Pulse
A Pregnant Pause
Some women with rheumatoid arthritis experience a break in their disease during pregnancy. What causes that reprieve is subject to speculation—and investigation.
For women with rheumatoid arthritis (RA), pregnancy can be unpredictable and double-edged as far as their arthritis pain goes. As many as 80 percent will experience improvement or even remission of their RA symptoms during pregnancy; but the symptom-free state is often only temporary, and the postpartum period can signal the return of even stronger, more severe flare-ups.
One of the first doctors to report on this enigmatic connection between childbearing and RA was Mayo Clinic rheumatologist Philip Hench, who in the 1930s, suggested that hormones released by the adrenal glands likely played a role. (His work on arthritis led to his discovery of the therapeutic effects of cortisone and a shared Nobel Prize in 1950.)
Since then, scientific inquiry has revealed that the reasons for the waning of symptoms are not quite so clear. If hormones were the only cause, some researchers contend the improvement in RA would be more uniform among all pregnant women or the remissions would extend to women with other inflammatory diseases such as lupus.
Seven decades after Hench’s exploration into the pregnancy-RA connection, researchers at Mayo and the University of Minnesota are again studying it. Led by Mayo Clinic rheumatologist Shreyasee Amin, M.D., they are now focused not on hormones but on immune system changes that occur in pregnancy. They hope to better understand precisely what is responsible for symptom-free episodes during pregnancy and why RA reappears soon after the baby is born.
Betting on Biomarkers
Amin first took an interest in the RA-pregnancy connection in the 1990s when she was working with Carl Laskin, M.D., a rheumatologist at the University of Toronto. Laskin was investigating a large cohort of women who were pregnant and had various autoimmune diseases including lupus and RA. Amin became interested in the differences in experience between women with lupus who are pregnant and those with RA. “I realized that we could learn a lot more about the pathogenesis of the diseases and maybe ultimately help our patients further if we could just understand what makes things worse for one group of patients and what makes things better for the other,” she says.
Amin has been attempting to do that in her work at Mayo. She believes the key to unraveling the mystery of why RA disappears during pregnancy lies in blood biomarkers—unique protein and gene signatures that manifest within the blood of pregnant women when they are in remission from RA.
To determine which proteins and genes are most active during this time, Amin, in collaboration with Ann Reed, M.D., at Mayo and Erik Peterson, M.D., and Emily Baechler, Ph.D., at the University of Minnesota, is enrolling pregnant women with RA in a study in which they are assessed three times during their pregnancy—once during each trimester—and then within three months postpartum. During each visit, a sample of the patient’s blood is drawn and tested for the presence of dozens of proteins—including cytokines and interleukin profiles—to determine which of these biomarkers are likely responsible for the disease improvement and/or remission. Amin is also working with Jane Salmon, M.D., a rheumatologist with the Hospital for Special Surgery in New York, to compare these blood assays against those of pregnant women who do not have RA or other autoimmune diseases. (Salmon is currently conducting a large study on lupus in pregnancy that includes a cohort of healthy pregnant women.) She says they’re looking for protein levels and trying to define the biomarkers that are sensitive to change with pregnancy and disease activity. Amin’s immediate goal is to identify the protein biomarkers that seem to be linked to RA and RA remission so that she can apply for funding from the National Institutes of Health or another agency to do a larger multi-clinic trial.
Since beginning the clinical assessments in 2006, Amin has enrolled 19 patients with RA. She hopes to have 30 before she begins to analyze the data in earnest. Although Amin is not yet able to release any findings from the biomarkers study, she’s optimistic that her work will shed new light on the questions that Hench and his colleagues raised seven decades ago. “We’re in a position to do much more detailed analyses of the immune system than was possible back then,” she says.
What Doctors Need to Know
One thing has become clear since Amin’s investigation began: The percentage of women with RA who experience a remission of their disease during pregnancy may not be nearly as high as what has been reported in the literature. “A lot of women with RA do improve during pregnancy, but whether it’s the 75 percent to 80 percent often cited, I haven’t found that so far,” she says. “What that means is that as physicians, we cannot assume that all women will have an improvement in RA symptoms during pregnancy—and that we should therefore be monitoring them a little more closely.”
Amin says primary care physicians and obstetricians/gynecologists should follow some general guidelines when working with women who have RA and wish to become pregnant or who are pregnant:
- Plan ahead and work with the patient’s rheumatologist. If a patient is considering pregnancy, cease any RA medications such as methotrexate that may be harmful to the fetus. “Do counseling before the pregnancy occurs, so you know which medications to stop and when they need to be stopped, and which ones can be continued safely,” she says.
- As the patient is trying to conceive, closely observe her status to help stave off flare-ups. Low-dose prednisone can be used to control symptoms relatively safely during pregnancy.
- Once the woman becomes pregnant, remain vigilant and don’t assume that her RA will go into remission.
Amin ultimately hopes that her team’s discoveries will not only begin to answer questions she’s been asking for years but also benefit all patients with RA, not just those who are pregnant. “If we can understand the changes that occur in the immune system during pregnancy that help some women with RA improve, perhaps we can begin to target our therapies for RA to mimic these changes,” she says, “and that would improve the care for rheumatoid arthritis patients in general.”—Jeanne Mettner