First Oral Medication to Treat Moderate-to-Severe Crohn’s Disease Completes Successful Phase 3 Trial and Earns FDA Approval

Patients with moderate-to-severe Crohn’s disease now have a new treatment option to suppress their intestinal inflammation and painful symptoms, and help them maintain their relief.

Data from a phase 3 trial published today in The New England Journal of Medicine show that upadacitinib—a breakthrough, once-daily oral medication—helps patients achieve and maintain clinical and endoscopic remission. As a result, upadacitinib garnered Food and Drug Administration approval on Thursday, May 18.

Crohn’s disease, a chronic inflammatory bowel disorder affecting millions worldwide, has long presented a significant challenge for both patients and health care providers. Existing treatment options often fall short in achieving sustained remission and controlling symptoms. However, the results of the upadacitinib study herald a promising breakthrough in managing this complex condition.

Corresponding author Jean-Frederic Colombel, MD, notes, “Upadacitinib addresses an unmet need in the treatment of Crohn’s disease and allows patients access to an oral medication that could put them in clinical and endoscopic remission. This therapy has the potential to transform the lives of individuals battling this chronic condition and offers a new hope for improved quality of life.” Dr. Colombel is the co-Director of the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at The Mount Sinai Hospital in New York City and Professor of Medicine (Gastroenterology) at the Icahn School of Medicine at Mount Sinai.

Upadacitinib is a selective Janus kinase (JAK) inhibitor. It precisely targets the underlying pathways of inflammation, thereby mitigating the symptoms and potentially minimizing the risk of adverse events associated with immunosuppression.

The study spanned 43 countries and 277 sites, and enrolled a diverse group of patients 18 to 75 years old who had moderate-to-severe Crohn’s disease for at least three months.

Participants were randomly assigned to receive 45 mg of upadacitinib or placebo (2:1) for induction therapy to assess its effectiveness in achieving remission in two double-blind phase 3 trials, U-EXCEL and U-EXCEED. The medication was taken once daily for 12 weeks. Patients who had a clinical response to upadacitinib induction therapy were then randomly assigned in the U-ENDURE maintenance trial to receive 15 mg or 30 mg of upadacitinib, or placebo (1:1:1) once daily for 52 weeks. The maintenance phase evaluated the drug’s ability to sustain remission and prevent relapse. (U-EXCEED had an additional 12-week open-label, active single-group induction period to allow for the accrual of enough patients for entry into U-ENDURE.)

The primary endpoints for induction (week 12) and maintenance (week 52) were clinical remission (defined as a Crohn’s Disease Activity Index score of <150 on a range of 0 to 600, with higher scores indicating more severe disease activity) and endoscopic response (defined as a decrease in the Simple Endoscopic Score for Crohn’s Disease [SES-CD; range, 0 to 56, with higher scores indicating more severe disease] of >50% from baseline of the induction trial [or for patients with an SES-CD of 4 at baseline, a decrease of ≥2 points from baseline]).

Upadacitinib demonstrated superior efficacy over placebo, with a statistically significant proportion of patients achieving clinical remission after induction therapy. During the maintenance phase, the therapy substantially reduced the rate of disease relapse, illustrating its potential as a long-term treatment option for Crohn’s disease.