expert roundtables

Clinical Considerations in Managing Women With Rheumatoid Arthritis Before, During, and After Pregnancy

by Alan L. Epstein, MD, James O’Dell, MD, MACR, MACP, Vibeke Strand, MD, MACR, FACP

Overview

Rheumatoid arthritis (RA) disease activity can change during and after pregnancy. Stabilization of disease prior to pregnancy is an important goal. Potential safety concerns with treatment must be considered in anticipation of pregnancy, during gestation, and after pregnancy.

Q: What are the treatment- and nontreatment-related clinical considerations in managing women with RA before, during, and after pregnancy?

James O’Dell, MD, MACR, MACP

Stokes Shackleford Distinguished Professor
Chief, Division of Rheumatology and Vice Chair for Education, Department of Internal Medicine
Director, Internal Medicine Residency Program
University of Nebraska Medical Center
Founder and Director, Rheumatoid Arthritis Investigational Network
Omaha, NE

“I always want to know whether my patients with RA who are considering becoming pregnant are anti-Ro/SSA positive. If they are, we will counsel them differently about prenatal care due to the increased risk of congenital heart block.” 

James O’Dell, MD, MACR, MACP

One of the most important points to emphasize is that all women with RA should be tested for anti-Ro/SSA positivity. This issue is sometimes ignored. Anti-Ro/SSA is commonly present in Sjögren’s syndrome and systemic lupus erythematosus, but it is also seen in patients with RA. I always want to know whether my patients with RA who are considering becoming pregnant are anti-Ro/SSA positive. If they are, we will counsel them differently about prenatal care due to the increased risk of congenital heart block. With respect to medications during pregnancy, there are a few that must be avoided, especially methotrexate and leflunomide. If a woman has ever taken leflunomide, blood levels should be drawn to ensure that there are no circulating levels because the drug can persist in blood for a long time; in fact, levels have been documented up to 2 years after discontinuing leflunomide therapy. With respect to anti–tumor necrosis factor (anti-TNF) agents, I differ from some of my colleagues in that I am conservative with them during pregnancy, particularly during the third trimester. A paper recently published in Arthritis and Rheumatology examined the risk of serious infections in RA offspring exposed to anti-TNF agents during pregnancy (vs unexposed RA offspring or general population controls), finding a trend toward increased risk. Although this risk was not statistically significant in this study, the study was underpowered, and I think that most mothers would be alarmed by these findings. Because of these concerns, I will use anti-TNF agents sparingly or not at all in the third trimester.

Alan L. Epstein, MD

Clinical Professor of Medicine
University of Pennsylvania School of Medicine
Attending Physician and Chief of Rheumatology
Pennsylvania Hospital
Philadelphia, PA

“On average, there is some reduction in disease activity during pregnancy, but not every pregnant woman goes into remission.” 

Alan L. Epstein, MD

I am generally more conservative than many of my colleagues regarding treatment during pregnancy. I generally stop biologics when a female patient is pregnant, and then we discuss disease activity during pregnancy. Women frequently go into relative remission during pregnancy, but the issue is how much of a remission they achieve. On average, there is some reduction in disease activity during pregnancy, but not every pregnant woman goes into remission. I have had the good fortune of not needing to restart biologics in almost all of my pregnant patients with RA. Another important conversation to have with your pregnant patients surrounds their expectations about their functional ability in the future. Many new mothers are concerned about meeting the challenges of parenthood, for instance. In the prebiologic era, roughly 40% to 80% of all patients with RA were disabled at 10 years. With our much-improved therapeutic armamentarium, those numbers have dramatically improved, and we can now paint an optimistic picture for almost all of our patients—whether they are pregnant or not. Regarding treatment during breastfeeding, my historical approach has been that I am reluctant to initiate biologic therapy in the postpartum period to prevent disease flare until the mother has finished breastfeeding.

Vibeke Strand, MD, MACR, FACP

Adjunct Clinical Professor, Division of Immunology/Rheumatology
Stanford University School of Medicine
Biopharmaceutical Consultant
Palo Alto, CA

“For women of childbearing potential, I will sit down with them and try to plan a long-term treatment strategy before they become pregnant.” 

Vibeke Strand, MD, MACR, FACP

Regarding the risks of certain medications to the fetus, I generally agree. The risk from leflunomide might not be as great as perceived, but the drug should be avoided during pregnancy, and we can assay for maternal blood levels to ensure that there is no exposure to the developing child, in utero. For women of childbearing potential, I will sit down with them and try to plan a long-term treatment strategy before they become pregnant. As part of this strategy, you definitely want to get patients off of methotrexate. It is also important to remember that, although patients often experience disease remission during pregnancy, not every woman experiences an improvement in disease activity, and not everyone stays better, even in the third trimester. It can be difficult to watch a woman experience a relapse following birth after she had previously experienced improvement during pregnancy. Furthermore, active disease increases the risks for low birthweight infants and other adverse pregnancy outcomes.

In some ways, women and treating physicians are in a difficult situation when deciding whether to continue anti-TNF therapy during pregnancy. The risks of untreated disease during pregnancy are evaluated against the risks related to drug exposure to the mother and fetus. However, clinical trial data on the effects of drugs on pregnancy outcomes are sparse. Thus, I found the emerging pharmacovigilance data with certolizumab pegol particularly reassuring. I favor continuing therapy during pregnancy as needed so that the patient does not experience such sudden changes in disease activity. I try to make any treatment changes while the woman is still responding to therapy because, if she loses response, and that is what prompts the treatment switch, you will not get as good a result—no matter what you do. Continuing therapy during pregnancy can also allow you to spread out doses if the patient is doing well, but that does not mean that you actually stop the therapy.

References

Clowse MEB, Scheuerle AE, Chambers C, et al. Pregnancy outcomes after exposure to certolizumab pegol: updated results from a pharmacovigilance safety database. Arthritis Rheumatol. 2018;70(9):1399-1407.

Desai RJ, Bateman BT, Huybrechts KF, et al. Risk of serious infections associated with use of immunosuppressive agents in pregnant women with autoimmune inflammatory conditions: cohort study. BMJ. 2017;356:j895.

Flint J, Panchal S, Hurrell A, et al; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford). 2016;55(9):1693-1697.

Götestam Skorpen C, Lydersen S, Gilboe IM, et al. Women with systemic lupus erythematosus get pregnant more easily than women with rheumatoid arthritis. Rheumatology (Oxford). 2018;57(6):1072-1079.

Jones PB, White DH. Reappraisal of the clinical use of leflunomide in rheumatoid arthritis and psoriatic arthritis. Open Access Rheumatol. 2010;2:53-71.

Smith CJF, Förger F, Bandoli G, Chambers CD. Factors associated with preterm delivery among women with rheumatoid arthritis and juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2018 Aug 21. doi: 10.1002/acr.23730. [Epub ahead of print]

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