Upadacitinib Optimization in a Patient With Protein-Losing Enteropathy Secondary to (Transient) Nonocclusive Mesenteric Ischemia, Idiopathic Myointimal Hyperplasia, and Hemodialysis: Grand Round

Background:We report a case of a 19-year-old man with severe total parenteral nutrition-dependent protein-losing enteropathy who was treated with upadacitinib. Treatment was complicated by renal failure requiring hemodialysis and severe diarrhea, which possibly hindered absorption.Methods:Therapeutic drug monitoring (TDM) and pharmacokinetic analyses were compared with published population pharmacokinetic data to determine the dose adjustments for each patient.Results:Based on TDM results, the dose was gradually increased from 30 mg once daily to 45 mg twice daily. Repeated sampling was performed to estimate the area under the curve (AUC)6.5 (402.5 mcg∗h/L), which was higher than data reported in the literature (AUC24 525, SD ± 123 mcg∗h/L dosing 30 mg extended release once daily). No AUC24 could be calculated because of the absence of concentrations in the descending part of the concentration-time curve. Clinical improvement was achieved at a higher dose, and no major signs and/or symptoms of drug-related toxicity occurred.Conclusions:Although TDM for Janus-kinase inhibitors is not yet a part of current clinical practice, in this case, the measurement of upadacitinib serum concentrations aided individualized dosing based on TDM.