Tildrakizumab Switching Study Shows Sustained Psoriasis Control

In a prospective real-world study published in Dermatology and Therapy, researchers evaluated the clinical effectiveness and patient-reported outcomes of switching to tildrakizumab after the failure of anti-IL-17 biologic therapies in patients with moderate-to-severe plaque psoriasis. The study followed 30 patients over a 52-week period, providing detailed insights into the durability of treatment and the management of dosing regimens in routine clinical practice. The findings indicate that switching to tildrakizumab resulted in significant and sustained improvements in both disease severity and quality of life, highlighting its potential as a therapeutic option for patients who do not respond adequately to previous biologic treatments.

Plaque psoriasis is a chronic immune-mediated inflammatory skin disease that affects approximately 2 to 3% of the global population. The pathogenesis of the disease is strongly driven by the interleukin-23 (IL-23) and interleukin-17 (IL-17) inflammatory axis. Advances in understanding this pathway have led to the development of targeted biologic therapies, including monoclonal antibodies targeting IL-17, such as secukinumab, ixekizumab, brodalumab, and bimekizumab. While these agents have demonstrated high levels of efficacy, a proportion of patients experience primary nonresponse, secondary loss of response, or inadequate disease control over time, necessitating therapeutic switching.

Tildrakizumab is a humanized immunoglobulin G1 kappa monoclonal antibody that selectively targets the p19 subunit of interleukin-23, a key cytokine involved in maintaining the T helper 17 inflammatory pathway. It has been approved in two dosing regimens, 100 mg and 200 mg, administered by subcutaneous injection. In pivotal phase III clinical trials, the 200 mg dose showed numerically higher efficacy compared with the 100 mg regimen, although no statistically significant differences were observed between the two doses. However, pooled analyses have suggested that the 200 mg regimen may provide improved clinical outcomes in selected patient populations, particularly those with greater body weight, higher disease burden, or previous biologic failure.

The study was conducted at the University of Campania Luigi Vanvitelli and included 30 patients with moderate-to-severe plaque psoriasis who had failed a single prior anti-IL-17 biologic agent. Eligibility criteria required an inadequate response or lack of response after at least six months of treatment with anti-IL-17 biologic agents. The study population included 21 males and 9 females, with a mean age of 54.2 years and a mean body mass index of 27.3 kg/m2. All patients had previously received anti-IL-17 therapy, with secukinumab being the most common prior agent, used in 63% of patients, followed by ixekizumab in 23% and brodalumab in 14%.

Patients were followed for 52 weeks, with assessments conducted at baseline, weeks 4, 16, and 52. Clinical outcomes were measured using the Psoriasis Area and Severity Index (PASI) and the Physician Global Assessment (PGA). Patient-reported outcomes were evaluated using the Dermatology Life Quality Index (DLQI), the World Health Organization-Five Well-Being Index (WHO-5), and the nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9). The initial tildrakizumab dose was selected by the treating physician based on routine clinical practice and individual patient characteristics, with dose allocation not being randomized.

At baseline, the mean PASI score was 12.2, indicating moderate disease severity. Over the course of the study, a progressive improvement in clinical disease severity was observed. The mean PASI score decreased to 5.4 at week 4, further declining to 3.7 at week 16, and reaching 1.1 at week 52. This marked and sustained reduction in psoriasis severity was statistically significant compared with baseline from week 4 onwards. Similarly, the mean PGA score improved from 2.1 at baseline to 0.0 at week 52, reflecting near-complete clinical clearance in the study population.

Clinical response rates also progressively increased during follow-up. At week 52, 88.9% of patients achieved a 75% improvement in PASI score (PASI75), 66.7% achieved a 90% improvement (PASI90), and 50% achieved a 100% improvement (PASI100). Additionally, 94.4% of patients reached an absolute PASI score of 3 or less, indicating minimal or absent residual disease in the vast majority of patients at long-term follow-up. These results suggest that switching to tildrakizumab can lead to substantial and sustained clinical improvement in patients with moderate-to-severe plaque psoriasis who have failed previous anti-IL-17 therapies.

