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.