Plan Ahead: Clinical Tips for Managing Reproductive Health in Patients with Rheumatic Disease

SINGAPORE—Most autoimmune diseases are more prevalent in women than men, and many female patients are of child-bearing age. Thus, it’s incumbent upon rheumatologists to discuss family planning with patients early and often.

At the 2024 Asia-Pacific League of Associations for Rheumatology (APLAR) Congress, May Ching Soh, MBChB, FRACP, head of the Department of Obstetric Medicine, Te Whatu Ora Counties Manukau, University of Auckland, New Zealand, gave an excellent lecture titled, Practical Tips for the Rheumatologist Dealing with Pregnant Patients.

Dr. Soh is both a rheumatologist and an obstetrician/gynecologist at the largest maternity unit in New Zealand. She has a wealth of experience in treating patients with rheumatic conditions, who often have multiple medical comorbidities.

Plan Ahead

Dr. Soh

Dr. Soh described why it’s important for rheumatologists to think about issues related to possible pregnancy in patients. These issues include the potential complex effects of autoimmune diseases and rheumatologic medications on the mother and fetus, the widely shared goal of helping patients plan for pregnancy when their disease is stable, the ever-present risk of disease flares during and after pregnancy, and the desire to care for patients holistically.

Dr. Soh said that one of the most joyous parts of her practice is helping a patient have a healthy and successful pregnancy as they seek to start or grow their family. She recommends discussing pregnancy planning with patients at the time of diagnosis because many rheumatic diseases affect fertility and pregnancy outcomes, as well as when medications are started or changing and when the patient’s disease is active.

Regarding medications used to treat rheumatic diseases, Dr. Soh noted that it’s important to avoid teratogenic medications during the first 12 weeks of pregnancy. This trimester is when clinical aspects of organogenesis of the fetus occur. Guidelines from major rheumatology organizations, such as the 2020 ACR guideline, can help steer providers in selecting or avoiding specific conventional, biologic and/or targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) based on their safety profiles in the context of pregnancy and breastfeeding.¹

Something rheumatologists may not know is that after 28 weeks’ gestation non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors should be avoided due to their associations with an increased risk of prenatal closure of the ductus arteriosus and the development of oligohydramnios.

Real-Life Scenarios

Dr. Soh highlighted several cases that illustrate the real-life management of reproductive issues in patients planning for conception or currently pregnant.

For a young woman with active seropositive, erosive rheumatoid arthritis who is planning to have children, it’s essential to ask when the pregnancy is desired. When Dr. Soh asks patients this question, she is frequently surprised to learn that the timeframe the patient has in mind is over the subsequent two to three years. This may provide a window of opportunity to quickly escalate therapy, treating the disease aggressively and then allowing for a period of drug washout prior to an intended pregnancy after the disease is stable.

In a second case, a young woman with previously well-controlled axial spondyloarthritis on NSAID therapy alone became wheelchair-bound due to acute worsening of back pain in her first trimester of pregnancy. Treatments beyond acetaminophen—or paracetamol, which is used in New Zealand—ought to be strongly considered. These treatments can and should include tumor necrosis factor (TNF) alpha (α) inhibitors and secukinumab.

Biologic Therapy

Dr. Soh expanded on the topic of biologic therapy in pregnancy and its possible effects on the fetus. She explained that fetal immunoglobulin G1 (IgG1) levels reach 50% that of maternal levels between 28 and 32 weeks of gestation. These levels increase exponentially thereafter because there is maximal placental immunoglobulin transfer from mother to baby in the final four weeks before delivery.²

Cord blood levels of biologic medications have been studied and depend on several factors:

• The point in gestation when the drug was used (i.e., the later in pregnancy, the higher the level);
• The structure of the Fc receptor because medications lacking an Fc portion, such as certolizumab, are less efficiently transported across the placenta; and
• The half-life of the drug because the longer its half-life, the more likely there will be placental transfer.³

One reason to be cautious with biologics during pregnancy is because of the potential for the fetus to develop immunosuppression. Such immunosuppression may have practical implications, including the risk of infection for the fetus in utero or after delivery.

Dr. Soh said that, in newborns with in utero biologic medication exposure, live vaccines should be avoided for the first six to eight months of life. The only potential exceptions are rotavirus vaccination and Bacillus Calmette-Guérin vaccination in newborns not exposed to TNF inhibitors.

Dr. Soh said that one of the most joyous parts of her practice is to help a patient have a healthy & successful pregnancy as they seek to start or grow their family.

Lupus Nephritis & Preeclampsia

Next, Dr. Soh discussed the challenging topic of differentiating lupus nephritis from preeclampsia in pregnant patients with systemic lupus erythematosus. Both lupus nephritis and preeclampsia can be associated with hypertension, proteinuria and many other similar clinical manifestations, and interpretation of lab studies can be confusing.

Example: Complement levels in active lupus nephritis may appear spuriously normal in patients who are pregnant. One lab test used to help differentiate lupus nephritis from preeclampsia is the soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio. This test has a high negative predictive value, and if the ratio of sFlt-1:PlGF is <38, then preeclampsia is effectively ruled out for the subsequent seven days. (Note: In the development cohort looking at this test, the negative predictive value using this threshold was 99.3%.)⁴

In cases in which lupus nephritis is confirmed in pregnancy, cyclophosphamide can be used after 12 weeks of gestation. In contrast, Dr. Soh cautions against using mycophenolate in the treatment of lupus nephritis during pregnancy because significant safety issues may be associated with its use.

The timing of delivery for patients with possible preeclampsia is important. Considerations to make regarding this decision include the presence or absence of worsening hypertension, rising creatinine levels and/or static growth of the fetus.

In Sum

As one member of the audience stated in the question-and-answer portion of the session, this area is an important topic, and it’s crucial for rheumatologists to work together with maternal fetal medicine physicians and other women’s health providers to ensure optimal care for patients.

Jason Liebowitz, MD, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.

References

1. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020 Apr;72(4):529–556.
2. Saji F, Samejima Y, Kamiura S, et al. Dynamics of immunoglobulins at the feto-maternal interface. Rev Reprod. 1999 May;4(2):81–89.
3. Soh MC, Moretto M. The use of biologics for autoimmune rheumatic diseases in fertility and pregnancy. Obstet Med. 2020 Mar; 13(1): 5–13.
4. Zeisler H, Llurba E, Chantraine F, et al. Predictive value of sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016 Jan 7;374(1):13–22.