P0958Safety of ustekinumab vs anti-TNF, immunomodulators, or no immunosuppressive therapy during pregnancy in IBD: DUMBO Registry

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. Conflict of interest: Aranguren, Ainhoa: No conflict of interest Garre, Ana: None Leo Carnerero, Eduardo: I have received grants or fees for scientific activities or as a scientific advisor for MSD, Pfizer, Abbvie, Takeda, Janssen, Tillotts Pharma, Shire Pharmaceuticals, Ferring, Dr. Falk Pharma, Lilly, Adacyte and Otsuka Pharmaceutical. Calviño Suárez, Cristina: CCS has served as a speaker for or has received research funding from MSD, AbbVie, Janssen, Takeda and Adacyte. Martin Arranz, Maria Dolores: No conflict of interest Calvo Moya, Marta Isabel: I have participated in presentations / advisory boards / research supported by: AbbVie, Takeda, Johnson & Johnson, Pfizer, Lilly, MSD, Chiesi, Dr Falk Pharma, Shire Pharmaceuticals, FAES, FERRING, Tillotts Pharma, Galapagos and Alfasigma Zabalba San Martín, Lucía: No conflict of interest Perez Martinez, Isabel: “No conflicts” Arroyo Villarino, Maria Teresa: No conflict of interest Fernandez Clotet, Agnes: None Marin Pedrosa, Sandra: NO Diz Lois Palomares, Maria Teresa: No conflict of interest Casanova, María José: María José Casanova, has received education funding from Pfizer, Takeda, Janssen, MSD, Dr. Falk, Shire, Ferring, Galápagos and Abbvie, and research funding from Lilly. Hernández Ramirez, Vicente: Vicent Hernandez has served as consultant, has served as speaker, has received travel support or research funding from MSD, AbbVie, Ferring, Dr. Falk Pharma, Tillotts Pharma, Pfizer, Takeda, Janssen, KernPharma Biologics, Adacyte, Sandoz, FAES Farma, Galapagos, Lilly and Casen-Recordati Rivero Tirado, Montserrat: No conflict of interest Ruiz-Cerulla, Alexandra: No conflict of interest Vicente Lidon, Raquel: No conflict of interest Huguet, José María: No conflict of interest Guerra Marina, Ivan: IG has served as speaker for Takeda and Tillots pharma. Arias Garcia, Maria Lara: No conflict of interest Camargo Camero, Raquel: No conflict of interest Valldosera, Gemma: No conflict of interest Bejarano Garcia, Ana: No conflict of interest Gutiérrez Casbas, Ana: No conflict of interest Gonzalez Lama, Yago: I have provided scientific advisory / participated in educational activities / received unrestricted research grants / received payments for lecturing from Janssen, Takeda, Pfizer, AbbVie, Lilly, Alfasigma, Ferring, Gilead, Amgen. Hervias Cruz, Daniel: No conflict of interest Rodríguez-Lago, Iago: Financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Alfasigma, Biogen, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Johnson & Johnson, Eli Lilly, Mirum Pharmaceuticals, Merck, Pfizer, Roche, Takeda, and Tillotts Pharma. Research support from AbbVie. Supported by a research grant from Gobierno Vasco-Eusko Jaurlaritza (Grant No 2020111061 and 2023222006). De Jorge Turrión, Miguel Ángel: No conflict of interest Ceballos Santos, Daniel: None Bujanda, Luis: Not López Serrano, Pilar: No conflict of interest Aguas, Peris: No conflict of interest Echarri Piudo, Ana: No conflict of interest Van Domselaar, Manuel: No conflict of interest Lucendo, Alfredo: No conflict of interest Tardillo Marin, Carlos Alberto: No conflict of interest Vega Villaamil, Pablo: None Hermida, Sandra: No conflict of interest Gisbert, Javier: Grant: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. Personal Fees: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. Other: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. Prof. Dr. Chaparro, María: No conflict of interest