Background/Purpose: Ustekinumab, an IL-12/23 inhibitor, is indicated in adult patients with inflammatory bowel disease (IBD), psoriasis (PsO), and psoriatic arthritis (PsA) and vedolizumab, an α₄β₇ receptor antagonist is indicated in IBD only. Both are monoclonal antibodies harbouring an Fc portion, which are actively transported across the placenta, often reaching higher fetal than maternal levels. As fetuses could be exposed to therapeutic or supra-therapeutic levels of these drugs, there are concerns that these agents could cause immunosuppression after birth. However, evidence is lacking.

We compared the risk of serious infections in offspring exposed to ustekinumab, vedolizumab, tumour necrosis factor inhibitors (TNFi), and non-biologic immunosupressives versus offspring unexposed during pregnancy among women with IBD, PsO and/or PsA.

Methods: We conducted a retrospective cohort study using the US MarketScan database, an employment insurance database. We included live births (01/2011-12/2018) among women with PsO, PsA, and/or IBD. Drug exposure was defined as ≥1 filled prescription or infusion procedure code during pregnancy. In offspring, we evaluated serious infections within the first year of life as any single inpatient infection code. We performed multivariate analyses using logistic regression, adjusting for maternal age, co-morbidities, corticosteroid use, concomitant drug use, preterm birth and disease state.

Results: We included 16,115 offspring born to 7,612 women with PsO/PsA, 8,315 with IBD, and 188 with PsO/PsA and IBD. A total of 52 offspring were exposed to ustekinumab, 43 to vedolizumab (including 7 to both TNFi and vedolizumab),1,585 to TNFi, 1,857 to non-biologic immunosuppressives alone, and 12,585 unexposed to any drug. The percentage of serious infections in offspring exposed to ustekinumab was 3.8% (95% CI 0.4-13.9), versus 2.7% (95% CI 1.9-3.6) for TNFi, 2.3% (95% CI 0.4-12.0) for vedolizumab and 2.6 (95% CI 2.3-2.8) for those unexposed to any drug, though all estimates had wide, overlapping confidence intervals. Compared to children unexposed to any drug, there was a potential trend for increased risk with ustekinumab (OR 1.6, 0.4-6.8), but CIs were wide and included the null. For those exposed to vedolizumab (OR 0.9, 0.1-6.2) or TNFi (OR 1.0, 0.6-1.4) there was no clear excess risk.

Conclusion: In a large cohort, we did not detect a clear excess risk for offspring exposed in-utero to, vedolizumab or anti-TNF’s, compared to unexposed patients; there was a signal for more events with ustekinumab, but confidence intervals were wide. Ongoing caution, as well as more research on short and long-term effects, is warranted for biologics actively transported across the placenta.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-of-serious-infections-in-offspring-exposed-in-utero-to-ustekinumab-or-vedolizumab/