Scoping review of biosimilar disease-modifying antirheumatic drugs in pregnancy: evidence gaps and proposed outcome reporting framework.

Abstract

Biologic disease-modifying antirheumatic drugs (DMARDs) have revolutionized the management of autoimmune diseases. Biosimilar DMARDs have emerged as highly similar, cost-efficient alternatives; however, the scope of their perinatal evidence remains unexplored. We conducted a scoping review to synthesize evidence on the impact of biosimilar DMARDs on pregnancy outcomes. We searched Embase, MEDLINE and CENTRAL databases in November 2023 and June 2025. Inclusion criteria were studies examining biosimilar DMARD exposure for autoimmune diseases in mothers during pregnancy, fathers prior to conception and/or fetuses/neonates in-utero. Data were extracted on sample size, study design, drug exposure (timing, duration), and pregnancy outcomes. Patterns in methodologic reporting across studies were also analyzed. Overall, 6 studies (5 descriptive, 1 cohort study) were eligible for inclusion. Biosimilars examined were tumor necrosis factor inhibitors (infliximab, n = 4; etanercept, n = 2; adalimumab, n = 1) and B-cell inhibitors (rituximab, n = 1) among 63 mothers with inflammatory bowel disease, rheumatoid arthritis, or ankylosing spondylitis. Twenty-four fetal/neonatal (i.e., congenital anomaly), fetal/neonatal-maternal (i.e., Caesarean-section, spontaneous abortion), and maternal (i.e., disease flare) outcomes were reported. For methodologic reporting, we observed inconsistencies in exposure and outcome measures. To enhance comparability and standardization, we encourage the use of our Reproductive Health Outcomes Reporting Framework. Our scoping review is the first synthesis of perinatal evidence to date on biosimilar DMARDs. Critical gaps include an overall limited number of studies and a lack of analytical research that evaluate associations between exposures and outcomes. These findings highlight key evidence gaps in understanding the perinatal impacts of these emerging drugs.