Background/Purpose: One-third of women with SLE develop lupus nephritis (LN), and most receive mycophenolate mofetil (MMF). However, MMF is teratogenic, and needs to be switched to a pregnancy-compatible drug before conception. Best practice guidelines strongly recommend azathioprine (AZA) as the immunosuppressive of choice in SLE pregnancy, but do not provide guidance on pharmacogenetic testing [for thiopurine methyltransferase (TMPT) and nudix hydrolase 15 (NUDT15) genes] and drug monitoring. Recent evidence suggests that 6-mercaptopurine (6-MP) metabolite monitoring in SLE women during preconception and/or gestation might provide key opportunities to personalize therapy during this critical time (e.g. identification of “shunting”, non-adherence, sub/supra-therapeutic dosing). We evaluated practice patterns pertaining to SLE women with LN in the preconception and gestational periods, with a focus on pharmacogenetic testing and drug monitoring.

Methods: In February 2022, we distributed an electronic survey via REDCap to 39 Systemic Lupus International Collaborating Clinics (SLICC) members affiliated with SLE referral centres (https://sliccgroup.org), with reminders after 2 and 6 weeks. Physicians were queried about number of LN patients seen for pregnancy planning in the preceding year, the wait time they recommend prior to conception after renal response, choice of pregnancy-compatible immunosuppressive when switching from MMF, pharmacogenetic testing prior to AZA initiation, and drug monitoring.

Results: We received 29 responses (rate 74%) from SLICC members in North America (52%), Europe (34%), Asia/Oceania (10%), and South America (3%). Mean number of LN patients seen in the prior 12 months for preconception counselling was 7.2 (standard deviation 6.6). Most (93%) recommended waiting for a minimal time after achieving renal response on MMF prior to transitioning to a pregnancy-compatible immunosuppressive, with 19% ≤6 months, 44% suggesting 6-11 months, and 30% 12-23 months. In patients with inactive LN for ≥2 years, most (86%) systematically switched MMF to a pregnancy-compatible drug prior to conception, while 14% discontinued MMF without substituting another drug. When transitioning MMF to a pregnancy-compatible drug, the first choice was AZA (90%). When AZA could not be used, tacrolimus (TAC) was preferred (over cyclosporine, CsA) by 96%. When initiating AZA, 38% never assessed the TPMT genotype and/or phenotype and the vast majority (97%) never tested for the NUDT15 gene. When switching MMF to AZA prior to conception, only 14% measured 6-MP levels. The majority (56%) faced barriers to 6-MP testing related to access, cost, and wait times. When caring for pregnant patients on TAC or CsA, 48% performed drug monitoring each trimester, while 44% never did.

Conclusion: Although pharmacogenetic testing and drug monitoring offer opportunities to personalize therapies for patients with LN prior to conception and/or during pregnancy, our findings showed low use of these strategies among physicians caring for SLE patients. Interestingly, the optimal waiting period prior to conception after LN lacks consensus. We identified potential care gaps, which could be addressed by future pragmatic trials.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/systemic-lupus-erythematosus-women-with-lupus-nephritis-in-pregnancy-therapeutic-challenge-switch-the-systemic-lupus-international-collaborating-clinics-experience/