Staggered immunosuppression with the interleukin-2 receptor antagonist daclizumab combined with tacrolimus, prednisolone, and mycophenolate mofetil after orthotopic liver transplantation: a pilot efficacy and safety study

Fahlke, Jörg; Wolff, S.; Mantke, René; Pross, M.; Weiss, Guenter; Buerger, Thomas; Lippert, H.

doi:10.1016/s0041-1345(02)02808-7

Cited by 5 publications

(5 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we recognize that both target and achieved levels were greater than those used in most centers currently. Daclizumab is not currently indicated for use in liver transplant patients, although it is effective and safe in this patient population (26,27); the 2 (n, %) BPAR = biopsy-proven acute rejection; GFR = glomerular filtration rate; MDRD = modification of diet in renal disease. 1 Post hoc analysis.…”

Section: Discussionmentioning

confidence: 99%

“…There were no clinically significant differences between groups A and B (26,27); the dose used in our study was agreed based on experience from renal allograft recipients (28). Although the combination of tacrolimus and MMF is not currently licensed for use in liver transplant recipients, they are commonly coprescribed (2) and are an effective combination (29)(30)(31)(32)(33) …”

Section: Other Endpointsmentioning

confidence: 96%

See 1 more Smart Citation

Delayed Introduction of Reduced-Dose Tacrolimus, and Renal Function in Liver Transplantation: The ‘ReSpECT’ Study

Neuberger

Mamelok

Neuhaus

et al. 2009

American Journal of Transplantation

259

194

View full text Add to dashboard Cite

We report a multicenter, prospective, randomized, open-label trial investigating the effect of lower levels and delayed introduction of tacrolimus on renal function in liver transplant recipients. Adult patients with good renal function undergoing primary liver transplant were randomized to either: group A (standarddose tacrolimus [target trough levels >10 ng/mL] and corticosteroids; n = 183); group B (mycophenolate mofetil [MMF] 2g/day, reduced-dose tacrolimus [target trough levels ≤8 ng/mL], and corticosteroids; n = 170); group C (daclizumab induction, MMF, reduced-dose tacrolimus delayed until the fifth day posttransplant and corticosteroids, n = 172). The primary endpoint was change from baseline in estimated glomerular filtration rate (eGFR) at 52 weeks. The eGFR decreased by 23.61, 21.22 and 13.63 mL/min in groups A, B and C, respectively (A vs C, p = 0.012; A vs B, p = 0.199). Renal dialysis was required less frequently in group C versus group A (4.2% vs. 9.9%; p = 0.037). Biopsy-proven acute rejection rates were 27.6%, 29.2% and 19.0%, respectively. Patient and graft survival was similar. In conclusion, daclizumab induction, MMF, corticosteroids and delayed reduced-dose tacrolimus was associated with less nephrotoxicity than therapy with standard-dose tacrolimus and corticosteroids without compromising efficacy or tolerability.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Other Endpointsmentioning

confidence: 96%

Delayed Introduction of Reduced-Dose Tacrolimus, and Renal Function in Liver Transplantation: The ‘ReSpECT’ Study

Neuberger

Mamelok

Neuhaus

et al. 2009

American Journal of Transplantation

259

194

View full text Add to dashboard Cite

show abstract

“…The sample size was determined according to Fleming's single‐stage method based on acute rejection rates in previous clinical trials of daclizumab and MMF [14,23,24,26–29,31]. The undesirable low response rate was based on a p 0 of 66.6% (i.e.…”

Section: Methodsmentioning

confidence: 99%

“…Daclizumab, a humanized monoclonal antibody that targets the 55‐kDa alpha chain of the interleukin‐2 receptor, suppresses clonal expansion of antigen‐activated T cells critical for causing acute allograft rejection [21,22]. Daclizumab has been widely evaluated in renal transplantation but has only recently been studied in liver transplant recipients, mainly as a calcineurin inhibitor‐sparing agent in the setting of perioperative renal impairment [23–31]. In the vast majority of the studies, the efficacy and tolerability of regimens including daclizumab and reduced doses of calcineurin inhibitors were similar to those achieved with standard immunosuppressive regimens not including daclizumab.…”

