SNOWMASS, COLO. – The prospect of preventing fetal heart block from neonatal lupus by using hydroxychloroquine to treat women with systemic lupus erythematosus and other anti-Ro antibody-positive rheumatologic diseases throughout pregnancy is drawing mounting physician interest.
"I think these new data are exciting. I actually now have changed my practice as a result of these two studies. I don’t think these studies demand that everybody else change what they’re doing, but I now give hydroxychloroquine to our pregnant patients who have anti-Ro antibodies," Dr. Megan E.B. Clowse said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Maternal anti-Ro antibodies readily transfer across the placenta starting at about week 16 of gestation. Roughly 2% of fetuses whose mothers are positive for these antibodies develop congenital complete heart block caused by inflammation at the atrioventricular node. It’s an irreversible condition with significant morbidity and even mortality.
Dr. Megan E.B. Clowse
Moreover, if the mother has previously given birth to a baby with any manifestation of neonatal lupus – even if limited to neonatal rash – the risk of congenital complete heart block in subsequent pregnancies climbs to about 15%, according to Dr. Clowse, a rheumatologist and director of the Duke Autoimmunity in Pregnancy Registry at Duke University, Durham, N.C.
She and her coinvestigators at Duke conducted one of the two studies that have led to her change in practice. It was a retrospective observational study of the recent Duke experience with pregnancies complicated by the presence of maternal anti-Ro antibodies. Twenty of the 33 subjects had systemic lupus erythematosus (SLE); most of the rest had unspecified rheumatologic disease or Sjögren’s syndrome.
Only 1 of 14 women treated with 200-400 mg/day of hydroxychloroquine throughout pregnancy had a baby with congenital heart block, while 7 of 19 pregnancies where hydroxychloroquine wasn’t prescribed resulted in this fetal cardiac disorder. This translated into an 86% relative risk reduction of fetal congenital complete heart block in hydroxychloroquine recipients (Am. J. Obstet. Gynecol. 2013;208:64.e1-7).
Dr. Clowse noted that the Duke study confirms a recent report by investigators at New York University, who searched three databases in the United States, France, and England and identified 257 pregnancies involving mothers positive for anti-Ro antibodies, all of whom had previously given birth to a child with cardiac neonatal lupus. Forty of the women were on hydroxychloroquine starting before 10 weeks of gestation and continued throughout pregnancy; the other 217 didn’t take hydroxychloroquine during the pregnancy. The incidence of recurrent neonatal congenital heart block was 7.5% in the hydroxychloroquine group, compared with 21.2% in mothers who didn’t receive the drug, for a 77% relative risk reduction (Circulation 2012;126:76-82).
The New York University researchers are in the midst of a confirmatory prospective nonrandomized study in women with a history of pregnancy complicated by fetal complete heart block who are on hydroxychloroquine in a subsequent pregnancy. But because it will probably take several more years to accumulate sufficient pregnancies to draw statistically significant conclusions, and in light of hydroxychloroquine’s favorable risk: benefit ratio in pregnancy, Dr. Clowse has decided to change her own practice.
Hydroxychloroquine is rated Pregnancy Class C by the Food and Drug Administration. It readily crosses the placenta. It has not been associated with pregnancy loss, prematurity, congenital anomalies, or any other adverse fetal effects. Dr. Clowse considers hydroxychloroquine to be the best medication for prevention of SLE flares in pregnancy.
She reported serving as a consultant to UCB.