A Systematic Review of the safety of non-TNF inhibitor biologic and targeted synthetic drugs in rheumatic disease in pregnancy.

Introduction: Despite increasing evidence to support safe use of tumour necrosis factor inhibitors (TNFi) and other biologic disease modifying anti-rheumatic drugs (bDMARDs) during pre-conception/pregnancy, there remains a paucity of evidence regarding the safety and compatibility of other non-TNFi and novel targeted synthetic (ts)DMARDs during pre-conception/pregnancy. Therefore, we conducted a systematic review to determine the compatibility of these drugs in pre-conception, during pregnancy and post-partum period. Method: Databases including; EMBASE, Pubmed (MEDLINE), and Cochrane were searched up to 23rd October 2020 to find relevant peer-reviewed papers, using keywords including; rheumatic disease, pregnancy, conception/pre-conception, lactation/breastfeeding, childhood and vaccination/infection, and commonly prescribed non-TNFi drugs and tsDMARDs.

Results: Our search yielded 1483 papers that were screened independently by two authors, and 109 full-text papers were eligible for final analysis. These studies reported 1291 maternal pregnancies exposed to non-TNFi bDMARDs and tsDMARDs with known outcomes, including 721 live births, 219 spontaneous miscarriages and 27 congenital abnormalities. Paternal exposures in 174 pregnancies had reassuring outcomes. A total of 48 breastfed infants were exposed to non-TNFi bDMARDs and no adverse events reported upon long-term follow-up. Fifteen infants exposed to bDMARDs received normal vaccination regimes, including live vaccines, and had normal developmental outcomes, without any complications or infections.

Conclusion: Overall, the findings are reassuring and do not suggest a cause for any major concerns or an increased risk of adverse pregnancy outcomes for maternal or paternal exposures to non-TNFi bDMARDs or tsDMARDs. There were no major concerns for breastfeeding exposures to non-TNFi bDMARDs.