Background: Rituximab is commonly used to treat patients with primary glomerular diseases; however, its pharmacokinetics in this population have not been fully described yet. Materials and methods: This single-center, open-label, uncontrolled clinical trial included adult patients with glomerular diseases who required rituximab treatment (NEFRTX; EudraCT: 2020-000484-23). Patients received 1 or 0.5 g of rituximab on day 1 (and d14 in some cases). Blood and urine samples were collected at days 1, 7, 14, 28, and 45 to measure biochemical parameters (proteinuria, albuminemia, plasma immunoglobulin, and urine immunoglobulin), rituximab, and antidrug antibody concentrations. The gene encoding the neonatal fragment-crystallizable receptor was also characterized. Linear regression and Win-Nonlin 1.1 were used for pharmacokinetic analysis. Results: Thirty-five cases (30 patients) were included in this study. Pharmacokinetic parameters were expressed as mean (SD): maximum plasma concentration, 179.4 (71.8) mcg/mL; volume of distribution, 78.9 (31.4) mL/kg; clearance, 0.30 (0.27) mL/h/kg; half-life (t _1/2 ), 11.6 (5.8) d; elimination rate constant, 0.0036 (0.0030) hour ⁻¹ ; and area under the curve, 117,756.1 (88,228.1) mcg·h/mL. Antidrug antibody was detected on d1 in 3 cases (8.6%) and was negative by d28. Rituximab t _1/2 was represented by the formula: t _1/2 = A-B·Log (Proteinuria)+C·Albuminemia, where A = 515.1 (128.8–901.3), B = 182.1 (−108.6 to −35.4), and C = 39.5 (−10.9 to 89.9). There were significant differences in rituximab t _1/2 based on diagnosis ( P = 0.025), early treatment ( P = 0.008), proteinuria >2.4 g /24h ( P < 0.001), plasma immunoglobulin 2.4 g /24h may require higher frequent dosing for adequate rituximab exposure. Establishing an optimal dosing regimen in this population remains warranted.

Background: This study evaluated the long-term effectiveness and safety of a multidisciplinary early proactive therapeutic drug monitoring (TDM) program combined with Bayesian forecasting for infliximab (IFX) dose adjustment in a real-world dataset of paediatric patients with inflammatory bowel disease (IBD). Methods: A descriptive, ambispective, single-centre study of paediatric patients with IBD who underwent IFX serum concentration measurements between September 2015 and September 2023. The patients received reactive TDM before September 2019 (n = 17) and proactive TDM thereafter (n = 21). We analysed for clinical, biological, and endoscopic remission; treatment failure; hospitalisations; emergency visits; and adverse drug reactions. The IFX doses were adjusted to maintain trough concentrations ≥ 5 µg/mL, with specific targets for proactive TDM. Results: Of the 38 patients, 21 had Crohn’s disease (CD), 16 ulcerative colitis (UC), and 1 undetermined IBD. The mean (standard deviation) IFX trough concentrations were 6.83 (5.66) µg/mL (reactive) and 12.38 (9.24) µg/mL (proactive) (p = 0.08). No statistically significant differences between groups were found in remission rates or treatment failure. The proactive group had fewer hospitalisations (14.29% vs. 23.53%; p = 0.47) and shorter median hospitalisation days (6 vs. 19; p = 0.50), although the difference was not statistically significant. The number of patients with adverse reactions (infusion related reactions and infections) was higher in the proactive group (38.10% vs. 23.53%; p = 0.34) but the difference was not significantly different. Conclusions: Proactive TDM showed no significant differences in treatment outcomes compared to reactive TDM. However, the results in both the reactive and proactive TDM groups were not worse than those reported in other studies. Further studies with larger samples are needed to optimize the treatment strategies for pediatric IBD patients.

Background/Objectives: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO patients are limited. Our objective is to evaluate Isavuconazole exposure and variability in critically ill COVID-19 patients receiving ECMO. Methods: We conducted a pharmacokinetic analysis of Isavuconazole in critically ill patients receiving Veno-Venous ECMO for respiratory support. Plasma concentrations were measured using therapeutic drug monitoring (TDM) at multiple time points, including sampling before and after the membrane oxygenator. PK parameters—Area Under Curve (AUC_0–24), Minimum Plasma Concentration (Cmin), Elimination Half-Life (T_1/2), volume of distribution (Vd), and clearance (CL)—were estimated and compared with published data in non-ECMO populations. Results: Five patients were included. The median AUC_0–24 was 227.3 µg·h/mL (IQR 182.4–311.35), higher than reported in non-ECMO patients. The median Vd was 761 L (727–832), suggesting extensive peripheral distribution and potential drug sequestration in the ECMO circuit. CL was increased (1.6 L/h, IQR 1.5–3.4). Two patients with recently replaced ECMO circuits exhibited significant drug loss across the membrane. Obesity and hypoalbuminemia were identified as factors associated with altered drug exposure. Conclusions: Isavuconazole pharmacokinetics show marked variability in critically ill ECMO patients. Increased AUC and Vd, along with reduced clearance, highlight the need for individualized dosing.

