Cornerstone immunosuppression with Prograf and successful steroid withdrawal/avoidance yields health benefits in kidney and liver transplantation BERLIN (German

Although low-dose corticosteroids remain a key component of post-transplant immunosuppressive regimens at many transplant centres, their use is associated with a myriad of potentially harmful side effects (hyperlipidaemia, diabetes mellitus, and bone disease). The 6-month results of a study presented by Dr Leszek Paczek (Transplantation Institute, Warsaw, Poland) at the WCN revealed that withdrawing steroids from Prograf(r) based regimens in renal transplant patients free from steroid-resistant rejection and with stable renal function at 3 months post-transplant was not associated with any increased risk of acute rejection.(1) In this multicentre study comparing the steroid-sparing potential of Prograf(r) in combination with either mycophenolate mofetil (MMF; n=243) or azathioprine (n=246), the incidence of biopsy- proven acute rejection between months 4 and 6 among all steroid- withdrawal patients - regardless of whether they were receiving Prograf(r) plus MMF or azathioprine - was very low, about 1.9%. Moreover, renal function at 6 months was excellent. Another key finding was that the overall 6-month incidence of biopsy-proven acute rejection was significantly lower in patients randomised to treatment with Prograf(r) plus MMF versus Prograf(r) plus azathioprine (18.9% vs 26.8%, respectively; p=0.038) and this permitted a higher proportion of patients in the Prograf(r)/MMF group to be withdrawn from steroids at month 3 (60.5% vs 48.8%; p <0.01). The full potential of steroid avoidance with Prograf(r) based regimens can be more fully exploited by employing the anti- interleukin-2-receptor monoclonal antibody induction agents basiliximab and daclizumab. Presenting on behalf of the ATLAS Study Group at the WCN, Dr Marian Klinger (Wroclaw Medical University, Wroclaw, Poland) showed several benefits of employing steroid-free immunosuppression with basiliximab induction followed by Prograf(r) monotherapy in terms of lower risks of diarrhoea, leukopenia and new-onset diabetes mellitus. The 6- month results of this three-way comparative study in 450 renal transplant patients also revealed Prograf(r) plus basiliximab induction prevents acute rejection as effectively as treatment based on Prograf(r) plus MMF.(2) Other newly available data presented at the WCN by Dr Diego Cantarovich (Nantes University Hospital, Nantes, France) provide additional support for steroid avoidance. In a multicentre, 6- month study, Prograf(r), MMF plus daclizumab induction had a superior metabolic profile to standard treatment with Prograf(r), MMF and steroids.(3) These conclusions, based on findings in 538 renal transplant recipients, are supported by analyses showing that the steroid-free regimen was associated with a significantly lower occurrence of new-onset diabetes mellitus than was seen with conventional therapy (0.4% vs 5.4%; p=0.001) plus a reduction in total cholesterol (from 5.22mmol/L at baseline to 4.97mmol/L at month 6). "Importantly, these safety benefits were achieved without any loss of efficacy," said Dr Cantarovich. Biopsy-proven acute rejection was identical in both the steroid- containing and steroid-free regimens at month 6 and there was no difference between treatments in terms of renal function. Sub-group analysis from this study presented by Dr Philippe Zaoui (CHU Grenoble, Grenoble, France) during the WCN showed that an added benefit of using Prograf(r) and MMF with daclizumab induction was prevention of the loss of bone mass after renal transplantation.(4) The benefits of steroid avoidance are not confined to kidney transplant recipients. As highlighted by Dr Olivier Boillot (Hôpital Edouard Herriot, Lyon, France) during the ATC meeting, liver transplant patients also benefit from steroid-free immunosuppression with Prograf(r) and daclizumab in terms of efficacy and safety. Presenting the 3-month results of the MASTER study, Dr Boillot showed that Prograf(r) and daclizumab induction was not associated with a heightened risk of acute rejection compared with a Prograf(r) plus corticosteroids regimen.