Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by recurrent skin lesions and systemic inflammation, which substantially impairs patients’ quality of life and requires long-term management [1]. Advances in immunological research have identified the interleukin (IL)-23/Th17 axis as a central pathway in psoriasis pathogenesis, leading to the development of biologic therapies targeting specific cytokines involved in this immune cascade [1].

Tildrakizumab is a humanized monoclonal antibody that selectively targets the p19 subunit of IL-23, thereby inhibiting IL-23–dependent Th17 responses while preserving upstream immune pathways [2]. By selectively blocking IL-23 without directly inhibiting IL-17, tildrakizumab allows targeted suppression of pathogenic inflammation while potentially minimizing broader immune perturbation [2, 3]. In phase III clinical trials, including the reSURFACE 1 and reSURFACE 2 studies, tildrakizumab demonstrated robust efficacy and a favorable long-term safety profile in patients with moderate-to-severe plaque psoriasis [3, 4].

However, clinical trial populations are highly selected and may not fully reflect patients encountered in routine practice. In particular, real-world data on tildrakizumab in Japanese patients remain limited, especially regarding long-term effectiveness, treatment persistence, safety, and factors influencing clinical response. Moreover, differences in baseline disease severity, prior treatments, and analytical approaches may substantially influence treatment outcomes in real-world settings.

Therefore, the present study aimed to evaluate the 52-week real-world effectiveness and safety of tildrakizumab in a Japanese clinical cohort, using both relative and absolute PASI outcomes and applying a conservative analytical approach.

A total of 30 patients were included (22 men and 8 women), with a mean age of 57.3 years (range, 26–81 years), a mean body weight of 69.44 kg, and a mean disease duration of 17.4 years (range, 2–43 years). Twelve patients (40.0%) had a body mass index (BMI) ≥25, and 21 patients (70.0%) were current or former smokers. Thirteen patients (43.3%) had a disease duration of ≥20 years, and nine patients (30.0%) were aged 65 years or older. Five patients (16.7%) had previous exposure to biologic therapy, whereas 25 patients (83.3%) were biologic-naïve; prior biologics included ustekinumab in 4 patients and risankizumab in 1 patient. Other prior treatments included apremilast in 15 patients, topical therapy alone in 7 patients, etretinate in 2 patients, and cyclosporine in 1 patient. Concomitant topical therapy was used in 27 patients (90.0%), and concomitant systemic therapy was used in 1 patient (3.3%; cyclosporine). Detailed patient characteristics are summarized in Table 1.

In this real-world Japanese cohort, tildrakizumab demonstrated sustained effectiveness over 52 weeks, with reductions in mean PASI scores and lower absolute PASI scores. Although PASI75 achievement rates were lower than those reported in some European real-world studies, PASI ≤3 was achieved in 60% of patients at week 52, indicating stable long-term disease control in routine clinical practice.

Real-world studies have reported heterogeneous effectiveness outcomes for tildrakizumab, likely reflecting differences in study design, patient characteristics, baseline disease severity, and analytical approaches. The findings of the present study are conceptually aligned with those of the TILOT study, a prospective German real-world cohort, in that both studies support sustained clinical benefit of tildrakizumab in routine practice and emphasize absolute disease control [5]. However, direct comparison should be made cautiously because TILOT primarily reported observed-case and LOCF analyses, whereas our study used a conservative NRI approach, and because response rates and baseline disease severity differed between the two cohorts.

By contrast, several other European real-world cohorts have reported markedly higher relative response rates than those observed in our study. The Italian IL-PSO multicenter retrospective study reported PASI75 achievement rates approaching 90% at week 52 [6], and a Spanish multicenter real-world study likewise reported high treatment response rates at 52 weeks [7]. More recently, a large multicenter real-world study from the Basque Country, Spain, including 212 patients, reported PASI75 in 66.4% of patients and PASI ≤3 in 68.8% at week 52 [8], while a German retrospective multicenter analysis over 76 weeks reported PASI75 in 85.5% and absolute PASI <3 in 79.7% at week 52 [9]. These differences should be interpreted in the context of substantial methodological and population-level differences between studies. In particular, cohorts with higher baseline PASI scores, relative response-based endpoints, and predominantly observed-case analyses are more likely to yield higher PASI75 rates. Thus, discrepancies among real-world studies are more plausibly attributable to differences in baseline disease severity, outcome definitions, and analytical strategies rather than true differences in drug efficacy.

In the Japanese subgroup analysis of reSURFACE 1, tildrakizumab demonstrated durable efficacy, and the subsequent 5-year extension study likewise showed sustained long-term efficacy and tolerability in Japanese patients [10, 11]. These trial-based data provide an important point of reference, while also highlighting the need for post-marketing real-world evidence from routine clinical practice. In this context, our cohort may help bridge the gap between Japanese clinical trial data and everyday treatment outcomes.

