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

Hanh Nguyen; Kawser Ahmed; Weike Luo; Julia Flint; Ian Giles

doi:10.1016/j.semarthrit.2021.09.004

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

Semin Arthritis Rheum. 2021 Dec;51(6):1205-1217. doi: 10.1016/j.semarthrit.2021.09.004. Epub 2021 Sep 16.

Authors

Hanh Nguyen¹, Kawser Ahmed², Weike Luo², Julia Flint², Ian Giles³

Affiliations

¹ Centre for Rheumatology Research, Rayne Institute, University College London (UCL), London, UK.
² University College London (UCL), London, UK.
³ Centre for Rheumatology Research, Rayne Institute, University College London (UCL), London, UK; Department of Rheumatology, University College London Hospital, London, UK. Electronic address: i.giles@ucl.ac.uk.

PMID: 34689007
DOI: 10.1016/j.semarthrit.2021.09.004

Abstract

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.

Keywords: Rheumatic disease; biologic; breastfeeding; disease modifying antirheumatic drugs; pregnancy; targeted synthetic drugs.

Publication types

Systematic Review

MeSH terms

Antirheumatic Agents* / adverse effects
Arthritis, Rheumatoid* / drug therapy
Biological Products* / therapeutic use
Child
Female
Humans
Male
Pregnancy
Rheumatic Diseases* / complications
Synthetic Drugs* / therapeutic use
Tumor Necrosis Factor Inhibitors / adverse effects

Substances

Antirheumatic Agents
Biological Products
Synthetic Drugs
Tumor Necrosis Factor Inhibitors