Controlling RA Flares During Pregnancy

Rheumatoid arthritis symptoms generally improve during pregnancy, but achieving and maintaining low disease activity for women who don’t experience spontaneous improvements during pregnancy can be challenging.

Physicians generally prefer to taper or stop medications during pregnancy because most women improve during pregnancy. However, some medications, such as prednisone, sulfasalazine and hydroxychloroquine (and increasingly TNF inhibitors), can be continued during pregnancy. But concerns persist.  Prednisone, for example, has been associated with shorter gestational age, gestational hypertension and diabetes, and premature rupture of the membranes, which most often occur during the third trimester.

Tapering medications can lead to disease flares, so in a study published in a November issue of Arthritis Care & Research, researchers attempted to determine which combination of clinical factors at the beginning of pregnancy are associated with low disease activity (DAS28-CRP3<3.2) and remission (DAS28-CRP3<2.6) in the third trimester.

The study was led by Radboud J.E.M. Dolhain, M.D., Ph.D., of Erasmus Medical Center, The Netherlands.

While spontaneous improvements occur during pregnancy in 40-70 percent of cases of women with rheumatoid arthritis, 16-27 percent of these women achieve remission and about 50 percent of them still have active disease in the third trimester, prospective studies show.

Because active maternal disease during pregnancy has been shown to correlate with adverse pregnancy outcomes, maintaining low disease activity is especially important.

Researchers found that a low disease activity score in the first trimester is associated with low disease activity or remission during the third trimester of pregnancy. The finding holds true, independent of autoantibody status or prednisone use during the first trimester.

Also, because tumor necrosis factor-inhibitors are transported to the fetus during the second and third trimester, discontinuation of tumor necrosis factor (TNF)-inhibitors after gestational week 20 is advised.

“It would be useful to identify those rheumatoid arthritis patients in whom medication can be tapered safely in the first trimester of pregnancy,” Dolhain et al. state.

The study, which included data on 190 pregnancies among 168 women with rheumatoid arthritis from first trimester to delivery, sought to identify the combination of clinical factors associated with low disease activity and remission in the third trimester of pregnancy. The data source was PARA (Pregnancy induced Amelioration of Rheumatoid Arthritis), a prospective cohort study.

Mean DAS28-CRP3 decreased from the first to the third trimesters, from 3.6(SD+/-1.2) to 3.3(SD+/-1.2). Thereafter, it increased to 3.5(SD+/-1.2) at 12 weeks postpartum (p=0.01) and was 3.4 at 26 weeks postpartum (p=0.03). Also, the percentage of patients with low disease activity (DAS28-CRP3 <3.2) increased from 40.5% in the first trimester to 50 percent in the third trimester, and the total number of patients in remission (DAS28-CRP3 <2.6) went up from 43 (22.6 percent) in the first trimester to 58 (30.5 percent) in the third trimester (p=0.03).

The analysis revealed three factors associated with low rheumatoid arthritis disease activity in the third trimester:  An initial low DAS28-CRP3, the absence of prednisone use and the absence of autoantibodies. The influence of other factors expected to be associated with rheumatoid arthritis disease course (sulfasalazine use in the first trimester, parity of the mother, methotrexate use in the past, presence of erosions and rheumatoid arthritis duration) did not reach statistical significance.

The results suggest that practitioners consider tapering medication in patients who are already in remission or who have low disease activity at the start of pregnancy, but even in those with higher disease activity - if they are not expressing auto-antibodies and not taking prednisone. Among those with moderate or high disease activity and are on prednisone or who express auto-antibodies, continuing medication throughout pregnancy, if possible, is advisable.

There were some limitations to the study:  Biologics were not used in this study; 42 percent of patients did not have a disease activity score; there was no significant difference between preconception DAS28-CRP3 and first trimester DAS28-CRP3 ; and, lowering or discontinuation of prednisone after the first trimester could cause an increased DAS28-CRP3 in the third trimester thereby leading to an association between prednisone use during first trimester and more disease activity during third trimester.

Offering more sound evidence-based recommendations would require a controlled trial with randomized tapering.

References:

Hilal Ince-Askan, Johanna M.W. Hazes, Radboud J.E.M. Dolhain. “Identifying clinical factors associated with low disease activity and remission of rheumatoid arthritis during pregnancy.” Arthritis Care & Research. Nov. 3, 2016. DOI 10.1002/acr.23143.