Advantage of First-Line Therapeutic Drug Monitoring-Driven Use of Infliximab for Treating Acute Intestinal and Liver GVHD in Children: A Prospective, Single-Center Study

SIMPLE SUMMARY: Acute GVHD is a common life-threatening complication of allogeneic HSCT and the second most common cause of death in allogeneic HSCT recipients following relapse of the primary disease. Despite advances in GVHD therapy, many patients do not respond sufficiently, and biomarkers to predict treatment success are not established. This issue also concerns the TNF-α blocker infliximab. This single-center prospective observational study was designed to assess the effectiveness of first-line infliximab treatment compared to infliximab use in second- or further-line therapy in pediatric allogeneic HSCT recipients. Our data show that using first-line, TDM-driven infliximab to treat aGVHD in children may result in better clinical outcomes and good tolerability, with a variable pattern of serum cytokines and drug clearance according to the timing of treatment and disease extension, respectively. ABSTRACT: The high serum concentrations of TNF-α characterize acute graft-versus-host disease (aGVHD), for which infliximab treatment may be beneficial. In 28 pediatric patients, four doses of 10 mg/kg infliximab every seven days were administered after steroid failure (Standard Group, n = 14) or as a first-line therapy (Early Group, n = 14). Population pharmacokinetic analyses and evaluation of serum cytokines were performed. After two months of treatment, complete response in gastrointestinal and liver aGVHD was achieved in 43% and 100% of patients in the Standard and Early groups, respectively. During follow-up, four patients in the Standard Group (but none in the Early Group) experienced an aGVHD recurrence. Viral infections occurred more frequently in the Standard Group after the fifth dose. Infliximab clearance did not differ between groups or according to treatment outcome for each organ involved in aGVHD, whereas serum levels of cytokines significantly differed. Therefore, present findings show that use of first-line, TDM-driven infliximab to treat aGVHD in children may result in better clinical outcomes and tolerability, with a different pattern of cytokines generated according to the moment of beginning of treatment.