Laurent Godinas1, Fabienne Dobbels2, Leni Hulst3, Ive Verbeeck2, Ines De Coninck2, Pieter Berrevoets2, Veronique Schaevers3, Jonas Yserbyt4, Lieven J Dupont4, Stijn E Verleden5, Bart M Vanaudenaerde5, Laurens J Ceulemans6, Dirk E Van Raemdonck6, Arne Neyrinck7, Geert M Verleden4, Robin Vos4. 1. Department of Respiratory Diseases, Lung Transplantation Group, UZ Leuven, Campus Gasthuisberg, Leuven, Belgium; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETA, KU Leuven, Leuven, Belgium. Electronic address: Laurent.Godinas@uzleuven.be. 2. Academic Center for Nursing and Midwifery, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. 3. Department of Respiratory Diseases, Lung Transplantation Group, UZ Leuven, Campus Gasthuisberg, Leuven, Belgium. 4. Department of Respiratory Diseases, Lung Transplantation Group, UZ Leuven, Campus Gasthuisberg, Leuven, Belgium; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETA, KU Leuven, Leuven, Belgium. 5. Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETA, KU Leuven, Leuven, Belgium. 6. Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETA, KU Leuven, Leuven, Belgium; Department of Thoracic Surgery, Lung transplantation group, UZ Leuven, Campus Gasthuisberg, Leuven, Belgium. 7. Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETA, KU Leuven, Leuven, Belgium; Department of Anesthesiology, Lung transplantation group, UZ Leuven, Campus Gasthuisberg, Leuven, Belgium.
Abstract
BACKGROUND: Lung transplantation (LTx) requires a calcineurin inhibitor-based immunosuppressive regimen. A once daily (QD) tacrolimus regimen was developed to increase medication adherence. However, data concerning its safety and efficacy in LTx are lacking. METHODS: In this prospective study, stable LTx patients were consecutively converted from twice daily (BID) tacrolimus to QD tacrolimus on a 1 mg:1 mg basis. Trough level (Cmin), renal function, cholesterol, fasting glucose, potassium and lung function were monitored six months before and up to one year after conversion. Adherence and its barriers were assessed by self-reported questionnaires (Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) and Identification of Medication Adherence Barriers questionnaire (IMAB)) and blood-based assays (mean Cmin and coefficient of variation (CV)). RESULTS: We included 372 patients, in whom we observed a decrease in tacrolimus Cmin of 18.5% (p < 0.0001) post-conversion, requiring subsequent daily dose adaptations in both cystic fibrosis (CF) (n = 72) and non-CF patients (n = 300). We observed a small decrease in eGFR one year post-conversion (p = 0.024). No significant changes in blood creatinine, potassium, fasting glucose, cholesterol or rate of lung function decline were observed. In a subgroup of 166 patients, significantly fewer patients missed doses (8.4% vs. 19.3%, p = 0.016) or had irregular intake post-conversion (19.3% vs. 32.5%, p = 0.019). Mean Cmin and CV, as well as the total number of barriers, also decreased significantly post-conversion. CONCLUSIONS: In LTx, conversion from BID to QD tacrolimus (1 mg:1 mg) requires close monitoring of tacrolimus Cmin. QD tacrolimus after transplantation is safe with respect to renal function, metabolic parameters and allograft function and improves LTx recipient adherence.
BACKGROUND: Lung transplantation (LTx) requires a calcineurin inhibitor-based immunosuppressive regimen. A once daily (QD) tacrolimus regimen was developed to increase medication adherence. However, data concerning its safety and efficacy in LTx are lacking. METHODS: In this prospective study, stable LTx patients were consecutively converted from twice daily (BID) tacrolimus to QD tacrolimus on a 1 mg:1 mg basis. Trough level (Cmin), renal function, cholesterol, fasting glucose, potassium and lung function were monitored six months before and up to one year after conversion. Adherence and its barriers were assessed by self-reported questionnaires (Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) and Identification of Medication Adherence Barriers questionnaire (IMAB)) and blood-based assays (mean Cmin and coefficient of variation (CV)). RESULTS: We included 372 patients, in whom we observed a decrease in tacrolimus Cmin of 18.5% (p < 0.0001) post-conversion, requiring subsequent daily dose adaptations in both cystic fibrosis (CF) (n = 72) and non-CF patients (n = 300). We observed a small decrease in eGFR one year post-conversion (p = 0.024). No significant changes in blood creatinine, potassium, fasting glucose, cholesterol or rate of lung function decline were observed. In a subgroup of 166 patients, significantly fewer patients missed doses (8.4% vs. 19.3%, p = 0.016) or had irregular intake post-conversion (19.3% vs. 32.5%, p = 0.019). Mean Cmin and CV, as well as the total number of barriers, also decreased significantly post-conversion. CONCLUSIONS: In LTx, conversion from BID to QD tacrolimus (1 mg:1 mg) requires close monitoring of tacrolimus Cmin. QD tacrolimus after transplantation is safe with respect to renal function, metabolic parameters and allograft function and improves LTx recipient adherence.