Cornerstone immunosuppressive therapy with Prograf reduces rejection risk in paediatric liver transplant patients

WASHINGTON, April 30 (PROTEXT/PRNewswire) - Paediatricpatients receiving liver transplants are less likely to sufferacute rejection if they receive immunosuppressive therapy basedon Prograf(r) (tacrolimus), as opposed to ciclosporinmicroemulsion. This was the key finding of a large, internationalclinical trial, (1) announced today at the American TransplantCongress by Professor Deirdre Kelly of Birmingham Children'sHospital, UK.

Acute rejection is a major threat to the survival oftransplanted organs during the first few months aftertransplantation and although immunosuppressant drugs help toprotect the transplant, their ability to prevent acute rejectionvaries. This study was a head-to-head comparison of the twocornerstone immunosuppressants, Prograf(r) and ciclosporinmicroemulsion, in paediatric patients undergoing livertransplantation.

The study was conducted at 10 European centres whichrecruited a total of 181 patients. The mean age of the patientsin the study was 3 years. Patients were randomly assigned toreceive antirejection therapy based either on Prograf(r) plussteroids (91 patients) or ciclosporin microemulsion incombination with azathioprine and steroids (90 patients). In bothgroups, steroids were tapered over 3 months with the option ofcomplete discontinuation if appropriate.

Both the study drugs were found to be associated with goodoverall survival rates. After 1 year, 93.4% of Prograf(r) and92.2% of ciclosporin-treated patients survived, all withfunctioning grafts. Notably, graft function, as assessed by meantotal bilirubin levels, recovered after the transplantmore quickly in patients treated with Prograf(r).

The most important difference between the two groups,however, concerned acute rejection, with significantly fewerpatients in the Prograf(r) group experiencing acute or steroid-resistant rejection during the year following transplantation. Intotal, 55.5% of Prograf(r)-treated patients remained acuterejection-free and 94.0% remained free of steroid-resistantrejection. By contrast, only 40.2% of ciclosporin-treatedpatients remained rejection-free (p=0.03), and just 70.4%remained free of steroid-resistant rejection (p<0.0001).

The difference between the rejection rates seen with the twodrugs is important since the incidence and severity of acuterejection during the first year may in subsequent years influencethe risk of chronic rejection and the prospects for long-termgraft survival.(2)

Importantly, the reduced rejection rates seen with Prograf(r)did not come at the expense of more adverse events since thesafety profiles of both therapies were closely comparable. (1)Hypomagnesaemia and otitis media were more common in the Prograf(r) group, whereas hypertension, hirsutism and gum hyperplasiawere all observed more frequently among patients treated withciclosporin.

These results confirm that, while immunosuppressive therapybased on either Prograf(r) or ciclosporin microemulsion iscomparable in terms of patient safety, Prograf(r)-based therapyis more effective in preventing acute rejection. In the longterm, this may translate into improved clinical outcomes.

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 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.References1. Kelly D, Jara P, Rodeck B, et al. Tacrolimus dual therapyversus cyclosporin-microemulsion triple therapy in paediatricliver transplantation: results from a multicentre randomisedtrial. Presented at the American Transplant Congress, Washington,USA, 26 April-1 May, 2002. Abstract 849.2. Vanrenterghem Y. Vascular rejection with tacrolimus andpotential long-term graft outcome. Transplant Proc 1999;31(Suppl7A):86S-87S.Contact:Marité CruzFujisawa GmbH, Munich, GermanyT: +49 89 45442249F: +49 89 434129marite.cruz@fujisawa.de Subscribers please note that material bearing the slug"PROTEXT" is not part of CTK's news service and is not to bepublished under the "CTK" slug. Protext is a commercial serviceproviding distribution of press releases from clients, who areidentified in the text of Protext reports and who bear fullresponsibility for their contents.

PROTEXT