Ospedale Santa Chiara

Psoriasis is a chronic inflammatory skin disease associated with significant physical and psychological burden. Tildrakizumab, an interleukin-23 p19 inhibitor, has demonstrated efficacy in treating moderate-to-severe plaque psoriasis both in clinical trials and real-world setting. However, limited data are available on the impact of the effective treatment of psoriasis on the psychological health of patients. The aim of this study was to assess changes in psychological well-being, as well as clinical and quality-of-life outcomes, in patients with moderate-to-severe plaque psoriasis treated with tildrakizumab in routine clinical practice in Italy. This was an interim analysis (IA) of a 52-week multicenter, prospective, observational study. Adults with moderate-to-severe plaque psoriasis initiating tildrakizumab were enrolled. Endpoints focused on well-being and psychological health and included changes, from baseline to week28, in Depression, Anxiety, and Stress Scale-21 (DASS-21) scores, Dermatology Life Quality Index (DLQI), European Social Survey (ESS) items, and World Health Organization-Five Well-Being Index (WHO-5). Effectiveness was also monitored via Psoriasis Area and Severity Index (PASI), and safety via treatment-emergent adverse event reporting. A total of 115 patients were included (mean age 52.5years, 60.8% male), 102 receiving ≥ 1 dose of tildrakizumab and completing DASS-21 evaluations at baseline and week28. At week28, improvements were observed in DASS-21 subscales [depression (-2.6, 95%CI -2.0 to -1.0), anxiety (-2.3, 95%CI -2.0 to -1.0), and stress (-3.4, 95%CI -4.0 to -2.0)], accompanied by marked PASI reduction (-13.7, 95%CI -12.8 to -10.1). DLQI, ESS, and WHO-5 scores also improved. Adverse events were generally mild or moderate, with no unexpected safety signals. In this real-world IA, tildrakizumab was observed to improve the psychological well-being of patients, reflected by a reduction in all items of the DASS-21 scale and, in parallel, confirmed its effectiveness in managing physical symptoms of psoriasis, establishing its role in the holistic management of psoriasis.

