FTY720 - a novel immunomodulator - Efficacy and safety results from the first phase 2a study in de novo renal transplantation
| Autor: | Barry D. Kahan, Shamkant Mulgaonkar, Søren Madsen, Helio Tedesco-Silva, Josep Grinyo Boira, Willem Weimar, Georges Mourad, Björn Nashan, Bernard Charpentier, Yves Vanrenterghem, Pascale Pellet |
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| Přispěvatelé: | Internal Medicine |
| Rok vydání: | 2004 |
| Předmět: |
Adult
Graft Rejection medicine.medical_specialty Time Factors Adolescent medicine.medical_treatment Urinary system Biopsy Infections Gastroenterology Mycophenolic acid Postoperative Complications Sphingosine hemic and lymphatic diseases Internal medicine medicine Cadaver Humans Kidney transplantation Aged Transplantation Kidney Dose-Response Relationship Drug business.industry Fingolimod Hydrochloride Middle Aged Mycophenolic Acid medicine.disease Kidney Transplantation Tissue Donors Surgery medicine.anatomical_structure Treatment Outcome Tolerability Propylene Glycols Pharmacodynamics Cyclosporine Drug Therapy Combination Safety business Immunosuppressive Agents Allotransplantation medicine.drug |
| Zdroj: | Transplantation, 77(12), 1826-1833. Lippincott Williams & Wilkins Madsen, S, Tedesco-Silver, H, Mourad, G, Kahan, B D, Boira, J G, Weimar, W, Mulgaonkar, S, Nashan, B, Charpentier, B, Pellet, P & Vanrenterghem, Y 2005, ' FTY720, a novel immunomodulator: Efficacy and safety results from the first phase 2A study in de novo renal transplantation. ' Transplantation, vol. 79, pp. 1553-1560 . Tedesco-Silva, H, Mourad, G, Kahan, B D, Boira, J G, Weimar, W, Mulgan, S, Nashan, B, Madsen, S, Charpentier, B, Pellet, P & Vanrenterghem, Y 2004, ' FTY-720, a novel immunomodulator: efficacy and safety results from the first phase 2a study in de novo renal transplantation ', Transplantation, no. 77, pp. 1826-1833 . |
| ISSN: | 0041-1337 |
| Popis: | BACKGROUND FTY720 is the first of a new drug class: sphingosine-1-phosphate receptor agonist. Its effect relates to the modulation of lymphocytes trafficking from blood and peripheral tissues to lymph nodes. This is the first study to evaluate the efficacy and safety of FTY720 in de novo renal transplantation. METHODS This phase 2a, multicenter, open-label, dose-finding study compared FTY720 (0.25, 0.5, 1.0, or 2.5 mg) with mycophenolate mofetil (MMF), in combination with cyclosporine and corticosteroids. Patients (n=208) received FTY720 (n=167) or MMF (n=41) for 3 months followed by a 3-month follow-up. RESULTS The incidence of biopsy-confirmed acute rejection at month 3 was 23.3%, 34.9%, 17.5%, and 9.8%, respectively, with FTY720 at doses of 0.25, 0.5, 1.0, and 2.5 mg, versus 17.1% with MMF. The incidence for the composite endpoint (biopsy-confirmed acute rejection, graft loss, or death) was lowest with FTY720 at a dose of 2.5 mg at month 3 (14.6%) compared with FTY720 at doses of 0.25 mg (25.6%), 0.5 mg (34.9%), and 1.0 mg (17.5%), and MMF (19.5%). Safety was comparable between FTY720 and MMF group. The main difference in tolerability was a mild and transient reduction in heart rate. A decrease in peripheral lymphocytes occurred in patients receiving FTY720, as expected from the mode of action, and this was reversible after treatment cessation. CONCLUSIONS FTY720 at 2.5 mg was found to be as effective as MMF in combination with cyclosporine for the prevention of acute rejection after renal transplantation. FTY720 was well tolerated and not associated with the side effects commonly observed with immunosuppressant therapies. |
| Databáze: | OpenAIRE |
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