FDA Expands Upadacitinib Label for Treating Inflammatory Bowel Disease

The FDA has approved an updated indication for upadacitinib (Rinvoq; AbbVie) in inflammatory bowel disease (IBD), allowing its use in adults with moderately to severely active ulcerative colitis or Crohn disease who have received at least 1 approved systemic therapy when tumor necrosis factor (TNF)–blocking agents are clinically inadvisable.1

According to an AbbVie news release, this approval broadens options for patients for whom anti-TNF therapy is not appropriate, and marks a shift from the prior US label that required an inadequate response or intolerance to at least 1 TNF blocker before initiating upadacitinib.

The FDA approved a label expansion for upadacitinib. | Image Credit: aznan – stock.adobe.com

“This label update gives healthcare providers the option to prescribe Rinvoq for patients with moderately to severely active inflammatory bowel disease after the use of one approved systemic therapy if TNF blockers are deemed clinically inadvisable by the prescribing physician,” said Kori Wallace, MD, PhD, vice president and global head of immunology clinical development at AbbVie.

Evidence Supporting IBD Indications

Upadacitinib is an oral selective Janus kinase (JAK) inhibitor with established efficacy in IBD. For ulcerative colitis, induction and maintenance results demonstrated significantly higher clinical remission rates with 45-mg induction in the U-ACHIEVE (26%) and U-ACCOMPLISH trials (34%) vs placebo (5% and 4%, respectively) at week 8, with durable remission during maintenance at 15 mg and 30 mg through week 52.2

In Crohn disease, the U-EXCEED and U-EXCEL induction trials and the U-ENDURE maintenance trial showed superiority of upadacitinib vs placebo for coprimary end points—clinical remission and endoscopic response—including in subgroups with prior biologic exposure.3 More recent peer-reviewed updates reported maintained efficacy and a consistent safety profile in maintenance, with no new safety signals.

Under the prior indication, upadacitinib could be started only after failure or intolerance to a TNF blocker in ulcerative colitis and Crohn disease.1 The updated language carves out a pathway for patients in whom TNF blockade is not advised—due to individual clinical risks or history, for example—provided they have already received at least 1 approved systemic therapy such as corticosteroids, immunomodulators, or another appropriate systemic agent. The new phrasing allows clinicians to consider upadacitinib earlier when anti-TNF therapy is not suitable.

Safety and Boxed Warnings

Key risks associated with upadacitinib include serious infections, malignancy, major adverse cardiovascular events, thrombosis, and death, particularly in adults 50 years and older with cardiovascular risk factors and in current or former smokers. According to the release, clinicians should screen for tuberculosis, avoid live vaccines, and monitor laboratory parameters per labeling.

Upadacitinib is also being studied in phase 3 trials for treating alopecia areata, hidradenitis suppurativa, Takayasu arteritis, systemic lupus erythematosus, and vitiligo.1

References

1. 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
2. Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022;399(10341):2113-2128. doi:10.1016/S0140-6736(22)00581-5
3. Loftus EV Jr, Panés J, Lacerda AP, et al. Upadacitinib induction and maintenance therapy for Crohn's disease. N Engl J Med. 2023;388(21):1966-1980. doi:10.1056/NEJMoa2212728