EULAR Task Force Expands Pregnancy-Safe Drug Options

Medscape

07-05-2025

All tumor necrosis factor (TNF) inhibitors are safe to use throughout pregnancy, according to new recommendations from the European Alliance of Associations for Rheumatology (EULAR).
All biologic disease-modifying antirheumatic drugs (bDMARDs) can also be continued while breastfeeding, and women should not be discouraged from breastfeeding while taking compatible medications.
These updated recommendations on antirheumatic drug use during conception and pregnancy and through lactation reflect additional data and treatment advances that have occurred since the previous version from 2016, wrote the international task force, led by Frauke Förger, MD, of the Department of Rheumatology and Immunology, Bern University Hospital, University of Bern, Bern, Switzerland, and HOCH Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
'Modern treatment approaches have evolved towards a treat-to-target concept to avoid the negative impact of active disease on fertility and pregnancy outcomes,' the authors wrote. 'Additionally, new relevant data about antirheumatic drugs in the context of pregnancy and breastfeeding as well as in male reproductive health have emerged.'
This revised guidance was published in Annals of the Rheumatic Diseases on April 26, 2025.
Antirheumatic Drugs During Pregnancy
In line with previous recommendations, the conventional synthetic DMARDS (csDMARDS) azathioprine or mercaptopurine, chloroquine, colchicine, cyclosporine, hydroxychloroquine, sulfasalazine, and tacrolimus are all compatible with pregnancy. The teratogenic medications methotrexate, mycophenolate, and cyclophosphamide should be stopped prior to conception.
The task force noted that while nonsteroidal anti-inflammatory drugs (NSAIDs) can be considered during pregnancy to control disease activity, they should be used intermittently and stopped after 28 weeks gestation. NSAIDs with a shorter half-life, like ibuprofen, are preferred. If a patient is having difficulty conceiving, discontinuing NSAIDs should be considered, the task force advised.
Corticosteroids should be tapered to a 5 mg daily dose or lower or stopped entirely, if possible.
This recommendation 'reflects the increasing recognition of the toxicity of chronic, higher dose glucocorticoids, including during pregnancy,' Lisa Sammaritano, MD, of Hospital for Special Surgery in New York City, told Medscape Medical News . She was not involved with creating the recommendations.
In cases with severe, refractory maternal disease, intravenous methylprednisolone pulses, intravenous immunoglobulin, or sildenafil can also be considered. In these severe cases, cyclophosphamide or mycophenolate can also be considered in the second and third trimesters.
In addition to all TNF inhibitor bDMARDs, abatacept, anakinra, belimumab, canakinumab, ixekizumab, rituximab, sarilumab, secukinumab, tocilizumab, and ustekinumab can be used if needed.
Due to lack of safety data in pregnancy, avoid using apremilast, avacopan, baricitinib, bosentan, filgotinib, leflunomide, mepacrine, tofacitinib, upadacitinib, and voclosporin. These drugs should also be avoided while breastfeeding.
While these recommendations align with the current guidelines from the American College of Rheumatology (ACR), the updated EULAR guidance mentions newer drugs developed after the 2020 ACR reproductive health guidelines were published, noted Mehret Birru Talabi, MD, PhD, director of the Women's and Reproductive Health Rheumatology Clinic at the University of Pittsburgh Medical Center in Pittsburgh.
'While we are lacking safety data in pregnancy and lactation for many of these drugs, the updated list of therapeutics is more reflective of treatment options that are available now,' she said.
Breastfeeding and Vaccinations
CsDMARDs and bDMARDs that are compatible with pregnancy can be continued while breastfeeding, along with celecoxib, nonselective NSAIDs, prednisone, and prednisolone. If no alternative breastfeeding-compatible medication can be used, bosentan, sildenafil, and methotrexate (weekly dosage at or below 25 mg) can be considered.
For infants with prenatal exposure to bDMARDs, nonlive vaccines can be administered according to the normal vaccination schedule. For infants exposed to TNF inhibitors in utero, the rotavirus vaccine can also be given in accordance with the normal vaccination schedule. For infants exposed to in utero to TNF inhibitors with transplacental transfer during the second half of pregnancy (eg, infliximab, adalimumab, or golimumab), the Bacille Calmette−Guérin vaccine should be delayed for 6 months.
Infants exposed to non–TNF inhibitor biologics in utero during the second and third trimester should have all live vaccines delayed for 6 months.
Male Patients
Cyclophosphamide is associated with a 'potential risk for irreversible infertility,' the task force wrote, and male patients should discontinue the medication at least 3 months before trying to conceive. Due to limited or no available safety data, male patients can also consider switching from the following drugs to alternatives when trying to conceive: Anifrolumab, apremilast, avacopan, baricitinib, bosentan, eculizumab, filgotinib, guselkumab, mepolizumab, risankizumab, tofacitinib, upadacitinib, and voclosporin.
Treatment with sulfasalazine 'has not demonstrated clinically-relevant impact on offspring outcome,' according to the EULAR recommendations, and can be continued in male patients trying to conceive. However, the medication 'can result in a transiently lowered sperm count,' Sammaritano said. 'Semen analysis is indicated if a couple has difficulty conceiving when the male partner is on sulfasalazine.'
In cases where conception is delayed, patients can consider discontinuing sulfasalazine, the EULAR task force advised.