Outcomes of de novo extended-release tacrolimus use (Advagraf®) in kidney transplantation: 1-year, single-center experience

Year 2022, Volume: 3 Issue: 3, 175 - 181, 26.09.2022

Gülçin Türkmen Sarıyıldız , Mehmet Emin Demir , Zafer Ercan , Ulaş Sözener , Canan Çiçek , Aykut İlker Arslan , Fatma Necla Özşeker

https://doi.org/10.47582/jompac.1145373

Abstract

Aim: Once daily extended-release tacrolimus (tac-ER) was introduced to support medication adherence in kidney transplant (KTx) recipients, with similar efficacy to immediate-release tacrolimus (tac-IR). However, most of the experiences regarding tac-ER efficacy were obtained from the switches from tac-IR to tac-ER in kidney transplant recipients (KTRs). In this study, we aimed to demonstrate 1-year outcomes of de novo use of tac-ER in KTRs.
Material and Method: This single-center retrospective study included 72 de novo KTRs between January 2020 and January 2021. KTRS were divided into two groups who received a tac-ER or tac-IR. 1-year allograft functions, allograft survival, daily doses of tacrolimus in milligram/day and milligram/kg/day, trough levels, and acute rejection episodes were compared between the two groups. The factors that might have an impact on allograft functions and acute rejection episodes also were investigated.
Results: A total of 69 de novo kidney allograft recipients (30 recipients in the tac-ER and 39 recipients in the tac-ER groups); were evaluated. Three KTRs were excluded due to the deaths within the early posttransplant period. Serum creatinine and tacrolimus trough levels were similar for 12 months after transplantation (p>0.05). More daily tacrolimus doses (in milligram/day and milligram/kg/day) were required to obtain a targeted trough level up to 3 months in the tac-ER group. Acute rejection rates also were found similar between the two groups (p=0.281). Univariate regression analysis demonstrated that higher total daily tacrolimus doses within a posttransplant month 1 may (milligram/kg/day) have an impact on lower acute rejection episode(s) independent of tacrolimus trough levels (p=0.02).
Conclusion: De novo use of extended-release tacrolimus Advagraf® is as effective as immediate-release tacrolimus in preventing acute rejection episode(s) and provides satisfactory 1-year allograft function and survival.

Keywords

Extended-release tacrolimus, acute rejection, kidney transplantation

Böbrek naklinde de novo uzamış salınımlı takrolimus kullanımı sonuçları: tek merkez, 1 yıllık sonuçlar

Abstract

Amaç: Böbrek nakli alıcılarında günde tek doz uzamış salınımlı takrolimus (tac-ER) kullanımı, erken salınımlı takrolimus (tac-IR) kullanımına benzer etkinlik ve daha iyi ilaç uyumu sağlaması amacıyla geliştirilmiştir. Ancak uzamış salınımlı takrolimus ile ilgili deneyimler daha çok nakil sonrası dönemde yapılan “switch” protokollerine dayanmaktadır. Bu çalışmada böbrek alıcılarında de novo tac-ER kullanımı ile ilgili deneyimlerimizi ve 1 yıllık sonuçları sunmayı amaçladık.
Gereç ve Yöntem: Bu tek merkezli retrospektif çalışmaya Ocak 2022-Ocak 2021 arasında yapılan 72 de novo böbrek nakli hastası dahil edilmiştir. Hastalar tac-ER ve tac-IR alan iki gruba ayrıldı. Bir yıllık allogreft fonksiyonları ve sağ kalımları, hastaların günlük ilaç dozları ve bunların akut rejeksiyon atakları ile ilişkileri karşılaştırıldı. Allogreft fonksiyonları ve akut rejeksiyon atakları üzerine etki eden faktörler incelendi.
Bulgular: Toplam 69 hastanın (uzamış salınımlı grupta 30 hasta ve erken salınımlı grupta 39 hasta) verileri incelendi. Üç hasta posttransplant erken dönemde öldüğü için analize dahil edilmedi. Nakil sonrası 12 aylık izlem boyunca her iki grup arasında serum kreatinin ve takrolimus çukur değerler bencer bulundu (p>0,05). İlk 3 ay içinde hedef takrolimus değerlere ulaşmak için, tac-ER grubunda daha yüksek günlük dozlar (milligra/gün ve milligram/gün/kg) gerekti (p<0,05). Nakil sonrası ilk 12 ay içinde her iki grupta da rejeksiyon oranları benzerdi (p=0,281). Tek değişkenli analizde posttransplant 1. aydaki takrolimus dozu (milligram/kg/gün) takrolimus çukur değerinin aksine rejeksiyon gelişimi üzerinde etkili görüldü (p=0,02).
Sonuç: Böbrek naklinde uzamış salınımlı takrolimusun (Advagraf®) de novo kullanımı, erken salınımlı takrolimus kullanımına benzer etkinlik, allogreft sağ kalımı ve fonksiyonu sağlar.

