FDA Approves Upadacitinib (Rinvoq) for Crohn's Disease

The US Food and Drug Administration (FDA) has approved the oral Janus kinase (JAK) inhibitor upadacitinib (Rinvoq, AbbVie) for adults with moderately to severely active Crohn's disease whose condition failed to respond adequately or who can't tolerate one or more tumor necrosis factor (TNF) inhibitors, the company has announced.

Upadacitinib is the first oral treatment approved by the FDA for Crohn's disease.

The indication in Crohn's disease marks the seventh in the US for the JAK inhibitor. Other indications include rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

The approval in Crohn's disease was supported by data from two induction studies (U-EXCEED and U-EXCEL) and one maintenance study (U-ENDURE).

In the two induction studies, 857 patients were randomly assigned to receive upadacitinib 45 mg or placebo once daily for 12 weeks. At week 12, a greater proportion of patients who received upadacitinib (vs those who received placebo) achieved clinical remission, as determined on the basis of the Crohn's Disease Activity Index (CDAI), and who showed improvement in intestinal inflammation, as assessed by colonoscopy.

In the maintenance study, 343 patients who responded to induction therapy with upadacitinib were again randomly assigned to receive either a maintenance regimen of 15 or 30 mg once daily or placebo for 52 weeks.

As at 12 week, at week 52, a greater proportion of patients who were treated with upadacitinib 15 mg or 30 mg, as compared to those who received placebo, achieved clinical remission, as indicated on the CDAI, and demonstrated improvement in intestinal inflammation, as assessed by colonoscopy.

Data from the trials of upadacitinib in Crohn's disease were presented at the European Crohn's and Colitis Organisation (ECCO) 2023 Congress in March and were reported by Medscape Medical News at that time.

"Symptoms of moderately to severely active Crohn's disease can be disruptive and uncomfortable for patients, so relief as early as possible is key. Given the progressive nature of the disease, endoscopic response is just as important," U-EXCEL study investigator Edward V. Loftus, Jr, MD, professor of medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota, said in a news release.

"Based on the clinical trial results, treatment with Rinvoq shows both early and long-term symptom relief along with evidence of a visible reduction of damage to the intestinal lining caused by excess inflammation," Loftus added.

Patients should initially be given 45 mg of upadacitinib once daily for 12 weeks. Following the 12-week period, the recommended maintenance dosage is 15 mg once a day. A maintenance dose of 30 mg once daily can be considered for patients with refractory, severe, or extensive Crohn's disease, the FDA says in a statement announcing approval.

The most common side effects of upadacitinib in patients with Crohn's disease are upper respiratory tract infection, anemia, fever, acne, herpes zoster, and headache.

Upadacitinib is not recommended for use in combination with other JAK inhibitors, biological therapies for Crohn's disease, or with strong immunosuppressants, such as azathioprine and cyclosporine.

Serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis have occurred with JAK inhibitors such as upadacitinib.

Full prescribing information is available online.

Loftus is a consultant and advisor for AbbVie.

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Cite this: FDA Approves Upadacitinib (Rinvoq) for Crohn's Disease - Medscape - May 18, 2023.