International Consensus on Corticosteroid Use in IBD Clinical Trials

The International Consensus on Corticosteroid Use in Inflammatory Bowel Disease (IBD) Clinical Trials represents the first global, expert-driven guidance to standardize corticosteroid management in IBD drug trials. This guidance aims to address the challenges and inconsistencies in corticosteroid use that have historically complicated the interpretation of trial outcomes, reduced comparability across studies, and posed barriers to patient participation.

Key Highlights of the Consensus:

1. Need for Standardization:

• Corticosteroid management in IBD trials has been highly variable.
• This variability can bias trial outcomes by masking true disease activity or inflating placebo response rates.
• Standardized protocols are essential to ensure consistency and reliability in trial results.

2. Impact on Trial Outcomes:

• Inconsistent corticosteroid handling can lead to incorrect efficacy assessments.
• Standardization reduces the risk of bias and improves the comparability of clinical trials.

3. Barrier to Patient Participation:

• Prolonged corticosteroid exposure, often required by trial protocols, discourages patient enrollment due to the associated risks and side effects.
• The new recommendations aim to reduce corticosteroid exposure, making trials more patient-friendly.

4. Defined Trial Phases:

• The consensus provides specific recommendations for corticosteroid management across all trial phases: screening, induction, maintenance, and endpoint assessment.

5. Screening Phase Recommendations:

• Permitted Oral Steroids: Oral systemic corticosteroids (e.g., prednisone) and oral enteric- or colonic-release corticosteroids (e.g., budesonide) are allowed under defined conditions.
• Intravenous Steroid Exclusion: Use of intravenous corticosteroids during screening is exclusionary due to concerns about disease severity and excessive exposure.
• Rectal Steroid Discontinuation: Rectal corticosteroids must be stopped at least two weeks before the baseline assessment.
• Stable Pretrial Dosing: Corticosteroid doses must remain stable for at least two weeks before randomization to ensure reliable baseline disease activity measurement.
• Maximum Screening Dose: The maximum allowed oral systemic corticosteroid dose is 20 mg/day (prednisone equivalent).
• Budesonide Dose Limit: Budesonide use before randomization should not exceed 9 mg/day.

6. Induction Phase Recommendations:

• Fixed Dosing Period: Corticosteroid doses should remain fixed for at least two weeks after randomization during the induction phase.
• Protocol-Mandated Tapering: Tapering decisions must be mandated by the trial protocol and not left to investigator discretion.
• Standardized Taper Schedule: A tapering schedule of 5 mg prednisone equivalent per week is recommended to minimize variability and exposure.
• Budesonide Exception: Enteric- or colonic-release budesonide formulations can be discontinued without tapering.
• Rescue Therapy Defines Failure: Initiation of any corticosteroid as rescue therapy during the induction phase is considered treatment failure.

7. Maintenance Phase Recommendations:

• Tapering at Start of Maintenance: If tapering was not completed during induction, it should begin at the start of the maintenance phase.
• Deviation Equals Failure: Any escalation or deviation from the mandated tapering schedule during maintenance is considered treatment failure.
• Steroid-Free Remission Denominator: Only patients using corticosteroids at the start of induction or maintenance phases should be included when calculating steroid-free remission rates.

8. Goals of the Consensus:

• Shorten corticosteroid exposure to reduce patient harm and align trial protocols with clinical practice.
• Minimize variability in corticosteroid use to improve the reliability and comparability of trial outcomes.
• Encourage patient participation in trials by reducing the burden of corticosteroid-related side effects.

Broader Implications:

This consensus-driven guidance is expected to significantly enhance the quality and interpretability of IBD clinical trials. By standardizing corticosteroid use, the recommendations aim to achieve more accurate assessments of drug efficacy, reduce the risk of bias, and improve patient safety. Additionally, the focus on reducing corticosteroid exposure aligns with the broader goal of minimizing steroid-related harm in clinical practice.

This international effort marks a critical step forward in harmonizing trial protocols and ensuring that outcomes are meaningful, reproducible, and clinically relevant.