Rheumatoid Arthritis and Safe Conception and Pregnancy

Originally published by our sister publication Specialty Pharmacy Continuum

By Fran Kritz

People with rheumatoid arthritis (RA) who are trying to conceive have many questions, according to two experts, and it is important to offer advice about how to safely manage their disease before, during and after the pregnancy. 

Mehret Birru Talabi, MD, PhD, an assistant professor of medicine in the Division of Rheumatology and Clinical Immunology at the University of Pittsburgh School of Medicine, said that a number of effective RA medications are safe to use during pregnancy and breastfeeding, such as oral medications (e.g., hydroxychloroquine and sulfasalazine) and biologic medications taken by injection (e.g., tumor necrosis factor-alpha inhibitors). “Women with RA who are prescribed these [specific] medications prior to pregnancy can safely continue these medications into the pregnancy time frame,” Dr. Talabi said.

However, some medications are clearly unsafe to use during pregnancy, such as methotrexate, or have the potential for being unsafe to a fetus, such as leflunomide.

“People who are using these medications should be weaned off … prior to pregnancy and transitioned to safer medications.”

Dr. Talabi said many RA drugs have not been studied for use in pregnancy. “In these cases, patients and their rheumatologists have to make the decisions about whether to transition to RA medications that are known to be safe during pregnancy, or to remain on their current medications.”

Leah Sera, PharmD, MA, BCPS, an associate professor and the vice chair of academic affairs in the Department of Practice, Sciences, and Health Outcomes Research at the University of Maryland School of Pharmacy, in Baltimore, agreed that some biologic medications are considered safe to use in pregnancy. “For instance, tumor necrosis factor-alpha inhibitors are considered ‘compatible with pregnancy,’ according to the American College of Rheumatology,” Dr. Sera said.

Healthcare providers should counsel patients about appropriate contraception since some drugs used to treat RA can cause birth defects or pregnancy loss, Dr. Sera said.

When pregnancy is planned, some drugs, including methotrexate and leflunomide, should be stopped several months prior to conception, and ideally, RA should be well controlled before conception to reduce the risk for complications. Uncontrolled RA can lead to complications such as low birth weight, preterm birth and preeclampsia, Dr. Sera said.

Managing RA should be addressed at all the stages of pregnancy, including preconception, when possible, according to Dr. Talabi. “I will often review figures and tables from the American College of Rheumatology Reproductive Health Guideline with patients to underscore key points about treatment and management during pregnancy and breastfeeding,” Dr. Talabi said.

Fertility and RA 

Dr. Talabi said some patients believe their RA will cause infertility, “which is not the case.” But because of widespread fear among people with RA, Dr. Talabi said she discusses those concerns with her patients and lets them know that it can be difficult for women with RA to conceive if their disease is highly active.

Although some medications aren’t safe for a pregnant woman with RA to take during conception, this doesn’t seem to be the case for men with RA, who should be able to continue most RA medications safely through conception. Sulfasalazine, however, may affect the counts and quality of sperm, so if a couple is having difficulty conceiving and the male partner is on the drug, he might want to discuss with his doctor temporarily discontinuing the medication, Dr. Talabi said. “Although some medications may theoretically impair male fertility, the American College of Rheumatology recommends that men with RA continue their medications in most situations,” Dr. Sera said.

“Well-controlled RA will reduce fatigue and joint pain and so may improve sexual health.”

Discussions should include maternal vaccinations such as influenza and COVID-19 to be received ahead of pregnancy, and which medications should be used during pregnancy and lactation. Dr. Talabi said she recommends starting prenatal vitamins at the point when women are thinking about becoming pregnant.

Dr. Talabi said a number of her patients have heard that RA goes into remission during pregnancy, and they will not require medication. “In actuality,” Dr. Talabi said, “remission is experienced by a minority of patients. I think as healthcare providers, we should express hope that the disease will go into remission, but also balance that with the reality that some women may experience symptoms during pregnancy that will benefit from treatment.”

At least half of women with RA will experience a flare within six months of delivery. Medications that are compatible with pregnancy are also generally compatible with breastfeeding, Dr. Talabi said.

“People with RA who have the best pregnancy outcomes appear to be more likely to have had well-controlled disease at the time they became pregnant and throughout pregnancy,” Dr. Talabi said. “In our research studies, sometimes women have understandably expressed concern that they need to stop treating their RA during pregnancy to prevent exposing their babies to potentially toxic medications. However, active inflammatory disease is also an exposure that can affect the health of a pregnancy and baby.”

Dr. Talabi said, if possible, women with RA who are planning to become pregnant meet with a maternal-fetal medicine specialist beforehand or when they first become pregnant for pre-pregnancy counseling, discussions about medication safety and to discuss low-dose aspirin to prevent preeclampsia, a risk for people with RA who are pregnant.

Patients often ask about the risk for women with RA giving birth to a baby with RA, and Drs. Talabi and Sera said there is not much information on the issue. “There is a genetic aspect to the development of RA;  however, it’s not the only factor that determines if a parent with RA will have a child who has RA.” According to the Arthritis Foundation, “while there’s a possibility that your child [can] develop RA or another autoimmune disease, it’s really important to remember that many women with autoimmune diseases have healthy babies who don’t develop arthritis or any other type of autoimmune disease,” Dr. Talabi said. 

Dr. Sera added: “Because genetics are a factor in the development of RA, children who have a parent with RA are at a higher risk of developing the disease themselves. However, environmental factors also play a role in determining whether those with a genetic predisposition will actually develop the disease.” These include obesity, smoking, infections and a person’s microbiome.