Active RA in pregnancy is associated with numerous negative outcomes including pre-term delivery, caesarean section and pre-eclampsia
Rheumatoid arthritis (RA) is an immune mediated inflammatory disease causing significant disability, morbidity and mortality. RA affects women three times more often than men, commonly in their childbearing years. Managing RA in the periconceptual period poses a challenge. The primary goal for all is a healthy mother and baby.
The British Society for Rheumatology (BSR) and British Health Professionals in Rheumatology (BHPR) have published recent recommendations on management of RA in pregnancy and this forms the basis of our approach.
Active RA in pregnancy is associated with numerous negative outcomes including pre-term delivery, caesarean section and pre-eclampsia. Thankfully, outcomes for women with well-controlled RA are comparable to the general population. The majority of patients have a normal vaginal delivery of a healthy baby.
Before pregnancy, the key aim is to establish stable remission on medications that are safe in pregnancy. A washout period is required for teratogenic medications (for example methotrexate – three months and leflunomide – two years*). Clinicians should enquire about family planning at every consultation. This allows patients to discuss any plans for conception or concerns.
Preconception risk assessment and counseling should be performed in every woman with autoimmune disease. This is the opportune time to alter treatment if required and to refer to maternal medicine, preferably in a combined clinic.
Pregnancy itself may reduce RA disease activity. A recent study suggested a remission rate of 48 per cent, although the mechanism is unclear, one theory is down to regulation of the maternal immune system in the presence of the fetus.
The postpartum period can be difficult. The patient and their partner and/or family should understand there is an increased rate of disease flare. A 2008 study showed a deterioration in RA control in 39 per cent of patients postpartum. There is also the additional strain of caring for an infant. Medication safety with lactation is another consideration.
Anti-Rheumatic Medications in Pregnancy
The Food and Drug Administration (FDA) does not classify any disease modifying agents in rheumatic disease (DMARDs) as category A (no risk in controlled human studies). However, there are a number of medications which are category B (no risk in animal studies) and class C (potential benefits may warrant use of the drug in pregnant women despite potential risks).
Methotrexate and leflunomide are class X and completely contra-indicated in pregnancy and require wash out periods outlined above. We should carefully consider the use of teratogenic agents in women of childbearing age. It is important to stress to women on these medications the importance of adequate contraception during any period of use and the washout period.
There is increasing use of biologic agents during pregnancy, as there is little evidence of adverse effects. Differing timelines for these agents are suggested in the BSR guidelines. Certolizumab pegol can be used throughout pregnancy and has reduced placental transfer compared to the other agents. Infliximab may be continued until 16 weeks. Etanercept and adalimumab may be continued until the end of the second trimester. Golimumab is unlikely to be harmful in the first trimester. If these drugs are continued later in pregnancy, then live vaccines should be avoided in the infant until 7 months of age.
MTX, methotrexate; HCQ, hydroxychloroquine; SSZ, sulfasalazine (with 5 mg folic acid); TNF, tumour necrosis factor; NSAIDs, Non steroidal anti-inflammatory drugs
There is an increased demand from RA patients for information and advice regarding treatment in and around pregnancy with an increasing number of relatively safe therapeutic options for both RA disease control and assisted fertility. It is therefore hoped we will soon commence a combined clinic with the National Maternity Hospital, Holles Street and are looking forward to innovation in this area of maternal medicine and rheumatology.
*Cholestyramine or activated charcoal can be used for rapid drug elimination of leflunomide.