Development of a novel nomogram for predicting delayed methotrexate excretion following high-dose methotrexate in adult patients with hematologic malignancies.

PURPOSE: High-dose methotrexate (HDMTX) is integral in treating hematologic malignancies but carries risks of severe toxicities due to prolonged MTX exposure. However, knowledge of delayed MTX excretion is primarily derived from pediatric and adolescent cohorts, with the reported predictors being presented as rough dichotomous values. This study aimed to identify risk factors for delayed MTX excretion exclusively in adult patients with hematologic malignancies and develop a more applicable predictive nomogram based on continuous clinical and laboratory variables. METHODS: 517 HDMTX cycles in 194 patients were retrospectively analyzed. Delayed MTX excretion was defined as either MTX concentration ≥ 1.0 µmol/L at 48 h or ≥ 0.1 µmol/L at 72 h after HDMTX initiation. Multivariate logistic regression analysis was used to construct the nomogram internally validated with the bootstrap method. RESULTS: Delayed MTX excretion was observed in 24.0% of cycles. Six significant predictors were identified: relapsed/refractory disease (Odds ratio [OR] 2.03), fewer HDMTX cycles (OR 0.771), treatment intent (OR 2.13), lower albumin (OR 0.563) and creatinine clearance levels (OR 0.993), and increased γ-glutamyl transpeptidase levels (OR 1.004, all P < 0.05). These were incorporated into a web-based nomogram as continuous variables with good prediction accuracy (area under the curve, 0.73) and without significant overfitting. Delayed MTX excretion increased risks of developing acute kidney injury, even solely at the 72 h timepoint (OR 2.57, P = 0.025), without providing any benefit of clinical outcomes. CONCLUSION: This study comprehensively characterized MTX elimination failure following HDMTX in adult patients and could pave the way for individualized risk prediction.

Factors Affecting Patients' Acceptance of Switching to Biosimilars Are Disease-Dependent: A Cross-Sectional Study.

Biosimilars (BS) are promoted worldwide because of the high cost of biologics. However, patients are apprehensive about switching to BS. For some diseases, several factors, which may be disease-dependent, influence patients' acceptance of switching to BS. Herein, we evaluated whether factors influencing acceptance for switching were disease-dependent among Japanese patients with different diseases. This cross-sectional study involved pharmacists' interviews with patients who used or planned to use biologics. Demographic and clinical characteristics were retrospectively investigated using the patients' medical records. Multivariate logistic regression showed that switch refusal was associated with a history of adverse reactions to biologics (odds ratio [95% confidence interval (CI)] = 3.38 [1.35-8.44]), history of complaints related to disease activity (3.57 [1.53-8.32]), and unacceptability of generic drugs (7.62 [2.70-21.60]). Subgroup analyses suggested that the unacceptability of generic drugs was a common factor, regardless of the disease. Concomitantly, histories of adverse reactions to biologics and complaints related to disease activity were disease-dependent factors. Healthcare professionals should help patients in selecting BS, considering these factors according to the disease.