Upadacitinib in a real-world data from UK

The real-world data on the use of upadacitinib for Crohn’s disease (CD) in the UK provides valuable insights into its effectiveness and safety in a challenging, clinically refractory patient population. Here is a detailed summary of the findings from a multicentre retrospective cohort analysis conducted across 19 UK hospitals:

Background:

• Upadacitinib is the first Janus kinase (JAK) inhibitor and oral advanced therapy approved for Crohn’s disease.
• In 2023, NICE (National Institute for Health and Care Excellence) approved upadacitinib for CD treatment, but real-world data on its outcomes had been limited until now.

Study Design:

• The study included 312 adult patients with active Crohn’s disease who initiated upadacitinib treatment between April 2023 and October 2023.
• Patients were followed for a minimum of 12 weeks, with outcomes assessed at 12 and 24 weeks.
• The cohort included patients with difficult-to-treat disease, with:
• 64% having failed three or more biologics.
• 51% exhibiting penetrating or stricturing disease.
• 41% requiring prior surgical resection.

Key Outcomes:

1. Clinical Remission:

• Defined as achieving a Harvey Bradshaw Index (HBI) score of <4.
• At 12 weeks: 50% (113/227) of patients achieved clinical remission.
• At 24 weeks: 45% (77/172) of patients achieved clinical remission.
• Patients with colonic disease had higher remission rates at 24 weeks compared to those with other disease locations.

2. Biochemical and Endoscopic Remission:

• Biochemical remission was assessed using faecal calprotectin (<200 μg/g) and C-reactive protein (≤5).
• Endoscopic remission was defined as a Simple Endoscopic Score for Crohn’s Disease (SES-CD) ≤3.
• These outcomes were also evaluated at 12 and 24 weeks, but specific percentages were not detailed in the summary.

3. Treatment Persistence:

• Persistence rates were high:
• 90.3% at 12 weeks.
• 84.1% at 24 weeks.
• This indicates that most patients continued treatment with upadacitinib during the study period.

4. Adverse Events (AEs):

• AEs were reported in 28% of patients.
• Serious AEs occurred in 18%, and 16.6% of patients required hospitalization.
• Despite the AEs, the treatment was generally well-tolerated in this cohort.

5. Drug Discontinuation:

• By 24 weeks, 16% (51 patients) had discontinued upadacitinib.

Conclusion:

• The study demonstrated good short-term effectiveness and tolerance of upadacitinib in a clinically refractory population with Crohn’s disease.
• The clinical remission rate of 45% at 24 weeks and high drug persistence rates suggest that upadacitinib is a promising treatment option for patients with difficult-to-treat CD.
• The favorable outcomes, including steroid-free clinical remission and high persistence rates, highlight the potential of upadacitinib in managing challenging cases of Crohn’s disease.

Implications for Research, Practice, and Policy:

• The findings support the use of upadacitinib as an effective treatment for patients with refractory Crohn’s disease.
• The real-world data aligns with clinical trial outcomes (U-EXCEED, U-EXCEL, and U-ENDURE) and provides additional evidence for its role in clinical practice.
• The high persistence rates and favorable remission outcomes could influence future treatment guidelines and policies for managing Crohn's disease.

This study represents a significant step in understanding the real-world impact of upadacitinib and demonstrates its potential as a viable treatment option for patients with Crohn’s disease who have limited therapeutic options.