Real-life effectiveness and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: A 104-week multicenter retrospective study - IL PSO (ITALIAN LANDSCAPE PSORIASIS).

BACKGROUND: Guselkumab is a fully human monoclonal antibody that binds selectively to the p19 subunit of interleukin-23, which has shown efficacy in patients with previous incomplete response to ustekinumab in the NAVIGATE clinical trial. [Correction added on [28-02-2023], after first online publication: 'humanized monoclonal antibody' has been changed to 'fully human monoclonal antibody' in the preceding sentence.] OBJECTIVES: We conducted a 104-week multicenter retrospective study to assess the effectiveness and safety of guselkumab in patients affected by plaque psoriasis with an inadequate response to ustekinumab in a real-life setting. METHODS: Our retrospective study included 233 adults affected by moderate-to-severe plaque psoriasis, enrolled in 14 different Italian centres, and treated with guselkumab after failing therapy with ustekinumab. Patient characteristics and PASI (Psoriasis Area and Severity Index) score at each visit (baseline, weeks 16, 52 and 104) were recorded. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI, compared with baseline, were registered. RESULTS: At week 52, PASI 75 was reached by 89.88% of patients, PASI 90 by 71.43%, PASI 100 by 58.83% and absolute PASI ≤2 by 90.48%. At week 104, similar effectiveness results were observed. Compared to the NAVIGATE trial, we observed higher rates of PASI 75/90/100. Patients with the involvement of difficult-to-treat areas were significantly less likely to achieve PASI90 and PASI100 at week 16. Obese patients had significantly lower rates of PASI75 and PASI ≤2 at week 52. At week 104, comparable responses were observed among all patients' subgroups, regardless of BMI status, involvement of difficult-to-treat areas, presence of cardiometabolic comorbidities and concomitant psoriatic arthritis. No significant safety findings were reported throughout the study. CONCLUSION: Our data suggest that the efficacy of guselkumab in patients with inadequate response to ustekinumab for plaque psoriasis in 'real-life' clinical practice is comparable with NAVIGATE study with higher percentages of patients achieving PASI90 and PASI100 at weeks 16, 52 and 104.

Successful long-term guselkumab treatment of severe plaque psoriasis in patients with class III obesity: A case series.

Data from real-world studies and clinical trials have documented the long-term efficacy and safety of guselkumab in patients with moderate-to-severe psoriasis. Limited data are available on the long-term use of guselkumab in morbidly obese individuals with severe psoriasis. Here, we present data on the outcome of three patients with class III obesity (body mass index (BMI) of ≥40 kg/m2) with severe plaque psoriasis treated with 100 mg guselkumab. At baseline, mean BMI was 46.5 ± 5.4 kg/m2 and mean PASI was 46.0 ± 18.5 and all patients were biologic naïve. After 12 weeks of guselkumab treatment, mean PASI decreased to 9.7 ± 4 and to 4.0 ± 1.7 at 28 weeks. After 1 year, two patients achieved complete remission and one patient had PASI of 6 (achieving remission by week 140). All three patients are still in complete remission. Our real-life results in specific patients burdened with class III obesity naïve to biologic treatment show excellent long-term psoriasis outcome with guselkumab.

Characterization of Super-Responder Profile in Chronic Plaque Psoriatic Patients under Guselkumab Treatment: A Long-Term Real-Life Experience.

Background: The term "super responder" identifies a group of patients who exhibit a rapid and optimal response to biological treatment compared to the overall treated population. The primary objective of our study is to characterize this subgroup of patients to enable the early identification of those who will respond most effectively to the proposed treatment while also evaluating clinical efficacy. Methods: This retrospective study evaluated 232 patients treated with guselkumab in monotherapy for at least 20 weeks between November 2018 and November 2023. Patients were divided into two groups: those who achieved complete clear skin (PASI = 0) during the first 20 weeks of treatment were defined as super responders (SRe) and non-super responders (nSRe) were the remaining patients. PASI was assessed at weeks 0, 4, and subsequently every eight weeks. Predictors of the SRe status were evaluated by univariate and multivariate logistic regression analyses. Results: The univariate analyses showed that patients with psoriatic arthritis at the baseline, bio-naïve patients, or those who had not received an interleukin (IL) 17 inhibitor as their last therapy before guselkumab administration were more likely to be super responders to the proposed treatment. Multivariate logistic analysis models suggested that the combination of psoriatic arthritis at the baseline and the bio-naïve condition was the strongest predictive model for the SRe status. At week 204, the main difference between the two groups concerned the achievement of PASI100, maintained by 86.8 of SRe compared to 62.8% of nSRe. Conclusions: The efficacy and safety of guselkumab are confirmed in our real-life experience. Identifying the SRe status will undoubtedly play a role in clinical practice and the therapeutic decision-making algorithm.

