To systematically evaluate the impact of therapeutic plasma exchange (TPE) on the clearance of antirheumatic drugs and its consequent effects on clinical efficacy, aiming to provide an evidence-based foundation for optimizing medication management during TPE.

This review synthesizes current evidence from 65 studies on the removal of antirheumatic drugs during TPE. Key pharmacokinetic determinants influencing clearance rates—including volume of distribution, protein binding, molecular size, and elimination half-life—were identified. Based on these parameters, a predictive model for assessing drug removal risk was constructed.

The analysis reveals that the risk of drug removal during TPE exists as a continuous spectrum. Large monoclonal antibodies with a low volume of distribution and slow redistribution from tissue compartments (e.g., rituximab, natalizumab) are cleared with high efficiency, supporting the clinical recommendation of administering such drugs after TPE sessions. For drugs lacking direct evidence, the predictive model based on fundamental pharmacokinetic parameters effectively estimates their removal risk.

Therapeutic plasma exchange is a critical intervention in managing severe rheumatic diseases, but it exerts a complex and significant influence on the pharmacokinetics of concurrently administered antirheumatic drugs. This systematic review demonstrates that the risk of drug removal by TPE is not unpredictable but is primarily governed by core pharmacokinetic parameters, notably the volume of distribution and plasma protein binding. Based on this, we successfully synthesized available evidence into a clear, hierarchical management framework: a risk-stratified management framework for chronic therapy (e.g., mandatory post-TPE dosing for large biologics) to preserve efficacy, which uses core pharmacokinetic parameters, such as Vd and protein binding, as the key feasibility filter. In summary, implementing pharmacokinetics-informed management strategies of antirheumatic drugs during TPE can help in mitigating unintended drug loss and guiding rational detoxification, which is essential for ensuring continuity of care for the primary disease, improving outcomes in critical care, and safeguarding patient safety. These improvements contribute to precision medicine in apheresis, with therapeutic drug monitoring being a key future direction.