# Prospective Bi-Centric Real-World Outcomes of Upadacitinib in Biologic-Experienced Patients with Crohn’s Disease

## TL;DR

Upadacitinib is effective and safe for Crohn’s disease patients who have not responded to previous biologic treatments, offering a new therapeutic option.

## Contribution

This study provides real-world evidence of upadacitinib's efficacy and safety in biologic-experienced Crohn’s disease patients.

## Key findings

- More than half of patients achieved clinical remission within one year of upadacitinib treatment.
- Upadacitinib improved intestinal inflammation in nearly half of the patients.
- The medication was well-tolerated with minimal side effects.

## Abstract

Crohn’s disease is a chronic inflammatory bowel condition that often requires biologics to control inflammation. However, some patients do not respond adequately to these treatments. Upadacitinib is a newer oral medication that works through a different mechanism than traditional biologics. This study examined whether upadacitinib is effective and safe in patients with Crohn’s disease who had failed previous biologic treatments. We followed 28 patients receiving upadacitinib for one year and measured their clinical symptoms, intestinal healing, and quality of life. More than half of patients achieved clinical remission, and the medication improved intestinal inflammation in nearly half of the patients. Most importantly, upadacitinib was well-tolerated with minimal side effects. These findings suggest that upadacitinib represents a valuable treatment option for patients with difficult-to-treat Crohn’s disease and could help expand therapeutic options in clinical practice.

Background: The efficacy of upadacitinib in patients with Crohn’s disease (CD) has been shown in pivotal randomized controlled trials. However, real-world data is needed to assess its effectiveness and safety in routine clinical care with biologic-experienced patients. This study aimed to evaluate the clinical and endoscopic efficacy, patient-reported outcomes (PROs), and safety of upadacitinib in biologic-experienced patients with CD in a real-world setting. Methods: This prospective bi-centric real-world study enrolled 28 anti-TNF-experienced patients with CD receiving upadacitinib 45 mg daily for 12 weeks (induction), followed by 30 mg daily maintenance through week 52. Primary endpoints included endoscopic response (≥50% SES-CD reduction or ≥2-point decrease from baseline for baseline SES-CD ≤ 4) and clinical remission (Harvey–Bradshaw Index [HBI] ≤ 4). Secondary endpoints included endoscopic remission, clinical response (HBI decrease ≥ 3 points), and quality of life (IBD-Disk). Statistical analysis used the Wilcoxon signed-rank test with 95% confidence intervals (CIs). Results: Median patient age was 37 years; 75% had ≥3 prior biologic failures. Clinical remission rates (HBI) were 59% (95% CI: 41–75%) at week 12, 44% (95% CI: 27–63%) at week 26, and 53% (95% CI: 29–76%) at week 52. Endoscopic response rates were 48% (95% CI: 44–52%) at week 26 and 46% (95% CI: 21–72%) at week 52. Endoscopic remission was achieved in 43% (95% CI: 40–48%) at week 26 and 27% (95% CI: 10–57%) at week 52. Clinical response (HBI) improved progressively from 65% at week 2 to 71% at week 52. Quality of life, as assessed by the IBD-Disk, showed significant improvement: Reduced Disease Burden (defined as a decrease of 70% or a CED-Disk Score of ≤15) was observed in 33% of patients at week 12 and 35% at week 52. Median SES-CD decreased from 9 points (IQR: 6–17) at baseline to 5 points (IQR: 1–12, p = 0.005) at week 52. Adverse events occurred in 11% of patients (4% lymphopenia, 7% skin disease), with no serious adverse events or deaths. Conclusions: Upadacitinib demonstrates significant clinical and endoscopic efficacy in biologic-experienced, anti-TNF-pretreated patients with CD, achieving remission rates comparable to or exceeding those of the pivotal trials despite a highly refractory population (75% with ≥3 prior biologic failures). The favorable safety profile supports upadacitinib as an important therapeutic option in sequential treatment of refractory CD.