Randomized controlled trial of a monoclonal antibody against the interleukin-2 receptor (33B3.1) as compared with rabbit antithymocyte globulin for prophylaxis against rejection of renal allografts

After patients receive kidney transplants, they either receive immunosuppressive drugs such as cyclosporine and steroids, or an agent such as polyclonal antilymphocyte serum (a different immunosuppressant), followed by cyclosporine and steroids two weeks later. An advantage of the latter regimen is that it allows the graft to recover from ischemia (decreased blood supply) during the time when it is especially sensitive to the toxic effects of cyclosporine. A monoclonal antibody has been developed that selectively inactivates only those lymphocytes that act against donor antigens, and this could be useful as an alternative to antilymphocyte serum, since it is more specific and does not inactivate all T cells. The substance, 33B3.1, acts by interfering with binding of interleukin-2 to its receptor on the T cell, thereby preventing proliferation of T cells. Its effectiveness was tested in 100 patients receiving their first renal transplants, half of whom received 33B3.1, and half of whom received antithymocyte globulin in a randomized study. Other medications were also administered. Patients were followed-up 5 to 22 months. Rejection was assessed clinically and by biopsy, when necessary, in both groups. The severity of infection with cytomegalovirus was noted. Results showed that the new antibody was tolerated better than antithymocyte globulin, a large percentage of whose recipients discontinued treatment during the first 14 days. One patient could not tolerate 33B3.1. Differences between the groups in subsets of T cells were found, such that antithymocyte globulin patients had greater drops in their CD2-, CD3-, CD4-, and CD8-positive cell counts. There were more rejection episodes in the 33B3.1 group (six) than the antithymocyte group (one), although the difference was not statistically significant. There were no group differences in patient (96 percent) or graft (85 percent) survival. Fewer infections were noted in the 33B3.1 group, including urinary tract infections, but the incidence of cytomegalovirus was about the same in both groups. Overall, it appears that the interleukin-2 receptor is an appropriate target for an immunosuppressive agent, and that 33B3.1 is an effective compound in this regard. (Consumer Summary produced by Reliance Medical Information, Inc.)