Practical and Clinical Implications of Emerging CNI-Free Immunosuppressive Regimens

Faculty

Needs Statement

One of the great dilemmas inmodern transplantation is the need to circumvent the alloimmune response by administering immunosuppressive agents that produce long-term, potentially
serious adverse events. Indeed, despite great strides in investigating, approving and utilizing new immunosuppressants in the clinic, the last 2 decades have witnessed significant graft and patient loss due
in part to the adverse effects of immunosuppressive agents on renal function and cardiovascular health.

Immunosuppressants that target the calcineurin pathway of T cell activation, the calcineurin inhibitors (CNIs), are widely believed to be principalmediators of the adverse events burden.
However, strategies tominimize their use have beenmet with limited success, due in part to a significantly increased risk of inadequate immunosuppression and therefore elevated risk of acute rejection.

Calcineurin activation is a necessary primary step in T cell activation, triggering subsequentmolecular events that result in cytokine production and T cell proliferation. Costimulation, one of the earlier downstreamevents in the cascade, ensures that the allopeptide-TcR/MHC binding that triggered calcineurin activation produces T cell differentiation and proliferation as opposed to anergy.

Transplant professionals are well acquainted with the double-edged effects of CNI-based immunosuppressive regimens. However, there is a need to raise awareness concerning emerging alternative strategies. The American Transplant Congress, held in Toronto, Canada,May 31-June 4, 2008, provided the opportunity to exchange new scientific and clinical information relevant to immunosuppression targeting the costimulatory pathway of
T cell activation. “Immunosuppression: Possible—Practical and Clinical Implications of Emerging Calcineurin Inhibitor-Free Immunosuppressive Regimens” was an evening satellite symposiumdevoted to a review of the limitations and benefits of CNI-based regimens, and a discussion of emerging therapy with belatacept, a costimulation inhibitor. The present Newsletter summarizes the state-of-the-art content presented by the three expert facultymembers during the symposium.

Target Audience

This programis designed to educatemedical professionals involved in themanagement of solid organ transplant patients including: surgeons, physicians, pharmacists, coordinators and nurses.

Objectives

1. Reduce the risk of nephrotoxicity and renal dysfunction;
2. Improve the potential for enhanced long-termoutcomes;
3. Impact the clinicalmanagement of transplant patients.

Accreditation

Medicine
This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the University of Kentucky College of Medicine and CTI Clinical Trial & Consulting Services. The University of Kentucky College of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

The University of Kentucky College of Medicine designates this educational activity for a maximum of 1.00 AMA PRA Category 1 Credits™. Each physician should claim only those hours of credit actually spent in the educational activity.

The University of Kentucky College of Medicine presents this activity for educational purposes only. Participants are expected to utilize their own expertise and judgment while engaged in the practice of medicine. The content of the presentations is provided solely by presenters who have been selected for presentations because of recognized expertise in their field.

Pharmacy
The University of Kentucky College of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

This activity has been assigned ACPE # 022-999-08-086-H04-P and will award up to 1.00 contact hours (0.1 CEUs) of continuing pharmacy education credit in states that recognize ACPE providers.

Statements of credit will indicate hours and CEUs based on participation and will be issued online at the conclusion of the activity. Successful completion includes completing the activity, its accompanying evaluation and/or posttest and requesting credit online at conclusion of the activity. The College complies with the Accreditation Standards for Continuing Pharmacy Education.

Nursing
Educational Review Systems is an approved provider of continuing education in nursing by ASNA, an accredited provider by the ANCC/Commission on Accreditation and designates this educational activity for a maximum of 1.00 hour(s). Provider #

Educational Review Systems is also approved for nursing continuing education by the state of California and the District of Columbia.

Faculty Disclosure

Dr. Ojo is on the speaker's bureau for Roche, Novartis, Genzyme, Wyeth and Astellas. He receives contract research support from Genzyme and Wyeth and consultation fees from Roche, Genzyme and Wyeth.

Dr. Meier-Kriesche is on the speaker's bureau for Astellas, receives contract research support from Isotechnika, Novartis and Pfizer, and receives consultation fees from Isotechnika and Wyeth.

Dr Woodle is on the speaker's bureau for Genzyme and Wyeth and receives contract research support from Astellas, BMS, Genzyme, Millenium, Novartis, Roche, Y Therapeutics and Wyeth.

 

Activity Sponsorship

This activity is jointly sponsored by the University of Kentucky and CTI Clinical Trial & Consulting Services. Supported by an unrestricted educational grant from Bristol-Myers Squibb Company.