Keywords

Uzamış salınımlı takrolimus, akut rejeksiyon, böbrek nakli

References

• Richter A, Anton SF, Koch P, Dennett SL. The impact of reducing dose frequency on health outcomes. Clin Ther 2003; 25: 2307-35.
• Ingersoll KS, Cohen J. The impact of medication regimen factors on adherence to chronic treatment: a review of the literature. J Behav Med 2008; 31: 213-24.
• Shrestha BM. Two Decades of Tacrolimus in Renal Transplant: Basic Science and Clinical Evidences. Exp Clin Transplant 2017; 15: 1-9.
• Yin J, Hsu T, Kerr JS, Steiner R, Awdishu L. Relationship between 2-Hour Tacrolimus Concentrations and Clinical Outcomes in Long Term Kidney Transplantation. Pharmacy (Basel) 2020; 8: 60.
• Bakr MA, Nagib AM, Donia AF, et al. Comparative analysis for optimizing the modified release tacrolimus (Advagraf) after kidney transplantation: a prospective randomized trial. Saudi J Kidney Dis Transpl 2018; 29: 1267-73.
• Shin TH, Ho MJ, Kim SR, et al. Formulation and in vivo pharmacokinetic evaluation of ethyl cellulose-coated sustained-release multiple-unit system of tacrolimus. Int J Biol Macromol 2018; 109: 544-50.
• Staatz CE, Tett SE. Clinical pharmacokinetics of once-daily tacrolimus in solid-organ transplant patients. Clin Pharmacokinet 2015; 54: 993-1025.
• Wakasugi N, Uchida H, Uno S. Safety and Effectiveness of Once-Daily, Prolonged-Release Tacrolimus in De Novo Kidney Transplant Recipients: 5-year, Multicenter Postmarketing Surveillance in Japan. Transplant Proc 2018; 50: 3296-305.
• Andrés A, Delgado-Arranz M, Morales E, et al. Extended-release tacrolimus therapy in de novo kidney transplant recipients: single-center experience. Transplant Proc 2010; 42: 3034-7.
• Rummo O, Carmellini M, Kamar N, et al. Long-term, prolonged-release tacrolimus-based immunosuppression in de novo kidney transplant recipients: 5-year prospective follow-up of the ADHERE study patients. Transpl Int 2020; 33: 161-73.
• Lee SY, Chu SH, Oh EG, Huh KH. Low adherence to ımmunosuppressants ıs associated with symptom experience among kidney transplant recipients. Transplant Proc 2015; 47: 2707-11.
• Sellarés J, de Freitas DG, Mengel M, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant 2012; 12: 388-99.
• Wiebe C, Gibson IW, Blydt-Hansen TD, et al. Rates and determinants of progression to graft failure in kidney allograft recipients with de novo donor-specific antibody. Am J Transplant 2015; 15: 2921-30.
• Ichimaru N, Kakuta Y, Abe T, et al. Treatment adherence in renal transplant recipients: a questionnaire survey on immunosuppressants. Transplant Proc 2008; 40: 1362-5.
• Saint-Marcoux F, Woillard JB, Monchaud C, et al. How to handle missed or delayed doses of tacrolimus in renal transplant recipients? A pharmacokinetic investigation. Pharmacol Res 2015; 100: 281-7.
• Lehner LJ, Reinke P, Hörstrup JH, et al. Evaluation of adherence and tolerability of prolonged-release tacrolimus (Advagraf™) in kidney transplant patients in Germany: A multicenter, noninterventional study. Clin Transplant 2018;32.
• Bonani M, Balaphas A, Bedino G, et al. Adherence to, and patient convenience of, prolonged-release tacrolimus in stable kidney and liver transplant recipients after conversion from immediate-release tacrolimus in routine clinical practice in Switzerland. Swiss Med Wkly 2021; 151: w20453.
• Tran D, Vallée M, Collette S, et al. Conversion from twice-daily to once-daily extended-release tacrolimus in renal transplant recipients: 2-year results and review of the literature. Exp Clin Transplant 2014; 12: 323-7.
• Cross SA, Perry CM. Tacrolimus once-daily formulation: in the prophylaxis of transplant rejection in renal or liver allograft recipients. Drugs 2007; 67: 1931-43.
• Saengram W, Vadcharavivad S, Poolsup N, Chancharoenthana W. Extended release versus immediate release tacrolimus in kidney transplant recipients: a systematic review and meta-analysis. Eur J Clin Pharmacol 2018; 74: 1249-60.
• Vadcharavivad S, Saengram W, Phupradit A, Poolsup N, Chancharoenthana W. Once-daily versus twice-daily tacrolimus in kidney transplantation: a systematic review and meta-analysis of observational studies. Drugs 2019; 79: 1947-62.
• Crespo M, Mir M, Marin M, et al. De novo kidney transplant recipients need higher doses of Advagraf compared with Prograf to get therapeutic levels. Transplant Proc 2009; 41: 2115-7