Abstract Background: Host metabolic status and body composition are increasingly recognized as modulators of treatment response and prognosis in early breast cancer (eBC). Nutritional and exercise interventions during neoadjuvant chemotherapy (NAT) may influence systemic inflammation, insulin sensitivity, and lipid metabolism, factors implicated in therapy resistance. However, prospective randomized data assessing their impact on metabolic health and treatment efficacy are limited. Based on prior findings from the SeNEOAD study we identified a metabolomic signature associated with a higher probability of achieving pCR after NAT. Among 445 small molecules analyzed, 61 were differentially expressed in patients with pCR versus residual disease (RD) (p<0.05); patients with RD showed lower levels of fatty acids, such as 9-hexadecenoic acid (p <0.001) and doconexent (p<0.001). These results support the rationale for a nutritional supplementation of these molecules in order to improve pCR rates. Methods: NEOMET is an ongoing randomized prospective multicenter study whose primary aim is to evaluate whether plasma metabolomic signatures can be modified by lifestyle interventions including dietary supplements and physical exercise in eBC patients undergoing NAT. Eligible patients are randomized to one of four groups: a) NAT according to molecular subtype; b) NAT plus nutritional supplementation; c) NAT plus supervised physical exercise; d) NAT plus nutritional supplementation plus supervised physical exercise. Nutritional supplementation consists of two main long-chain polyunsaturated fatty acids omega-3 (n-3 Lc-PUFA), EPA and DHA, plus a source of palmitoleic acid (hexadecenoic acid). Body composition is assessed by bioelectrical impedance analysis (BIA) at baseline and at the end of NACT, before surgery. Quality of life (QoL) is evaluated using the EORTC QLQ-C30 and QLQ-BR45 questionnaires. In this preliminary analysis we present data on BIA and QoL assessments. Results: Between October 2024 and June 2025, 27 patients with stage I-III eBC were enrolled. Of these, 6 are allocated to arm A, 8 to arm B, 6 to arm C and 7 to arm D. Median age is 53 years (range 30-69), and median BMI is 25 kg/m2. Tumor subtypes included HER2+ (n=12), triple-negative (n=7), and luminal-like (n=8). Fifteen patients completed NACT and had paired data on body composition and quality of life (QoL). QoL assessments using EORTC QLQ-C30 and BR45 revealed a significant deterioration in global health status (mean score from 148.8 to 116.7, p=0.041), fatigue (26.2 to 45.2, p=0.033), and pain (4.8 to 23.8, p=0.017); physical functioning improved significantly (8.1 to 21.0, p=0.009) and emotional functioning remained stable. Paired BIA assessments showed a trend toward improved body composition: fat-free mass increased from a mean of 44.9 kg to 46.4 kg (p=0.096) and skeletal muscle mass increased from 21.2 kg to 22.1 kg; fat mass remained stable (18.9 kg to 19.0 kg, p=0.47). Adverse event rates were assessed after at least 1 cycle in 26 patients. No significant differences in grade ≥2 toxicities (CTCAE v5.0) were observed between patients receiving standard treatment and those in the experimental arms. Conclusion: The preliminary analysis from the ongoing NEOMET trial supports the safety and feasibility of integrating nutritional and exercise interventions during NAT in eBC. Despite the limited sample size, observed trends suggest potential benefits in preserving lean body mass and improving physical functioning. These findings will be further investigated in the NEOMET trial as more patients will be randomized, to clarify the clinical impact on treatment tolerance and patient well-being. Additional clinical and translational results, including omega-3 index and metabolomic analysis, will be presented at the meeting. Citation Format: I. Taglialatela, B. Conte, S. Nardin, F. D'Avanzo, V. Rossi, B. Ruffilli, T. Landolfo, G. Isingrini, G. Griguolo, D. Soldato, A. Coassolo, F. Condorelli, E. Del Grosso, C. Bengala, C. Branni, J. Gennari, G. Di Foggia, M. Rossato, G. Tarantino, M. Manfredi, V. Martini, S. Gobbato, L. Boni, L. Del Mastro, V. Guarneri, A. Gennari. Preliminary Results from the NEOMET Trial: Nutritional and Exercise Interventions During Neoadjuvant Chemotherapy in Early Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-09-23.

Neurofilament light chain (NfL) is a promising biomarker for monitoring disease activity and treatment response in multiple sclerosis (MS). This meta-regression assesses the relationship between treatment effects on serum/plasma NfL (s/pNfL) and clinical and radiological endpoints in randomized controlled trials (RCTs). A systematic PubMed search identified RCTs in MS (1999-2023) with ⩾24 months' duration and s/pNfL data. Extracted outcomes included treatment effects on s/pNfL, annualized relapse rate (ARR), confirmed disability worsening (CDW), magnetic resonance imaging (MRI) new/enlarging T2 lesions, and percentage brain volume change (PBVC). We evaluated the association of treatment effect on the selected outcomes at the trial level by a meta-regression, weighted by trial size and duration. Fifteen RCTs (n = 6814) were included, nine in relapsing MS (RMS, n = 5221), and six in progressive MS (PMS, n = 1593). Treatment effects on s/pNfL showed a moderate association with treatment effects on MRI new/enlarging T2 lesions (R2 = 0.42, p = 0.01), ARR (R2= 0.33, p = 0.03) and CDW (R2= 0.30, p = 0.04), but not with PBVC. In RMS-only trials, association with ARR (R2= 0.45, p = 0.05) and CDW (R2= 0.50, p = 0.03) was more pronounced. In MS, treatment effects on s/pNfL are moderately associated with therapeutic effects on ARR, MRI new/enlarging T2 lesions, and CDW, whereas no consistent association was observed with PBVC.

The authors declare no conflicts of interest. The data that supports the findings of this study is available in the Supporting Information of this article. Data S1: References contained in Table 1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.