Few serious infections in offspring with exposure to non-TNFi biologics or tofacitinib

In utero contact with the small molecule tofacitinib or new non-TNF inhibitor (TNFi) biologics through treatment of their mothers was associated with low rates of serious infection in babies [1].

Drug-induced immunosuppression due to (supra-)therapeutic levels of biologics and small molecules in offspring of mothers treated for chronic inflammatory diseases is a major concern. It is known that TNFi and other biologics can pass the placenta. Whether or not small molecules have the same potential has been suggested but is not yet clear.

Dr Evelyne Vinet (McGill University, Montreal, Canada), lead author of this cohort study, compared the risk of serious infections in children whose mothers had chronic inflammatory diseases and were treated with tofacitinib, TNFi, and non-TNFi biologics (e.g. abatacept, rituximab, tocilizumab, ustekinumab, vedolizumab) during pregnancy. “Our overarching goal is to provide pregnancy safety data on new biologic and small molecule drugs used to treat women with inflammatory arthritis. These conditions predominantly affect women, particularly during their childbearing years. In pregnant women with inflammatory arthritis, flares are common and associated with adverse pregnancy outcomes. Disease control with effective drugs is often warranted,” Dr Vinet pointed out. Study subjects were identified using the MarketScan database information from 2011-2016. Serious infections were defined by ≥1 hospitalisation with infection as a primary diagnosis, during the first year from birth.

Data of 16,490 children of mothers with chronic inflammatory disease was included. Distribution of maternal diagnoses was: 4,142 rheumatoid arthritis, 381 ankylosing spondylitis, 5,743 psoriasis/psoriatic arthritis, and 6,731 inflammatory bowel diseases. Controls consisted of matched mothers and their 164,553 babies. “In total, 1,611 children had in utero exposure to TNFi and 105 to non-TNFi biologics or tofacitinib.

Within the latter group, 2 cases of serious infections were observed (1.9%): 1 case with exposure to tofacitinib and 1 with exposure to abatacept. Offspring of mothers treated with TNFi during pregnancy had a rate of 2.3% for serious infections, while the percentage for children of mothers with inflammatory disease but without TNFi therapy was 2.1%. Serious infections happened to babies of unaffected mothers at a rate of 1.6%. So, infections were rare in the offspring exposed. “We provide the first data on infectious risk in this population,” commented Dr Vinet.” This is a first step, as we need more data to confirm safety, particularly regarding other pregnancy outcomes. It is imperative that we further study this issue to provide firm evidence to guide treatment decisions prior to conception and throughout pregnancy,” she concluded.

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   1. Vinet E, et al. Abstract 1901. ACR 2019. 8-13 November, Atlanta (GA/USA).

 



Posted on 4 February, 202016 February, 2024