Treatment Considerations for Childbearing and Autoimmune Disease

Megan E.B. Clowse, MD: When a woman comes in and tells me that she’s ready to get pregnant, we first take a look at how active her disease is. Then we take a look at her medications. Then we take a look at the rest of her comorbid conditions.

So, first we look at her disease activity. We see how her joints have been doing during the prior 6 months. We might talk about how she’s done in prior pregnancies. We look at how much pain she lives with on a daily basis. Our goal is to improve or at least maintain a good level of control of her disease. It’s my goal to ensure that women do not live with high levels of pain and ongoing inflammation, which particularly cause joint destruction and long-term disability.

So, next we look at her medications. We switch from medications that would be risky in pregnancy to pregnancy-compatible medications. An example of a pregnancy-compatible medication that I often consider for women with rheumatoid arthritis or other inflammatory arthritis is hydroxychloroquine. It is a drug that’s been around for decades and has been shown to be very safe in pregnancy, with no known complications for the developing fetus. We use sulfasalazine, which is also kind of an ancient drug. It’s been around for decades but has also shown to be very safe in pregnancy. It’s not used often in inflammatory arthritis, but I personally think it’s a great drug. If you have a patient who is on methotrexate and you’re stopping it, sulfasalazine is a great choice.

In terms of the biologics, when you step beyond the sort of older oral medications, TNF [tumor necrosis factor] inhibitors are really what I use. So, the medications that go on the not-compatible list: Methotrexate is on that list. Leflunomide stays on the not-compatible list but is worth discussing. When it came on the market, data from animals suggested that it caused major birth defects in a large number of offspring. It was thought to be extraordinarily problematic in pregnancy. Twenty years or 15 years later, there was finally a collection of pregnancies that was large enough to say, “Oh, it doesn’t appear to actually cause major complications in human pregnancies.”

There was a very lovely study that was published in 2010 that compared women who conceived while taking leflunomide and stopped it—everybody stopped it—to women who also had rheumatoid arthritis but weren’t taking it and to a healthy control: healthy women out in the population. It was found that there was no increase in pregnancy loss in patients taking leflunomide and no increase in birth defects.

That’s not to say that you should be taking leflunomide during pregnancy, but it tells you that it’s probably not a crisis if a woman conceives on it. I still recommend that you stop taking leflunomide prior to pregnancy. You should check the blood level of the drug, because you really would like there to be no drug in the patient when she conceives. You give the patient cholestyramine, which is basically a medication that washes out the drug if she still has the drug in her system. If she conceives on it, you stop it immediately and give her the cholestyramine. So leflunomide stays on my not-compatible-with-pregnancy list, but not because it actually appears to cause major pregnancy complications in people. We are just worried that it might.

I also don’t consider using anything newer than TNF inhibitors during pregnancy, and that’s because there are very limited data on them. We are still waiting for any kind of data that help us understand the safety of any of the newer biologics and, particularly, any of the newer small molecule drugs that are on the market. We don’t have that data yet, and so at this point, I’m really not recommending those when a woman is trying to get pregnant.