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Treat to Target in CD
Interactive Case Challenge 1: Treat-to-Target in Crohn’s Disease 

Released: March 17, 2025

Jordan E. Axelrad
Jordan E. Axelrad, MD, MPH, FACG
Russell D. Cohen
Russell D. Cohen, MD, FACG, AGAF
Activity Information

Activity

Progress
1
Course Completed

Case Conclusion
Ms Lewis continues mirikizumab at its approved maintenance dosing to sustain remission and prevent future flares. She is scheduled for follow-ups every 6 months to monitor symptoms, biomarkers (CRP, fecal calprotectin), and imaging findings to ensure continued disease control. She is advised to maintain a healthy lifestyle, including a nutrient-rich diet and regular physical activity, but not as a substitute for biologic therapy. Given her excellent response to treatment, long-term adherence to IL-23 inhibitor therapy remains the best strategy to prevent disease recurrence and complications. With proper disease management, Ms Lewis can expect to maintain a high quality of life and reduce the risk of future hospitalizations or surgical interventions.  

Discussion
This case highlights the treat-to-target approach in managing patients with moderate to severe CD—emphasizing biomarker-driven adjustments, therapeutic drug monitoring, and timely biologic therapy optimization. Ms Lewis is a 28-year-old woman who initially presented with persistent abdominal pain and loose stools, as well as elevated inflammatory markers like CRP 12 mg/L and fecal calprotectin 350 μg/g, despite treatment with azathioprine daily and adalimumab every 2 weeks. Based on her low adalimumab trough level (3.4 mcg/mL with no neutralizing antibodies), therapy was optimized by increasing adalimumab to 40 mg/week (or 80 mg every 2 weeks). This approach aligns with the STRIDE-II guidelines, which emphasize achieving clinical, biomarker, and endoscopic remission as key treatment goals.1

After 8 weeks on adalimumab, Ms Lewis experienced partial symptomatic improvement with a decrease in  CRP to 8 mg/L, but elevated fecal calprotectin (400 μg/g) persisted, indicating ongoing intestinal inflammation. Her adalimumab level reached therapeutic levels of 12 mcg/mL with no neutralizing antibodies, which suggests there was a secondary loss of response rather than underdosing. According to current American Gastroenterological Association and ECCO guidelines, switching to a biologic of a different class can be considered when therapeutic drug levels are adequate but inflammation persists.2,3 Therefore, Ms Lewis transitioned from adalimumab to mirikizumab (an IL-23 inhibitor), which has demonstrated significantly greater in patients with previous treatment failure with biologics.4

After 6 months on mirikizumab, Ms Lewis achieved complete symptom resolution, biomarker normalization via CRP 1 mg/L and fecal calprotectin 40 μg/g, as well as confirmed mucosal healing on imaging. This outcome aligns with recent trials demonstrating that IL-23 inhibitors like mirikizumab effectively induce and maintain remission in patients with moderate to severe CD.4,5

To sustain remission, the optimal strategy includes maintaining mirikizumab at its FDA-approved maintenance dosing (300 mg every 4 weeks subcutaneously), regular biomarker monitoring every 3-6 months to detect early signs of disease recurrence, and adopting lifestyle modifications like a nutrient-rich diet.3,6,7 These strategies should support patients’ overall health and complement—not replace—biologic therapy. 

The 2024 ECCO guidelines emphasize long-term maintenance with effective biologic therapy to prevent relapse and complications.3 Stopping biologic therapy in patients with deep remission remains controversial, as studies show that approximately 30% to 50% of patients relapse within 1 year of discontinuation.8 Therefore, continuing mirikizumab and closely monitoring biomarkers remains the best approach for Ms Lewis to maintain disease control.