How does tildrakizumab compare to ustekinumab (Stelara) in the treatment of moderate to severe plaque psoriasis in adults?

Tildrakizumab vs. Ustekinumab for Moderate-to-Severe Plaque Psoriasis

Tildrakizumab demonstrates comparable efficacy to ustekinumab for moderate-to-severe plaque psoriasis, with both agents achieving PASI 75 rates of 61-66% at week 12, though ustekinumab offers the distinct advantage of FDA approval for concomitant psoriatic arthritis while tildrakizumab does not. 1, 2

Comparative Efficacy

PASI 75 Response Rates at Week 12

• Tildrakizumab 100 mg: 61% achieved PASI 75 1, 2
• Tildrakizumab 200 mg: 66% achieved PASI 75 1, 2
• Ustekinumab 45 mg: 66.7-67.1% achieved PASI 75 1
• Ustekinumab 90 mg: 66.4-75.7% achieved PASI 75 1

The efficacy profiles are remarkably similar, with both agents demonstrating robust response rates in the 60-75% range for PASI 75 at the primary endpoint. 1

PASI 90 Response Rates

• Tildrakizumab 100 mg: 39% achieved PASI 90 at week 12 1
• Tildrakizumab 200 mg: 37% achieved PASI 90 at week 12 1
• Ustekinumab: PASI 90 data not explicitly provided in the pivotal trials at week 12, though the drug demonstrates sustained efficacy through longer follow-up 1

Dosing Considerations

Tildrakizumab Dosing

• Standard dose: 100 mg subcutaneously at weeks 0,4, then every 12 weeks 1, 2
• Higher dose option: 200 mg available but not routinely recommended 1
• Administration: In-office physician-administered injection 1

Ustekinumab Dosing

• Weight-based dosing: 45 mg for patients ≤100 kg; 90 mg for patients >100 kg 1
• Schedule: Weeks 0,4, then every 12 weeks 1
• Dose escalation option: Can increase to 90 mg in lighter patients or shorten interval to every 8 weeks for inadequate responders 1

The key advantage of ustekinumab is its flexible dosing strategy with established dose escalation pathways for partial responders, whereas tildrakizumab has a more fixed dosing approach. 1

Critical Clinical Distinctions

Psoriatic Arthritis

• Ustekinumab: FDA-approved for psoriatic arthritis with Grade A recommendation 1
• Tildrakizumab: No FDA approval or established efficacy data for psoriatic arthritis 1, 2

If your patient has or may develop psoriatic arthritis, ustekinumab is the clear choice as it addresses both skin and joint manifestations with Level I evidence. 1

Special Psoriasis Subtypes

Ustekinumab has broader evidence for special presentations: 1

• Palmoplantar psoriasis: Grade B recommendation, with 67% clearance at 90 mg dose 1
• Nail psoriasis: Grade B recommendation, with 100% median NAPSI improvement by week 40 1
• Scalp psoriasis: Grade C recommendation (case report level) 1
• Pustular/erythrodermic variants: Grade C recommendation 1

Tildrakizumab lacks specific guideline recommendations or robust data for these special presentations. 1, 2

Long-Term Efficacy and Durability

Tildrakizumab

• Real-world data shows 83.1% reduction in BSA through 64 weeks 3
• 87% achieved PASI 75 at week 52 in real-world settings 3
• Efficacy maintained for at least 5 years in clinical trials 4

Ustekinumab

• Established long-term efficacy data from PHOENIX trials 1
• Response rates peak at week 22 and maintain through extended follow-up 1

Safety Profile

Both agents demonstrate excellent safety profiles:

• Tildrakizumab: No dose-related differences in adverse events, low discontinuation rates, no increased malignancy risk through 5 years 4, 3
• Ustekinumab: Well-established safety profile with extensive post-marketing data 1
• Neither agent shows definitive evidence of increased solid tumor or lymphoreticular malignancy risk, though long-term surveillance continues 1

Mechanism of Action Nuance

• Tildrakizumab: Selectively targets IL-23 p19 subunit only 1, 2
• Ustekinumab: Targets shared p40 subunit of both IL-12 and IL-23 1, 5

The more selective IL-23 inhibition of tildrakizumab theoretically offers a more targeted approach, though this has not translated to superior clinical outcomes compared to ustekinumab's dual IL-12/IL-23 blockade. 1, 5

Clinical Decision Algorithm

Choose ustekinumab if:

• Patient has or is at risk for psoriatic arthritis 1
• Patient has palmoplantar or nail psoriasis requiring specific evidence-based treatment 1
• Patient may need dose escalation flexibility for partial response 1
• Patient weighs >100 kg and would benefit from weight-based dosing 1

Choose tildrakizumab if:

• Patient has pure plaque psoriasis without joint involvement 1, 2
• Patient prefers fixed dosing without weight-based calculations 1, 2
• Patient has failed or has contraindications to other biologics 4, 6
• Cost considerations favor tildrakizumab in your healthcare system 3

Common Pitfalls to Avoid

• Do not use tildrakizumab as first-line therapy in patients with any signs or symptoms of psoriatic arthritis, as it lacks efficacy data for joint disease 1
• Do not assume higher tildrakizumab doses (200 mg) provide superior efficacy—the 100 mg dose achieved similar PASI 90 rates (39% vs 37%) 1
• Do not overlook ustekinumab's dose escalation options (every 8 weeks or higher dose) for partial responders before switching agents 1
• Assess response definitively at 12 weeks for both agents before making treatment modifications 1, 2