Janssen (Italy)

Adaptive deep brain stimulation (aDBS) is a closed-loop system that adjusts stimulation based on patient biomarkers. This study evaluated the cognitive safety of aDBS in Parkinson's disease (PD). Sixteen PD patients with bilateral subthalamic DBS underwent cognitive assessments (attention, language, memory) 6days post-surgery during an 8h protocol. Testing occurred at five time points: T1 (aDBS, medication "off"), T2/T4 (aDBS, medication "on"), and T3/T5 (aDBS "on", medication "off"). Four patients followed the same protocol with continuousDBS (cDBS). Results showed no cognitive fluctuations in aDBS patients (p ≥ 0.110). However, cDBS patients exhibited significant reaction time (RT) variations (p = 0.019), with RTs lower at T1 than T3 (p = 0.011) and T5 (p = 0.021), and at T4 compared to T2 (p = 0.002). These findings suggest that 8h aDBS may not adversely affect cognitive performance, providing preliminary evidence of its cognitive safety and stability in PD.

Selexipag is an oral selective prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension (PAH) in adults. To date, no treatment targeting the prostacyclin pathway is approved for pediatric patients. Our goal is to identify a pediatric dose regimen that results in comparable exposures to selexipag and its active metabolite JNJ‐68006861 as those shown to be efficacious in adult PAH patients. Extrapolation from the population pharmacokinetic (PK) model developed in adults (GRIPHON study; NCT01106014) resulted in the definition of three different pediatric body weight groups (≥9 to <25 kg, ≥25 to <50 kg, and ≥50 kg) with corresponding starting doses (100, 150, and 200 μg twice daily) and maximum allowed doses (800, 1200, and 1600 μg twice daily). The proposed pediatric dose regimen was subsequently tested in a clinical study (NCT03492177), including 63 pediatric PAH patients ≥2 to <18 years of age and a body weight range of 9.9–93.5 kg. The body weight‐adjusted dose regimen for selexipag resulted in comparable systemic exposures to selexipag and its active metabolite in pediatric patients as previously observed in adult PAH patients. Updating the adult selexipag population PK model provided overall consistent parameters and confirmed that the PK characteristics of selexipag and its active metabolite were comparable between pediatric and adult patients. The presented selexipag dose regimen for pediatric PAH patients is considered appropriate for continuing the clinical evaluation of the safety and efficacy of selexipag in pediatric patients ≥2 years of age.

Abstract The European Medicines Agency approved ustekinumab for psoriasis treatment in adolescents (12–17 years) in 2015 (CADMUS trial), and children (6–11 years) in 2020. Interim results are reported from a post-authorization study (NCT03218488) evaluating the long-term safety profile of ustekinumab. This ongoing, prospective, observational, multicentre study enrolled patients (6–17 years) diagnosed with moderate-to-severe plaque psoriasis initiating ustekinumab. Clinical data and all adverse events (AEs) through approximately 54 months (data cut-off) are reported. Younger children (6–11 years) were included later in the study. Data are reported by age (younger cohort, 6–11; older cohort, 12–17). At data cut-off, 85 patients, 10 younger (median follow-up, 0.24 years) and 75 older (median follow-up, 1.69 years), had been enrolled. Ustekinumab therapy was discontinued in 11 (12.9%) patients, all from the older cohort. Overall, 50/85 (58.8%) patients reported 290 AEs and 27 (31.8%) reported 96 AEs considered related to ustekinumab. The most commonly reported AEs were nasopharyngitis (n = 8, 9.4%), fatigue (n = 7, 8.2%) and headache (n = 7, 8.2%). Most AEs were mild and did not result in treatment change. Nine (10.6%) patients reported 13 serious AEs; one (appendicitis) was considered related to ustekinumab. One younger patient reported two AEs considered related to ustekinumab, although neither was serious and therapy continued. No malignancies or deaths were reported in either cohort. These findings revealed no new safety concerns and are generally consistent with the known safety profile for ustekinumab in paediatric patients.

<b>Background:</b> pulmonary arterial hypertension (PAH) is a chronic, progressive disease; the use of narrative medicine may help investigate patient perspective, their self-perception and quality of life to better address the burden of disease. <b>Aims:</b> to gain insights into how PAH patient and their caregivers experience PAH, by evaluating narrative plots collected within the INSPECTIO study. <b>Methods:</b> INSPECTIO&nbsp;is an ongoing, observational, multicentre, prospective study of patients with PAH. We aimed to enrol 200 already diagnosed patients and already in treatment with macitentan and/or selexipag as part of combination therapy. Enrolment began in November 2020 and narratives are collected from patients and their caregivers at enrolment of the patients (V1) and at 12 months, then analysed through MAXQDA software. <b>Results:</b> as of January 2022, the study has enrolled 96 patients; 62 of them and 12 caregivers accepted to write narrative plots of their experience, and 17 patients (13 women, mean age 59 years) and 6 caregivers (4 spouses) completed V1 narrative plots. The narratives highlight the anguish and concern experienced by caregivers. For patients, despite confusion at diagnosis, they reported an improvement in their general condition over time. Nonetheless, only few patients describe PAH as a battle to be fought, while “threat” and “limitation” are the words mainly used to describe the disease. <b>Conclusion:</b> to our knowledge, this is the first PAH study using narrative medicine. Preliminary findings suggest that caregivers might feel a heavier burden of PAH than patients themselves and this should be considered in clinical practice to help managing this illness.