Background Many SLE patients develop lupus nephritis (LN) and receive mycophenolate mofetil (MMF), a teratogenic drug. Guidelines recommend azathioprine (AZA) in SLE pregnancy without providing guidance on pharmacogenetic testing and therapeutic monitoring although these may help personalize therapy (e.g., identifying ‘shunters’, non-adherence). We evaluated practice patterns pertaining to SLE women with LN in preconception and gestational periods, focusing on pharmacogenetic testing and drug monitoring.
Methods In 02/2022, we distributed an electronic survey to 39 Systemic Lupus International Collaborating Clinics (SLICC) members. Physicians were queried about number of LN patients seen for pregnancy planning, wait time physicians recommend preconception after renal response, choice of pregnancy-compatible immunosuppressive when switching from MMF, pharmacogenetic testing before AZA initiation, and therapeutic monitoring.
Results Response rate was 74%. On average, respondents saw 7.2 (standard deviation 6.6) LN patients in the preceding year for pre-pregnancy counselling. Most (93%) recommended waiting for a minimal time after achieving renal response on MMF before transitioning to a pregnancy-compatible immunosuppressive (19% suggested ≤ 6 months, 44% 6–11 months, 30% 12–23 months). In patients with inactive LN for ≥ 2 years, 86% switched immunosuppressives, while 14% discontinued MMF without switching. First choice of pregnancy-compatible immunosuppressive was AZA (90%). Tacrolimus (TAC) was preferred over cyclosporine (CsA) by 96% as second option. When initiating AZA, 38% never assessed thiopurine methyltransferase (TPMT) genotype and/or phenotype and 97% never tested for nudix hydrolase 15 (NUDT15) gene. When switching MMF to AZA preconception, 14% measured 6-mercaptopurine (6-MP) levels. Most (56%) faced barriers to 6-MP testing related to access, cost, and wait times. When patients were on TAC or CsA, 48% monitored drug each trimester, while 44% never did.
Conclusions There is low use of pharmacogenetic testing and therapeutic monitoring when transitioning MMF to a pregnancy-compatible drug preconception. We identified potential care gaps, which could be addressed by future pragmatic trials.
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