Cornerstone immunosuppression with Prograf plus early steroid withdrawal cuts post-transplant cardiovascular risk

LISBON, Portugal, Oct 10 (PROTEXT/PRNewswire) - In the longterm, cardiovascular disease presents an even greater threat thanacute rejection to transplant patients (cardiovascular diseaseaccounts for approximately 40% of all patient deaths with afunctioning transplant). A new study has shown that serumcholesterol - a key risk factor for cardiovascular disease - canbe reduced substantially by the controlled withdrawal of steroidsfrom renal transplant patients receiving anti-rejection therapybased on the cornerstone immunosuppressant, Prograf(r)(tacrolimus).Steroids are given to patients following transplantation, as anadjunct to the primary immunosuppressant, Prograf(r) orcyclosporin. Since the side effects of steroids are potentiallyharmful, the dose is reduced progressively over the weeks andmonths following the operation, but it has been traditionalpractice to keep patients on low-dose steroids indefinitely.Because of their side effects, including raised cholesterol,there has been longstanding interest in the possibility ofdiscontinuing steroid treatment completely and relying on theprimary immunosuppressant (plus other non-steroidal adjunctivemedications) to prevent rejection. However, there have beendoubts that this can be done safely without exposing the patientto an unacceptable risk of rejection.Now, a new clinical study, the THOMAS trial, (1) has revealed astrategy for discontinuing steroid therapy and reaping the rewardof lower cholesterol levels. Results of the trial were announcedtoday by Professor Yves Vanrenterghem of University HospitalGasthuisberg (Leuven, Belgium) during the 10th Congress of theEuropean Society for Organ Transplantation (ESOT), held inLisbon.In this large, multinational, European trial, kidney transplantpatients were given cornerstone immunosuppression with Prograf(r), supported by two adjunctive therapies - steroids andmycophenolate mofetil (MMF). After 3 months, patients eligible toenter the withdrawal phase of the study were randomly assignedeither to remain on all three drugs (233 patients) or to bewithdrawn from treatment with either MMF (227 patients) orsteroids (228 patients)."Either treatment could be successfully withdrawn without anysignificant increase in the risk of rejection," said DrVanrenterghem, "but what was particularly striking was theimprovement in the blood cholesterol profile following withdrawalof steroids." Whereas the mean level of total cholesterolincreased during the 6 months of the trial by 6.6mg/dL in thetriple therapy group and by 3.0mg/dL in the MMF withdrawal group,cholesterol levels decreased by 19.7mg/dL in the steroidwithdrawal group. This decline was highly statisticallysignificant (p<0.001). Moreover, levels of low-densitylipoprotein (LDL) cholesterol - the form particularly associatedwith cardiovascular disease - also fell by 8.1mg/dL in thesteroid withdrawal group, but increased in the groups in whichsteroid therapy was continued. Again, the result was highlystatistically significant (p<0.001)."These results confirm that Prograf(r) -based immunosuppressionplus controlled early steroid withdrawal reduces the burden ofcardiovascular risk factors in kidney transplant patients," saidDr Vanrenterghem. "The challenge has always been to withdrawsteroids without increasing the risk of rejection - by basingimmunosuppression on Prograf(r) plus adjunct therapy with MMF,this goal can now be achieved."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, andis 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 50countries and forms the centrepiece of Fujisawa's continuinggrowth. Additional information on Fujisawa GmbH can be found onthe Company's Web site at http://www.fujisawaeurope.com .Reference1. Vanrenterghem Y, van Hooff J, Squifflet JP, Salmela K.Controlled withdrawal of steroids or MMF following three monthsof tacrolimus/steroids/MMF therapy: results of a large,prospective, multicentre study. Presented at the 10th Congress ofthe European Society for Organ Transplantation, Lisbon, 6-11October 2001.For further information please contact:Marité Cruz,Fujisawa GmbH, Munich, Germany,T: +49 89 45442249,F: +49 89 434129,marite.cruz@fujisawa.de .

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