Comparing EULAR (2025) and ACR (2020) Guidelines on Safety of Lupus Medications in Pregnancy Save

Catherine Sims, MD

May 12, 2025 8:00 am

What are the major differences between these two guidelines?

Attendees at the 2025 RheumaPreg meeting were excited to discuss the newly released European Alliance of Associations for Rheumatology (EULAR) recommendations for use of antirheumatic drugs in reproduction, pregnancy, and lactation1. Table 1 summarizes the major recommendations from EULAR (2025) and the American College of Rheumatology (ACR) (2020) reproductive guidelines for commonly used medications in systemic lupus erythematosus (SLE) [differences denoted by bolded boxes]1,2. It should be noted that these two sets of guidelines largely align, however, the updated EULAR guidelines have included some additional medications incorporating data from the last five years.

What are the specific updates from EULAR?

An important addition to the EULAR guidelines is the inclusion of anifrolumab, belimumab, and voclosporin. While these are relatively newer medications for the treatment of SLE, EULAR recommended use of anifrolumab and belimumab with specific conditions. Anifrolumab (Saphnelo®), which inhibits type I interferon signaling, is commonly used to treat cutaneous lupus erythematosus. The EULAR guidelines acknowledge there is no available data on safe use of anifrolumab in pregnancy and it should only be used if no pregnancy-compatible medication can effectively control maternal disease1. The Saphnelo® Pregnancy Registry is currently enrolling patients.

Alternatively, belimumab has limited data that does not raise concerns about the impact of in utero exposure. It should be noted that administration of anti-B cell agents (rituximab, belimumab) in the second half of pregnancy could result in transient B cell depletion or other cytopenias in the neonate but without serious infections and with recovery of B cells within 6 months1.

Lastly, voclosporin, which is largely used to treat lupus nephritis, has insufficient safety data on use in pregnancy should be avoided until further evidence is available.

How does this compare to the ACR guidelines?

The 2020 ACR guidelines do not include anifrolumab or voclosporin and they were unable to make a recommendation for belimumab due to limited safety data. The ACR does conditionally recommend use of rituximab in organ and life threatening disease2. As noted by both ACR and EULAR guidelines, use of B cell depleting therapies in pregnancy, especially in the second and third trimesters, can lead to transiently low B cell populations in neonates with in utero exposure. The 2022 ACR vaccination guidelines recommend delaying rotavirus vaccination in neonates exposed to B-cell depleting therapies in utero for at least 6 months3.

How can the updated EULAR guidelines impact my clinical practice?

These updated guidelines provide some additional options for treatment of SLE disease activity during pregnancy. While there is less available data for newer biologic medications compared to disease modifying anti-rheumatic drugs (DMARDs), like azathioprine and hydroxychloroquine, some pregnant patients may require additional medications for adequate control of their disease activity. For example, if a pregnant patient with SLE has diffuse cutaneous disease activity despite use of hydroxychloroquine, tacrolimus, and glucocorticoids, providers can consider the addition of rituximab or anifrolumab. The use of these biologics in pregnancy could (1) decrease the need for higher doses of glucocorticoids in pregnancy and (2) result in improved control of disease activity; both of which could decrease risk of adverse pregnancy outcomes (e.g., preterm delivery).

Drug	American College of Rheumatology (2020)	European League Against Rheumatism (2025)
Anifrolumab	N/A	To treat severe, refractory maternal disease if no alternative medication available
Azathioprine	Strongly recommended in pregnancy	Compatible with pregnancy
Benlysta	Unable to make a recommendation due to limited data	May be used if needed to effectively control maternal disease
Cyclophosphamide	Strongly recommended against in pregnancy	Discontinue prior to pregnancy due to teratogenicity
Cyclosporin/Tacrolimus	Conditionally recommended in pregnancy	Compatible with pregnancy
Glucocorticoids	Conditionally recommended in pregnancy; taper to < 20 mg/day by adding pregnancy-compatible immunosuppressants	Compatible with pregnancy; aiming at < 5 mg/day
Hydroxychloroquine	Strongly recommended in pregnancy	Compatible with pregnancy
Leflunomide	Strongly recommended against in pregnancy; stop and give cholestyramine washout	Should be avoided due to insufficient data
Mycophenolate	Strongly recommended against in pregnancy	Discontinue prior to pregnancy due to teratogenicity
Methotrexate	Strongly recommended against; stop 1-3 months prior pregnancy. If taken during pregnancy, give folic acid 5 mg/day.	Discontinue prior to pregnancy due to teratogenicity
Non-Steroidal Anti-Inflammatory Drugs	Conditionally recommended in pregnancy	Compatible with pregnancy
Rituximab	Conditionally recommended in pregnancy specifically in cases of organ and/or life-threatening disease	May be used if needed to effectively control maternal disease
Sulfasalazine	Strongly recommended in pregnancy	Compatible with pregnancy
Voclosporin	N/A	Should be avoided due to insufficient data
N/A: not applicable. ACR: A strong recommendation indicates that continuation of the medication during pregnancy is safe. A conditional recommendation generally reflects lack of data, limited data, or conflicting data.

Rüegg L, Pluma A, Hamroun S, Cecchi I, Perez-Garcia LF, Anderson PO, et al. EULAR recommendations for use of antirheumatic drugs in reproduction, pregnancy, and lactation: 2024 update. Ann Rheum Dis. 2025 Apr 25:S0003-4967(25)00818-0. doi: 10.1016/j.ard.2025.02.023. Epub ahead of print. PMID: 40287311.
Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Care Res (Hoboken). 2020 Apr;72(4):461-488. doi: 10.1002/acr.24130. Epub 2020 Feb 26. PMID: 32090466.
Bass AR, Chakravarty E, Akl EA, Bingham CO, Calabrese L, Cappelli LC, et al. 2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases. Arthritis Care Res (Hoboken). 2023 Mar;75(3):449-464. doi: 10.1002/acr.25045. Epub 2023 Jan 4. PMID: 36597813; PMCID: PMC10291822.