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Systemic Lupus Erythematosus Women with Lupus Nephritis in Pregnancy Therapeutic Challenge (SWITCH): The Systemic Lupus International Collaborating Clinics experience
  1. Joo-Young E Lee1,
  2. Arielle Mendel1,2,
  3. Anca Askanase3,
  4. Sang-Cheol Bae4,
  5. Jill P Buyon5,
  6. Ann Elaine Clarke6,
  7. Nathalie Costedoat-Chalumeau7,
  8. Paul R Fortin8,
  9. Dafna D Gladman9,
  10. Rosalind Ramsey-Goldman10,
  11. John G Hanly11,
  12. Murat Inanç12,
  13. David Alan Isenberg13,
  14. Anselm Mak14,
  15. Marta Mosca15,
  16. Michelle Petri16,
  17. Anisur Rahman13,
  18. Jorge Sanchez-Guerrero9,
  19. Murray Urowitz17,
  20. Daniel J Wallace18,
  21. Sasha Bernatsky1,2,
  22. Évelyne Vinet1,2
  1. 1 Centre for Outcomes Research and Evaluation (CORE), Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
  2. 2 Division of Rheumatology, McGill University Health Centre, Montreal, Quebec, Canada
  3. 3 Department of Rheumatology, Columbia University Irving Medical Center, New York, New York, USA
  4. 4 Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Hanyang University Institute for Rheumatology and Hanyang University Institute of Bioscience and Biotechnology, Seoul, South Korea
  5. 5 Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA
  6. 6 Division of Rheumatology, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
  7. 7 APHP, Centre de Reference Maladies Auto-immunes et Systémiques Rares, Service de Médecine Interne, Hôpital Cochin, Paris, France
  8. 8 Division of Rheumatology, Department of Medicine, Centre ARThrite, Centre Hospitalier Universitaire de Québec, Université Laval, Quebec, Quebec, Canada
  9. 9 Lupus Program, Centre for Prognosis Studies in the Rheumatic Disease and Krembil Research Institute, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada
  10. 10 Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  11. 11 Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada
  12. 12 Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Istanbul University, Istanbul, Turkey
  13. 13 Department of Rheumatology, University College London, London, UK
  14. 14 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  15. 15 Department of Clinical and Experimental Medicine, Rheumatology Unit, University of Pisa, Pisa, Italy
  16. 16 Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  17. 17 Centre for Prognosis Studies in the Rheumatic Diseases, Professor Emeritus Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  18. 18 Division of Rheumatology, Department of Medicine, Cedars-Sinai/David Geffen School of Medicine at UCLA, Cedars-Sinai Medical Center, Los Angeles, California, USA
  1. Correspondence to Dr Évelyne Vinet, Centre for Outcomes Research and Evaluation (CORE), Research Institute of the McGill University Health Centre, Montreal, Canada; evelyne.vinet{at}mcgill.ca

https://doi.org/10.1136/ard-2023-224197

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    One-third of women with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), and most receive mycophenolate mofetil (MMF), which is teratogenic and needs to be switched to a pregnancy-compatible drug before conception.1 2 Azathioprine (AZA) is the immunosuppressive of choice in SLE pregnancies, but best practice guidelines in rheumatology provide recommendations on neither pharmacogenetic testing (for thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) genes) nor therapeutic drug monitoring,2 3 likely due to lack of data in rheumatic diseases and limited indirect evidence in other populations (eg, inflammatory bowel disease).

    Recent evidence in a small number of patients suggests that AZA metabolite monitoring in women with SLE during preconception and/or gestation might provide key opportunities to personalise therapy during this critical time (eg, identification of ‘shunting’, non-adherence, subtherapeutic/supratherapeutic dosing).4 Therefore, we aimed to evaluate practice patterns pertaining to management of women with LN in the preconception and gestational periods, in particular pharmacogenetic testing and drug monitoring.

    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 the number of women with LN seen for pregnancy planning in the preceding year, time recommended waiting to conceive after renal response, choice of pregnancy-compatible immunosuppressive agents when switching from MMF, pharmacogenetic …

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    Footnotes

    • Handling editor Josef S Smolen

    • Presented at Prior conference presentation and published abstracts

      1. Lee JYE, Mendel A, Askanase A, Bae S, Buyon J et al. 'Systemic lupus erythematosus Women with lupus nephritis In pregnancy Therapeutic CHallenge (SWITCH)': The Systemic Lupus International Collaborating Clinics experience. American College of Rheumatology (ACR) Convergence 2022 – Philadelphia, PA, USA. 10–14 November 2022. Arthritis & Rheumatology. 2022; 74 (suppl 9) (Abstract number 0949) (Poster Presentation, accepted 18 August 2022)

      2. Lee JYE, Mendel A, Askanase A, Bae S, Buyon J et al. 'Systemic lupus erythematosus Women with lupus nephritis In pregnancy Therapeutic CHallenge (SWITCH)': The Systemic Lupus International Collaborating Clinics experience. Canadian Rheumatology Association (CRA) & Arthritis Health Professions Association (AHPA) Annual Scientific Meeting 2023 – Quebec City, QC, Canada. 8–11 February 2023. To be published (Abstract 2023–195) (Poster Presentation, accepted 25 November 2022)

      3. Lee JYE, Mendel A, Askanase A, Bae S, Buyon J et al. 'Systemic lupus erythematosus Women with lupus nephritis In pregnancy Therapeutic CHallenge (SWITCH)': The Systemic Lupus International Collaborating Clinics experience. Lupus & Korean College of Rheumatology (LUPUS & KCR) – Seoul, Republic of Korea. 17–20 May 2023. To be published (Abstract LSO-083) (Short Oral Presentation, accepted 15 February 2023).

    • Contributors J-YEL conducted the data analysis and drafted the first version of the manuscript. AMe, AA, S-CB, JPB, AEC, NC-C, PRF, DDG, RR-G, JGH, MI, DAI, AMa, MM, MP, AR, JS-G, MU, DJW and SB contributed to the data interpretation. EV conceived and designed the study and interpreted the data.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests J-YEL, AMe, AA, S-CB, JPB, NC-C, PRF, DDG, JGH, MI, DAI, MM, AR, JS-G, MU, DJW, SB and EV all have nothing to disclose; AEC reports research funds from GSK outside the scope of this work and consulting fees (less than $10 000) from AstraZeneca, Bristol Myers Squibb and GSK outside the submitted work. RR-G reports consulting fees (less than $10 000) from Ampel Solutions, Exagen Diagnostics, Biogen and AstraZeneca, outside the submitted work. AMa is supported by the GSK’s Supported Studies Program (proposal ID 10743) and National Medical Council Clinicial Scientist-Individual Research Grant (MOH-001093), and received honoraria from Pfizer and GlaxoSmithKline for lectures/speakers (less than USD 10 000). MP received grant support from NIAMS R01-AR-069572.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.