Liver transplantation
Mark Davenport, James D. Geiger, Nigel J. Hall, Steven S. Rothenberg in Operative Pediatric Surgery, 2020
A detailed discussion of immunomodulatory regimens is beyond the scope of this chapter, but the overall strategy remains fairly simple: Minimizing adverse effects of immune suppressants, namely bacterial, viral, or fungal infection and malignancy while optimizing graft survival by preventing rejection. There is no universally accepted standard regimen immunomodulation following pediatric LT. At the authors’ center, a single preoperative dose of 10 mg/kg of methylprednisolone is administered. About 12 hours postoperatively, both mycophenolate (10 mg/kg/dose) and tacrolimus (0.1 mg/kg/dose) are given twice daily with a tacrolimus level desired range of 10–12 ng/mL. Methylprednisolone is tapered over the following month from 2.0–0.3 mg/kg per day and converted to an oral equivalent after return of bowel function. Mycophenolate is started immediately after surgery in order to reduce dependence on calcineurin inhibitors. Rapamycin can be added later. Anti-interleukin-2 receptor monoclonal antibodies, such as basiliximab, are sometimes used. Steroid-sparing regimens are becoming increasingly popular, but are not appropriate for patients with a history of autoimmune hepatitis.
Immunosuppressants, rheumatic and gastrointestinal topics
Evelyne Jacqz-Aigrain, Imti Choonara in Paediatric Clinical Pharmacology, 2021
Basiliximab is a chimeric human/mouse monoclonal antibody against the α chain of the IL-2 receptor CD25. It was demonstrated to reduce acute rejection in adult renal transplanted patients under dual or triple immunotherapy, without increasing the incidence of adverse events (including infection and malignancy) [42]. Although involving a limited number of children, immunoprophylaxis with basiliximab given intravenously at day 0 (pre-operatively) and 4, associated with dual therapy, reduced acute rejection in the first six months and maintained graft survival and function [43–44]. Adverse drug reactions were similar in baxiliximab and placebo treated adult renal transplant recipients receiving immunosuppressants. Tolerability data are however limited in paediatric patients. Anaphylactic shock is a very rare event, reported after a second course of basiliximaab [45].
Future therapies in lung transplantation
Wickii T. Vigneswaran, Edward R. Garrity, John A. Odell in LUNG Transplantation, 2016
Anticytokine therapy is a far from new concept that has evolved to be the mainstay of therapy in patients with moderate to severe autoimmune disease such as rheumatoid arthritis and Crohn’s disease. Its goal is to block a particular immune response characterized by the cytokine contributing to a disease state but not all immune responses. The success with several agents, including infliximab (Remicade) and etanercept (Enbrel), both of which block TNF-a in autoimmune disease, has sparked great interest in the development of new anticytokine therapies for autoimmune and inflammatory disease states. Because rejection of transplanted organs is characterized by the production of effector cytokines, such therapies could potentially be used in transplantation as well. Of note, two anticytokine agents, basiliximab and daclizumab, are already being widely used for induction in lung and other solid-organ transplantation. Both are mAbs that target the receptor for IL-2 (CD25) and are being widely used for induction of immunosuppressive therapy.
Outcomes of thymoglobulin versus basiliximab induction therapies in living donor kidney transplant recipients with mild to moderate immunological risk – a retrospective analysis of UNOS database
Published in Annals of Medicine, 2023
Hatem Ali, Mahmoud Mohammed, Tibor Fülöp, Shafi Malik
The recommendations for using thymoglobulin ([rabbit-derived] polyclonal anti-thymocyte globulin) induction therapy are based on the results of a previous meta-analysis that compared basiliximab and thymoglobulin induction therapies in kidney transplant patients [7]. However, the maintenance immunosuppression in most of the reviewed studies was in the era of cyclosporine-based immunomodulating therapy. Currently, most transplant centres depend on tacrolimus as an efficacious cornerstone immunosuppressant in kidney transplantation [8]. Many randomized, multicentre studies conducted in Europe and the US with long follow-up periods showed a significantly lower incidence of acute rejection and improved survival in renal transplant recipients receiving tacrolimus-based immunosuppression compared to those receiving cyclosporine [9,10]. This raises the question of whether basiliximab can be an effective induction therapy in mild to moderate immunological risk kidney transplant patients maintained on tacrolimus or not. Living-related transplant recipient have minimized cold ischaemia times, affording elimination one of the largest variables impacting allograft survival and affording a much cleaner clinical model to assess impact of immunologic incompatibilities and applied therapies. Thus, we aimed to examine the outcomes of basiliximab induction therapy in comparison to thymoglobulin induction therapy in mild to moderate immunological risk living donor kidney transplant recipients (KTRs) maintained on tacrolimus and mycophenolate-based immunomodulating therapy.
Tailoring tacrolimus therapy in kidney transplantation
Published in Expert Review of Clinical Pharmacology, 2018
Thomas Jouve, Johan Noble, Lionel Rostaing, Paolo Malvezzi
What about Envarsus? In this two-groups, parallel-groups, randomized, double-blind, double-dummy, multicenter, 2-year phase-3 study that included 543 de novo kidney recipients that were randomly assigned to receive Envarsus (once daily at 0.17 mg/kg/d; n = 268) or Prograf (twice daily at 0.1 mg/kg/d; n = 275). Both arms were adjusted to maintain target trough ranges (first 30 days, 6–11 ng/mL; thereafter, 4–11 ng/mL). In addition, patients received basiliximab as an induction therapy, and MPA + steroids as a maintenance therapy. Within 24 months after randomization, 24 of 88 (27.3%) and 12 of 74 (16.2%) at-risk patients in the Envarsus and Prograf groups, respectively, had developed PTDM (p = .1). The changes from baseline in hemoglobin A1c levels were similar for both treatment groups over the entire study [28]. However, a pooled analysis of two phase-3 randomized controlled studies (one that included de novo and the other of maintenance kidney-transplant patients) showed that, compared to Prograf, Envarsus was associated with significantly better outcomes in Black recipients as well as patients aged >65 years [29].
Pharmacotherapeutic options for the prevention of kidney transplant rejection: the evidence to date
Published in Expert Opinion on Pharmacotherapy, 2022
Goce Spasovski, Lada Trajceska, Irena Rambabova-Bushljetik
Acute rejections most frequently occur in the first post-transplant year and strongly affect the long-term renal graft survival [16]. Thus, a need for more selective induction therapy including interleukin 2 receptor antagonists (IL-2RA), basiliximab, and daclizumab was considered. Basiliximab is a monoclonal antibody specifically binding the α-subunit of the IL-2R known as CD25 surface antigen that interrupts the critical pathway of the allograft rejection through inhibition of IL-2-mediated lymphocyte activation. Basiliximab delivers a safer and expectable therapeutic action compared with polyclonal antibodies as well-tolerated drug, with minimal side effects [17]. The IL-2R inhibition lasts for 4 weeks when administered intravenously 2 times 20 mg (days 0 and 4) [18].
Related Knowledge Centers
- Antibody
- Chimera
- Immunosuppressive Drug
- Monoclonal Antibody
- T Cell
- Transplant Rejection
- Kidney
- Il2Ra
- Il-2 Receptor
- Indication