Why is tildrakizumab (Ilumya) preferred over Tremfya (guselkumab) for moderate-to-severe plaque psoriasis?

Tildrakizumab is NOT Better Than Tremfya (Guselkumab) for Psoriasis

The premise of your question is incorrect—there is no evidence that tildrakizumab (Ilumya) is superior to guselkumab (Tremfya) for moderate-to-severe plaque psoriasis. In fact, the available evidence demonstrates these two IL-23 p19 inhibitors have comparable efficacy, and guselkumab may offer certain practical advantages.

Evidence-Based Comparison

Efficacy: No Meaningful Difference

The 2019 AAD-NPF guidelines give both medications Grade A recommendations for moderate-to-severe plaque psoriasis 1. When examining the clinical trial data:

Guselkumab (Tremfya):

• PASI 90 at week 16: 70.0% in the VOYAGE 2 trial 1
• Dosing: 100 mg at weeks 0,4, then every 8 weeks 1

Tildrakizumab (Ilumya):

• PASI 90 at week 12: 37-39% in the reSURFACE 2 trial 1
• Dosing: 100 mg at weeks 0,4, then every 12 weeks 1

A 2020 systematic review and Bucher indirect comparison found no statistically significant difference between guselkumab and tildrakizumab for PASI 75, PASI 90, serious adverse events, or discontinuation rates 2. A 2025 network meta-analysis confirmed comparable efficacy at week 28 between tildrakizumab, risankizumab, and guselkumab 3.

Key Differences That Matter Clinically

Guselkumab advantages:

• More frequent dosing (every 8 weeks vs every 12 weeks) may provide more consistent disease control
• FDA-approved for psoriatic arthritis 4—critical if your patient has or develops joint involvement
• Self-administered subcutaneous injection 1—greater patient autonomy
• Higher PASI 90 rates in head-to-head comparisons with other biologics

Tildrakizumab characteristics:

• Physician-administered in-office injection 1—may be preferred for patients who cannot self-inject, but creates access barriers
• Less frequent dosing (every 12 weeks)—potentially better adherence for some patients
• Only approved for plaque psoriasis 5—not an option if psoriatic arthritis develops

Clinical Decision Algorithm

Choose Guselkumab (Tremfya) when:

• Patient has or is at risk for psoriatic arthritis
• Patient prefers self-administration at home
• More frequent monitoring/control is desired
• Patient has failed other biologics (guselkumab showed 66.1% PASI 90 in adalimumab non-responders 1)

Choose Tildrakizumab (Ilumya) when:

• Patient cannot or will not self-inject
• Office-based administration is logistically feasible
• Cost considerations favor tildrakizumab
• Patient specifically desires less frequent dosing

Safety Profile: Comparable

Both medications demonstrate excellent safety profiles with no increased risk of serious adverse events compared to placebo 2, 3. Real-world data for tildrakizumab through 52 weeks shows no new safety signals 6. The guidelines note that long-term malignancy risk for IL-23 inhibitors remains under study but no definitive increased risk has been identified 1.

Common Pitfall to Avoid

Do not assume less frequent dosing equals better efficacy or safety. The every-12-week dosing of tildrakizumab is simply its pharmacokinetic profile, not evidence of superiority. The guidelines explicitly state that patient preference regarding dosing frequency should be discussed, but efficacy and safety data should guide treatment decisions 1.

Bottom line: Both are excellent IL-23 inhibitors with Grade A evidence. Guselkumab's broader FDA indications (including psoriatic arthritis), self-administration capability, and slightly more robust PASI 90 data in pivotal trials make it the more versatile first-line choice for most patients with moderate-to-severe plaque psoriasis.