0949: Systemic Lupus Erythematosus Women with Lupus Nephritis in Pregnancy Therapeutic CHallenge (SWITCH): The Systemic Lupus International Collaborating Clinics Experience

Joo Young (Esther) Lee¹, Arielle Mendel², Anca Askanase³, Sang-Cheol Bae⁴, Jill Buyon⁵, Ann E Clarke⁶, Nathalie Costedoat-Chalumeau⁷, Paul R Fortin⁸, Dafna Gladman⁹, John Hanly¹⁰, Murat Inanc¹¹, David Isenberg¹², Anselm Mak¹³, Marta Mosca¹⁴, Michelle Petri¹⁵, Anisur Rahman¹⁶, Rosalind Ramsey-Goldman¹⁷, Jorge Sanchez-Guerrero¹⁸, Murray Urowitz¹⁹, Daniel Wallace²⁰, Sasha Bernatsky²¹ and Evelyne Vinet², ¹McGill University, Montréal, QC, Canada, ²McGill University Health Centre, Montréal, QC, Canada, ³Columbia University Medical Center, New York, NY, ⁴Hanyang University Medical Center, Seoul, Republic of Korea, ⁵NYU Grossman School of Medicine, New York, NY, ⁶University of Calgary, Division of Rheumatology, Cumming School of Medicine, Calgary, AB, Canada, ⁷Inserm DR Paris 5, Paris, France, ⁸Centre ARThrite - CHU de Québec - Université Laval, Québec, QC, Canada, ⁹Toronto Western Hospital, Schroeder Arthritis Institute, Toronto, ON, Canada, ¹⁰Division of Rheumatology, Queen Elizabeth II Health Sciences Center (Nova Scotia Rehabilitation Site) and Dalhousie University, Halifax, NS, Canada, ¹¹Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istambul, Turkey, ¹²University College London, London, United Kingdom, ¹³Division of Rheumatology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, ¹⁴Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, ¹⁵Johns Hopkins University School of Medicine, Division of Rheumatology, Baltimore, MD, ¹⁶Centre for Rheumatology, Department of Medicine, University College London, London, United Kingdom, ¹⁷Northwestern University Feinberg School of Medicine, Chicago, USA, Chicago, IL, ¹⁸Sinai Health System, Toronto, ON, Canada, ¹⁹University of Toronto, University Health Network, Schroeder Arthritis Institute, Toronto, ON, Canada, ²⁰Cedars-Sinai Medical Center, Los Angeles, CA, ²¹Research Institute of the McGill University Health Centre, Montréal, QC, Canada

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.

Disclosures: J. Lee, None; A. Mendel, None; A. Askanase, AstraZeneca, GlaxoSmithKlein(GSK), Aurinia, Amgen, Pfizer, Idorsia, Eli Lilly, UCB, AbbVie/Abbott, Janssen, Bristol-Myers Squibb(BMS); S. Bae, None; J. Buyon, None; A. Clarke, AstraZeneca, Bristol Myers Squibb (BMS), GlaxoSmithKline (GSK); N. Costedoat-Chalumeau, UCB, Roche; P. Fortin, AstraZeneca, GlaxoSmithKlein(GSK); D. Gladman, AbbVie, Amgen, Eli Lilly, Janssen, Gilead, Novartis, Pfizer, Bristol-Myers Squibb(BMS), Galapagos, UCB Pharma, Celgene; J. Hanly, None; M. Inanc, None; D. Isenberg, Merck/MSD, astra zeneca, Eli Lilly, Servier, Amgen; A. Mak, None; M. Mosca, None; M. Petri, Exagen, AstraZeneca, Alexion, Amgen, AnaptysBio, Argenx, Aurinia, Biogen, Caribou Biosciences, CVS Health, EMD Serono, Eli Lilly, Emergent Biosolutions, GlaxoSmithKline (GSK), IQVIA, Janssen, Kira Pharmaceuticals, MedShr, Sanofi, SinoMab, Thermofisher, BPR Scientific Advisory Committee; A. Rahman, None; R. Ramsey-Goldman, None; J. Sanchez-Guerrero, None; M. Urowitz, None; D. Wallace, None; S. Bernatsky, None; E. Vinet, None.