Safety of ustekinumab vs anti-TNF, immunomodulators, or no immunosuppressive therapy during pregnancy in IBD: DUMBO Registry

Abstract

Background Introduction: Although ustekinumab is generally considered a low-risk therapy during pregnancy, its impact compared with other treatment options for inflammatory bowel disease (IBD) has been scarcely investigated.

Aim To provide updated safety data on ustekinumab exposure during pregnancy in women with IBD, compared with those treated with anti-TNF agents, immunomodulators, or with no immunosuppressive exposure.

Methods Pregnant women with IBD enrolled in DUMBO Registry were classified into four exposure groups: mesalamine/no treatment (G1), immunosuppressants/steroids (G2), anti-TNF agents (G3), and ustekinumab (G4). DUMBO is a prospective, observational, and multicentre registry, endorsed by GETECCU, in which pregnant women with IBD have been enrolled over 5 years at 62 centres in Spain (figure 1). The primary outcome was the occurrence of serious adverse events (SAEs) in mothers or infants up to 7 days after delivery. To assess the effect of ustekinumab exposure, a logistic regression model weighted by inverse probability of treatment weighting (IPTW) was performed to adjust for confounding factors.

Results 1,060 patients were included, 100 of them under ustekinumab (table 1). A total of 80 patients (24%) under anti-TNF agents and 26 (26%) under ustekinumab interrupted the treatment during pregnancy, being elective discontinuation the main reason in both groups. SAEs were reported in 346 pregnancies (33%), occurring either during pregnancy or in the neonatal period: 115 (30%) in G1, 88 (35%) in G2, 114 (35%) in G3 and 29 (29%) in G4. SAEs registered during pregnancy and in the neonatal period are summarized in table 2. After adjustment (using IPTW for maternal age at conception, previous pregnancy complications, IBD type, baseline disease activity, baseline body mass index, smoking status, and prior IBD surgery), Crohn’s disease was associated with a lower risk of SAEs compared with ulcerative colitis (OR 0.86; 95% CI 0.74–0.99). However, ustekinumab treatment was not associated with an increased risk of SAEs compared with other groups: mesalazine/no treatment vs ustekinumab (OR 0.88; 95% CI 0.71–1.09), immunosuppressants vs ustekinumab (OR 1.04; 95% CI 0.84–1.29), and anti-TNF agents vs ustekinumab (OR 1.03; 95% CI 0.84–1.28).

Conclusion In this large prospective registry, ustekinumab exposure was not associated with an increased risk of SAEs during pregnancy or the neonatal period compared with anti-TNF agents, immunosuppressants, or no immunosuppressive therapy. These findings support the good safety profile of ustekinumab during pregnancy in women with IBD.