How to manage your pregnant patients with inflammatory RA

Charlotte, NC—Although managing rheumatoid arthritis (RA) in patients who are pregnant or trying to conceive may be challenging, rheumatologists should aim to improve disease activity and pregnancy outcomes, according to Megan E. B. Clowse, MD, MPH, Associate Professor of Medicine, Director, Duke Autoimmunity in Pregnancy Registry, Duke University Medical Center, at the North Carolina Regional Association 2014 annual meeting.

“I really have seen from both data and personal experience that stopping all medications in a rheumatoid arthritis patient when she wants to conceive is really the wrong thing to do,” Dr Clowse emphasized at the beginning of her talk. “What we see are patients flaring, not getting pregnant, and having a lot of difficulty during their pregnancies.” Treating these patients with prednisone when they flare after all medication has been stopped is not the best approach, she added.

Most patients with RA get better, Dr Clowse explained, citing previous research, with 77% of patients going into remission during pregnancy and 81% of patients relapsing during the first 3 months after delivery. “Patients who are on TNF [tumor necrosis factor]-inhibitors, stop them, and then get pregnant, are never doing as well as they did when they were on their TNF-inhibitor,” Dr Clowse added.

Does RA Activity Impact Pregnancy Outcomes?
Pregnancy outcomes in patients with RA are good overall, Dr Clowse stated, citing previously published data. In particular, the risk of preterm delivery increases approximately 30% in patients with RA, and preeclampsia is increased by approximately 75% in patients with RA compared with the general population. “But I think that what we need to determine is who is actually going to have those problems, as opposed to what the overall rates are,” Dr Clowse noted.

Growing evidence indicates that RA impacts pregnancy outcomes, she continued. In the Pregnancy-Induced Amelioration of Rheumatoid Arthritis study, 81 prospective pregnancies were evaluated. The investigators found that increased disease activity was associated with lower birth weight, and increased prednisone use was associated with shorter gestational age. Results from another study by Chakravarty and colleagues, which evaluated 42 retrospective pregnancies, found that there was no change in pregnancy outcomes with RA activity; patients who stopped taking their RA medication tended to have earlier delivery.

The Duke Autoimmunity in Pregnancy Registry, which was started in 2008, has approximately 230 patients with various rheumatic disorders. Overall, approximately half of the women included in the registry were diagnosed with systemic lupus erythematosus; other diagnoses included RA, other inflammatory arthritis, and Ro antibody-positive.

“What we found was that disease activity in the early part of pregnancy correlated highly with pregnancy outcomes,” Dr Clowse explained, citing results from the prospective cohort study. “In particular, with timing of the delivery.” All of the patients with preterm births had moderate-to-severe disease activity in the first and second trimesters compared with patients who delivered full-term. Only 1 patient who delivered full-term had moderate-to-severe disease activity, she noted.

Treating Pregnant Patients with RA
The goal is to improve RA activity and improve pregnancy outcomes, Dr Clowse stated.

Unfortunately, prednisone therapy has adverse events associated with its use, she explained. In particular, data have shown that prednisone is associated with a 3-fold increase in the occurrence of cleft lip or palate and long-term neurocognitive changes in the offspring of patients taking the drug. Increased preterm birth, preeclampsia, gestational diabetes, maternal hypertension, and excessive weight gain have also been observed.

“There are other really good options that I really want you to think about when a patient comes in and is sitting in front of you,” Dr Clowse continued. These include hydroxychloroquine and sulfasalazine. The former has some effect on mild arthritis and is a pregnancy Category C drug, with no human toxicity reports. The latter has shown good efficacy for peripheral arthritis and is a pregnancy Category B drug with a good safety profile in pregnancy.

Both methotrexate and leflunomide are classified as pregnancy Category X and are not good options for pregnant patients with RA. Data indicate a 25% to 50% risk for pregnancy loss and a 10% risk for congenital anomalies associated with methotrexate. Although human data are reassuring for the use of leflunomide, the pregnancy profile is terrible in animals. “I would certainly not recommend that anybody get pregnant on leflunomide, but I also would never recommend a termination, particularly without any evidence of anomalies,” she stated. If the patient’s obstetrician insists on a pregnancy termination, Dr Clowse suggested recommending the patient get a second opinion.

TNF inhibitors, as well as all antibodies, can transfer across the placenta and that transfer increases as patients get closer to term. If the patient is taking immunoglobulin-based med­ications, there will be a significant amount of transfer during the time of delivery, she explained. Taking a closer look at specific TNF inhibitors, infliximab and adalimumab levels are higher in the cord blood serum than in maternal serum levels, while etanercept and certolizumab levels are lower in the infant than they are in the mother.

Overall, the pregnancy outcomes of patients taking TNF inhibitors are not worrisome for the most part, according to Dr Clowse. Results from a 2009 review by Vinet and colleagues indicated that pregnancy outcomes are similar among pregnant patients taking TNF inhibitors and the general US population: live-birth rates (76%), miscarriage rate (13%), termination rate (11%), and rate of congenital abnormalities (3%).

“Infants who are exposed to TNF-inhibitors, particularly toward the end of term, may have immunosuppression,” Dr Clowse emphasized. “These babies should not get live vaccines in the first 5 months of life.” The only live vaccine given to infants before 1 year of age in the United States is rotavirus.

Investigators using data from the Duke Autoimmunity in Pregnancy Registry evaluated whether TNF-inhibitors may improve pregnancy outcomes in RA. Patients were divided based on the medication they were taking during the first trimester. Overall, 11 patients were taking prednisone, 7 were taking anti-TNF inhibitors, and 11 were taking neither drugs. Patients taking prednisone had a high level of disease activity, with 54.4% resulting in abnormal outcomes, and patients taking anti-TNF inhibitors also had a high level of disease activity, with 14.3% resulting in abnormal outcomes. Patients who did not take either drug, however, had a low level of disease activity and no abnormal outcomes.

Related Items

Subscribe to
Rheumatology Practice Management

Stay up to date with rheumatology news & updates by subscribing to receive the free RPM print publications or weekly e‑Newsletter.

I'd like to receive: