Tacrolimus could be the immunosuppressant of choice in liver transplantation, according to the preliminary results of a new study.
The tacrolimus (Prograf) versus microemulsified ciclosporin (Neoral) study (TMC study) is being conducted by the UK and Republic of Ireland liver study group which consists of all eight liver transplantation centres in the UK and Ireland. The preliminary results, presented at the American Society of Transplantation meeting in Chicago on May 14, are based on 425 patients after six months follow-up. The study included 606 patients and the final 12-month results are expected by next Spring. Dr John O'Grady (consultant hepatologist, King's College hospital, London, and a lead investigator of the TMC study) said at a press conference on May 19 that he was "confident" that the final results would confirm the interim results.
The interim results showed that tacrolimus was statistically significantly better than ciclosporin when the endpoints of death, retransplantation and treatment failure for immunological reasons were considered together, said Dr O'Grady. Toxicity profiles were similar for both groups. Acute rejection occurred in 112 patients taking tacrolimus and 114 on ciclosporin. In liver transplantation, acute rejection was not of concern on the first occasion, said Dr O'Grady. The incidence of chronic rejection in patients taking tacrolimus was lower at six months (two patients compared with 10 on ciclosporin). He added that practice had been changed at King's liver transplant unit as a result of the study.
The balance between preventing rejection and avoiding infection was different for different organ transplants, said Dr Andrew Burroughs (consultant hepatologist, Royal Free hospital, London, and lead investigator with Dr O'Grady of the TMC study). Minor rejection in liver transplantation was far less important than it was in kidney transplantation. However, the risk of infection was greater after liver surgery because of the nature of the procedure. This affected the amount of immunosuppressant given.
In the TMC study, 211 patients were given tacrolimus 0.1mg/kg (blood level 5-15ng/ml) and 214 were given ciclosporin microemulsion 10mg/kg (blood level 150-300ng/ml). All patients received 20mg prednisolone (reducing to 7.5mg at three months) and azathioprine 1mg/kg daily.
Dr O'Grady commented that the study would also investigate the economics of the two treatments. While tacrolimus was 20 per cent more expensive than ciclosporin, the benefits of reduced hospital costs had to be taken into account, he said.
The TMC study is co-sponsored by Fujisawa (manufacturer of Prograf) and Novartis (manufacturer of Neoral). Dr Detlef Niese (transplantation clinical researcher, Novartis) told The Journal on May 23 that a full set of data was needed before serious conclusions could be drawn. The interim analysis included only a proportion of patients and had not originally been intended for presentation because the study was incomplete. A full set of outcomes could only come after the whole data set, including saftey and toxicity, had been examined. Dr Niese added that in the three years since the TMC study was designed, controlled trials had provided data on how to use Neoral more effectively.