Modified treat-to-target approach paves road to LDA, remission in RA during pregnancy

Low disease activity (LDA) and remission in women with rheumatoid arthritis (RA) can be easily achieved during pregnancy with the help of a modified treat-to-target (T2T) approach that incorporates the use of tumour necrosis factor inhibitors (TNFIs), as shown in the PreCARA* study.

“Until recently, rheumatologists assumed that almost all patients with RA reach a state of remission during pregnancy independent of treatment; however, more literature shows that over half of the patients still has active disease during pregnancy,” according to the investigators. [Semin Arthritis Rheum 2019;49:S32-35; Arthritis Rheum 2008;59:1241-1248; J Rheumatol 2019;46:245-250]

“Our results show that entering pregnancy in LDA or remission, as advised by the American College of Rheumatology (ACR) guidelines, is attainable when applying T2T,” they said.

A vast majority of the PreCARA population was in LDA at their last visit before pregnancy, same as during pregnancy and postpartum, indicating that T2T and an immediate restart of medication after delivery could prevent an increase in disease activity postpartum, the investigators added.

In accordance with the T2T protocol, the patients had been initiated on sulfasalazine and/or hydroxychloroquine prior to pregnancy. This was followed by prednisone (preferably in a maximum daily dosage of 7.5 mg) and/or a TNFI, preferably certolizumab pegol.

Patients could conceive while on TNFI, which was stopped at the gestational age as advised by the European League Against Rheumatism (EULAR). A switch to certolizumab pegol or prednisone was considered. [Ann Rheum Dis 2016;75:795-810]

The analysis included 309 female patients with RA, from whom 188 children were born. A total of 87 (47.3 percent) women used a TNFI at any time during pregnancy. The median gestational week when treatment was discontinued was 15.3 weeks for infliximab, 18.4 weeks for adalimumab, 23.4 weeks for etanercept, and 35.6 weeks for certolizumab pegol.

Among patients who used TNFIs in the third trimester of pregnancy (n=56), 62.5 percent, 46.4 percent, and 35.7 percent concomitantly used sulfasalazine, hydroxychloroquine, and prednisone, respectively.

The number of patients in LDA or remission rose from 75.4 percent prior to conception to 90.4 percent in the third trimester of pregnancy. These numbers were much higher in comparison with the reference PARA** cohort (treated according to the standards of that time [2002–2010]), going from 33.2 percent to 47.3 percent. Accordingly, mean disease activity over time was lower in the PreCARA cohort than in the reference cohort (p<0.001). [Ann Rheum Dis 2021;doi:10.1136/annrheumdis-2020-219547]

“Half of the patients in our study were able to get in LDA or remission using only conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or prednisone. In a large percentage of the patients, csDMARDs were prescribed in combination,” according to the investigators.

“We showed that TNF inhibitors were efficacious during pregnancy, no significant difference in disease activity over time between patients that used a TNF inhibitor during pregnancy and patients who used csDMARDs were observed,” they added.

It clearly indicates that physicians can differentiate between pregnant patients who have stable enough disease to allow discontinuation of TNF inhibitors and pregnant patients who, despite having LDA, require a switch in medication during pregnancy to prevent an increase in disease activity, the investigators pointed out. Hence, the present data should not be interpreted as if TNFIs can be stopped during pregnancy without a higher risk of increase in disease activity.

The investigators called for the application of a T2T approach in clinical practice, including prescription of TNFIs in all patients who are planning to conceive and are already pregnant. “We advise pregnancy counselling and regular visits during pregnancy and postpartum, [as this should facilitate] improved disease outcomes like we observed in our study.”

The study was limited by the comparison of the results with that of a historic cohort, which was slightly different compared with the current patient population. There is also a possible selection bias, given that “the study was performed in one tertiary referral centre, which could have resulted in an over-representation of patients with more severe disease.”

*Preconception Counseling in Active RA

**Pregnancy-induced Amelioration of Rheumatoid Arthritis