Daily Literature Update

Efficacy and safety of tildrakizumab for the treatment of moderate-to-severe plaque psoriasis of the scalp: Week 52 results from a phase 3b, randomized, double-blind, placebo-controlled trial

Sofen HL, Gebauer K, Spelman L, Yamauchi PS, Yao SL, Nishandar T, Kopeloff I, Crane M, Gogineni R, Kothekar M, Bagel J. J Am Acad Dermatol. 2025 Apr;92(4):816-824. doi:10.1016/j.jaad.2024.12.018. Epub 2024 Dec 23. PMID: 39722400.

Introduction

Scalp involvement is a common and often challenging manifestation of moderate-to-severe plaque psoriasis with significant impact on patients’ quality of life. While multiple biologic therapies are approved for plaque psoriasis, targeted treatments specifically addressing scalp symptoms are essential to improve disease control and patient outcomes. This phase 3b, randomized, double-blind, placebo-controlled trial evaluated the long-term efficacy and safety of tildrakizumab, an anti-interleukin-23 p19 antibody, administered every 12 weeks, specifically for scalp psoriasis over 52 weeks.

The investigation included a placebo-controlled design with a crossover to active therapy at week 16, allowing assessment of sustained response with tildrakizumab. Safety monitoring focused on treatment-emergent adverse events, critical for chronic management strategies.

Study Overview

Efficacy Outcomes: Investigator Global Assessment modified 2011 (scalp) score of 0 or 1 with ≥2-grade improvement, and ≥90% improvement in Psoriasis Scalp Severity Index (PSSI) from baseline.

Safety Outcomes: Treatment-emergent adverse events and serious adverse events reported.

Key Findings

• For patients originally randomized to tildrakizumab, Investigator Global Assessment modified 2011 (scalp) response rate increased from 49.4% at week 16 to 62.9% at week 52.
• PSSI ≥90% improvement rose from 60.7% at week 16 to 65.2% at week 52 in the tildrakizumab group.
• Placebo patients who switched to tildrakizumab at week 16 showed Investigator Global Assessment response improvements from 7.3% to 56.1% by week 52.
• Similarly, their PSSI ≥90% improvements increased from 4.9% at week 16 to 57.3% at week 52.
• More than 80% of week 16 responders to tildrakizumab maintained response through week 52.
• No treatment-related serious adverse events were reported, confirming favorable long-term safety under trial conditions.

Evidence Synthesis & Clinical Context

The efficacy of tildrakizumab in scalp psoriasis is consistent with foundational and real-world evidence supporting its role in plaque psoriasis management. Key supportive studies include pivotal Phase 3 trials and real-world research.

Foundational Efficacy – Phase 3 Trials

• Reich K et al., 2017: reSURFACE 1 and 2 Phase 3 RCTs demonstrating tildrakizumab’s superior efficacy versus placebo and etanercept in moderate-to-severe plaque psoriasis (PMID: 28596043).

Real-World Long-term Effectiveness & Safety

• Ruggiero A et al., 2023: A 52-week retrospective study showing sustained PASI improvements validating trial durability in routine clinical practice (PMID: 36873660).
• Megna M et al., 2024: Real-life evidence of effectiveness and safety in patients with prior anti-IL17 failures, indicating utility in difficult-to-treat populations (PMID: 38737943).
• Heim J et al., 2024: Phase 4 real-world study confirming safety and effectiveness over 64 weeks (PMID: 39093661).

Key Themes and Evidence Gaps

• Strong foundational evidence for tildrakizumab efficacy in plaque psoriasis is mirrored in scalp-specific long-term responses.
• Demonstrated sustained safety profile with no new safety signal emerging over extended treatment.
• Evidence gaps remain for direct comparative scalp efficacy versus other biologics and more extensive prospective real-world scalp datasets.

Clinical Implications

• Tildrakizumab 100 mg every 12 weeks is an effective long-term option for moderate-to-severe scalp psoriasis, providing robust sustained responses through 52 weeks.
• The safety profile is reassuring, with no treatment-related serious adverse events reported under controlled trial conditions, supporting chronic use.
• Clinicians may consider tildrakizumab in patients with scalp involvement including those who may have failed other biologics, although head-to-head scalp data are lacking.

Strengths & Limitations

Future Directions

Research is needed to generate large prospective real-world datasets focused on scalp psoriasis outcomes, as well as direct head-to-head comparative studies versus other biologics to establish relative efficacy and safety. Peer-reviewed publications confirming long-term real-world effectiveness specifically for scalp involvement are warranted to further inform clinical decision-making.

Conclusion

Tildrakizumab maintains sustained long-term efficacy and a favorable safety profile for moderate-to-severe scalp psoriasis over 52 weeks, supporting its role as a valuable treatment option in this challenging patient population.

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References