Patient Selection and Safety With TNF Inhibitors - Episode 17
Megan E.B. Clowse, MD: There [have] been data collected for over 40 years that show that women with rheumatoid arthritis appear to have a higher risk of infertility. Going back to data from the 1960s, it appears that women who had rheumatoid arthritis had fewer children than their neighbors. Interestingly, this held true in women who were diagnosed with rheumatoid arthritis after they had all of their kids. Even when they were diagnosed in their 50s and 60s, well after they had children, they still had fewer children than their neighbors. This suggests that there may be something in women with rheumatoid arthritis that makes it harder for them to get pregnant.
We’ve done studies more recently that have shown similar information—that women with rheumatoid arthritis appear to have more difficulty getting pregnant, particularly women who are diagnosed at a younger age. For patients who are diagnosed before having children, we tend to see pretty high rates of infertility. In some studies, up to 30% to 40% of patients will have a hard time getting pregnant. Fortunately, most women will succeed in getting pregnant, but a lot of them will actually need fertility treatment in order to achieve a pregnancy.
We found a few things that seem to drive the infertility to some extent. One of the things that seems to drive it is the age of the woman. That’s just a general factor. Women who are over the age of 30, particularly over the age of 35, have a harder time getting pregnant than women who are younger. Specific to rheumatoid arthritis, we see that taking a lot of NSAIDs [nonsteroidal anti-inflammatory drugs] at multiple doses per week—medications like ibuprofen and naproxen—seem to make it difficult to get pregnant. We think it actually might be changing the way that a woman is ovulating, to some extent.
In addition, women who have really active rheumatoid arthritis appear to not conceive as well. Women who have quiet disease do better in terms of getting pregnant. In addition, in women who are taking higher doses of prednisone, it looks like 7.5 mg or higher really seems to be the cutoff. Requiring that much prednisone every day also seems to be associated with not getting pregnant.
The old way that we used to manage pregnancy and the old way that people used to manage pregnancy is that the doctor would just tell the woman to stop all of her rheumatoid arthritis medications when she wanted to get pregnant: “We’ll just manage you with some ibuprofen and some prednisone if you need it.” I can tell you—and I’m sure that most women living with rheumatoid arthritis can tell you—that when they stop all of their medicines, a lot of them will have increased disease activity and flares. They’ll have active disease. They’ll need a fair amount of ibuprofen to get through the day, and they’ll probably need prednisone. These are all things that make it really hard to get pregnant, so my approach to avoid issues with fertility is to actually control disease activity with pregnancy-compatible medications. We don’t let people flare ahead of time if we can help it. We try to avoid prednisone if we can help it. We also try to avoid NSAIDs, keeping women comfortable by decreasing inflammation with other drugs.
Women with inflammatory arthritis are at a slight increased risk of having some pregnancy complications. The key ones we see are preterm delivery, as well as babies being born a bit smaller than you would expect them to be—what we call small for gestational age. When we talk about preterm delivery, most pregnancies are 40 weeks long. As long as you deliver within 3 weeks of that—so, up to 37 weeks— that’s considered to be a normal or term delivery. But delivering before that—4, 5, or 6 weeks before your due date—is when we really call a baby preterm. We see this more often when we look at women with rheumatoid arthritis.
When we think about women with lupus or systemic internal organ disease, we tend to see even higher rates of preterm delivery than we do with inflammatory arthritis. But we do see that inflammatory arthritis causes preterm birth, and it seems to be particularly associated with times when the inflammatory arthritis is really active in pregnancy. So in my experience, women who have their disease well controlled on compatible medications go to term more often, whereas patients who are not taking medications during pregnancy if their arthritis is active, or those whose arthritis is bad and we just can’t get it under control with pregnancy-safe medicines, tend to be the people who have more preterm deliveries.