A 33-year-old female presents with a three-month history of a polyarthritis affecting her wrists, MCP and PIP joints in her hands, right knee and MTP joints.
Rheumatoid factor is raised at 38 (N<20) and anti-CCP antibody is also raised at 186 (N<5).
She is diagnosed with seropositive rheumatoid arthritis (RA) and started on weekly methotrexate and a tapering dose of prednisone. Her RA only partially responds to this, so sulfasalazine is added as a second DMARD.
Two years into treatment, she experiences a flare of her RA and she starts etanercept, a TNF inhibitor, given as a weekly subcutaneous injection. She responds very well and her arthritis goes into remission.
Now, at age 35, she wants to fall pregnant. At this time she is taking methotrexate and etanercept and her RA is well-controlled.
What considerations need to be taken into account with pregnancy and rheumatoid arthritis?
- Pregnancy and breastfeeding can be challenging for patients with RA and indeed any chronic disease. Plenty of time needs to be allocated to ensure the patient is fully informed and educated about the implications of both the disease and the treatment on the pregnancy, all the available management options and concerns addressed.
- Planning a pregnancy is very important. Medications may need to be adjusted and there may be a washout period for medications. The Australian Rheumatology Association has a regularly updated resource to help guide clinicians on the use of rheumatic medications in pregnancy.
- Fertility drops with uncontrolled RA so it is important to have well-controlled disease when trying to conceive.
- Poorly controlled RA has been linked to higher rates of miscarriage and adverse pregnancy outcomes. A healthy mother is important for a healthy baby.
- It is often advisable to stay on some (safe) medications rather than stopping all medications and risk a major RA flare.
- RA disease is usually less active in pregnancy. However, for some women the disease activity remains unchanged, and for an unfortunate few the disease activity increases. As an aside, disease control for psoriatic arthritis often improves in pregnancy but there are higher rates of flares for SLE and ankylosing spondylitis in pregnancy.
- The postpartum period is associated with a high rate of RA flares. It may be advisable to stay on (safe) medications over this time to minimise the risk, especially as a number of DMARDs take time to work.
- After consideration of these options, methotrexate is stopped three months prior to trying to fall pregnant (to allow adequate washout) and etanercept is continued.
The data on safety of TNF inhibitors is relatively reassuring in pregnancy.
Rubella serology had been checked prior to starting etanercept and IgG was strongly positive. This is important as the MMR (measles, mumps, rubella) is a live vaccine and cannot be given while on a biologic medication. If the IgG had been negative or low titre, the young female would have been vaccinated prior to starting the biologic.
SSA antibody was positive, a finding that can occur in RA and other autoimmune disease.
I generally test for both SSA and SSB antibodies in women with autoimmune disease, as these antibodies are associated with a small (about 1%) but significant risk of congenital heart block in the neonate. A positive finding requires close monitoring of the fetal heart rate at from week 16 to week 26, the critical developmental period of the cardiac conduction system.
She successfully falls pregnant but her RA worsens early in pregnancy. At 12 weeks gestation, sulfasalazine is restarted as this medication is safe in pregnancy. She continues on etanercept until week 32, at which time the biologic is stopped.
Stopping the etanercept at this time allows adequate washout of the biologic prior to delivery. If the baby is born prematurely, or if the etanercept is continued until close to delivery, there may be immunosuppression in the newborn, which can be an issue for the administration of live vaccines (particularly the rotavirus vaccine) as directed by the normal childhood vaccination schedule.
Her RA improves and she delivers a healthy baby boy at term. Three weeks postpartum, she has a major RA flare. Her hands and feet are extremely swollen, she is unable to look after her baby and can barely walk. At the time she is only taking sulfasalazine.
A decision is made not to breastfeed, mostly to enable her to treat her severe disease flare. Etanercept and methotrexate are subsequently restarted. She also requires moderate doses of prednisone to control her acute RA flare. If she had decided to continue breastfeeding, etanercept could be used (generally thought to be compatible with breastfeeding) but methotrexate would be contraindicated.
Eventually her RA stabilises and prednisone and sulfasalazine can be stopped. She remains on methotrexate and etanercept.
As this case demonstrates, managing pregnancy in chronic autoimmune illness can be challenging.
The known risks of each medication need to be balanced with the risk of poorly controlled disease adversely impacting maternal and pregnancy outcomes.
As more information is gathered on the safety of medications in pregnancy, rheumatologists can be more confident in continuing certain medications throughout pregnancy and breastfeeding.
Dr Andrew Jordan is a rheumatologist based in Parramatta, Sydney, with an interest in inflammatory arthritis, gout and osteoporosis