A Randomized Trial Comparing Safety and Efficacy of Okt3 and a Monoclonal Anti-Interleukin-2 Receptor Antibody (Bt563) in the Prevention of Acute Rejection After Heart Transplantation

Abstract

In a prospective randomized trial, BT563, a murine IgG, anti-interleukin-2 receptor antibody, was compared with OKT3 for use as an early rejection prophylaxis after heart transplantation. Patients received either BT563 (n=31) or OKT3 (n=29) during the first 7 days after transplantation; cyclosporine was started on day 3. Median follow-up was 34 months. A cytokine release syndrome occurred in the majority of patients of the OKT3-treated group but in none of the BT563 recipients. The mean duration of electrical stimulation of the heart in the BT563 group was longer than in the OKT3 group (5.1 vs. 2.1 days). In both groups, one patient required insertion of a permanent pacemaker. Freedom from acute rejection at 3 months was not significantly different between the two groups (BT563: 5/29, 17%; OKT3: 6/29, 21%). In the BT563 group, however, rejection tended to occur earlier after transplantation. There was no difference in the overall incidence of rejection. The incidence of infectious complications was evenly distributed in both groups. Malignancies occurred in two patients, both in the OKT3 group. In conclusion, the use of this anti-interleukin-2 receptor monoclonal antibody in heart transplant recipients is safe and devoid of the side effects that accompany the use of OKT3. OKT3 and BT563 result in a similar freedom from rejection at 3 and 12 months after heart transplantation.

Interleukin-2 Receptor Antagonists as Induction Therapy After Heart Transplantation: Systematic Review With Meta-Analysis of Randomized Trials

“…The IL-2Ra used was daclizumab in 3 trials, 16 -18 basiliximab in 4 trials 19 -22 and BT563 in 2 trials. 23,24 Baseline immunosuppressive therapy was the same within trials, but varied among the trials. Cyclosporine and steroids were used in all trials.…”

Ten-year Follow-up of a Prospective, Randomized Trial of BT563/BB10 Versus Anti-thymocyte Globulin as Induction Therapy After Heart Transplantation

“…Over a median follow-up period of 34 months, rejection tended to occur earlier in the BT563-treated group than in the OKT3-treated group, but 3-and 12-month rejection and infection rates were similar. 11 In a recent retrospective study, ATG and daclizumab were found to be equally effective in preventing acute rejections requiring treatment. However, due to the significantly higher frequency of Grade 1 rejections, daclizumab was associated with an increased need for biopsies to monitor rejection status.…”

“…20 For this reason we believe that using higher doses of BT563 in our study probably would not have increased the efficacy of the drug with regard to prevention of rejection, as both BT563 and ATG were applied according to existing literature. 11,19 Based on the fact that non-T-cell-derived T-cell growth factors can be actively involved in supporting the IL-2-independent allograft rejection response, the investigators proposed that the redundancy of the cytokine network may account for this phenomenon and, in another study, showed that other cytokines, such as IL-15, can fulfill the role of the blocked IL-2. 21,22 Interestingly, a vigorous classical T-cell-dependent rejection of islet allografts can still be mounted in mouse recipients devoid of both IL-2 and IL-4.…”

“…9,10 In the only prospective, randomized trial evaluating the use of BT563/BB10 vs OKT3 as induction after heart transplantation, over a median follow-up period of 34 months, rejection tended to occur earlier in the first group, but 3-and 12-month rejection and infection rates were similar. 11 Recent developments have resulted in a murine humanized anti-IL-2R monoclonal antibody (daclizumab) that has the murine antigen-binding sequences molecularly engrafted onto a human antibody and a chimeric (mouse/ human) monoclonal antibody (basiliximab) with mouse variable regions fused to the constant regions of a human IgG. The first clinical trials demonstrated a decreased incidence of acute rejection episodes in comparison to placebo.…”

New immunosuppressive drugs in heart transplantation

“…The use of monoclonal antibodies directed against epitopes of these receptors has been shown to prolong allograft survival in animal models. In a prospective randomized trial, BT53, a murine IgG1 anti-IL-2 receptor antibody, was compared with OKT3 for the prevention of early post-HT rejection [9]. Over a median follow-up period of 34 months, rejection tended to occur earlier in the BT563-treated group than in the OKT3-treated group, but 3-month and 12-month rejection and infection rates were similar.…”