Eight Drugs a Week Episode 21 – Her Majesty: How the Symphony Study Crowned Tacrolimus

This episode launches Paper(back) Writer, our new series revisiting the milestone papers in clinical pharmacology. If you look after a kidney transplant patient today, they’re very likely taking tacrolimus with mycophenolate, at concentration targets that are widely established. But in the early 2000s, that choice was far from obvious. Cyclosporine had transformed transplantation, yet clinicians were watching grafts fail, and there was concern the drug’s own kidney toxicity was partly to blame. Tacrolimus and the newer mTOR inhibitors were competing to take its place, yet nobody knew which strategy would result in the best patient outcomes.
To settle the matter, investigators designed Symphony: a four-arm trial of more than 1,600 patients across several continents, in which drug doses were adjusted to hit target blood concentrations. Its results reshaped international guidelines within a year. But how “low” was the winning low-dose regimen really, and what did the trial leave unanswered? Professor Teun van Gelder joins us to tell the story behind the study, and to explain why its lessons still matter for how we set and report drug concentration targets today.
 

In this episode we’ll hear about:

• Why concern about cyclosporine kidney toxicity and chronic graft loss drove a search for lower-dose immunosuppressive regimens in the early 2000s
• How Symphony pitted standard-dose cyclosporine against low-dose cyclosporine, tacrolimus and sirolimus, each with its own concentration target
• Why concentration-controlled trials must report how many patients actually hit their targets
• What unmeasured mycophenolate exposure may have meant for the cyclosporine arms

Papers/data discussed:

• SYMPHONY
• SYMPHONY trough concentration analysis
• CEASAR
• KDIGO 2009
• CTS registry data
• APOMYGRE
• Tacrolimus TDM second consensus report (IATDMCT, 2019)

About our guest:

• Prof. Teun van Gelder is an internist, nephrologist and clinical pharmacologist at Leiden University Medical Center, and a former President of the IATDMCT. His research focuses on the pharmacokinetics and therapeutic drug monitoring of immunosuppressive drugs in transplantation.

 
Eight Drugs a Week is supported by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). The personal views of the hosts and guests do not necessarily reflect the position of the Association.
 

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