Long-term, Prolonged-release Tacrolimus-based Immunosuppression in De Novo Liver Transplant Recipients: 5-year Prospective Follow-up of Patients in the DIAMOND Study
Background. Immunosuppression with calcineurin inhibitors (CNIs) is reportedly associated with risk of renal impairment in liver transplant recipients. It is believed that this can be mitigated by decreasing initial exposure to CNIs or delaying CNI introduction until 3–4 d posttransplantation. The A...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2021-08-01
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| Series: | Transplantation Direct |
| Online Access: | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001166 |
| _version_ | 1818671585162166272 |
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| author | Styrbjörn Friman, MD, PhD Giuseppe Tisone, MD Frederik Nevens, MD, PhD Frank Lehner, MD Walter Santaniello, MD Wolf O. Bechstein, MD, PhD Sergey V. Zhuvarel, MD Helena Isoniemi, MD, PhD Oleg O. Rummo, MD Jürgen Klempnauer, MD Swapneel Anaokar, MBBS, MD Martin Hurst, MBBS, FRCP Gbenga Kazeem, PhD Nasrullah Undre, PhD Pavel Trunečka, MD, PhD |
| author_facet | Styrbjörn Friman, MD, PhD Giuseppe Tisone, MD Frederik Nevens, MD, PhD Frank Lehner, MD Walter Santaniello, MD Wolf O. Bechstein, MD, PhD Sergey V. Zhuvarel, MD Helena Isoniemi, MD, PhD Oleg O. Rummo, MD Jürgen Klempnauer, MD Swapneel Anaokar, MBBS, MD Martin Hurst, MBBS, FRCP Gbenga Kazeem, PhD Nasrullah Undre, PhD Pavel Trunečka, MD, PhD |
| author_sort | Styrbjörn Friman, MD, PhD |
| collection | DOAJ |
| description | Background. Immunosuppression with calcineurin inhibitors (CNIs) is reportedly associated with risk of renal impairment in liver transplant recipients. It is believed that this can be mitigated by decreasing initial exposure to CNIs or delaying CNI introduction until 3–4 d posttransplantation. The ADVAGRAF studied in combination with mycophenolate mofetil and basiliximab in liver transplantation (DIAMOND) trial evaluated different administration strategies for prolonged-release tacrolimus (PR-T).
Methods. DIAMOND was a 24-wk, open-label, phase 3b trial in de novo liver transplant recipients randomized to: PR-T 0.2 mg/kg/d (Arm 1); PR-T 0.15–0.175 mg/kg/d plus basiliximab (Arm 2); or PR-T 0.2 mg/kg/d delayed until day 5 posttransplant plus basiliximab (Arm 3). In a 5-y follow-up, patients were maintained on an immunosuppressive regimen according to standard clinical practice (NCT02057484). Primary endpoint: graft survival (Kaplan-Meier analysis).
Results. Follow-up study included 856 patients. Overall graft survival was 84.6% and 73.5% at 1 and 5 y post transplant, respectively. Five-year rates for Arms 1, 2, and 3 were 74.7%, 71.5%, and 74.5%, respectively. At 5 y, death-censored graft survival in the entire cohort was 74.7%. Overall graft survival in patients remaining on PR-T for ≥30 d was 79.1%. Graft survival in patients who remained on PR-T at 5 y was 87.3%. Patient survival was 86.6% at 1 y and 76.3% at 5 y, with survival rates similar in the 3 treatment arms at 5 y. Estimated glomerular filtration rate at the end of the 24-wk initial study and 5 y posttransplant was 62.1 and 61.5 mL/min/1.73 m2, respectively, and was similar between the 3 treatment arms at 5 y. Overall, 18 (2.9%) patients had ≥1 adverse drug reaction, considered possibly related to PR-T in 6 patients.