Patient-reported outcomes also showed significant improvements during the study period. The mean DLQI score decreased from 10.7 at baseline to 1.8 at week 52, indicating a marked reduction in the impact of psoriasis on patients’ quality of life. Psychological well-being, as assessed by the WHO-5 questionnaire, also improved significantly, with mean scores increasing from 51.6 at baseline to 70.4 at week 52. Treatment satisfaction, measured by the TSQM-9, remained high throughout the study, with the side effects domain consistently at the maximum value of 100, indicating excellent perceived tolerability.

Regarding dosing, 46.7% of patients initially started tildrakizumab at a dose of 100 mg, mainly due to lower disease burden and body mass index. However, none of these patients maintained the 100 mg dosage throughout the study period; all were subsequently escalated to 200 mg based on clinical judgment and treatment response. The remaining 16 patients started treatment directly with 200 mg and continued this regimen throughout follow-up. The study authors noted that while dose escalation was frequently observed, the absence of a comparator group maintained on 100 mg precludes conclusions regarding the comparative effectiveness of the two dosing regimens.

The safety profile of tildrakizumab in this cohort was favorable. No treatment discontinuations due to adverse events were observed. Adverse events were reported in only two patients, consisting exclusively of mild injection-site reactions that did not require treatment discontinuation. Routine laboratory parameters remained stable, with no clinically relevant abnormalities observed at weeks 16 or 52. No serious adverse events were reported, supporting the well-tolerated nature of the drug in this real-world setting.

The study has several strengths, including its prospective real-world design, which allowed for a comprehensive evaluation of treatment effectiveness in routine clinical practice. The cohort specifically included patients who experienced failure of anti-IL-17 therapies, a population that remains relatively underrepresented in the current literature on tildrakizumab. The 52-week follow-up period enabled the assessment of both short-term and sustained treatment responses, and the integration of multiple patient-reported outcome measures provided a multidimensional evaluation of treatment impact.

However, the study also has limitations that should be acknowledged. The relatively small sample size and single-center design may limit the generalizability of the findings. All patients had experienced failure of a single anti-IL-17 biologic, so the results may not be generalizable to more treatment-refractory populations with multiple previous biologic failures. Furthermore, the absence of a comparator group maintained on the 100 mg regimen prevents any direct assessment of the comparative effectiveness of the two tildrakizumab doses. Initial dose selection and subsequent dose escalation were based on clinical judgment rather than random allocation, introducing the possibility of confounding by indication.

These findings contribute to the growing body of evidence supporting the effectiveness of switching from IL-17 to IL-23 inhibition in patients with inadequate response to previous biologic therapies. The study highlights the potential role of tildrakizumab as a valuable therapeutic option in this challenging clinical setting. While the dosing pattern observed reflects routine clinical practice, further research is needed to clarify the optimal dosing strategy for patients switching from anti-IL-17 therapies. Larger studies with randomized dose allocation and larger sample sizes are required to investigate potential predictors of treatment response and to adjust for relevant confounding factors.

In conclusion, switching to tildrakizumab after failure of anti-IL-17 therapies resulted in rapid, sustained, and clinically meaningful disease control in patients with moderate-to-severe plaque psoriasis. The treatment was associated with marked benefits in patients’ quality of life and psychological well-being, along with a favorable safety profile. These results support the biological rationale for switching to IL-23 inhibition and suggest that tildrakizumab may represent a valuable and reliable therapeutic option for patients with an inadequate response to previous anti-IL-17 biologics in real-world clinical practice.

Subject of Research: Clinical effectiveness and patient-reported outcomes of switching to tildrakizumab after anti-IL-17 failure in moderate-to-severe psoriasis

Article Title: Switching to Tildrakizumab 200 mg after Anti-IL-17 Failure in Moderate-to-Severe Psoriasis: A 52-Week Prospective Real-World Study

Article References: Di Brizzi, E. V., Carlo, P., Nicoletti, M. M., Franzese, P., Caccavale, S., Argenziano, G., & Balato, A. (2026). Switching to Tildrakizumab 200 mg after Anti-IL-17 Failure in Moderate-to-Severe Psoriasis: A 52-Week Prospective Real-World Study. Dermatology and Therapy. https://doi.org/10.1007/s13555-026-01973-x

Image Credits: AI Generated

DOI: 10.1007/s13555-026-01973-x

Keywords: psoriasis, tildrakizumab, biologic therapy, real-world study, IL-23 inhibitor, IL-17 inhibitor, clinical outcomes, patient-reported outcomes, dose escalation, dermatology, Switching, Anti-IL-17