Background Optimized pharmaceutical treatment during pregnancy remains a challenge in women with rheumatoid arthritis (RA), mainly due to safety concerns. TNF inhibitors (TNFi) are nowadays routinely used in patients (pat.) intending to become pregnant. Nevertheless it is recommended to discontinue TNFi as soon as pregnancy is recognized. Thus far, prospective data on the risk of flares during pregnancy in this patient population are lacking.
Objectives We compared the frequency of RA flares in pregnancies in women discontinuing TNFi at conception with pregnancies in women treated with conventional drugs.
Methods Pat. from a prospective pregnancy registry were evaluated before conception and during each trimester. Clinical characteristics, disease activity (DAS28-CRP), medication use, and pregnancy outcome were analyzed. A flare was defined as increase in clinical activity leading to intensified therapy with at least one of: new prednisolone, increase in dosage ≥5 mg/day, treatment with i.a. glucocorticoids, (re-)treatment with DMARDS/TNFi. We applied a multivariate logistic regression model to assess the association between the use of TNFi at conception and the occurrence of flares during pregnancy. Adjustment for potential confounders was performed using logistic regression.
Results A total of 46 RA-pregnancies were enrolled. Four pregnancies ended with early miscarriages. Eighteen of the remaining 42 pregnancies occurred in pat. with TNFi at conception (TNFi-G), 24 in pat. treated with conventional drugs (CO-G). We observed at least one flare in 18 pregnancies (67% [TNFi-G] vs. 17% [CO-G]). After shared decision, 5 pat. restarted therapy with TNFi during pregnancy. Use of TNFi at conception was significantly associated with flares during pregnancy (OR 8.2, 95% CI 2.1-33.2, p=0.003). The strength of association was nearly constant after adjusting for age, RF, CCP, previous joint surgery, DAS28 at conception, use/dosage of prednisolone during pregnancy. Twelve of 42 (28.5%) live births were accompanied by complications (10 preterm deliveries, 2 preeclampsia). 70% of preterm births occurred in pat. with a flare during pregnancy. Cumulative prednisolone doses throughout pregnancy were significantly associated with prematurity (p 0.04).
Conclusions Women with RA who discontinue TNFi at conception face a significant higher risk for flares during pregnancy compared to conventional treated ones. Pregnancies with a flare and increased use of prednisolone have a higher risk of ensuing complications. To avoid flares and additional need of steroids the paradigm of suspending TNFi when RA patients get pregnant may need to be reconsidered. Bridging the control of RA activity with medications considered relatively safe in pregnancy, we may be able to improve both, the pregnancy experience and pregnancy outcomes.
Disclosure of Interest None declared