CHICAGO — The only “sure thing” about the medical management of pregnant women who have a rheumatic disease is that there are no sure things, advises a rheumatologist with particular expertise in lupus.
“In an ideal world, pregnancy in these women would always be planned; the rheumatic disease would have been in remission for at least 6 months at the time of conception, and there would be a plan for treatment if the disease flares. Unfortunately, clinical medicine isn't an ideal world,” said Dr. Bonnie L. Bermas, director of the Center for Lupus and Antiphospholipid Antibody at Brigham and Women's Hospital, Boston.
Exacerbating the challenge is the absence of any one-size-fits-all management formula, Dr. Bermas said, noting that the interplay among the individual patient, disease, and treatment variables—all of which are unpredictable—drives therapeutic decisions.
With rheumatoid arthritis (RA), for example, “the literature supports that about 70%-80% of patients will go into remission during pregnancy, though most will flare post partum,” said Dr. Bermas at a symposium sponsored by the American College of Rheumatology (ACR). Even though this knowledge provides clinicians with some flexibility with respect to medication during pregnancy, “we really can't predict who's going to go into remission, so we can't say up front, 'I guarantee you'll be able to go off treatment once you become pregnant,'” she said.
Systemic lupus erythematosus (SLE), on the other hand, is thought to be associated with a slightly increased risk of flare during pregnancy, said Dr. Bermas. “This means that we will approach a lupus patient differently than a rheumatoid arthritis patient in terms of our management plan, and the answers to the critical questions—'Will the disease flare? Will the baby be affected by the disease? What medications are safe to take during pregnancy?'—will be different.”
Although the Food and Drug Administration's use-in-pregnancy ratings for the mainstays of rheumatic disease therapies provide a management framework, there is often a discrepancy between what the FDA says is allowable during pregnancy and what clinicians feel comfortable prescribing, Dr. Bermas said.
NSAIDs, Cyclooxygenase-2 Inhibitors
Although animal studies have shown an increased risk of congenital anomalies with these agents, “when you get to the human studies, there really is no increased risk of congenital anomalies,” said Dr. Bermas. “There is an increased risk of premature closure of the ductus arteriosus in patients exposed to nonsteroidals late in pregnancy, so we counsel patients that they can use nonsteroidals up to 24 weeks' gestation. We could probably protract this out to 30 weeks, but it's easier to say, 'stop the NSAIDS in the third trimester.'”
For patients trying to conceive, “we advise that they avoid using COX-2s and NSAIDs during the conception cycle because both can have an impact on implantation,” Dr. Bermas noted.
A single case report of congenital defects in three of four babies born to one mother who took 250 mg of chloroquine two times a day during each of her four pregnancies earned antimalarials an FDA category C rating, “which is sort of representative of how the literature about medication in pregnancy has been interpreted over the years,” said Dr. Bermas. In the meantime, she said, there have been several case series in which no increased risk of congenital anomalies has been seen, and the literature on the use of these drugs as malarial prophylaxis (at higher doses than are used to treat rheumatic disease) has identified no untoward effects in pregnant women.
“For many years, we didn't use any of these drugs during pregnancy, but a recent ACR survey showed that most rheumatologists today are comfortable leaving patients on antimalarials during pregnancy,” said Dr. Berman. “Having said that, if I have an RA patient whose main medication is hydroxychloroquine, that patient probably has fairly mild disease. Considering that most RA patients go into remission during pregnancy, I usually recommend stopping the drug during gestation.”
But for a patient with SLE who is well maintained on hydroxychloroquine, “I'd probably keep the medication on board,” because additional data show that patients with lupus who remain on therapy have better outcomes.
For flares of most rheumatic diseases, steroids are considered “the ace in the hole,” said Dr. Bermas.
“During pregnancy, if rheumatoid arthritis, for example, becomes active, most clinicians recommend starting treatment with the lowest dose possible of a glucocorticoid medication, most commonly prednisone.” Both prednisone and methylprednisolone cross the placenta, but only at low levels, she said.
The data on steroid safety during pregnancy are mixed. “Originally, there were some case reports of cleft palate formation in offspring, although no increased risk of fetal anomalies was found in a large series of asthma patients treated with steroids throughout pregnancy,” said Dr. Bermas. “In a meta-analysis of epidemiological studies, however, there was a 3.4-fold increase in the incidence of cleft palate formation associated with maternal exposure to corticosteroids [Teratology, 2000;62:385–92],” she said. “The key time frame seems to be between weeks 6 and 12, when the palate is forming.”