Maternal use of non-TNF inhibitor biologic, tofacitinib pose minimal infectious risk to offspring
ATLANTA — The use of either non-TNF inhibitor biologics or tofacitinib for chronic inflammatory diseases during pregnancy did not significantly increase risk for serious infections among infants, according to findings presented at the 2019 ACR/ARP Annual Meeting.
“Infants could be exposed to therapeutic and potentially supratherapeutic levels of biologic and small-molecule drugs during pregnancy, leading to concerns that these agents could cause immunosuppression and, therefore, serious infection in offspring,” Evelyne Vinet, MD, PhD, associate professor of rheumatology and clinical epidemiology at McGill University in Montreal, said during a press conference. “[However] data on serious infections in offspring exposed to non-TNF inhibitors and small-molecule [drugs] are lacking, because pregnant women are routinely excluded from clinical trials.”
She added, “The goal of our study was to address this important knowledge gap and to compare the risk of serious infection born to mothers with chronic inflammatory diseases who used non-TNF inhibitor biologic or small-molecules during pregnancy vs. offspring exposed to TNF inhibitors as well as unexposed offspring.”
To determine whether the use of these agents during pregnancy could inhibit postnatal immune function among infants and increase risk for infection, Vinet and colleagues analyzed the MarketScan database to identify a cohort of women with one or more hospitalizations for delivery following a diagnosis of rheumatoid arthritis (n = 4,142), ankylosing spondylitis (n = 381), psoriasis or psoriatic arthritis (n = 5,743), or inflammatory bowel diseases (n = 6,731). In addition, the researchers compiled a randomly selected group of unaffected mothers (n=164,553), matched 4:1 for age, year of delivery and state of residence.
Vinet and colleagues defined exposure to tofacitinib (Xeljanz, Pfizer), TNF inhibitors and non-TNF inhibitor biologics — including abatacept (Orencia, Bristol Myers Squibb), rituximab (Rituxan, Genentech) tocilizumab (Actemra, Genentech), ustekinumab (Stelara, Janssen) and vedolizumab (Entyvio, Takeda) — based on at least one filled prescription and/or infusion procedure code during pregnancy and/or the preconception period. The researchers then established serious infections in offspring based on at least one hospitalization with infection within the first year of life; exposure groups were categorized according to maternal demographics, comorbidities, disease type, pregnancy complications and type of drug use.
According to study results, among pregnant women with inflammatory disease, 105 children were exposed to tofacitinib (n = 4) or non-TNF inhibitor biologics — including abatacept (n = 33), rituximab (n = 4), tocilizumab (n = 12), ustekinumab (n = 42) and vedolizumab (n = 10) — and 1,611 were exposed to TNF inhibitors during pregnancy. Vinet and colleagues found two cases of serious infections among children exposed to tofacitinib and abatacept.
Serious infections were reported in only 2.3% of children born to women with inflammatory diseases who were treated with TNF inhibitors (95% CI 1.9-2.3), compared with 2.1% among children born to women with inflammatory diseases not treated with TNF inhibitors (95% CI 1.6-3), and 1.6% of children whose mothers had no chronic diseases (95% CI 1.6-1.7).
“In our large cohort, we detected very few cases of serious infection in children exposed to non-TNF inhibitors or tofacitinib,” Vinet said. “This will help guide clinicians consult women with chronic inflammatory disease who need treatment during pregnancy, and should also help inform best practice guidelines for use during pregnancy in rheumatic disease.” – by Robert Stott
Vinet E. Abstract #1901. Serious infections in offspring exposed in utero to non-TNFi biologics and tofacitinib. Presented at ACR/ARP Annual Meeting, Nov. 8-13, 2019; Atlanta.
Disclosure: Vinet reports no relevant financial disclosures.