PHOENIX—Combination biologic and small-molecule therapies have an acceptable safety profile in patients with severe, treatment-refractory inflammatory bowel disease, according to a new study from researchers at Weill Cornell Medicine and the Jill Roberts Center for Inflammatory Bowel Disease, in New York City.
In a retrospective analysis presented at ACG 2025, the researchers examined 125 treatment regimens used to treat 64 adults with Crohn’s disease and 38 with ulcerative colitis (poster 1100). The individuals had been treated with two concomitant biologics and/or small-molecule therapies for at least six weeks.
Lead investigator Jacob Jamison, a medical student at Weill Cornell Medicine, and his co-investigators focused on patients with advanced disease severity, including 72% who had failed at least two prior advanced therapies, 92% who received prior steroids, 88% with prior tumor necrosis factor antagonist exposure, and 56% of the CD patients had undergone prior surgery. Mean disease duration at the time of combination treatment initiation was 14 years (±12 years).
The study population was 49% female, 9% Black, and 11% Hispanic, with a mean age of 40 years (±17 years). Combination regimens included TNF blockers, anti-integrin agents, interleukin-12/IL-23 inhibitors, Janus kinase inhibitors, and sphingosine-1-phosphate receptor modulators.
Over a mean combination treatment duration of 12.1 months (±12.7 months), overall infection rates were 31%, and IBD-related hospitalization rates were 13%. Of the 62 combinations that were discontinued during the study period, 13 (21%) were stopped due to adverse events. Serious infections were rare, with one instance each of herpes zoster, Clostridioides difficile infection, and a thrombotic event. Among patients who stopped combination treatment, 11% required surgery within 12 weeks.
Mr. Jamison and his co-investigators found a safety signal related to baseline steroid use. At the time of combination initiation, corticosteroids were being used in 41 of the regimens (33%). The regimens that included corticosteroid use were significantly more likely to be associated with an infection (44% vs. 24%; P=0.02), infections requiring antibiotics (41% vs. 17%; P=0.003), and infections requiring hospitalization (7% vs. 0%; P=0.01).
“Baseline treatment with steroids at combination initiation was associated with a more than two times higher rate of serious infection and more than three times higher rate of IBD-related hospitalization, though the latter did not reach statistical significance,” the investigators wrote.
Mr. Jamison and his co-investigators concluded that while combination therapy seems to be a viable option for patients with refractory IBD, concurrent steroid use at initiation warrants careful consideration due to substantially elevated infection risk.
—David Wild
Mr. Jamison reported no relevant financial disclosures.
