Corticosteroids in Clinical Trials in Inflammatory Bowel Disease

Corticosteroids play a significant role in managing inflammatory bowel disease (IBD), but their use in clinical trials has been inconsistent, leading to challenges in interpreting study outcomes. To address this issue, an international consensus was developed to standardize corticosteroid management in randomized controlled trials (RCTs) involving adult patients with moderate-to-severe Crohn's disease (CD) and ulcerative colitis (UC). Below is a detailed overview of corticosteroid use in clinical trials for IBD based on the consensus recommendations:

### Purpose of the Consensus

The consensus aims to address the heterogeneity in corticosteroid dosing, tapering schedules, and remission definitions across IBD trials. By establishing standardized guidelines, the consensus seeks to:

• Minimize prolonged corticosteroid exposure.
• Improve patient safety and participation in trials.
• Reduce bias in therapeutic outcomes.
• Align trial practices with real-world clinical management.

### Key Recommendations for Corticosteroid Use in IBD Trials

#### 1. **Corticosteroids During Screening**

• Only oral systemic and oral enteric/colonic-release corticosteroids are permitted during the screening phase of the trial.
• Patients receiving intravenous corticosteroids during screening are disqualified from participating in the trial.

#### 2. **Rectal Corticosteroid Restrictions**

• Patients with UC or CD must discontinue rectally administered corticosteroids at least two weeks before screening or randomization.

#### 3. **Dose Limitations Before Randomization**

• Prednisone-equivalent doses should not exceed **20 mg/day**.
• Budesonide doses should not exceed **9 mg/day**.
• This ensures participants enter the trial with a manageable corticosteroid exposure level.

#### 4. **Stable Dose Period**

• Patients must maintain a stable corticosteroid dose for at least **two weeks** prior to baseline or randomization to ensure consistent baseline disease activity.

#### 5. **Tapering During Induction**

• Tapering of corticosteroids must begin within **two weeks** of randomization.
• A fixed tapering rate of **5 mg/week** is recommended for prednisone-equivalent doses.
• The tapering schedule should be protocol-defined to ensure uniform application across participants.

#### 6. **Defining Treatment Failure**

• Patients who start corticosteroids de novo during induction or maintenance phases, or require intravenous rescue therapy, are considered treatment failures.
• This definition helps identify patients who do not respond adequately to the trial intervention.

#### 7. **Maintenance Phase Guidelines**

• Oral corticosteroids should begin tapering at the start of the maintenance phase if tapering has not already been initiated.
• Budesonide may be discontinued without tapering during the maintenance phase.

#### 8. **Rescue Steroid Use**

• Patients requiring more than **one rescue corticosteroid course** during the maintenance phase are deemed treatment failures.
• An exception is made for short-term steroid use to manage unrelated conditions, such as asthma.

#### 9. **Corticosteroid-Free Remission Definition**

• Only patients who were using corticosteroids at the start of the trial should be included in the denominator for calculating corticosteroid-free remission rates.
• The consensus debated the withdrawal duration for remission; most experts supported defining remission as withdrawal of corticosteroids for **≥12 weeks** before the final study visit.

#### 10. **Standardized Reporting**

• The consensus strongly recommends transparent reporting of cumulative corticosteroid exposure, rescue therapy use, and tapering deviations in future trials.
• This will improve comparability across studies and provide better insights into therapeutic outcomes.

### Patient Feedback

Patients expressed a preference for earlier tapering and minimized steroid use due to adverse effects such as:

• Weight gain.
• Mood swings.
• Sleep disturbances.

This feedback highlights the importance of balancing corticosteroid use with patient quality of life during trials.

### Clinical Implications

The standardized corticosteroid management framework aims to:

• Optimize trial design and execution.
• Reduce steroid-related harm.
• Enhance the validity and interpretability of therapeutic outcomes.
• Align trial practices with real-world clinical scenarios.

### Future Outlook

This is the first international corticosteroid management framework specifically designed for IBD RCTs. It is expected to:

• Improve patient safety.
• Increase trial validity globally.
• Serve as a blueprint for future clinical trials focusing on IBD and other inflammatory conditions.

### Scope of Consensus

It is important to note that these recommendations apply only to adult patients with moderate-to-severe CD or UC in pharmacologic RCTs. The guidelines do not address pediatric populations or surgical interventions.

### Conclusion

The consensus on corticosteroid use in IBD clinical trials represents a groundbreaking effort to harmonize trial protocols, improve patient outcomes, and enhance the reliability of therapeutic evaluations. By implementing these standardized practices, researchers can ensure a consistent approach to corticosteroid management while addressing patient concerns and minimizing adverse effects.