Professional football training and recovery: A longitudinal study on the effects of weekly conditioning session and workload variables.

The main purpose of this longitudinal study was to investigate football players' recovery status, through hormonal response, in relation to accumulated workload at two comparable time points of the first (T1) and second half (T2) of the competitive season. Moreover, this study investigated athletes' hormonal response to a typical weekly conditioning session (5 days before match: MD-5), at T1 and T2, to detect changes in players' recovery capability over time. Salivary cortisol (sC) and testosterone (sT) of 24 professional players (27.8 ± 4.1 years of age) were collected before, after, and 24 hours following MD-5 in two comparable microcycles of T1 and T2. GPS training data (total and high-intensity distance) of the 7 and 28 days before sampling were used to obtain athletes' acute and chronic workloads. Results showed a pre-training significant decrease of sT and an increase of sC (p<0.05) in T2, compared to T1. Moreover, athletes showed high sC and low sT levels before, after and 24 hours following MD-5 in T2. Workload analysis revealed significant correlations of chronic load with sC (r = 0.45, p = 0.056) and T/C ratio (r = -0.59; p = 0.007). These results suggested that, in professional football, chronic workload has a greater impact on players' recovery time than acute workload over the sport season. Moreover, athletes' hormonal response to the weekly conditioning session at T2 revealed an altered anabolic/catabolic balance, highlighting the key role of continuous internal and external workload monitoring during the season.

Deucravacitinib, a selective tyrosine kinase 2 inhibitor, for the treatment of moderate-to-severe plaque psoriasis.

INTRODUCTION: Protein kinases play a crucial role in intracellular signaling pathways that lead to inflammation and cell proliferation. New understandings of the involvement of these metabolic pathways in the pathogenesis of psoriasis allowed the development of a new class of drugs. Unlike biologics, these compounds work by blocking intracellular targets involved in the immune response. AREAS COVERED: Deucravacitinib is an oral small-molecule inhibitor of TYK2 that binds the pseudokinase domain and locks the kinase in an inactive state by an allosteric mechanism, arresting TYK2-mediated signaling cascades and disabling the upregulation of proinflammatory genes implicated in psoriasis. The authors present the results of phase I-III clinical trials of deucravacitinib for the treatment of psoriasis. EXPERT OPINION: At week 16 about 56% of the patients treated with deucravacitinib achieved PASI75. No serious infections were reported, nor were thromboembolic events or laboratory abnormalities. Efficacy was reported to be persistent and safety profiles were shown to be consistent for up to 2 years. Deucravacitinib can potentially become a safe, effective, well-tolerated treatment for patients suffering from moderate-to-severe disease. Future studies and real-life experiences will be important to determine the exact role of this drug in the treatment of psoriasis.

Relative age effect in Italian soccer: a cultural issue in talent management?

BACKGROUND: Relative age effect (RAE) is a well-known phenomenon among those involved in youth sports, especially when the sport being investigated is widespread and involves early selection for participation in national and international competitions. METHODS: The purpose of this study was to verify whether the Italian youth soccer ecosystem has adapted to this issue over the years, comparing players born in 1995 and in 2005 and been playing in Under 16 teams in the appropriate years. The sample included 13 professional Italian soccer teams. The number of players analysed was 260 (1995) and 344 boys (2005), respectively, making a total of 604 players enrolled in this study. RESULTS: Relative age effects were detected by χ2 goodness of fit tests both in players born in 1995 (P<0.000;V=0.40) and in 2005 (P<0.0001;V=0.39). χ2 test of independence showed no significant difference between the two groups of players (P=0.986;V=0.02), confirming a substantial parity of the phenomenon over the two investigated birth years. CONCLUSIONS: Ten years of research and dissemination of RAE did not change the selection policies adopted by coaches and/or scouts, who favor relatively older players during the selection processes. Therefore, RAE appears as the result of the Talent Identification and Development Structures, characterized by early selection and early specialization, and which consider performance as the pre-requisite for gaining access to the next developmental stages. Sport organizations should be aware of this issue and counteract accordingly, since it is important to mitigate the presence of RAE, as it causes inequality of opportunity.

