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| |  Severe Adverse Events With Sirolimus More Frequent Than Past Studies Suggest: Presented at EASL By Cameron Johnston COPENHAGEN, Denmark -- April 28, 2009 -- Almost one-third of patients who were treated with sirolimus after liver transplantation discontinued the drug because of intolerable adverse events (AEs), according to a study presented here at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL). The study, presented by Douglas Thorburn, MD, Hepato-Biliary and Liver Transplant Unit, University Hospitals Birmingham, Birmingham, United Kingdom, in a poster presentation on Aril 26, also showed that many of those patients experienced intolerable AEs within 1 month of starting treatment. The findings are at odds with the results from other retrospective and prospective trials conducted between 2003 and 2008, which reported rates of all AEs ranging from 26% to 69% and rates of discontinuation due to intolerable AEs ranging from 4.8% to 26.0%. In contrast to these controlled trials, in a real-life setting, sirolimus is "relatively poorly tolerated," with almost one-third of those who were receiving it as monotherapy discontinuing treatment because of intolerable AEs, the researchers noted. In a review of 109 patients who underwent liver transplantation between 2002 and 2007 at the Birmingham hospital, 71 patients received sirolimus because they had compromised renal function. Twenty-three patients were at high risk of graft rejection, and 15 could not tolerate other immunosuppressive drugs. The median time on sirolimus was 295 days (interquartile range 72-693 days). Of the 109 patients, 20 died while receiving sirolimus treatment, including 2 who had chronic organ rejection, 2 who had recurrent disease, and 2 who had renal failure. One patient died of multiple organ failure, and 3 died from metastatic spread of their hepatocellular carcinoma. The remainder died of causes not related to treatment or their cancer. Of the surviving 89 patients, all received sirolimus, and 43 continued to receive calcineurin inhibitors (CNIs) as immunosuppressive agents. Of these, 22 (51.2%) discontinued use of sirolimus because of severe AEs. Out of 46 patients who did not receive CNIs, 14 (32.6%) discontinued because of severe AEs. Of the 29 total patients (27%) who discontinued therapy, 12 experienced severe AEs and stopped treatment within the first month. The most frequent AEs recorded were ulcerations of the mouth, deterioration of renal function, graft hepatitis, pneumonitis, neutropenia, and gastrointestinal upset. Patients who are undergoing liver transplantation and may be candidates for immunosuppressive treatment with sirolimus should be counselled about the potential for these adverse events, as well as the potential risks of changing treatments, the authors concluded.
[Presentation title: Sirolimus Is Associated With Frequent Adverse Effects Requiring Drug Cessation in Liver Transplant Recipients. Poster 490]
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