ibrutinib

Generational safety profiles of BTK inhibitors: adverse reaction signals and real-world evidence from the FAERS database.

Tu Jiachen J, Wang Zhe Z, Zhang Jingjing J, Xu Haojie H et al.

The development of Bruton's tyrosine kinase (BTK) inhibitors has revolutionized the management of B-cell malignancies and holds potential in autoimmune diseases. However, safety concerns remain regarding treatment-associated adverse events: first-generation ibrutinib has been associated with off-target adverse event profiles, second-generation agents (acalabrutinib and zanubrutinib) require further validation of long-term safety patterns, and the real-world safety characteristics of third-generation pirtobrutinib continue to be evaluated. This study aims to characterize differences in adverse event (AE) disproportionality reporting signal patterns among four BTK inhibitors using data from the FDA Adverse Event Reporting System (FAERS). This study analyzed AE reports for four BTK inhibitors from the FAERS database via disproportionality analysis with four distinct algorithms, complemented by a clinical prioritization scoring system. Disproportionality reporting signal patterns were characterized across System Organ Class (SOC), Preferred Term (PT), and temporal distribution dimensions. A standardized 2-year observation window was applied for sensitivity analysis, and AE-mortality associations were evaluated. A total of 77,014 AE reports were included in this study. The four BTK inhibitors showed positive disproportionality reporting signals in blood and lymphatic system disorders, cardiac disorders, and infections and infestations. However, distinct disproportionality signal patterns were observed at the PT level. Ibrutinib showed prominent cardiovascular-related disproportionality reporting signals, particularly for atrial fibrillation (ROR = 9.8). Acalabrutinib was characterized by a distinct headache signal. Zanubrutinib showed prominent signals for myelosuppression (ROR = 16.24) and haemorrhage subcutaneous (ROR = 146.81). Pirtobrutinib demonstrated the strongest signal for increased white blood cell count (ROR = 54.28). Descriptive analysis of reported time-to-onset distributions showed that pneumonia reports for ibrutinib represented a larger proportion among cases reported after longer treatment durations, whereas haemorrhage and decreased white blood cell count reports were more frequently observed within earlier reporting intervals. In terms of fatal outcomes, multiple PTs associated with ibrutinib showed statistically significant associations with reported death outcomes within the FAERS dataset. This descriptive pharmacovigilance study identified distinct disproportionality reporting signal patterns for four BTK inhibitors based on FAERS data, providing potential signals for post-marketing safety surveillance. These findings should be interpreted as differences in reporting patterns.

Development and validation of a blood-based diagnostic model for pulmonary tuberculosis combining GBP5 expression and routine laboratory indicators.

Zhao Miaomiao M, Hu Qiuxiang Q, Wang Qing Q, Cha Xinlang X et al.

WHO reports that only 54% of tuberculosis (TB) patients received rapid diagnostic tests at their initial presentation. Conventional laboratory methods in TB detection have high specificity (>90%) but low sensitivity (<50%). This means a large number of tuberculosis patients are missed. A better diagnostic approach is essential to decrease the TB burden. Studies on multi-indicator blood-based models for rapid TB diagnosis remain limited. We developed a rapid, non-sputum-based model to improve the efficiency of TB diagnosis. This was a retrospective case-control study including 301 patients with active tuberculosis (ATB) and 191 patients with other pulmonary diseases (OPD) who were evaluated at the Department of Pulmonary Medicine of the Affiliated Infectious Diseases Hospital of Soochow University between May 2023 and May 2024. A composite clinical diagnosis served as the gold standard for ATB diagnosis, including either a clinical diagnosis or bacteriological confirmation. The diagnostic outcome of ATB (ATB vs OPD) was defined as the dependent variable, while guanylate-binding protein 5 (GBP5) expression levels and routine laboratory indicators (including blood cell counts and plasma protein measurements) were defined as independent variables. Univariate and multivariate logistic regression analyses were performed to identify key predictors, and an AdaBoost algorithm was used to construct a TB diagnostic model. The performance of the model was compared with traditional laboratory-based TB tests. DeLong's Test was used to evaluate the statistical difference of AUC between AdaBoost and traditional methods. Through univariate and multivariate logistic regression analyses, the GBP5 gene, white blood cell (WBC) count, platelet (PLT) count, and prothrombin time (PT) were selected to construct an ATB diagnosis model using the AdaBoost algorithm. The AdaBoost model achieved an AUC of 0.808 in the training set and 0.805 in the test set, while the AUC of smear microscopy, MTB culture, Xpert MTB/RIF, and IGRA were 0.67, 0.59, 0.63 and 0.75 respectively. Therefore, our model demonstrated better diagnostic performance than conventional methods. This study preliminarily demonstrates that our AdaBoost diagnostic model based on GBP5 gene expression and routine blood indicators could serve as a potential tool for the clinical diagnosis of ATB. However, to be applied to the clinic, large samples are needed to validate the performance of the model.

From diagnostic accuracy to clinical utility in molecular dermatopathology.

Yılmaz Ercan E, Özer Nezihe Koker NK, Topal Erdem E

Response: Diagnostic utility of APRI, FIB-4, and FIB-5 in intrahepatic cholestasis of pregnancy.

Cicek Sevil S, Kapudere Bilge B, Kaya Parspancı Yasemin Beyza YB, Tavukcuoglu Zehra Z et al.