INCLIVA Health Research Institute

CHRONOS is a multicenter, retrospective, cohort study involving acute graft-versus-host disease (aGvHD) adult patients with gastrointestinal (GI) symptoms, steroid- and ruxolitinib refractory, who initiated third-line therapy between 30 May 2019 and 30 September 2024. Primary endpoints were all-organ overall response rate (ORR) and GI-specific ORR (GI-ORR) around 28 days after treatment initiation. Secondary endpoints included duration of response, real-world progression-free survival (rwPFS) of underlying malignancy, and overall survival (OS). Fifty-nine patients from 16 sites in Europe were included. On Day 28, ORR was 36% (95% CI: 24-49%), GI-ORR was 37% (95% CI: 25-51%); 29% (95% CI: 11-49%) of responders lost response within 30 days, and 52% (95% CI: 29-72%) within 90 days. Median rwPFS and median OS were both 86 days (95% CI: 54-128 days). Median OS was higher in responders than in non-responders (186 versus 45 days). Over the 12-month follow-up period, 41 patients died, mainly due to aGvHD progression (n = 25), and infectious complications (n = 9). Within 3 months, Grade ≥ 2 infectious events occurred in 51% of patients; Grade 3-4 thrombocytopenia and neutropenia in 64% and 32%, respectively. These findings demonstrate limited effectiveness of third-line therapy in this cohort of steroid- and ruxolitinib-refractory aGvHD patients with GI symptoms.

ABSTRACT Background Fingerprint patterns are developed during pregnancy and share a common embryogenic origin with the central nervous system. Considering the observed relationship between prenatal abnormalities and higher risk for schizophrenia, we previously built fingerprint‐based algorithms achieving validation accuracies up to 70% in a large sample of patients with schizophrenia. In this new study, we apply them to a sample of patients with bipolar disorder. Methods Besides validating the developed algorithms with an independent sample of fingerprints from N = 127 patients with schizophrenia and N = 116 healthy controls, here we applied them to a sample of N = 118 bipolar disorder patients. Scores from a premorbid IQ scale were also obtained from all participants, and the link between these scores and the algorithm outcomes was analyzed. Results The initial validation provided balanced accuracies similar to those of the original study (57%–68%). When applied to subjects with bipolar disorder (against healthy individuals), algorithms also showed significant predictive power (accuracies: 55%–68%). Consequently, the capacity to discriminate between schizophrenia and bipolar disorder was poor (accuracies: 47%–57%). Regression analyses between averaged probabilities and premorbid IQ scores were significant in schizophrenia (r = −0.184; p = 0.041) and in the whole sample (r = −0.159; p = 0.002). Conclusions Algorithms were predictive of bipolarity, highlighting the existence of fingerprint abnormalities also in bipolar disorder. In addition, the observed associations with premorbid IQ underline the neurodevelopmental origin of fingerprint patterns and suggest the potential use of fingerprints for prediction in other neurodevelopmental disorders. The lack of specificity with the diagnosis of schizophrenia, though, points to the need for new algorithms for differential diagnosis in psychosis.

Generalized myasthenia gravis (gMG) is a rare, chronic autoimmune neuromuscular disorder that currently lacks a curative treatment. Efgartigimod alfa is the first human IgG1 Fc fragment approved in Spain for the management of this condition. This study aims to evaluate the value of efgartigimod for treating gMG with anti-acetylcholine receptor (gMG AChR+) antibodies compared with ravulizumab, zilucoplan, and rozanolixizumab using a multi-criteria decision analysis (MCDA) framework. A multidisciplinary group of eight experts evaluated the value of efgartigimod against ravulizumab, zilucoplan, and rozanolixizumab. The MCDA framework adapted for evaluating orphan drugs (ODs) in Spain, comprising nine quantitative and three qualitative criteria, was used. gMG AChR+ has been recognised as a severe and debilitating condition with considerable unmet needs. Efgartigimod achieved favourable average scores compared with ravulizumab, zilucoplan, and rozanolixizumab across all comparative parameters, including efficacy, safety, and patient-reported outcomes (PROs), potentially resulting in cost savings. Efgartigimod was deemed to have a significant therapeutic impact, with supporting data considered high quality. Efgartigimod alfa showed a higher overall value contribution than the three comparators, with the difference being most notable for ravulizumab. Furthermore, it was concluded that efgartigimod aligns well with the specific priorities, objectives, and capacities of the National Healthcare System (NHS). Efgartigimod has been recognised as a valuable option for gMG AChR+ treatment in Spain by a multidisciplinary panel of experts through the application of MCDA, receiving higher scores compared with ravulizumab, zilucoplan, and rozanolixizumab.

