Three-year outcomes of de novo tacrolimus extended-release tablets (LCPT) compared to twice-daily tacrolimus in adult heart transplantation

• Published in: Transplant immunology 2024-04, Vol.83, p.102009-102009, Article 102009
• Main Authors: Alam, Amit, van Zyl, Johanna S., Patel, Raksha, Jamil, Aayla K., Felius, Joost, Carey, Sandra A., Gottlieb, Robert L., Guerrero-Miranda, Cesar Y., Kale, Parag, Hall, Shelley A., Sam, Teena
• Format: Article
• Language: English
• Subjects: Acute cellular rejection; Antibody-mediated rejection; Cardiac transplantation; Immunosuppressive therapy; Outcomes
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2024.102009

Extended-release tacrolimus for prophylaxis of allograft rejection in heart transplant (HT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release (IR-) tacrolimus. We compared long-term efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. 25 prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 3 years following transplant was compared between groups using non-inferiority analysis. LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 16% (90%CI, −37%, −1%, non-inferiority p = 0.002) up to 3 years following heart transplant. Up to 3-years post-transplant, 14 patients remained on once-daily LCPT and 10 patients were switched to IR-tacrolimus due to lack of insurance coverage. There were no significant differences in the rate of chronic kidney disease requiring dialysis, cytomegalovirus requiring treatment, cardiac allograft vasculopathy, and malignancy within 3 years following transplant. LCPT is non-inferior in efficacy to IR-tacrolimus in heart transplantation with a similar safety profile. Narrowly-constrained FDA labels specific to kidney transplant remain a barrier to consistent access to many immunosuppressant medications for recipients of non-kidney solid organs. We recommend the FDA consider developing facile pathways for expanding the approved label of extended-release tacrolimus formulations to heart transplant recipients. •First long-term outcomes of extended-release tacrolimus (LCPT) post-heart transplant.•LCPT during first post-transplant year yields non-inferior 3-year outcomes compared to twice-daily tacrolimus.•LCPT currently off-label in heart transplant; present data may support approval.