NEORAL IS ASSOCIATED WITH LESS NEUROTOXICITY AFTER LIVER TRANSPLANTATION

Abstract

738 Toxic side effects from Neoral (NEO) or Tacrolimus (TAC) continue to limit their effective use. We examined 16 pre-transplant variables to determine their association with the development of neurologic, hypertensive, or diabetic side effects in 122 liver transplant recipients from a single center. Thirty-nine patients were given NEO and 83 received TAC as primary immunosuppression. There was no significant difference in the frequency of new seizures, tremors, headaches, diabetes or hypertension after transplant. Significantly fewer patients given NEO developed severe speech pathology (5.1% v 24.1% p=0.01) and NEO patients had fewer new neurologic side effects overall (23.1% v 44.6% p=0.02). In a multivariable analysis, the odds for developing new neurologic disease were significantly decreased for NEO (OR=0.28, CI 0.11-0.73) and increased for corticosteroid use of 2000 mg or more (OR=2.6, CI=1.1-6.1), pre-transplant encephalopathy (OR=4.5, CI=1.5-13.5), and a pre-transplant Child-Pugh Score greater than 10 (OR=3.1, CI=1.1-8.4). A total of 34 patients were converted from their primary immunosuppression. Nine were converted from NEO, 6 for lack of efficacy and 3 for neurologic toxicity. Twenty-five were converted from TAC, 7 for lack of efficacy and 18 for toxicity (17 for neurologic, 1 for diabetic). For patients developing neurologic toxicities, mean drug levels for the 7 days preceding the toxic event were elevated in 44.4% of NEO patients compared with 5.9% of TAC patients (p=0.003). Year 1 infection (64% v 69%, p=0.75), rejection (61% v 56% p=0.47) and survival (87% v 80%, p=0.32) rates were similar between NEO and TAC treated groups. We conclude that, encephalopathy and Child-Pugh Score before transplant, as well as TAC and increased cortico-steroid bolus medication after transplant, are risk factors for neurologic side effects. Neoral is associated with significantly less neurotoxicity and no difference in efficacy. This research was supported in part by Novartis Pharmaceuticals. E. Hannover, N.J.