Clinical Management of Antirheumatic Drug Exposure During Therapeutic Plasma Exchange

Therapeutic plasma exchange (TPE) is being increasingly utilized in the clinical management of severe rheumatic immune diseases, providing an effective means for rapidly removing pathogenic autoantibodies and inflammatory mediators. However, the non-selective nature of this technique can also lead to the unintended clearance of concomitantly administered antirheumatic drugs, potentially compromising therapeutic efficacy and disease control. Therefore, effective management of potential drug removal process during TPE and the implementation of individualized risk assessment are crucial for optimizing treatment outcomes in patients undergoing TPE. The variability in the extent of drug removal during TPE is primarily determined by their distinct pharmacokinetic characteristics, necessitating the establishment of a systematic, evidence-based strategy for adjusting drug administration regimens in patients receiving TPE treatment. This review synthesizes current evidence from 65 studies on the removal of antirheumatic drugs during TPE, identifying key determinants influencing clearance rates, including volume of distribution, protein binding, molecular size, and elimination half-life. Our analysis reveals that the risk of drug removal exists as a continuous spectrum: large monoclonal antibodies (e.g., rituximab, natalizumab), characterized by a large molecule size, low volume of distribution, with which mostly confined to the vascular space, are cleared with high efficiency. This finding supports the clinical recommendation of administering such drugs after TPE. For drugs with limited direct evidence, we propose a predictive model based on fundamental pharmacokinetic parameters to estimate their removal risk and guide clinical decision-making. Based on this evidence, we have constructed a stratified clinical management framework. It aims to maintain effective therapeutic drug exposure levels during chronic TPE therapy and to provide a rationale for the judicious application of TPE in overdose scenarios. Implementing this pharmacokinetic-informed, risk-adapted individualized strategy is important for ensuring treatment continuity, enhancing patient safety, and advancing empiricism-based therapy towards precision medicine.