FDA Approves Updated Indication for Upadacitinib in IBD

The U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) updating the indication statement for upadacitinib for the treatment of adults with moderately to severely active inflammatory bowel disease (IBD).

With this indication change, upadacitinib may be used for patients who have received any approved systemic therapy for IBD if anti-TNFs are considered “clinically inadvisable.”

Upadacitinib was originally approved for adults with moderately to severely active IBD—but only after patients had shown inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.

The limitation on the use of Janus kinase (JAK) inhibitors followed results of the ORAL Surveillance safety study of tofacitinib. That post-marketing study showed increased risks for major adverse cardiovascular events (MACE), including heart attack and stroke, among patients with rheumatoid arthritis who were more than 50 years of age with at least one cardiovascular risk factor.

When approved for ulcerative colitis in 2022 and for Crohn’s disease in 2023, upadacitinib also carried the same warning, as the FDA considered the entire class of JAK inhibitors to carry the similar risks for heart disease, infection, and cancers. However, more recent observational studies patients with IBD treated with JAK inhibitors have not supported earlier fears of higher risks in comparison with anti-TNFs.

“The update of the label for upadacitinib will help providers get this highly effective therapy to patients with IBD earlier in the treatment sequence. Now, if anti-TNF therapy is clinically inadvisable for patients, any other prior approved systemic therapy will be sufficient before starting upadacitinib,” commented Corey A. Siegel, MD, MS, director of the Walter and Carole Young Center for Digestive Health and the Constantine and Joyce Hampers Professor of Medicine at the Geisel School of Medicine at Dartmouth. “While we would prefer to have the option to use upadacitinib as first line in appropriate patients, this change at least gives clinicians new flexibility to make more personalized treatment  decisions for patients.”

Source:

U.S. Food and Drug Administration (FDA) approves updated indication statement for RINVOQ® (upadacitinib) for the treatment of inflammatory bowel disease. News release. AbbVie; October 13, 2025. Accessed October 14, 2025. https://news.abbvie.com/2025-10-13-U-S-Food-and-Drug-Administration-FDA-Approves-Updated-Indication-Statement-for-RINVOQ-R-upadacitinib-for-the-Treatment-of-Inflammatory-Bowel-Disease