Cytisinicline has proven to be an effective, efficient, and safe molecule in smoking cessation. However, the established 25-day regimen could be insufficient in a high percentage of smokers, so it is necessary to study maintained therapies of this drug. This study aims to compare the efficacy of the cytisinicline regimen used in routine clinical practice versus 2 maintained regimens of 50 and 75 days, respectively. In addition, the safety and economic impact of each regime will be determined. A prospective, multicenter, open-label, controlled, parallel, phase IV clinical trial of 402 smoker patients prepared to quit smoking. The study was conducted in 10 hospitals in Spain. A control group is compared to 2 intervention groups in which the duration of the drug is increased without increasing its dose, administering half and all, respectively, of an additional marketed container that includes 100 tablets. Thus, participants will be randomized to three groups in a 1:1:1 ratio to receive cytisinicline: (1) a control group treated with cytisinicline according to the usual clinical guidelines and product information (25 days); (2) a group with a 50-day cytisinicline regimen (an additional 25 days at a dose of 1.5 mg every 12 hours), seeking to increase its efficacy while minimally impacting adherence; and (3) a group with a 75-day regimen (an additional 50 days at a dose of 1.5 mg every 12 hours), attempting to increase its efficacy, although the longer duration of the drug may threaten adherence. Efficacy in the 3 arms will be analyzed through sustained abstinence at 6 and 12 months, point abstinence rate assessed every 7 days, and abstinence rate from Day 25 to Day 50 and from Day 25 to Day 75 in the 3 study arms. (1) The variation in withdrawal and craving symptoms in the 3 groups, (2) safety through the percentage of adverse events in the 3 treatment arms, and (3) economic impact by evaluating the cost-effectiveness and cost-utility ratios of the 2 prolonged regimens versus the usual clinical cytisinicline regimen. To calculate the differences between the 3 groups for each outcome variable, a univariate analysis will be performed. Statistically significant variables will be included in a multivariate model. Recruitment for the trial and patient enrollment were completed in November 2026. Follow-up of all participants will extend to December 2027. In conclusion, this study evaluates the optimization of cytisinicline in daily clinical practice, increasing the benefits of its pharmaceutical properties without affecting patient safety. All of this will improve the effectiveness of smoking cessation by reducing the number of smokers, which implies lower morbidity and mortality and lower costs associated with smoking. European Clinical Trials Register 2024-518936-36-00; https://euclinicaltrials.eu/ctis-public/view/2024-518936-36-00. PRR1-10.2196/76815.

Novel bioimpedance analysis (BIA) devices may improve the precision of fluid overload assessment, potentially offering additional prognostic information beyond clinical parameters in patients with HF. This study aimed to evaluate the association between fluid overload indexes obtained with a novel bioelectrical impedance device (BioScan touch i8 IVF, MALTRON®) and the risk of cardiovascular events in ambulatory patients with HF. Volume excess was assessed using BioScan Touch i8 IVF (MALTRON), which differentiates fluid distribution across body compartments. Volume-excess variables (total, intravascular, and tissue) were analysed both as quartiles (Q) and as continuous measures. Their independent associations with the composite of all-cause death or worsening HF were adjusted for established prognostic markers, including a clinical congestion score (CCS) and N-terminal pro-B-type natriuretic peptide. Among 386 ambulatory patients with stage C chronic HF, median total, intravascular, and tissue fluid excess were 1.3 L (Q1-Q3: 0.5, 2.3), 0.1 L (Q1-Q3: -0.1, 0.4), and 1.9 L (Q1-Q3: 1.1, 2.8), respectively. Total and tissue fluid excess had the strongest correlation with the CCS (Total fluid excess rho = 0.31; P < .001, tissue fluid excess rho = 0.33; P < .001). In adjusted analyses, patients in the highest quartile had significantly higher risk of the composite outcome compared with Q1: total fluid excess hazard ratio (HR) 2.11 [95% confidence interval (CI) 1.21-4.05, P = .010], intravascular fluid excess HR 2.16 (1.19-3.90, P = .011), and tissue fluid excess HR 2.81 (1.49-5.32, P = .001). Compartment-specific estimates of fluid overload obtained with the BioScan Touch i8 IVF were independently associated with adverse outcomes in ambulatory patients with chronic HF, beyond NT-proBNP and clinical surrogates of congestion. These findings support the potential role of BIA-derived indexes, particularly tissue fluid excess, as complementary tools for risk stratification in this population.