Switching from ciclosporin to Prograf reduces cosmetic side effects and heart disease risk factors

WASHINGTON, April 30 (PROTEXT/PRNewswire) - Clinical trialresults announced today by Professor Raimund Margreiter ofInnsbruck University Hospital, Austria, demonstrate that some ofthe most serious long-term side effects experienced by transplantpatients receiving antirejection therapy based on ciclosporin canbe reduced by switching treatment to the cornerstoneimmunosuppressant Prograf(r)(tacrolimus). (1)

Transplant patients face long-term health risks not only fromorgan rejection, but from other forms of illness, most notablycardiovascular disease.(2) Ironically, some of the very drugsthat are used to prevent rejection contribute to these widerhealth risks. Data from this study show that by switchingpatients from ciclosporin to Prograf(r), cardiovascular riskfactors can be reduced and that some problematical cosmeticeffects associated with ciclosporin treatment are avoided.

Professor Margreiter's conclusions arose from the results ofa large, prospective, multinational, European study in adultkidney transplant patients.(1) A total of 301 patients took partin the study, all of whom were receiving immunosuppressivetherapy based on ciclosporin microemulsion at the time the studybegan. Patients had been in receipt of their transplantedorgan for widely varying times, from as little as 6 months toover 20 years, with a mean time from transplantation of 5.4years.

All these patients were, however, suffering from side effectsassociated with ciclosporin treatment. In total, 116 patientssuffered from hypertrichosis (excessive hairiness) and 32patients had gingival hyperplasia (enlarged gums). These are sideeffects that can impact significantly on self-image and qualityof life and while not directly life-threatening they shouldbe avoided wherever possible. The remaining patients wereswitched to Prograf(r) in order to reduce side effects whichincreased their risk of cardiovascular disease - a major cause ofdeath after the first year following transplant.(3) Theseincluded 78 patients with abnormal cholesterol levels and 75patients with hypertension, despite the use of lipid-lowering andantihypertensive drugs to treat these conditions. (1)

The switch from ciclosporin to Prograf(r)-based treatmentbenefited all these symptoms.

After 6 months of treatment with Prograf(r), there had been adramatic improvement in the cosmetic side effects of ciclosporin.Gingival hyperplasia had completely or strongly resolved in 73%of affected patients, while hypertrichosis had completely orstrongly resolved in 72% of patients.

The severity of cardiovascular risk factors was also markedlyimproved by the switch to Prograf(r). Total cholesterol levelswere reduced from a mean of 255mg/dL at baseline to 218mg/dLafter 6 months on Prograf(r). Moreover, LDL cholesterol, which isan independent risk factor for heart disease, fell from a mean of138mg/dL to 120mg/dL after switch, but HDL cholesterol wasunchanged, leading to an improvement in the LDL/HDL ratio -another predictor of heart disease - from 2.9 to 2.5. Similarly,blood pressure was reduced following the switch to Prograf(r)-based therapy. Mean systolic blood pressure fell from 152mmHg to138mmHg, and diastolic blood pressure from 91 to 86mmHg.

Prograf(r)-based treatment was well tolerated in otherrespects. Importantly, new-onset diabetes, once thought to be acommon problem with Prograf(r), only occurred in 1.1% ofpatients. Kidney function remained stable, there were only twoepisodes of rejection and no episodes of graft loss. Theseresults show that the gains made by switching from ciclosporinmicroemulsion to Prograf(r) are not significantly offset by new,Prograf(r)-related side effects.

Clinical trials have shown previously that the risk of acuterejection is lower with Prograf(r) than with ciclosporin. Now itis clear that Prograf(r) is not only effective in protectingagainst rejection, but also improves ciclosporin-related sideeffects - resulting in a better quality of life and an improvedcardiovascular risk profile.

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 (in Japan in 1993, the first in the world,Fujisawa has become one of the world's leading transplant andimmunosuppression 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. Margreiter R, Pohanka E, Sparacino V, Sperschneider H,Kunzendorf U. Large European study of the switch to tacrolimusfor cyclosporin-related side effects. Presented at the AmericanTransplant Congress, Washington, USA, 26 April-1 May, 2002.Abstract 1060.2. Pascual M, Theruvath T, Kawai T, Tolkoff-Rubin N, Cosimi AB.Strategies to improve long-term outcomes after renaltransplantation. New Engl J Med 2002;346:580-90.3. Aakhus S, Dahl K, Wideroe TE. Cardiovascular morbidity andrisk factors in renal transplant patients. Nephrol DialTransplant 1999;14(3):648-54.Contact:Marité CruzFujisawa GmbH, Munich, GermanyT: +49 89 45442249F: +49 89 434129marite.cruz@fujisawa.de

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