Several factors may explain why the week-52 PASI75 rate in our cohort was lower than those reported in some previous studies. First, our cohort had a relatively low baseline mean PASI score (11.45), compared with 16.0 in TILOT and 14.45 in IL-PSO, and was closer to that reported in the Basque Country cohort (11.21) and the German multicenter cohort (median 12.6). These differences in baseline disease severity may have influenced the likelihood of achieving relative response thresholds such as PASI75. Second, our primary responder analyses used non-responder imputation (NRI), whereas many real-world studies preferentially reported observed-case outcomes. In our cohort, as-observed response rates at week 52 were higher than NRI-based estimates, reaching 68.0% for PASI75% and 72.0% for PASI ≤3, compared with 56.7% and 60.0%, respectively, using NRI (Supplementary Table 1). Third, differences in treatment history and cohort composition, including prior biologic exposure, may also have contributed to cross-study variability. In patients with relatively low baseline PASI scores, absolute disease activity measures such as PASI ≤3 may provide a more informative assessment of treatment response than relative thresholds alone [12]. In routine Japanese clinical practice, maintaining stable low disease activity may represent a more practical therapeutic goal than achieving large relative improvements. Taken together, these considerations suggest that the relatively lower PASI75 rate observed in our study should be interpreted in the context of a conservative analytic strategy and a lower-severity real-world Japanese cohort, rather than as evidence of inferior drug performance.

From an immunological perspective, selective inhibition of the interleukin-23 (IL-23) p19 subunit by tildrakizumab allows targeted suppression of the IL-23/Th17 axis while preserving upstream immune pathways involved in host defense [1, 2]. Accumulating immunological evidence suggests that such selective IL-23 inhibition may provide durable control of pathogenic inflammation with limited immune perturbation, which could contribute to long-term disease stability and favorable safety outcomes [13].

Although no statistically significant age-related differences were detected in the present exploratory analyses, the numerically comparable or favorable responses observed in older patients are consistent with previous real-world studies reporting maintained effectiveness and tolerability of tildrakizumab in elderly and frail elderly populations [14, 15]. These findings support the clinical applicability of IL-23p19 inhibition in older patients requiring long-term treatment.

This immunological selectivity may be particularly relevant in real-world populations, including older patients and those requiring prolonged therapy. In the present cohort, seven adverse events were documented in the electronic medical records during the observation period, and no patients discontinued treatment because of safety concerns. However, safety findings should be interpreted cautiously because adverse events were retrospectively ascertained from routine medical records rather than through protocolized surveillance, and minor events not documented in the records may have been missed. Nevertheless, the absence of safety-related discontinuations is consistent with the generally favorable tolerability profile of tildrakizumab observed in clinical trials and long-term extension studies [3, 4]. Furthermore, accumulating evidence indicates that IL-23 inhibitors as a therapeutic class are associated with a favorable long-term safety profile, supporting their suitability for chronic disease management in psoriasis [16].

Exploratory subgroup analyses generally did not identify patient background factors associated with differential treatment response. At week 52, non-smokers showed a numerically higher PASI ≤3 achievement rate than current or former smokers in unadjusted analysis; however, this association was no longer significant after adjustment for multiple comparisons. This finding should therefore be considered exploratory and hypothesis-generating, particularly given the small sample size and the lack of adjustment for potential confounders such as body mass index, disease duration, and prior biologic exposure. Nevertheless, smoking has been reported to adversely affect treatment response in patients with psoriasis receiving biologic therapies [17]. Our observation may warrant further investigation in larger cohorts.

This study has several limitations. First, its retrospective, single-center design and limited sample size restrict statistical power and generalizability. Second, no formal a priori sample size calculation was performed because this was an exploratory real-world study. Third, adverse events were retrospectively ascertained from routine electronic medical records rather than through protocolized surveillance, and minor events may therefore have been underdetected. Fourth, subgroup analyses were exploratory and underpowered, and residual confounding could not be excluded. Despite these limitations, the present findings provide valuable real-world evidence supporting the effectiveness and safety of tildrakizumab in Japanese patients with psoriasis. By emphasizing absolute disease control and applying conservative analytical methods, this study offers a clinically relevant perspective on long-term treatment outcomes and may serve as a hypothesis-generating basis for future multicenter investigations.

In this real-world Japanese cohort, tildrakizumab provided sustained long-term effectiveness and low absolute disease activity over 52 weeks. Interpretation of the safety and subgroup findings should take into account the retrospective single-center design and exploratory nature of the analyses.