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Histology in CD
Interactive Case Challenge 3: Evolving Role of Histology in Crohn’s Disease Management 

Released: March 18, 2025

Ryan Ungaro
Ryan Ungaro, MD, MS
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Case Conclusion
Given persistent symptoms despite therapeutic adalimumab levels and no detectable antidrug antibodies, Mr Smith’s CD is classified as a biologic failure. Based on his disease profile and treatment history, his physician switches him to mirikizumab, an IL-23 inhibitor, to better target his inflammation. At his 3-month follow-up, Mr Smith reports significant improvement in his symptoms. He expresses relief in finally achieving better symptom control. CRP is 2.5 mg/L, fecal calprotectin is 75 µg/g, and mirikizumab trough level is within therapeutic range. A repeat colonoscopy is performed in 6 months and shows marked mucosal healing in the terminal ileum, SES-CD is now 2, and only mild residual erythema is seen. Histology reveals resolution of neutrophilic infiltration, reduced crypt distortion and basal plasmacytosis with no active granulomas.   

Although histologic remission is not yet a validated treatment target in CD, these findings suggest a deeper level of disease control, correlating with Mr Smith’s clinical and endoscopic response. 

Discussion
Mr Smith’s case underscores the importance of TDM in CD. It plays a central role in biologic therapy optimization by allowing healthcare professionals to optimize appropriate drug exposure and avoid unnecessary dose escalation in the setting of uncontrolled disease.1  

When failure occurs with a biologic despite TDM, switching to an alternative biologic class vs increasing the dose is the preferred treatment strategy.2 Therefore, instead of having Mr Smith continue ineffective anti-TNF therapy, switching to mirikizumab (an IL-23 inhibitor) resulted in significant clinical, biochemical, endoscopic, and histologic improvement. IL-23 inhibitors offer a novel approach for patients who experience treatment failure with anti-TNF therapy by targeting chronic inflammation through a distinct mechanism.2 At his 6-month follow-up and after transitioning to mirikizumab, Mr Smith exhibited significant clinical improvement, including minimal abdominal pain, normalized stool frequency, and increased energy levels. Biochemical markers stabilized with CRP at 2.5 mg/L and fecal calprotectin at 75 µg/g.  

Histologic assessment, although not yet a primary treatment target, provides valuable insight into subclinical disease activity and may guide therapeutic decisions before clinical or endoscopic relapse occurs. Recent studies indicate that histologic remission correlates with improved long-term outcomes, including sustained remission and fewer disease complications.3,4 Furthermore, histologic assessment can identify persistent inflammation despite clinical or biomarker remission, guiding more effective therapeutic adjustments.5,6 For Mr Smith, endoscopic evaluation demonstrated mucosal healing via SES-CD improving from 9 to 2, showing no deep ulcerations. Histologic analysis then confirmed the resolution of neutrophilic infiltration, crypt distortion, and basal plasmacytosis, which supports deeper remission. 

The STRIDE-II guidelines emphasize the importance of a treat-to-target framework in CD, focusing on achieving clinical, biomarker, and endoscopic remission as key treatment goals. Although histologic assessment has been explored as a potential marker of disease activity, its role in treat-to-target strategies remains under investigation. Integrating TDM and biomarker-driven monitoring into a treat-to-target approach may allow for better long-term outcomes in patients with moderate to severe CD.