A few months ago, we presented the results from a case-control study evaluating solid organ transplantation (SOT) recipients’ outcomes after COVID-19 requiring hospitalization, which showed a trend towards higher mortality among SOT patients compared to controls¹. Other authors reported similar results regarding mortality², whereas Chavarto et al. found no increased risk of death among kidney recipients compared to controls³. We hypothesize that COVID-19 might affect long-term survival of SOT recipients, drug-drug interactions (DDI) might contribute to graft rejection and COVID-19 unknown long-term effects might specially affect immunosuppressed patients⁴; here, we aim to evaluate the long-term outcomes of SOT patients affected by COVID-19.

Objectives To evaluate the potential association between chronic exposure to medication and death related to COVID-19. Methods This is a retrospective cross-sectional study that included all patients hospitalised due to COVID-19 from 11 March to 4 June 2020 in our centre. Chronic patient medication was classified by the Anatomical Therapeutic Chemical (ATC) classification; demographic and clinical data were analysed. Multivariate logistic regression models were used to estimate the adjusted odds ratios (aOR) of death for each drug exposure; each aOR represents an independent model adjusted by clinical factors related to COVID-19 mortality. Results The study included 978 patients with a mean (SD) age of 64.5 (17.7) years who were predominantly male (531, 54.3%). Of all 978 patients, 182 (18.61%) died during the follow-up of the study. The most common Charlson Comorbidity Index (CCI) was 0, 4.2% were smokers, 16.7% were obese, 47.4% had hypertension, and 19.4% were diabetic. Most patients (70.8%) were prescribed at least one treatment, 32.5% used >5 treatments, and 8.6% >10. Our data suggest that COVID-19 hospitalised patients taking trimethoprim and analogues, leukotriene receptor antagonists, calcineurin inhibitors, aldosterone antagonists, selective immunosuppressants, propulsives, insulins and analogues, and benzodiazepine derivatives have a higher risk of death. Conclusions This study investigated the association between chronic exposure to drugs and the risk of death in COVID-19 patients. Our results have shed some light on the impact of chronic drug exposure on the risk of severe COVID-19; however, further research is needed to increase the understanding about its relevance.

Background: Evidence suggests a relationship between ustekinumab (UST) concentrations and therapeutic outcomes in inflammatory bowel disease. Objectives: This study aimed to evaluate the association between UST concentrations during the induction phase and treatment outcomes at week 24 in patients with Crohn’s disease (CD) and ulcerative colitis (UC). The primary outcome was endoscopic remission at week 24, defined as a simple endoscopic score (SES-CD) ⩽2 for CD and a Mayo endoscopic score = 0 for UC. Secondary outcomes included endoscopic response, clinical remission, and treatment persistence. Design: This was a prospective observational study assessing clinical and endoscopic outcomes in CD and UC patients starting UST therapy. Methods: Consecutive patients with CD and UC were included at the initiation of UST treatment. Trough UST concentrations were measured at weeks 8, 16, and 24 after the first intravenous dose, and the main outcomes were assessed at week 24. Endoscopic and clinical parameters were used to evaluate treatment efficacy and persistence. Results: Seventy patients (45 with CD) were enrolled. Those achieving endoscopic remission and response at week 24 had higher UST levels at week 8 (4.5 vs 2.6 μg/mL, p = 0.0028; 4.1 vs 2.4 μg/mL, p = 0.0024, respectively). Patients with UST concentrations in the fourth quartile (Q4) at week 8 (>4.5 μg/mL) had higher rates of endoscopic remission (66.7% (Q4) vs 20% (Q1); 33.3% (Q2); 28.6% (Q3); p = 0.012). A UST concentration threshold of 4.5 μg/mL at week 8 was the best predictor of endoscopic remission (AUC = 0.7, sensitivity 54.5%, specificity 83.8%), while 3.5 μg/mL predicted endoscopic response (AUC = 0.732, sensitivity 53.8%, specificity 87%). Longer disease duration correlated with a higher risk of UST discontinuation (odds ratio, 1.034, 95% confidence interval, 1.002–1.068, p = 0.035). Higher UST concentrations in Q4 did not result in greater drug persistence ( p = 0.319). Conclusion: UST concentrations at week 8 were positively associated with endoscopic outcomes at week 24, with a threshold of 4.5 μg/mL reliably predicting endoscopic remission. Further randomized clinical trials are warranted to explore whether optimizing UST treatment based on post-induction concentrations can enhance therapeutic outcomes.