A Consensus Blueprint for Steroid Stewardship in IBD Trials

The "Consensus Blueprint for Steroid Stewardship in IBD Trials" is a globally agreed-upon framework developed by a panel of 45 international experts through the Delphi process to standardize and optimize the use of steroids in clinical trials for inflammatory bowel disease (IBD). This blueprint addresses the critical need to reduce the adverse effects associated with long-term steroid use and improve the reliability, efficiency, and patient-centered approach of IBD trials.

### Key Components of the Blueprint:

#### 1. **Need for Steroid Stewardship**

• **Rationale:** Long-term steroid use in IBD leads to serious adverse effects, including infections, metabolic complications, osteoporosis, mood swings, insomnia, weight gain, and increased mortality risks (e.g., during the COVID-19 pandemic). These issues highlight the necessity for tighter control of steroid exposure.
• **Objective:** To reduce steroid dependency and exposure in IBD trials while maintaining therapeutic efficacy and ensuring patient safety.

#### 2. **Challenges in Current Clinical Trials**

• Many IBD trials permit high or prolonged steroid use, which results in:
• Inflated placebo responses.
• Inconsistent efficacy estimates for investigational therapies.
• Reduced patient recruitment due to steroid-related side effects.
• Patients often avoid trials with long "stable-dose" steroid phases due to the negative impact on quality of life.

#### 3. **Baseline Steroid Use Criteria**

• **Entry Criteria:** Participants must limit baseline steroid doses to ≤20 mg prednisone-equivalent or ≤9 mg budesonide.
• **Stabilization Period:** Reduced from the traditional 6 weeks to just 2 weeks to align with real-world practices and minimize prolonged exposure.

#### 4. **Mandatory Early Tapering**

• **Timing:** Steroid tapering must begin within 2 weeks of randomization.
• **Protocol:** Reduce steroid doses by 5 mg per week, irrespective of patient response, to align with rapid-onset therapies like upadacitinib and guselkumab.
• This approach ensures faster withdrawal of systemic steroids while maintaining therapeutic goals.

#### 5. **Maintenance Phase Rules**

• **Systemic Steroids:** All systemic steroids must be discontinued before entering the maintenance phase of the trial.
• **Re-escalation:** Any need to reintroduce systemic steroids is considered treatment failure.
• **Budesonide Exception:** Budesonide can be stopped abruptly due to its minimal impact on adrenal suppression.

#### 6. **Endpoint Definition Clarity**

• **Corticosteroid-Free Clinical Remission (CSF-CR):** This endpoint should only be calculated for participants who were using steroids at the start of the maintenance phase, avoiding inflated success rates.
• Clear endpoint definitions improve data comparability across trials.

#### 7. **Patient-Centered Trial Design**

• **Shorter Steroid Exposure:** Patients strongly prefer trials with shorter steroid phases, as prolonged use leads to significant side effects like mood swings, insomnia, and weight gain—59% of patients reported such experiences.
• **Improved Recruitment:** Patient-friendly designs, including reduced steroid exposure, enhance trial participation and retention.

#### 8. **Clinical Impact**

• **Standardization:** Uniform tapering protocols and clear remission definitions will improve the comparability of trial data across studies.
• **Efficiency:** Reducing placebo effects and shortening steroid phases will make trials more efficient and effective.
• **Patient Experience:** By prioritizing patient preferences, trials become more appealing and less burdensome.

#### 9. **Future Directions**

• **Real-World Adoption:** Encourage early steroid tapering protocols in clinical practice to mirror trial designs.
• **Patient-Reported Outcomes:** Integrate measures like sleep quality, mood, and overall well-being to assess patient-centric endpoints.
• **Biomarker Integration:** Use biomarkers such as fecal calprotectin to personalize steroid withdrawal strategies, ensuring tailored treatment approaches.

### Conclusion:

The Consensus Blueprint for Steroid Stewardship in IBD Trials represents a significant step forward in optimizing the use of steroids in clinical research. By addressing the adverse effects of long-term steroid use, standardizing tapering protocols, and focusing on patient-centered designs, the blueprint aims to enhance the reliability, efficiency, and appeal of IBD trials. It also sets the stage for real-world adoption of these practices, paving the way for improved patient outcomes and more personalized treatment strategies.