In contrast, Janus kinase inhibitors should be avoided, due to insufficient data in this population, as should the calcineurin inhibitor voclosporin. Other agents should be discontinued during pregnancy due to clearly established teratogenicity, including methotrexate, mycophenolate mofetil (MMF) and cyclophosphamide.
“They are on a spectrum of teratogenicity,” Dr. Vinet explained. Correspondingly, and based on their half-lives, methotrexate should ideally be held for four weeks prior to conception and MMF for six weeks. Cyclophosphamide should be held a full three months prior; however, cyclophosphamide may be employed for life-threatening manifestations during the second or third trimester if other options are not available.
Biologic DMARDs
Per EULAR guidelines, Dr. Vinet noted that belimumab can be used if needed to control disease throughout pregnancy.6 However, she explained that rituximab may cause B cell–depletion in neonates who are exposed during the second or third trimester. At present it’s unclear how significant the resulting infection risk might be, although B cells seem to fully recover within six months of birth. “So, we can use it in certain circumstances, but we need to be mindful of that and weigh the risks and benefits,” Dr. Vinet said.
Anifrolumab is an option if other agents cannot be used, Dr. Vinet explained, but because it is such a new therapy, little is known about its specific impact in pregnancy.
Considerations in Lupus Nephritis
Dr. Vinet discussed recent ACR guidelines on lupus nephritis, which recommend first-line triple therapy with glucocorticoids, MMF and a third agent (belimumab or a calcineurin inhibitor).8 However, a different approach is needed during a lupus nephritis flare during pregnancy due to teratogenicity concerns from MMF.
At Dr. Vinet’s institution, clinicians typically treat with intravenous pulse, followed by oral, glucocorticoids at 20 mg/daily or above (but with a rapid taper), along with azathioprine, tacrolimus and potentially belimumab (in addition to background low-dose aspirin and hydroxychloroquine). They may consider rituximab for inadequate response, escalating in very rare circumstances to MMF or cyclophosphamide in a rapidly deteriorating patient, but only during the late second or third trimester.
In a different setting, many non-flaring patients with previous lupus nephritis are kept on MMF as a maintenance therapy. Such patients need to be switched to a safer medication prior to pregnancy, and Dr. Vinet shared that clinicians often choose azathioprine in this situation.
Ruth Jessen Hickman, MD, a graduate of the Indiana University School of Medicine, is a medical and science writer in Bloomington, Ind.
