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 ofpost-transplant immunosuppressive regimens at many transplantcentres, their use is associated with a myriad of potentiallyharmful side effects (hyperlipidaemia, diabetes mellitus, andbone disease).

The 6-month results of a study presented by Dr Leszek Paczek(Transplantation Institute, Warsaw, Poland) at the WCN revealedthat withdrawing steroids from Prograf(r) based regimens in renaltransplant patients free from steroid-resistant rejection andwith stable renal function at 3 months post-transplant was notassociated with any increased risk of acute rejection.(1) In thismulticentre study comparing the steroid-sparing potential ofPrograf(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 receivingPrograf(r) plus MMF or azathioprine - was very low, about 1.9%.Moreover, renal function at 6 months was excellent. Another keyfinding was that the overall 6-month incidence of biopsy-provenacute rejection was significantly lower in patients randomised totreatment with Prograf(r) plus MMF versus Prograf(r) plusazathioprine (18.9% vs 26.8%, respectively; p=0.038) and thispermitted a higher proportion of patients in the Prograf(r)/MMFgroup to be withdrawn from steroids at month 3 (60.5% vs 48.8%; p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) basedregimens can be more fully exploited by employing the anti-interleukin-2-receptor monoclonal antibody induction agentsbasiliximab and daclizumab. Presenting on behalf of the ATLASStudy Group at the WCN, Dr Marian Klinger (Wroclaw MedicalUniversity, Wroclaw, Poland) showed several benefits of employingsteroid-free immunosuppression with basiliximab inductionfollowed by Prograf(r) monotherapy in terms of lower risks ofdiarrhoea, leukopenia and new-onset diabetes mellitus. The 6-month results of this three-way comparative study in 450 renaltransplant patients also revealed Prograf(r) plus basiliximabinduction prevents acute rejection as effectively as treatmentbased on Prograf(r) plus MMF.(2)

Other newly available data presented at the WCN by Dr DiegoCantarovich (Nantes University Hospital, Nantes, France) provideadditional support for steroid avoidance. In a multicentre, 6-month study, Prograf(r), MMF plus daclizumab induction had asuperior metabolic profile to standard treatment with Prograf(r),MMF and steroids.(3) These conclusions, based on findings in 538renal transplant recipients, are supported by analyses showingthat the steroid-free regimen was associated with a significantlylower occurrence of new-onset diabetes mellitus than was seenwith conventional therapy (0.4% vs 5.4%; p=0.001) plus areduction in total cholesterol (from 5.22mmol/L at baseline to4.97mmol/L at month 6). "Importantly, these safety benefits wereachieved 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 nodifference between treatments in terms of renal function.

Sub-group analysis from this study presented by Dr PhilippeZaoui (CHU Grenoble, Grenoble, France) during the WCN showed thatan added benefit of using Prograf(r) and MMF with daclizumabinduction was prevention of the loss of bone mass after renaltransplantation.(4)

The benefits of steroid avoidance are not confined to kidneytransplant recipients. As highlighted by Dr Olivier Boillot(Hôpital Edouard Herriot, Lyon, France) during the ATC meeting,liver transplant patients also benefit from steroid-freeimmunosuppression with Prograf(r) and daclizumab in terms ofefficacy and safety. Presenting the 3-month results of theMASTER study, Dr Boillot showed that Prograf(r) and daclizumabinduction was not associated with a heightened risk of acuterejection compared with a Prograf(r) plus corticosteroidsregimen.(5) Moreover, the occurrence of corticosteroid-resistantacute rejection was significantly lower (2.8% vs 6.3%,respectively; p=0.027). "The Prograf(r)/daclizumab regimen alsoshowed a much lower incidence - thus reflecting the reality today- of diabetes mellitus (5.7% vs 15.3%; p<0.001) andcytomegalovirus infection (5.1% vs 11.5%; p=0.002)," commented DrBoillot.

Taken together these data firmly position Prograf(r)cornerstone immunosuppressive therapy at the centre of successfulsteroid-avoidance regimens for kidney and liver transplantrecipients.Notes to Editors:

Prograf(r) is a cornerstone immunosuppressant for theprevention of graft rejection in kidney and livertransplantation. Prograf(r) is currently available in nearly 70countries and currently forms the centrepiece of Fujisawa'scontinuing growth.

The monoclonal antibodies - basiliximab and daclizumab - areused primarily as induction therapy (i.e. they are used tosuppress the immune response at the time of transplantation andin the immediate post-transplant). The goal is to provide short-term protection against rejection immediately followingtransplantation 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 eventsassociated with immunosuppressive agents - remains a keychallenge in transplantation. Bone disease (osteoporosis), acommon complication after renal transplantation, is associatedwith an increased risk of fracture while events such ashyperlipidaemia and diabetes mellitus increase the risk ofcardiovascular disease.

Fujisawa GmbH is a subsidiary of Fujisawa Pharmaceutical Co.,Ltd., based in Osaka, Japan. Fujisawa Pharmaceutical Co., Ltd. isamong the world's top 30 pharmaceutical companies and employsover 8000 people in Japan, Europe, North America and Asia. Sinceits launch of Prograf(r) in Japan in 1993, the first in theworld, Fujisawa has become one of the world's leading transplantand immunosuppression companies.

Fujisawa plans to maintain its commitment to transplantation,and is dedicated both to improving the results of solid-organtransplantation and to ensuring the health and quality of life ofpatients. Prograf(r) is currently available in nearly 70 ountriesand forms the centrepiece of Fujisawa's continuing growth.Additional information on Fujisawa GmbH can be found on theCompany's Web site at www.fujisawaeurope.com.References(1) Paczek L, et al. Absence of rejection and stable serumcreatinine are excellent criteria for steroid-withdrawal inkidney 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 evaluatingsteroid-free immunosuppression with tacrolimus/basiliximab andtacrolimus/MMF compared with tacrolimus/MMF/steroids in renaltransplantation. 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-freeimmunosuppressive regimen after renal transplantation. Results ofa large multicentre trial. Presented at the World Congress ofNephrology, Berlin, 8-12 June, 2003. Abstract W747.(4) Zaoui P, et al. A steroid-free immunosuppressive regimen ofdaclizumab, tacrolimus and MMF prevents loss of bone massfollowing renal transplantation. Presented at the World Congressof Nephrology, Berlin, 8-12 June, 2003. Abstract T670.(5) Boillot O, et al. Effective and safe steroid-freeimmunosuppression with a tacrolimus/daclizumab regimen afterliver transplantation. Presented at the American TransplantCongress, Washington, DC, 30 May-4 June, 2003. Abstract 671.Contact:Marité CruzFujisawa GmbHMunichGermanytel +49 89 45442249fax +49 89 434129email marite.cruz@fujisawa.de

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