PICO question 3
In adult lung transplant recipients, should mycophenolate mofetil be used over azathioprine to prevent the onset of CLAD?

Recommendation
• In adult lung transplant recipients, we suggest using either mycophenolate mofetil or azathioprine to prevent the onset of CLAD. (Conditional recommendation for either the intervention or the comparison, low certainty of evidence)

Remarks

There may be specific patient subgroups in which selecting one agent over the other is clinically justified. For example, in patients planning pregnancy, azathioprine (AZA) is preferred due to the teratogenic potential of mycophenolate mofetil (MMF). The choice of cell cycle inhibitor may also be influenced by individual susceptibility. AZA may be preferred in patients susceptible to or with persistent gastrointestinal side effects due to mycophenolic acid. Conversely, in patients with or susceptible to myelotoxicity, MMF might be preferred. Similarly, patients with gout requiring treatment with allopurinol (which may cause a serious drug interaction with AZA) may benefit from MMF. Finally, patients with genetic mutations in the thiopurine S-methyltransferase (TPMT) gene should avoid AZA (when homozygous deficient) or require reduced dosing (when heterozygous), as AZA treatment may induce severe, potentially fatal, bone marrow suppression by accumulation of toxic metabolites (6-thioguanine nucleotides) in these patients, which does not occur when treated with MMF