Upadacitinib in a real-world cohort of patients with Crohn’s disease in the UK

The real-world study on upadacitinib in patients with moderate-to-severe Crohn’s disease (CD) was conducted across 19 hospitals in the UK between April and October 2023. The study aimed to evaluate the effectiveness, persistence, and safety of upadacitinib in a challenging cohort of patients with active CD. Below is a detailed overview of the study findings:

Study Design and Patient Cohort:

1. Multicentre Retrospective Cohort Study: The study involved data collection from 19 hospitals in the UK.

2. Patient Population: Included 312 adults with active moderate-to-severe Crohn’s disease.

• 64% of patients had failed three or more biologic therapies, indicating a highly refractory population.
• 51% had penetrating or stricturing disease, which are more severe phenotypes of Crohn’s disease.

Effectiveness:

1. Primary Endpoint: Clinical remission was defined as a Harvey Bradshaw Index (HBI) score of <4, assessed at 12 and 24 weeks.

2. Induction Remission (12 weeks):

• 50% (113/227) of patients achieved clinical remission.
• Of those achieving remission, 93% were steroid-free, highlighting the efficacy of upadacitinib without reliance on corticosteroids.

3. Maintenance Remission (24 weeks):

• 45% (77/172) of patients maintained clinical remission.
• 96% of these patients were steroid-free.

4. Biochemical Remission:

• Faecal calprotectin and C-reactive protein (CRP) levels normalized in 28% of patients by week 12 and 18% by week 24.

5. Endoscopic Remission:

• Mucosal healing (endoscopic remission) was slower compared to symptomatic improvements, with 6% achieving remission at 12 weeks and 12% at 24 weeks.

Persistence:

1. Drug Persistence: Upadacitinib showed strong adherence and tolerability.

• Persistence rates were 90.3% at 12 weeks and 84.1% at 24 weeks.

Predictors of Remission:

1. Disease Location:

• Patients with colonic (L2) and ileocolonic (L3) disease had higher odds of remission compared to those with isolated ileal (L1) disease.
• Colonic disease was the strongest predictor of remission (OR 9.16, p=0.003), followed by ileocolonic disease (OR 3.44, p=0.043).

2. Smoking Status:

• Ex-smokers had significantly lower odds of achieving remission compared to never-smokers (OR 0.08, p=0.006).

3. Stoma Patients:

• Patients with stomas had reduced remission rates due to limitations in the Harvey Bradshaw Index (HBI), which does not accurately measure stool frequency in stoma patients.

4. Early Response:

• Early response was predictive of long-term success; 80% of patients in remission at 12 weeks remained in remission at 24 weeks.

Safety Profile:

1. Adverse Events (AEs):

• AEs were reported in 28% of patients, with 18% experiencing serious AEs.
• The most frequent AEs included infections (7.7%) and lipid abnormalities (4.8%).

2. Severe Events:

• Serious AEs included resections (5.4%), symptom worsening (4.8%), obstructions (2.2%), and venous thromboembolism (1%).

3. Discontinuation Rate:

• 8% of patients discontinued upadacitinib due to side effects, which aligns with rates observed in prior real-world studies.

Comparison with Clinical Trials:

• Remission rates in this real-world study (45%) were consistent with results from clinical trials such as U-EXCEL and U-EXCEED (39–50%), validating the efficacy of upadacitinib in real-world settings.

Limitations:

1. Retrospective Design: The study's retrospective nature may introduce biases.

2. Incomplete Endoscopy Data: Limited availability of endoscopic data restricts the ability to comprehensively assess mucosal healing.

3. Challenges in Stoma Patients: Difficulty in quantifying outcomes for stoma patients due to limitations in the HBI scoring system.

Conclusion:

Upadacitinib demonstrated good short-term effectiveness, strong drug persistence, and an acceptable safety profile in a highly refractory population of Crohn’s disease patients in the UK. The study supports upadacitinib as an effective oral therapy for moderate-to-severe Crohn’s disease in real-world clinical practice. Despite certain limitations, the findings align closely with clinical trial data, further validating the use of upadacitinib in managing this chronic inflammatory condition.