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Satish Arora - One of the best experts on this subject based on the ideXlab platform.
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everolimus initiation with early Calcineurin Inhibitor withdrawal in de novo heart transplant recipients three year results from the randomized schedule study
American Journal of Transplantation, 2016Co-Authors: Arne K Andreassen, Hans Eiskjaer, Kjell Jansson, Finn Gustafsson, Goran Radegran, Einar Gude, D Solbu, B Andersson, Kristjan Karason, Satish AroraAbstract:In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6 ng/mL) with reduced-exposure Calcineurin Inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10 ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4 mL/min (standard deviation [SD] 20.2 mL/min) versus 59.2 mL/min (SD 17.4 mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3 mL/min (95% CI 11.1-25.6 mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade ≥2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p = 0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage.
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the effect of everolimus initiation and Calcineurin Inhibitor elimination on cardiac allograft vasculopathy in de novo recipients one year results of a scandinavian randomized trial
American Journal of Transplantation, 2015Co-Authors: Satish Arora, Hans Eiskjaer, Arne K Andreassen, Bengt Ronny Andersson, Finn Gustafsson, Hans Erik Botker, Goran Radegran, Einar Gude, Dan Ioanes, D SolbuAbstract:Early initiation of everolimus with Calcineurin Inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of Calcineurin Inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete Calcineurin Inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (± SD) recipient age was 49.9 ± 13.1 years. The everolimus group (n = 47) demonstrated significantly reduced CAV progression as compared to the Calcineurin Inhibitor group (n = 48) (ΔMaximal Intimal Thickness 0.03 ± 0.06 and 0.08 ± 0.12 mm, ΔPercent Atheroma Volume 1.3 ± 2.3 and 4.2 ± 5.0%, ΔTotal Atheroma Volume 1.1 ± 19.2 mm(3) and 13.8 ± 28.0 mm(3) [all p-values ≤ 0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the Calcineurin Inhibitor group (p = 0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.
Nina Singh - One of the best experts on this subject based on the ideXlab platform.
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cryptococcus neoformans in organ transplant recipients impact of Calcineurin Inhibitor agents on mortality
The Journal of Infectious Diseases, 2007Co-Authors: Nina Singh, Barbara D Alexander, Olivier Lortholary, Francoise Dromer, Krishan Lal Gupta, George T John, Ramon Del Busto, Goran B Klintmalm, Jyoti Somani, Marshall G LyonAbstract:Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixty-one percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P=.048). The overall mortality rate at 90 days was 14% (16/111). The mortality rate was higher in patients with abnormal mental status (P=.023), renal failure at baseline (P=.028), fungemia (P=.006), and disseminated infection (P=.035) and was lower in those receiving a Calcineurin-Inhibitor agent (P=.003). In a multivariable analysis, the receipt of a Calcineurin-Inhibitor agent was independently associated with a lower mortality (adjusted HR, 0.21; P=.008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P=.037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type-specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients.
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infectious complications in organ transplant recipients with the use of Calcineurin Inhibitor agent based immunosuppressive regimens
Current Opinion in Infectious Diseases, 2005Co-Authors: Nina SinghAbstract:Purpose of review The rates and types of infections associated with conventional immunosuppression regimens comprising Calcineurin-Inhibitor agents, tacrolimus, and cyclosporine could be used to compare similar data with the use of novel immunosuppressive regimens in organ transplant recipients. Recent findings Tacrolimus appears to be superior to cyclosporine in preventing rejection. The frequency and spectrum of infections in organ transplant recipients does not appear to be notably modified by the choice of Calcineurin-Inhibitor agents per se. A higher risk of cytomegalovirus and poorer outcomes associated with hepatitis C virus with cyclosporine in some studies may be related to a greater requirement of adjunctive immunosuppression with cyclosporine-based regimens. Potent immunosuppression with tacrolimus, however, particularly when combined with mycophenolate mofetil, is believed to be a significant contributor to a higher incidence of BK virus nephropathy in renal transplant recipients in recent years. Calcineurin-Inhibitor agents possess in-vitro activity against a number of fungal pathogens. In the clinical setting, however, the immunosuppressive effect outweighs their antifungal activity. Summary Calcineurin Inhibitor-based regimens have been the mainstay of immunosuppression after organ transplantation for almost two decades. However, suboptimal long-term outcomes in transplant recipients have led to a growing interest in the use of Calcineurin Inhibitor agent-sparing regimens. Whether novel immunosuppressive agents with a more selective mechanism of action would lead to a further reduction in the risk of posttransplant infections remains to be discerned.
D Solbu - One of the best experts on this subject based on the ideXlab platform.
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everolimus initiation with early Calcineurin Inhibitor withdrawal in de novo heart transplant recipients three year results from the randomized schedule study
American Journal of Transplantation, 2016Co-Authors: Arne K Andreassen, Hans Eiskjaer, Kjell Jansson, Finn Gustafsson, Goran Radegran, Einar Gude, D Solbu, B Andersson, Kristjan Karason, Satish AroraAbstract:In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6 ng/mL) with reduced-exposure Calcineurin Inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10 ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4 mL/min (standard deviation [SD] 20.2 mL/min) versus 59.2 mL/min (SD 17.4 mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3 mL/min (95% CI 11.1-25.6 mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade ≥2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p = 0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage.
