title: Efficacy and safety of immunosuppressive drugs approved in EU through the centralised procedure.
abstract: BACKGROUND
  The aim of the present work is to evaluate the efficacy and safety data used by the European Medicines Agency (EMEA) between 1995 and June 2006 to approve new immunosuppressive drugs with indications in solid organ transplantation.
  
  
  METHODS
  The information about the approval of new agents was retrieved mainly from the European Public Assessment Report (EPAR) and Summary of Product Characteristics (SPC) on the EMEA web site. The design, type of control, primary endpoints, duration of follow-up, and safety profile of pivotal trials were examined.
  
  
  RESULTS
  Four immunosuppressive drugs belonging to three different therapeutic classes, with different clinical uses, were identified. Not all pivotal clinical trials compared the investigational agent with cyclosporin/corticosteroid/azathioprine triple therapy, which was the best therapeutic option available at the time of approval. Acute rejection, graft survival and efficacy failure at 6 months or 1 year post-transplant were the most frequent endpoints. Although some of the new agents reduce calcineurin inhibitor-associated nephrotoxicity, their adverse cardiovascular profile is of particular concern.
  
  
  CONCLUSIONS
  Recent improvements in the short-term efficacy of immunosuppressive therapy make short-term outcome measures inadequate for predicting long-term clinical benefit. Clinical outcomes such as 3- or 5-year graft and patient survival should be used in clinical trials in order to take into account non-immunosuppressive-related morbidity and to assess better whether the therapeutic advantage of the new agents over standard therapy is maintained in the long term.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Via Eritrea 62, 20157 Milano, Italy. bertele@marionegri.it
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bertele'
authors.forename: Carmela
authors.initials: C
authors.lastname: Buonocore
authors.forename: Francesca
authors.initials: F
authors.lastname: Michelacci
authors.forename: Maria
authors.initials: M
authors.lastname: Vitocolonna
authors.forename: Silvio
authors.initials: S
authors.lastname: Garattini
mesh_terms: D017277:Drug Approval / Q000331:legislation & jurisprudence*; D005062:European Union; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016377:Organ Transplantation / Q000331:legislation & jurisprudence
chemical_list: D007166:Immunosuppressive Agents