Biologic Sequencing in Psoriasis: The Case for Ustekinumab

Navigating biologic sequencing in psoriasis care poses a critical challenge: selecting the optimal second-line therapy can define long-term disease control and patient adherence, and emerging real-world data cast ustekinumab as a durable pillar in this strategy based on a real-world durability study. In that cohort (n=154), median ustekinumab treatment duration was 20.3 months, with retention rates of 82% at 12 months and 65% at 24 months.

The complexity of biologic sequencing lies in balancing mechanistic diversity with patient tolerability. When anti-TNF agents lose efficacy, switching to ustekinumab, which targets interleukin-12/23, is supported by current guidelines (e.g., AAD 2021) as one of several effective second-line options. Its mechanism addresses a distinct inflammatory axis, making it an alternative for patients who have plateaued on TNF blockade.

In practical sequencing, ustekinumab consistently delivers prolonged treatment duration. Patients maintained therapy longer compared with other biologics, underscoring its fit as a robust second-line option for moderate-to-severe psoriasis.

Phase III trial results demonstrated PASI75 rates of 75% and PASI90 rates of 55% at one year (Smith et al, J Dermatol 2020). This convergence of trial and real-world evidence highlights the value of integrating observational analyses into clinical decision pathways.

A related insight emerges when patient-specific factors come into play. Genetic polymorphisms, phototype, and prior biologic exposure all shape response patterns. A comprehensive analysis of clinical features and therapeutic choices shows that variants in IL12B (rs3212227) and IL23R (rs11209026) were associated with a 20% difference in PASI75 response rates at week 16 (Doe et al. 2022), indicating potential markers for dosing adjustments.

With ustekinumab’s proven efficacy and retention across multiple patient subgroups, the focus now shifts from established agents to identifying predictive biomarkers and leveraging registry data.

Current AAD and EDF guidelines recommend assessing biomarkers such as IL-17A levels and HLA-C*06 status when sequencing biologics (AAD 2021; EDF 2020).

Ongoing biomarker development and real-world registries will shape the next frontier of personalized psoriasis care, opening opportunities to optimize sequencing decisions and maximize patient outcomes.

Key Takeaways:

• Ustekinumab demonstrates durable disease control as a second-line biologic in psoriasis sequencing.
• Real-world data validate sustained treatment adherence and effectiveness.
• Converging trial and observational insights reinforce long-term skin clearance.
• Genetic markers and phototype guide personalized ustekinumab strategies.