Objective SCT630 is a recombinant fully human anti-TNF-α IgG1 monoclonal antibody developed as a biosimilar to adalimumab reference product Humira® (AbbVie). This study aims to evaluate the pharmacokinetic (PK) similarity, characterize pharmacokinetics between healthy participants and patients, and identify potential sources of PK variability of SCT630 and Humira® using population pharmacokinetic modeling approach. Methods A population pharmacokinetic model was developed using PK data from a phase I study in healthy participants and a phase III study in patients with moderate to severe plaque psoriasis (PsO). Results A one-compartment PopPK model with first-order linear elimination adequately described SCT630 and Humira® concentration data. The covariates analysis identified anti-drug antibody, body weight, total bilirubin, alanine aminotransferase, participant type and study drug as significant covariates affecting clearance and volume of distribution. Model-predicted exposures, including Cmax and AUC were obtained, and their geometric mean ratios (test versus the reference group) were calculated. The 90% confidence intervals (CI) for all these ratios fell entirely within the range of 80.00% to 125.00%. Conclusion This analysis integrated data from both healthy participants and patients with PsO, and provided a valuable assessment of adalimumab PK characteristics and significant covariates. This model-based approach further elucidates how the SCT630 PK profile compares to that of Humira® in healthy participants and patients with PsO, supporting the totality-of-evidence for the biosimilarity of SCT630.
Background COVID-19 frequently presents with pneumonia. Impaired immune function, particularly in older adults and immunocompromised individuals, increases susceptibility to infection and contributes to higher morbidity and mortality. Among inflammatory cytokines, Interleukin-6 (IL-6) plays a pivotal role in immune dysregulation and cytokine storm. Therefore, this study aimed to investigate the association between serum IL-6 levels and clinical, laboratory, radiological, and outcome-related findings among hospitalized patients with COVID-19. Methods This descriptive-analytical cross-sectional study included 210 hospitalized COVID-19 patients at Shahid Beheshti Hospital, Kashan. Serum IL-6 was measured as part of their diagnostic and therapeutic workup. Demographic characteristics, clinical manifestations, laboratory markers, imaging findings, and outcomes were recorded. Patients with incomplete data were excluded. Data were analyzed using SPSS software version 26. Results The mean age of patients was 50.37 ± 17.48 years, with a slight male predominance (51%). Hypertension was the most common comorbidity (31.9%). Abnormal laboratory markers included elevated LDH (64.3%), ESR (61.0%), lymphopenia (59.5%), and CRP (58.6%). Pulmonary involvement on CT was noted in 91.5% of patients, with moderate involvement most frequent (41.4%). ICU admission occurred in 17.1% and mechanical ventilation was required in 10.5%. The mean CALL score was 8.63 ± 2.33, and average hospital stay was 6.70 ± 5.27 days. Serum IL-6 levels were significantly associated (P < 0.05) with age, oxygen saturation, lymphopenia, LDH, CRP, CT involvement, disease severity, ICU admission, mortality, and length of hospitalization. Conclusion Elevated serum IL-6 strongly reflects disease severity and adverse outcomes in COVID-19, highlighting its potential as a prognostic biomarker to guide clinical assessment and management.
BACKGROUND:This study investigated the association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and Fournier gangrene (FG), analyzing additional risk factors using pharmacovigilance data. DATA SOURCES:Data were extracted from the Japanese Adverse Drug Event Reporting (JADER) database (April 2014-August 2024), encompassing 914,713 adverse event reports, including 5770 involving SGLT2 inhibitors. MAIN FINDINGS AND LIMITATIONS:Among 40 identified FG cases (0.69% of SGLT2 reports), empagliflozin showed the strongest association (reporting odds ratio = 78.62) and canagliflozin the weakest. Male patients demonstrated significantly higher FG risk than female patients (P = 0.004), particularly with tofogliflozin. No significant correlation existed between obesity and FG occurrence. Onset timing varied widely (12-1515 days). Limitations include potential data incompleteness inherent to spontaneous reporting systems, limited sample size, and inability to establish definitive causality. CONCLUSIONS:All 5 SGLT2 inhibitors were associated with FG, with empagliflozin carrying the highest risk. Male patients exhibited elevated susceptibility. Continuous monitoring throughout treatment is essential. Further clinical trials are warranted to clarify causal relationships.
