CHICAGO – The risk of active disease in pregnant women with systemic lupus erythematosus far outweighs the risks of most medications.
Indeed, the risk of pregnancy loss doubles if lupus is active during pregnancy and jumps fourfold if the autoimmune disease is active in the 3 months before conception.
"My general rule is that the inflammation of active lupus is more dangerous to a pregnancy than medications," said Dr. Megan Clowse, director of the Duke University Autoimmunity in Pregnancy Registry in Durham, N.C. "We don’t have a medication that will cause a 40% pregnancy loss. So I think it’s important to continue medications within this population, although some drugs are certainly better than others."
Patrice Wendling/IMNG Medical Media
Dr. Megan Clowse
She advocates the use of hydroxychloroquine (Plaquenil) as the best way to prevent a systemic lupus erythematosus (SLE) flare. It’s a pregnancy category C drug because of reports of hearing abnormalities in children exposed to high doses of chloroquine (Aralen), but there are no clear fetal risks with hydroxychloroquine itself, particularly at the doses used by rheumatologists, she said. Moreover, several reports have suggested that hydroxychloroquine discontinuation during pregnancy may precipitate SLE flares, thereby worsening pregnancy prognosis.
The one exception to hydroxychloroquine use in SLE is the patient who’s been off the drug for years and is no longer symptomatic but becomes pregnant. "I don’t force those women back on their hydroxychloroquine, but basically everybody else should be on it," Dr. Clowse said at a symposium sponsored by the American College of Rheumatology.
For women with more active SLE, consider the use of azathioprine (Azasan, Imuran). It is a pregnancy category D drug due to the risk for fetal immunosuppression at delivery, but its use in SLE pregnancy is supported by extensive data among renal transplant patients, who have a higher rate of prematurity than SLE patients.
Azathioprine is most effective in preventing SLE flare in pregnancy, but Dr. Clowse said she has not been as impressed with its ability to treat flares during pregnancy. In her own recent study, azathioprine did not prevent pregnancy loss, and was actually associated with higher rates of loss among women with high-activity SLE.
When SLE flares occur, they need to be treated promptly, she stressed. Prednisone is probably the most effective treatment, although intravenous immunoglobulin may be a reasonable option. Prednisone is metabolized by the placenta, allowing only 10% of the maternal dose to reach the fetus. In contrast, the fluorinated corticosteroid betamethasone (Betnesol injection) is not metabolized and is transferred to the fetus, so it should not be used during pregnancy. Prednisone may decrease birth weight and is associated with a modest, threefold increased risk for cleft lip and palate, but this is really a first-trimester risk, she noted.
Drugs to avoid in pregnancy include cyclophosphamide (Cytoxan), mycophenolate mofetil (CellCept), and belimumab (Benlysta). A review of 26 pregnancies in 18 renal transplant patients receiving mycophenolate reported that 11 ended in spontaneous abortions and 10 in preterm births, and there were 4 cases of congenital anomalies (Transplantation 2006;82:1698-702). Not only was the 26% birth defect rate staggering compared with the 3% seen in the general population, but three of the infants had microtia. This was not simply underdeveloped pinnae, but the ears were located in the wrong place on the head, resulting in the babies being deaf, Dr. Clowse warned.
Although teratogenicity has not been observed in animals on belimumab, GlaxoSmithKline recently launched a global Benlysta Pregnancy Registry to prospectively collect data on birth defects and other pregnancy outcomes from women receiving belimumab within the 4 months prior to and/or during pregnancy (telephone: 1-877-681-6296).
Dr. Clowse said she recently began putting most of her pregnant SLE patients on aspirin 81 mg/day to prevent preeclampsia. Data from high-risk, nonlupus patients suggest aspirin may decrease the risk of preterm birth, preeclampsia, maternal hypertension, and low-birth weight without increasing the risk of congenital anomalies or ductus arteriosus closure observed with regular aspirin.
"It also, to be honest, takes away that whole discussion of low anticardiolipin antibodies and what do you do," she added.
Pregnant women with SLE should be closely monitored by a rheumatologist and an obstetrician skilled in high-risk pregnancies. Key parameters to monitor are hypertension, particularly in the first trimester, as this can increase the risk of pregnancy loss, preterm birth, and preeclampsia by up to 40%; and proteinuria, which may rise modestly during pregnancy due to increased renal function. More than a doubling or a 1-g increase of proteinuria, however, should raise the alarm, Dr. Clowse said.