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the effect of everolimus initiation and Calcineurin Inhibitor elimination on cardiac allograft vasculopathy in de novo recipients one year results of a scandinavian randomized trial
American Journal of Transplantation, 2015Co-Authors: Satish Arora, Hans Eiskjaer, Arne K Andreassen, Bengt Ronny Andersson, Finn Gustafsson, Hans Erik Botker, Goran Radegran, Einar Gude, Dan Ioanes, D SolbuAbstract:Early initiation of everolimus with Calcineurin Inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of Calcineurin Inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete Calcineurin Inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (± SD) recipient age was 49.9 ± 13.1 years. The everolimus group (n = 47) demonstrated significantly reduced CAV progression as compared to the Calcineurin Inhibitor group (n = 48) (ΔMaximal Intimal Thickness 0.03 ± 0.06 and 0.08 ± 0.12 mm, ΔPercent Atheroma Volume 1.3 ± 2.3 and 4.2 ± 5.0%, ΔTotal Atheroma Volume 1.1 ± 19.2 mm(3) and 13.8 ± 28.0 mm(3) [all p-values ≤ 0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the Calcineurin Inhibitor group (p = 0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.
Hans Eiskjaer - One of the best experts on this subject based on the ideXlab platform.
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everolimus initiation with early Calcineurin Inhibitor withdrawal in de novo heart transplant recipients three year results from the randomized schedule study
American Journal of Transplantation, 2016Co-Authors: Arne K Andreassen, Hans Eiskjaer, Kjell Jansson, Finn Gustafsson, Goran Radegran, Einar Gude, D Solbu, B Andersson, Kristjan Karason, Satish AroraAbstract:In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6 ng/mL) with reduced-exposure Calcineurin Inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10 ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4 mL/min (standard deviation [SD] 20.2 mL/min) versus 59.2 mL/min (SD 17.4 mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3 mL/min (95% CI 11.1-25.6 mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade ≥2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p = 0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage.
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the effect of everolimus initiation and Calcineurin Inhibitor elimination on cardiac allograft vasculopathy in de novo recipients one year results of a scandinavian randomized trial
American Journal of Transplantation, 2015Co-Authors: Satish Arora, Hans Eiskjaer, Arne K Andreassen, Bengt Ronny Andersson, Finn Gustafsson, Hans Erik Botker, Goran Radegran, Einar Gude, Dan Ioanes, D SolbuAbstract:Early initiation of everolimus with Calcineurin Inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of Calcineurin Inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete Calcineurin Inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (± SD) recipient age was 49.9 ± 13.1 years. The everolimus group (n = 47) demonstrated significantly reduced CAV progression as compared to the Calcineurin Inhibitor group (n = 48) (ΔMaximal Intimal Thickness 0.03 ± 0.06 and 0.08 ± 0.12 mm, ΔPercent Atheroma Volume 1.3 ± 2.3 and 4.2 ± 5.0%, ΔTotal Atheroma Volume 1.1 ± 19.2 mm(3) and 13.8 ± 28.0 mm(3) [all p-values ≤ 0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the Calcineurin Inhibitor group (p = 0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.
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everolimus with reduced Calcineurin Inhibitor in thoracic transplant recipients with renal dysfunction a multicenter randomized trial
Transplantation, 2010Co-Authors: Lars Gullestad, Hans Eiskjaer, Kjell Jansson, Martin Iversen, Svendaage Mortensen, Gerdt C Riise, Lena Mared, Oystein Bjortuft, Bjorn Ekmehag, Svein SimonsenAbstract:BACKGROUND.: The proliferation signal Inhibitor everolimus offers the potential to reduce Calcineurin Inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. METHODS.: In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate >/=20 mL/min/1.73m and 1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. RESULTS.: Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (P<0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). CONCLUSION.: Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.
Arne K Andreassen - One of the best experts on this subject based on the ideXlab platform.
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everolimus initiation with early Calcineurin Inhibitor withdrawal in de novo heart transplant recipients three year results from the randomized schedule study
American Journal of Transplantation, 2016Co-Authors: Arne K Andreassen, Hans Eiskjaer, Kjell Jansson, Finn Gustafsson, Goran Radegran, Einar Gude, D Solbu, B Andersson, Kristjan Karason, Satish AroraAbstract:In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6 ng/mL) with reduced-exposure Calcineurin Inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10 ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4 mL/min (standard deviation [SD] 20.2 mL/min) versus 59.2 mL/min (SD 17.4 mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3 mL/min (95% CI 11.1-25.6 mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade ≥2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p = 0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage.
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the effect of everolimus initiation and Calcineurin Inhibitor elimination on cardiac allograft vasculopathy in de novo recipients one year results of a scandinavian randomized trial
American Journal of Transplantation, 2015Co-Authors: Satish Arora, Hans Eiskjaer, Arne K Andreassen, Bengt Ronny Andersson, Finn Gustafsson, Hans Erik Botker, Goran Radegran, Einar Gude, Dan Ioanes, D SolbuAbstract:Early initiation of everolimus with Calcineurin Inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of Calcineurin Inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete Calcineurin Inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (± SD) recipient age was 49.9 ± 13.1 years. The everolimus group (n = 47) demonstrated significantly reduced CAV progression as compared to the Calcineurin Inhibitor group (n = 48) (ΔMaximal Intimal Thickness 0.03 ± 0.06 and 0.08 ± 0.12 mm, ΔPercent Atheroma Volume 1.3 ± 2.3 and 4.2 ± 5.0%, ΔTotal Atheroma Volume 1.1 ± 19.2 mm(3) and 13.8 ± 28.0 mm(3) [all p-values ≤ 0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the Calcineurin Inhibitor group (p = 0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.