Conclusions. In the DIAMOND study patient cohort, renal function, graft survival, and patient survival were similar between treatment arms at 5 y posttransplant. |
| first_indexed | 2024-12-17T07:26:20Z |
| format | Article |
| id | doaj.art-03070658369a4d6a8b22fd3cb723f616 |
| institution | Directory Open Access Journal |
| issn | 2373-8731 |
| language | English |
| last_indexed | 2024-12-17T07:26:20Z |
| publishDate | 2021-08-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Transplantation Direct |
| spelling | doaj.art-03070658369a4d6a8b22fd3cb723f6162022-12-21T21:58:37ZengWolters KluwerTransplantation Direct2373-87312021-08-0178e72210.1097/TXD.0000000000001166202108000-00004Long-term, Prolonged-release Tacrolimus-based Immunosuppression in De Novo Liver Transplant Recipients: 5-year Prospective Follow-up of Patients in the DIAMOND StudyStyrbjörn Friman, MD, PhD0Giuseppe Tisone, MD1Frederik Nevens, MD, PhD2Frank Lehner, MD3Walter Santaniello, MD4Wolf O. Bechstein, MD, PhD5Sergey V. Zhuvarel, MD6Helena Isoniemi, MD, PhD7Oleg O. Rummo, MD8Jürgen Klempnauer, MD9Swapneel Anaokar, MBBS, MD10Martin Hurst, MBBS, FRCP11Gbenga Kazeem, PhD12Nasrullah Undre, PhD13Pavel Trunečka, MD, PhD141 Transplant Institute, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.2 Department of Surgical Sciences, University of Rome “Tor Vergata,” Rome, Italy.3 Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium.4 Department of General, Visceral, and Transplantation Surgery, Hannover Medical School, Hannover, Germany.5 Unit of Hepatobiliary Surgery and Liver Transplant Center, Department of Gastroenterology and Transplantation, “A. Cardarelli” Hospital, Naples, Italy.6 Department of Surgery, Goethe University Hospital and Clinics, Frankfurt, Germany.7 N.V. Sklifosovsky Research Institute, Moscow, Russian Federation.8 Department of Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland.9 Republican Scientific and Practical Center for Organ and Tissue Transplantation, Minsk, Belarus.4 Department of General, Visceral, and Transplantation Surgery, Hannover Medical School, Hannover, Germany.10 Astellas Pharma Europe, Chertsey, United Kingdom.10 Astellas Pharma Europe, Chertsey, United Kingdom.10 Astellas Pharma Europe, Chertsey, United Kingdom.10 Astellas Pharma Europe, Chertsey, United Kingdom.12 Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.Background. Immunosuppression with calcineurin inhibitors (CNIs) is reportedly associated with risk of renal impairment in liver transplant recipients. It is believed that this can be mitigated by decreasing initial exposure to CNIs or delaying CNI introduction until 3–4 d posttransplantation. The ADVAGRAF studied in combination with mycophenolate mofetil and basiliximab in liver transplantation (DIAMOND) trial evaluated different administration strategies for prolonged-release tacrolimus (PR-T). Methods. DIAMOND was a 24-wk, open-label, phase 3b trial in de novo liver transplant recipients randomized to: PR-T 0.2 mg/kg/d (Arm 1); PR-T 0.15–0.175 mg/kg/d plus basiliximab (Arm 2); or PR-T 0.2 mg/kg/d delayed until day 5 posttransplant plus basiliximab (Arm 3). In a 5-y follow-up, patients were maintained on an immunosuppressive regimen according to standard clinical practice (NCT02057484). Primary endpoint: graft survival (Kaplan-Meier analysis). Results. Follow-up study included 856 patients. Overall graft survival was 84.6% and 73.5% at 1 and 5 y post transplant, respectively. Five-year rates for Arms 1, 2, and 3 were 74.7%, 71.5%, and 74.5%, respectively. At 5 y, death-censored graft survival in the entire cohort was 74.7%. Overall graft survival in patients remaining on PR-T for ≥30 d was 79.1%. Graft survival in patients who remained on PR-T at 5 y was 87.3%. Patient survival was 86.6% at 1 y and 76.3% at 5 y, with survival rates similar in the 3 treatment arms at 5 y. Estimated glomerular filtration rate at the end of the 24-wk initial study and 5 y posttransplant was 62.1 and 61.5 mL/min/1.73 m2, respectively, and was similar between the 3 treatment arms at 5 y. Overall, 18 (2.9%) patients had ≥1 adverse drug reaction, considered possibly related to PR-T in 6 patients. Conclusions. In the DIAMOND study patient cohort, renal function, graft survival, and patient survival were similar between treatment arms at 5 y posttransplant.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001166 |
| spellingShingle | Styrbjörn Friman, MD, PhD Giuseppe Tisone, MD Frederik Nevens, MD, PhD Frank Lehner, MD Walter Santaniello, MD Wolf O. Bechstein, MD, PhD Sergey V. Zhuvarel, MD Helena Isoniemi, MD, PhD Oleg O. Rummo, MD Jürgen Klempnauer, MD Swapneel Anaokar, MBBS, MD Martin Hurst, MBBS, FRCP Gbenga Kazeem, PhD Nasrullah Undre, PhD Pavel Trunečka, MD, PhD Long-term, Prolonged-release Tacrolimus-based Immunosuppression in De Novo Liver Transplant Recipients: 5-year Prospective Follow-up of Patients in the DIAMOND Study Transplantation Direct |
| title | Long-term, Prolonged-release Tacrolimus-based Immunosuppression in De Novo Liver Transplant Recipients: 5-year Prospective Follow-up of Patients in the DIAMOND Study |
| title_full | Long-term, Prolonged-release Tacrolimus-based Immunosuppression in De Novo Liver Transplant Recipients: 5-year Prospective Follow-up of Patients in the DIAMOND Study |
| title_fullStr | Long-term, Prolonged-release Tacrolimus-based Immunosuppression in De Novo Liver Transplant Recipients: 5-year Prospective Follow-up of Patients in the DIAMOND Study |
| title_full_unstemmed | Long-term, Prolonged-release Tacrolimus-based Immunosuppression in De Novo Liver Transplant Recipients: 5-year Prospective Follow-up of Patients in the DIAMOND Study |
| title_short | Long-term, Prolonged-release Tacrolimus-based Immunosuppression in De Novo Liver Transplant Recipients: 5-year Prospective Follow-up of Patients in the DIAMOND Study |
| title_sort | long term prolonged release tacrolimus based immunosuppression in de novo liver transplant recipients 5 year prospective follow up of patients in the diamond study |
| url | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001166 |
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