Section: Introductionmentioning

confidence: 99%

Daclizumab induction and maintenance steroid-free immunosuppression with mycophenolate mofetil and tacrolimus to prevent acute rejection of hepatic allografts

Figueras¹,

Prieto²,

Bernardos³

et al. 2006

Transplant Int

View full text Add to dashboard Cite

Summary Steroid‐free immunosuppressive regimens reduce corticosteroid‐related side effects in liver transplant recipients although their efficacy is very variable. We evaluated the efficacy and safety of a steroid‐free regimen in a 6‐month, open‐label, multicenter, pilot study, which involved 102 liver transplant patients treated with daclizumab (2 mg/kg within 6 h following transplant and 1 mg/kg on day 7), mycophenolate mofetil (MMF, 1 g b.i.d) and tacrolimus (trough levels of 5–15 ng/ml in the first month and 5–10 ng/ml thereafter). One intra‐operative dose of methylprednisolone was administered. At 6 months, the acute rejection rate was 9.8%, and patient and graft survival rates were 96% and 95%, respectively. Acute rejection rates were similar for hepatitis C‐positive patients (8.6%) and hepatitis C‐negative patients (10.4%). Infections occurred in 22% of patients; most cases were considered mild or moderate. Post‐transplantation hypertension and diabetes mellitus developed in 37% and 14% of patients, respectively, during the study period, but were markedly less frequent (8% and 6%, respectively) at 6 months. Hypercholesterolemia was observed in only 2% of patients. In conclusion, the steroid‐free immunosuppressive regimen of daclizumab, MMF, and tacrolimus effectively prevents acute rejection after liver transplantation without decreasing safety.

show abstract

“…The addition of one agent may counteract some deleterious effects of the other. A low dosage of two different agents minimizes the clinical and metabolic effects that may occur with a maximal dosage of the individual components [12][13][14][15][16]. MMF has a steroid sparing effect, which means that if the combination therapy is changed to single therapy, the withdrawal affects will be minimum [17].…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Novel Dual Wavelength UV-Spectrophotometric Method for the Simultaneous Estimation of Mycophenolate Mofetil and Prednisolone

Kaur

Sharma

Namdev³

et al. 2014

J Appl Spectrosc

View full text Add to dashboard Cite

A dual wavelength UV-spectrophotometric method has been developed for the simultaneous estimation of mycophenolate mofetil and prednisolone. In this method two wavelengths were selected for the estimation of each drug in such a way that the difference in the absorbance was zero for the second drug on the respective wavelength for the fi rst drug. This method was selected because of the overlapping of the absorbance maxima of the drugs. Prednisolone has equal absorbance value at wavelengths 235.11 and 261.33 nm; therefore, these two wavelengths were used to determine the concentration of mycophenolate mofetil in the combination. Similarly, 270.3 and 277.4 nm wavelengths were selected to determine the concentrations of prednisolone, where mycophenolate mofetil was observed with equal absorbance values. Regression analysis for the method shows good correlation in the concentration ranges 10-50 μg/ml for mycophenolate mofetil and 2-10 μg/ml for prednisolone. The method was validated using parameters provided as per ICH guidelines.

show abstract

Staggered immunosuppression with the interleukin-2 receptor antagonist daclizumab combined with tacrolimus, prednisolone, and mycophenolate mofetil after orthotopic liver transplantation: a pilot efficacy and safety study

Cited by 5 publications

References 13 publications

Delayed Introduction of Reduced-Dose Tacrolimus, and Renal Function in Liver Transplantation: The ‘ReSpECT’ Study

Delayed Introduction of Reduced-Dose Tacrolimus, and Renal Function in Liver Transplantation: The ‘ReSpECT’ Study

Daclizumab induction and maintenance steroid-free immunosuppression with mycophenolate mofetil and tacrolimus to prevent acute rejection of hepatic allografts

Development and Validation of a Novel Dual Wavelength UV-Spectrophotometric Method for the Simultaneous Estimation of Mycophenolate Mofetil and Prednisolone

Contact Info

Product

Resources

About