A Phase I/II Randomized Open-Label Multicenter Trial of Efalizumab, a Humanized Anti-CD11a, Anti-LFA-1 in Renal Transplantation

Abstract

Leukocyte function associated antigen-1 (LFA-1) has a multifaceted role in the immune response, including adhesion and trafficking of leukocytes, stabilizing the immune synapse of the MHC-TCR complex and providing costimulation signals. Monoclonal antibodies to the CD11a chain of LFA-1 have been seen to result in effective immunosuppression in experimental models. Efalizumab, a humanized IgG1 antiCD11a, is approved for use in psoriasis and may provide effective immunosuppression in organ transplantation. Thirty-eight patients undergoing their first living donor or deceased renal transplant were randomized to receive efalizumab 0.5 or 2 mg/kg weekly subcutaneously for 12 weeks. Patients were maintained on full dose cyclosporine, mycophenolate mofetil and steroids or half dose cyclosporine, sirolimus and prednisone. At 6 months following transplant patient survival was 97% and graft survival was 95%. Clinical biopsy-proven acute rejection in the first 6 months after transplantation was confirmed in 4 of 38 patients (11%). Three patients (8%) developed post transplant lymphoproliferative disease, all treated with the higher dose efalizumab and full dose cyclosporine. The two doses of efalizumab resulted in comparable saturation and modulation of CD11a. This phase II trial suggests that efalizumab may warrant further investigation in transplantation.

Overview of immunosuppression in liver transplantation

“…This agent was approved for the treatment of psoriasis in 2003 and has not yet been used in liver transplantation, although a few clinical trials have been carried out in renal transplant patients with mixed results [106] . Although the results regarding immunosuppression were promising, an increased risk for PTLD was shown when efalizumab was used in combination with highdose CYA.…”

New targets for immunosuppression in kidney transplantation: Focus on recent clinical trials

“…The biologic that best epitomizes this paradigm shift is belatacept. 24 Another biologic that appears promising is alefacept 25,26 (Table II).…”

Induction Immunosuppressive Therapy in Kidney Transplantation

“…A study to replace calcineurin inhibitors with efalizumab soon after transplant in patients who had mildly impaired renal function was planned but terminated. 34 Alefacept Alefacept (Amevive, Astellas Pharmas, Deerfield, IL, USA) is an inhibitor of the costimulation of T cells by CD2 and lymphocyte function-associated antigen 3. 35 It was approved by the FDA for treatment of moderate-to-severe chronic plaque psoriasis in adults (15 mg/wk, intramuscular, for 12 wk).…”