with the 100 mg dose at week 12 4
• Response rates peaked at week 22 and continued to improve through week 28 2
• Superior to etanercept: 66% (tildrakizumab 200 mg) vs 48% (etanercept) achieved PASI 75 at week 12 4

Long-Term Efficacy (Up to 3 Years)

At week 148 (approximately 3 years), 72.6% of responders to tildrakizumab 100 mg maintained PASI 75 response, with 53.8% achieving PASI 90 and 28.9% achieving PASI 100. 5 For the 200 mg dose, these rates were even higher: 80.2% (PASI 75), 59.9% (PASI 90), and 32.6% (PASI 100). 5

Real-World Effectiveness

In real-world settings through 64 weeks, tildrakizumab demonstrated:

• 87.0% of patients achieved PASI 75 at week 52 6
• 56.5% achieved PASI 90 6
• 32.6% achieved complete clearance (PASI 100) 6
• Mean body surface area decreased by 83.1% from baseline to week 64 6

Guideline Recommendations

The American Academy of Dermatology and National Psoriasis Foundation provide a Grade A (strongest) recommendation for tildrakizumab as monotherapy in adult patients with moderate-to-severe plaque psoriasis. 4 This recommendation is based on Level I evidence from multiple randomized controlled trials. 4

Important Clinical Considerations:

• Time to assess response: Definitive response should be assessed after 12 weeks of continuous therapy 4
• Partial responders: Consider adding topical corticosteroids, vitamin D analogues, methotrexate, or ultraviolet B light for patients with partial response 4
• Dose escalation: While not FDA-approved, consider dose escalation in partially responding patients 4

Safety Profile

Tildrakizumab is generally well tolerated with a favorable long-term safety profile. 5, 7 The most common adverse reactions (≥1%) are:

• Upper respiratory infections 1
• Injection site reactions 1
• Diarrhea 1

Long-Term Safety Data (Up to 3 Years):

• Low discontinuation rate: 1.7 per 100 patient-years for adverse events with 100 mg dose 5
• Serious adverse events: 5.9 per 100 patient-years 5
• Severe infections: 1.1 per 100 patient-years 5
• Malignancies: 0.6 per 100 patient-years 5
• Major adverse cardiovascular events: 0.4 per 100 patient-years 5
• No new safety signals identified in real-world studies 6

Contraindications and Warnings

Tildrakizumab is contraindicated in patients with serious hypersensitivity reaction to tildrakizumab or any excipients. 1

Key Warnings:

• Infections: May increase risk of infection; discontinue if serious infection develops until resolved 1
• Tuberculosis screening: Evaluate for TB prior to initiating treatment 1
• Immunizations: Avoid use of live vaccines 1
• Hypersensitivity: Discontinue immediately if serious allergic reaction occurs 1

Clinical Positioning

Tildrakizumab expands the therapeutic options for moderate-to-severe plaque psoriasis, particularly for patients with inadequate response to phototherapy and conventional systemic agents. 2 The every-12-week dosing schedule may be preferred by patients who value less frequent administration compared to biologics requiring more frequent dosing. 4

Comparative Context:

While tildrakizumab demonstrates slightly lower efficacy compared to other IL-23p19 inhibitors like guselkumab (which achieves 70-73% PASI 90 at week 16), 8 it remains a valuable option with excellent long-term safety data and convenient dosing. 3, 7