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Induction treatment with alemtuzumab (Campath) diminished the risk of acute rejection in kidney transplant therapy compared with basiliximab (Simulect) induction, researchers found.
In the 3C Study, patients randomized to alemtuzumab induction, which diminished the need for calcineurin inhibitors and mycophenolate and negated the need for steroids, had a significantly lower risk of acute rejection compared with those given basiliximab induction, according to Peter Friend, MD, of Oxford University, and colleagues.
Basiliximab induction involved a standard dose of tacrolimus and mycophenolate plus prednisolone, they explained.
Calcineurin inhibitors like tacrolimus are adept at preventing rejection but may contribute to transplant failure in the long run, the researchers said. They wanted to test whether using the lymphocyte-depleting antibody alemtuzumab would enable a less toxic regimen than that enabled by the nondepleting antibody basiliximab.
Between 2010 and 2013, they randomized 852 patients to either alemtuzumab-based induction treatment (low-dose tacrolimus and mycophenolate without steroids) or to basiliximab-based induction (standard-dose tacrolimus, mycophenolate, and prednisolone).
Overall, they found that fewer patients in the alemtuzumab group had acute rejection than in the basiliximab group (7% versus 16%), translating to a 58% reduction in biopsy-proven acute rejection (P<0.0001).
During the first 6 months after transplantation, there was no difference between groups in terms of transplant failure (4% versus 3%) or serious infection (32% for both groups). Also during that time period, 3% of patients given alemtuzumab-based treatment and 1% of patients given basiliximab-based treatment died (HR 1.79, 95% CI 0.66-4.83, P=0.25).
The authors acknowledged that there were more more deaths in the study arm, but the difference between the two groups was nonsignificant, explaining that "any adverse effects on mortality would probably arise through fatal infections or death from cancer ... there were no signiﬁcant excesses in the incidence of nonfatal infections or of incident cancer in our trial, [which] was reassuring."
Friend said in a statement that he hopes the findings will guide future treatments, noting that alemtuzumab has been available for many years but its use has been limited by concerns about possible side effects, particularly infections.
The researchers are planning a long-term follow-up of the study to determine whether these differences persist in the long run.
Anupam Agarwal, MD, of the University of Alabama at Birmingham, who was not involved in the study, said the findings could be important if they are shown to work long term.
"There are a lot of regimens being tried in transplant, and most include calcineurin inhibitors that have significant toxicity," he told MedPage Today. "Hence, if one could safely reduce the dose of the calcineurin inhibitor and still benefit from its immunosuppressive properties, it would be huge advance."
The study was supported by the U.K. National Health Service, Pfizer, and Novartis.
The researchers disclosed relevant relationships with the U.K. Medical Research Council, the British Heart Foundation, Cancer Research U.K., Sanofi, Astellas, and OrganOx.