NEW YORK (Reuters Health) – Rates of acute rejection of lung transplants are not improved when sirolimus is added to the immunosuppressive regimen instead of azathioprine, a multicenter team reports.
“These results differ from previous results in cardiac and renal transplantation,” they say, “and emphasize the need for multicenter randomized controlled trials in lung transplantation.”
Dr. Sangeeta Bhorade, with the University of Chicago Medical Center, Illinois and colleagues explain in the American Journal of Respiratory and Critical Care Medicine online September 10 that acute rejection is still a limiting factor in the longevity of lung transplants.
Sirolimus has proven effective in cardiac, liver and renal transplantation and it is synergistic with calcineurin inhibitors. On that basis, the team conducted an open-label study comparing sirolimus to azathioprine in a tacrolimus-based immunosuppressive regimen in 181 lung transplant recipients.
Sirolimus was started 3 months after transplantation in order to avoid airway anastomotic complications seen with early administration of the agent in a previous trial.
However, outcomes in the current study were not encouraging. “There was a higher rate of adverse events leading to early discontinuation of sirolimus (64%) compared to azathioprine (49%) during the course of this study,” the researchers found. In particular, rates of thromboembolic events were higher in the sirolimus arm (17%) than the azathioprine arm (3%).
Furthermore, rates of grade A rejection at 1 year were not significantly improved: 39% with sirolimus and 49% with azathioprine (relative risk 0.96, p=0.82). Similarly, at 3 years the relative risk of grade A rejection was 1.08.
“The use of sirolimus in lung transplant recipients is limited by significant adverse events,” Dr. Bhorade summed up in an email. “Perhaps in lung transplant recipients who are able to tolerate sirolimus, this drug may be beneficial. It would be ideal to identify clinical factors that enable some patients to tolerate sirolimus.”
Comparison of Sirolimus to Azathioprine in a Tacrolimus Based Immunosuppressive Regimen in Lung Transplantation
Am J Respir Crit Care Med 2010.