(5) Moreover, the occurrence of corticosteroid-resistant acute rejection was significantly lower (2.8% vs 6.3%, respectively; p=0.027). "The Prograf(r)/daclizumab regimen also showed a much lower incidence - thus reflecting the reality today - of diabetes mellitus (5.7% vs 15.3%; p<0.001) and cytomegalovirus infection (5.1% vs 11.5%; p=0.002)," commented Dr Boillot. Taken together these data firmly position Prograf(r) cornerstone immunosuppressive therapy at the centre of successful steroid-avoidance regimens for kidney and liver transplant recipients. Notes to Editors: Prograf(r) is a cornerstone immunosuppressant for the prevention of graft rejection in kidney and liver transplantation. Prograf(r) is currently available in nearly 70 countries and currently forms the centrepiece of Fujisawa's continuing growth. The monoclonal antibodies - basiliximab and daclizumab - are used primarily as induction therapy (i.e. they are used to suppress the immune response at the time of transplantation and in the immediate post-transplant). The goal is to provide short- term protection against rejection immediately following transplantation when the risk of rejection is highest. Maximising patient health and quality of life over the long- term post-transplant - by minimising the risk of adverse events associated with immunosuppressive agents - remains a key challenge in transplantation. Bone disease (osteoporosis), a common complication after renal transplantation, is associated with an increased risk of fracture while events such as hyperlipidaemia and diabetes mellitus increase the risk of cardiovascular disease. Fujisawa GmbH is a subsidiary of Fujisawa Pharmaceutical Co., Ltd., based in Osaka, Japan. Fujisawa Pharmaceutical Co., Ltd. is among the world's top 30 pharmaceutical companies and employs over 8000 people in Japan, Europe, North America and Asia. Since its launch of Prograf(r) in Japan in 1993, the first in the world, Fujisawa has become one of the world's leading transplant and immunosuppression companies. Fujisawa plans to maintain its commitment to transplantation, and is dedicated both to improving the results of solid-organ transplantation and to ensuring the health and quality of life of patients. Prograf(r) is currently available in nearly 70 ountries and forms the centrepiece of Fujisawa's continuing growth. Additional information on Fujisawa GmbH can be found on the Company's Web site at www.fujisawaeurope.com. References (1) Paczek L, et al. Absence of rejection and stable serum creatinine are excellent criteria for steroid-withdrawal in kidney transplant patients receiving tacrolimus treatment. Presented at the World Congress of Nephrology, Berlin, 8-12 June, 2003. Abstract W745. (2) Klinger M, et al. Large, prospective study evaluating steroid-free immunosuppression with tacrolimus/basiliximab and tacrolimus/MMF compared with tacrolimus/MMF/steroids in renal transplantation. Presented at the World Congress of Nephrology, Berlin, 8-12 June, 2003. Abstract W748. (3) Cantarovich D, et al. The combination of daclizumab, tacrolimus, and MMF is an effective and safe steroid-free immunosuppressive regimen after renal transplantation. Results of a large multicentre trial. Presented at the World Congress of Nephrology, Berlin, 8-12 June, 2003. Abstract W747. (4) Zaoui P, et al. A steroid-free immunosuppressive regimen of daclizumab, tacrolimus and MMF prevents loss of bone mass following renal transplantation. Presented at the World Congress of Nephrology, Berlin, 8-12 June, 2003. Abstract T670. (5) Boillot O, et al. Effective and safe steroid-free immunosuppression with a tacrolimus/daclizumab regimen after liver transplantation. Presented at the American Transplant Congress, Washington, DC, 30 May-4 June, 2003. Abstract 671. Contact: Marité Cruz Fujisawa GmbH Munich Germany tel +49 89 45442249 fax +49 89 434129 email marite.cruz@fujisawa.de Subscribers please note that material bearing the slug PROTEXT is not part of CTK's news service and is not to be published under the CTK slug. Protext is a commercial service providing distribution of press releases from clients, who are identified in the text of Protext reports and who bear full responsibility for their contents. PROTEXT