Real‐World Effectiveness, Safety and Drug Survival of Tildrakizumab in Adult Patients With Plaque Psoriasis: A 2‐Year Portuguese Multicenter Retrospective Cohort Study

Although biologic therapies have demonstrated significant efficacy and a favorable safety profile in randomized clinical trials (RCTs) in psoriasis, assessing their performance in real-world, heterogeneous patient populations remains crucial. Tildrakizumab, a monoclonal antibody targeting interleukin-23 (IL-23), has been approved by both the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of psoriasis since March 2018 and September 2018, respectively [1]. Although phase III RCTs have demonstrated its efficacy and safety [2], real-world long-term data on the effectiveness, safety, and tolerability of tildrakizumab remain limited [3, 4]. Our study aims to evaluate 2-year real-world outcomes of tildrakizumab in adult patients with plaque psoriasis in Portugal. We conducted a retrospective study across 13 centers, including adult patients with plaque psoriasis who initiated tildrakizumab 100 mg between September 2021 and December 2023, with data collected until a cutoff date of December 2024. Effectiveness was assessed based on absolute Psoriasis Area and Severity Index (PASI) scores. A modified nonresponder imputation (mNRI) analysis was applied, where patients who discontinued treatment due to lack of response were classified as nonresponders. Kaplan–Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. Safety outcomes, including adverse events (AE) and reasons for treatment discontinuation, were analyzed. A total of 245 patients were included in the study (mean age: 53.3 ± 15.6 years; male: 57.6%). The mean disease duration was 19.0 ± 17.8 years, and the mean body mass index (BMI) was 26.9 ± 4.7 kg/m2, with 18.4% classified as obese. At baseline, the mean PASI score was 15.7 ± 9.2, and 16.7% of patients had a diagnosis of psoriatic arthritis (PsA). Additionally, 54.7% were bio-naïve, whereas 34.3% had previously failed at least one biologic therapy (Table 1). PASI < 3, < 1, and 0 were achieved by 80.7%, 62.7%, and 42.5% of patients at 1 year, and by 78.0%, 67.0%, and 53.8% at 2 years, respectively (Figure 1a). Obesity had no significant impact on clinical outcomes; prior biologic exposure showed no consistent effect, although at Week 24, significantly more biologic-naïve patients achieved PASI < 3 and PASI < 1 compared to biologic-experienced patients (data not shown). Discontinuation was reported in 19.9% of patients, with lack of efficacy being the most common reason (12.6%), including primary and secondary failure of skin response (4.9% and 5.7%, respectively), and PsA nonresponse (2.0%) (Table 1). The cumulative probability of drug survival at 6 months, 1, and 2 years was 0.95 (95% confidence interval [CI]: 0.92–0.98), 0.88 (95% CI: 0.85–0.93), and 0.80 (95% CI: 0.74–0.85), respectively (Figure 1b). In the multivariate analysis, no significant predictors of tildrakizumab discontinuation were identified; however, weight demonstrated a nonsignificant trend (p = 0.060) (data not shown). AEs occurred in 10.1% of patients over the two-year treatment period, with infections being the most frequently reported (6.5%), followed by malignancy (1.2%), which was considered unrelated to treatment (Table 1). This study confirms the favorable safety and effectiveness profile of tildrakizumab in routine clinical practice, consistent with findings from phase III RCT [2] and recently published real-world studies [3, 4]. At 2 years, nearly 80% of patients achieved the treatment goals recommended by most national and international guidelines, with more than 50% achieving complete skin clearance. Drug survival at 2 years was 0.80 (95% CI: 0.74–0.85). Although some real-world studies suggested that BMI and prior biologic exposure may influence clinical outcomes, our findings did not demonstrate a significant impact of either obesity or prior biologic use on the effectiveness of tildrakizumab. Strengths of our study include a large patient cohort, 2-year follow-up, use of absolute PASI as the primary outcome, and mNRI analysis instead of as-observed analysis (commonly used in real-world studies), which often overestimates long-term effectiveness [5]. Limitations include its retrospective design, absence of a control group, potential selection bias, and missing data. In conclusion, these findings provide valuable real-world evidence supporting tildrakizumab as an effective, durable, and well-tolerated treatment option for psoriasis. The present study was conducted in accordance with the Declaration of Helsinki, initially published in 1964 on Ethical Principles for Medical Research Involving Human Subjects, and after approval by the local ethical committees. Tiago Torres has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Amgen, Almirall, Amgen, Apogee Therapeutics, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius-Kabi, Johnson & Johnson Innovative Medicine, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme, Sandoz, STADA, and UCB. Barbara Vieira Granja, Rita Guedes, Maria João Cruz, Joana Rocha, Luiz Leite, Joana Valério, Barbara Leal, Joana Matos, Gustavo Silva, Martinha Henrique, Luiz Leite, and Sofia Magina have no conflicts of interest. Joana Antunes has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Boehringer Ingelheim, Johnson & Johnson Innovative Medicine, LEO Pharma, Eli Lilly, Moonlake Immunotherapeutics, Novartis, Pfizer, and Sanofi-Genzyme. Ana Brasileiro has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Eli-Lilly, Janssen-Cilag, Leo-Pharma, Novartis, and Sanofi. João Alves has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by Abbvie, Novartis, and Galderma. Hugo Leme has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by Leo. Paulo Varela has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by and received continuous medical education support from AbbVie, Almirall, Eli-Lilly, Johnson & Johnson Innovative Medicina, Leo-Pharma, L'Oreal, Novartis, Pfizer, Pierre Fabre, Sandoz, and Sanofi. Pedro Mendes-Bastos has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Alumis, Amgen, Apogee, Biogen, CS Labs, Eli-Lilly, Evelo Biosciences, Janssen-Cilag, Leo-Pharma, L'Oreal, Novartis, Organon, Pfizer, Pierre Fabre, Regeneron, Sanofi, and Viatris. Ângela Roda has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Janssen, and Novartis. Paulo Ferreira has received consultancy and/or speaker's honoraria from Abbvie, Almirall, Janssen, LEO Pharma, Lilly, and Novartis. The data that supports the findings of this article is available from the corresponding author upon reasonable request.