Guselkumab for treatment of moderate-to-severe plaque psoriasis: real-life effectiveness and drug-survival for up to 148 weeks.

BACKGROUND: Real-world data are useful to guide the management of psoriasis. Here, we present data on the effectiveness and survival of guselkumab in moderate-to-severe chronic plaque psoriasis for up to 148 weeks. RESEARCH DESIGN AND METHODS: Cross-sectional study of 122 patients receiving guselkumab (100 mg at weeks 0 and 4, and then every 8 weeks thereafter) for>12 weeks, from November 2018 to April 2022. MAIN OUTCOME MEASURES: Clinical features and drug survival were analyzed up to 148 weeks. RESULTS: Obese patients (32.8%) and those receiving prior biologics (64.8%) were included. Guselkumab treatment was associated with a rapid decrease in PASI, from 16.2 to 3.2 at week 12, and long-term improvements in all subgroups (97.6%, 82.9%, and 63.4% of patients, respectively, achieved PASI 75, 90, and 100 after 148 weeks). More non-obese than obese patients achieved PASI 100 at week 148 (86.4% vs 38.9%), as did bio-naïve vs bio-experienced patients (86.7% vs 50.0%). Previous biologic therapy was a negative prognostic factor for achieving PASI 100 over the long-term by multivariate analysis (p = 0.005). Overall, 96% of patients were on treatment after 2 years. CONCLUSIONS: Real-world data confirm the long-term effectiveness of guselkumab in patients with psoriasis.

Temporal patterns of fatigue in repeated sprint ability testing in soccer players and acute effects of different IHRs: a comparison between genders.

BACKGROUND: Repeated sprint ability (RSA) in soccer is deemed fundamental to ensure high level of performance. The aim of this study was to investigate the acute effects of two different Initial Heart Rates (IHR) on fatigue when testing RSA in males and females' soccer players and to compare the respective patterns of fatigue. METHODS: Nineteen female soccer players (age: 22.5±3.3 years, height 163.9±7.3 cm, body weight 54.3±6.4 kg, BMI 20.6±1.5 kg·m-2) and 15 male soccer players (age: 17.9±1.5 years, height 175.9±5.8 cm, body weight 68.5±9.6 kg, BMI 22.3±1.5 kg·m-2) participated in this study. HRs reached at the end of two different warm-up protocols (~90 vs. ~ 60% HRmax), have been selected and the respective RSA performances were compared, within and between the groups of participants. Two sets of ten shuttle-sprints (15+15 m) with a 1:3 exercise to rest ratio with different IHR% were administered, in different days, in randomized order. To compare the different sprint performances, we employed the calculated Fatigue Index (FI%). Blood lactate concentration (BLa-) was also measured before and after testing, to compare metabolic energy. RESULTS: Significant differences among trials within each set (P<0.01) were found in both genders. Differences between sets were found in male players, (Factorial ANOVA 2x5; P<0.001), not in female. BLa- after warm-up was higher in 90% vs. 60% HRmax (P<0.05), in both genders but at the completion of RSA tests (after 3 minutes) the differences were not significant (P>0.05). CONCLUSIONS: difference between genders were found, suggesting specific approach in testing and training RSA in soccer players.

Gender differences in instep soccer kicking biomechanics, investigated through a 3D human motion tracker system.

BACKGROUND: This study aims at describing and comparing each other male and female soccer players kicking instep a stationary ball. The different measures we collected by the 3D motion capture system Movit G1 and the High-Speed Camera (240 fps) were considered as dependent variables, whereas the gender was considered as the independent one. METHODS: Twenty soccer well trained non-professional players: 10 men (age: 25.3±6.5 yrs; height 1.80±0.07 m; body mass 76.9±13.2 kg) and 10 women (age: 19±3.34 yrs; height 1.64±0.07 m; body mass 58.2±7.2 kg) volunteered to participate in the study. RESULTS: Gender differences were found, with a statistical significance (P<0.05) or interesting magnitude (Cohen d>0.5). The most relevant ones were the differences in hip extension of the kicking leg when the foot of the supporting one touches the ground, just before the impact on the ball (independent sample t-Test; P=0.03; Cohen d=1.64) and the speed of the ball, reached immediately after kicking (P<0.001;d=1.23). CONCLUSIONS: These results, together with the greater pelvic acceleration shown by men compared to women, highlight the need to develop a gender-differentiated training model, in order to customize the kicking technique in women and to reduce the likelihood, currently higher than for men, of kicking related injuries.