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J Am Soc Nephrol 10:1366-1380, 1999
© 1999 American Society of Nephrology

SYMPOSIUM : New Approaches in Transplant Therapy

Newer Immunosuppressive Drugs

A Review

JAN F. GUMMERT, TUIJA IKONEN and RANDALL E. MORRIS

Transplantation Immunology, Department of Cardiothoracic Surgery, Standford University Medical School, Stanford, California.

Correspondence to Dr. Randall E. Morris, Transplantation Immunology, Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305-5407. Phone: 650-725-3751; Fax: 650-725-3846; E-mail: rem{at}leland.stanford.edu

Abstract

Abstract. In recent years, many new immunosuppressive drugs have been discovered and developed for clinical use in transplantation. This review focuses on those drugs (leflunomide, mycophenolate mofetil, sirolimus, tacrolimus) that have been shown to have immunosuppressive activity in patients. Different anti-interleukin-2 receptor antibodies are also reviewed as an example of a resurgence of development in the area of monoclonal antibodies. The price for reducing the incidence of allograft rejection by improved immunosuppression was thought to be a proportional increase in the incidence of infection and malignancy. Data from Phase III clinical trials of new immunosuppressants, however, show a statistically significant reduction in the incidence of acute rejection produced by these new drugs, which has not been accompanied by increases in infection and malignancy rates. The wide array of new drugs offers the opportunity to use combinations that block different pathways of immune activation while at the same time selecting drug combinations with nonoverlapping toxicity profiles so that doses of each single drug can be reduced below toxicity levels. The immunosuppressive therapy for patients can be tailored according to their individual needs.




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