Background/Purpose:  Despite the high incidence of rheumatic diseases during reproductive years, little is known about the perinatal impact of traditional and biologic disease modifying antirheumatic drugs (DMARDs). Systematic reviews of the evidence, which are widely based on case reports and cross-sectional studies, are scarce; only one exists on the use of methotrexate in pregnancy. Our objective was to systematically review the evidence on the perinatal use of traditional and biologic DMARDs on congenital malformation outcomes in babies born to women with rheumatic diseases. 

Methods:  We conducted a systematic search of MEDLINE (1946-), EMBASE (1974-), and INTERNATIONAL PHARMACEUTICAL ABSTRACTS (1970-) databases for peer-reviewed articles. Inclusion criteria were: 1) study sample that included women with rheumatic disease; 2) use of traditional and/or biologic DMARDs during pregnancy; and 3) congenital malformation outcome(s) reported. To ensure wide capture, we did not set limits on study design. We extracted information on study design, data source, number of exposed pregnancies, type of DMARD, type of exposure (single DMARD or combination), number of live births, and number of congenital malformations reported. While not the focus of our review, we extracted data on other perinatal outcomes in live births including prematurity and birthweight.

Results:  We identified 1,141 articles and report on 53 that met eligibility criteria.  We divided studies according to those with no unexposed comparison groups (case report [21], case series [17], cross-sectional [5], and surveys [3]) and observational studies and trials with unexposed comparators (cohort study [6] and controlled trial [1]). With respect to the former group, most studies reported primarily on single DMARD exposures with cyclophosphamide and methotrexate most widely studied among traditional DMARDs and etanercept and adalimumab among biologics. For traditional DMARDs, eligible studies reported 176 pregnancies among women with rheumatic diseases, 134 live births, and 12 malformations. For biologics, eligible studies included 11 pregnancies with rheumatic disease, 11 live births, and 1 malformation. Studies that included a comparator group were limited to traditional DMARDs, namely hydroxychloroquine, and report no differences between groups. Overall, data on DMARDs and congenital malformations are largely limited, particularly with biologics. We also identified the need for better reporting in terms of identifying patients with rheumatic disease, directly attributing medication exposures to patients, and delineating timing of medication use to pregnancy course.

Conclusion:  This is the first systematic review on the use of both traditional and biologic DMARDs during pregnancy among women with rheumatic diseases, with focus on congenital malformations. Findings confirm the limited number of studies in this area. As controlled trials in this patient population are unlikely, systematic reporting and reviewing of medication exposures and perinatal outcomes provides a valuable resource for synthesizing evidence on the use of DMARDs among women with rheumatic diseases during pregnancy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/perinatal-exposure-to-traditional-and-biologic-disease-modifying-antirheumatic-drugs-in-rheumatic-diseases-a-systematic-review-of-congenital-outcomes/