Tildrakizumab Enhances Regulatory T Cells, Inhibits PsA Progression in Elderly Patients

Takemichi Fukasawa, MD, PhD

Credit: Loop

Results of a multicenter cohort study revealed elderly patients with psoriasis vulgaris treated with tildrakizumab had improvements in skin lesions due to improvements in the number and function of regulatory T cells (Tregs), according to a study published in Frontiers of Immunology.¹ Additionally, the drug aided in inhibiting psoriatic arthritis (PsA) progression by improving capillary enlargement and nailfold bleeding (NFB) activity.

“Previous clinical trials have not provided sufficient evidence to determine the efficacy of tildrakizumab in elderly patients, likely due to the limited number of participants in this age group,” wrote a group of investigators led by Takemichi Fukasawa, MD, PhD, assistant professor in the Department of Dermatology, Psoriasis Center, at the University of Tokyo Graduate School of Medicine, Japan. “Therefore, the objective of this study was to investigate the effectiveness of tildrakizumab in patients as part of a precision medicine approach.”

Choosing which treatment is right for a patient is often difficult as an individual can respond differently to the same medication. Precision medicine, often defined as the ability to predict treatment responses to deliver the most suitable therapy for an individual, remains a challenge due to the current limitations in predicting these responses in advance.² Although tildrakizumab, a human monoclonal antibody which targets interleukin (IL)-23p19, has shown efficacy in previous clinical trials, the specific populations it may benefit most is unknown.

To better understand the mechanism of action and efficacy of tildrakizumab in reducing PsA occurrence, the prospective study included 246 patients with psoriasis vulgaris who had not been treated with any topical finger therapy or systemic therapy between January 2020 and April 2023. Investigators analyzed the incidence of new PsA diagnosis, as well as nailfold capillary (NFC) abnormalities, including NFB and enlarged capillaries. Psoriasis response after 7 months of receiving the drug was evaluated, as were the quantity and role of Tregs and T helper 17 cells pre- and post-treatment with tildrakizumab. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI) and “elderly” was defined as ≥65 years.

The severity of psoriasis was greater in the tildrakizumab cohort (n = 20) when compared with the topical cohort (n = 226) according to PASI scores (7.5 ± 8.6 vs 2.3 ± 3.1, P < .0001). These patients also reported a significantly higher proportion with NFB (19 [95.0%] vs 81 [35.8%], P < .0001), a significantly higher proportion with enlarged capillaries (19 [95.0%] vs 59 [26.1%], P < .0001), and significantly more scalp lesions (18 [90.0%] vs 109 [48.2%], P = .0003).

At the 7-month mark, multivariate analysis revealed patients aged ≥65 years reported a significantly better response to tildrakizumab in patients who obtained PASI clear or PASI ≤2 (Likelihood ratio [LR] 16.15, P <.0001; LR 6. 16, P = .01, respectively).

Additionally, treatment with tildrakizumab enhanced both the number and function of Tregs. The drug also improved a variety of pathological factors linked with the development of PsA, such as reductions in NFB, enlargement of capillaries, and inhibition of PsA progression.

A significant reduction in the risk of developing PsA was observed in the tildrakizumab cohort, and the hazard ratio for PsA progression was reported as .06 (95% confidence interval [CI]: .0007 - .46, P = .007).

Investigators noted the study was limited by exclusively including Japanese patients, which may hinder generalizability to other ethnic groups, as well as the small number of patients.

“Taken together, tildrakizumab is particularly effective in the elderly,” investigators concluded. “Its high safety profile also makes it safe for use on the elderly.”

References

1. ^{Fukasawa T, Yamashita T, Enomoto A, et al. The optimal use of tildrakizumab in the elderly via improvement of Treg function and its preventive effect of psoriatic arthritis. Front Immunol. 2023;14:1286251. Published 2023 Oct 19. doi:10.3389/fimmu.2023.1286251}
2. ^{Fritzsche MC, Buyx AM, Hangel N. Mapping ethical and social aspects of biomarker research and its application in atopic dermatitis and psoriasis: a systematic review of reason. J Eur Acad Dermatol Venereol (2022) 36(8):1201–13. doi: 10.1111/JDV.18128}