Exploring the concept of deep remission in Crohn’s disease: correlation between transmural healing and biomarkers

BACKGROUND: While mucosal healing (MH) and transmural healing (TH) predict relevant clinical outcomes in Crohn’s disease (CD), little is known about the real significance and clinical impact of deep remission (DR). OBJECTIVES: To better explore the concept of DR, toward a direct correlation between MH, TH, and biomarkers. DESIGN: Real-world observational longitudinal study to evaluate the rate of clinical remission (CR), MH and TH, and the fecal calprotectin (FC)/C-reactive protein (CRP) levels in all consecutive CD patients on biologics. METHODS: A receiver operating characteristic (ROC) curve was constructed to define the best FC and CRP cut-offs associated with MH and TH. Finally, patients achieving CR, MH, and TH, in association with the target FC/CRP values, were considered in DR. RESULTS: Among 118 CD patients, CR, MH, and TH were achieved in 62.7, 44.1, and 32.2%, respectively. After 2 years, the mean FC levels decreased from 494 ± 15.4 μg/g to 260 ± 354.9 μg/g (p < 0.01). Using the ROC curve analysis, an FC cut-off value of 94 μg/g was associated with both MH [sensitivity: 94.2%, specificity: 84.8%, positive predictive value (PPV): 83.05%, negative predictive value (NPV): 94.92%, area under the curve (AUC): 0.95] and TH (sensitivity: 92.1%, specificity: 70%, PPV: 64.4%, NPV: 94.9%, AUC: 0.88). CRP < 5 mg/L was associated with both MH (sensitivity: 96.1%, specificity: 62.1%, PPV: 66.7%, NPV: 95.35%, AUC: 0.85) and TH (sensitivity: 97.4%, specificity: 52.5%, PPV: 52%, NPV: 95.35%, AUC: 0.78). When considering CD patients with concomitant CR, MH, and TH associated with an FC < 94 μg/g and CRP < 5 mg/L, this association was found identified in 33 patients (27.9%). CONCLUSION: An FC < 94 μg/g and a normal CRP are associated with CR, MH, and TH and could be included in the definition of DR in association. So by definition, DR could be achieved in approximately 30% of CD patients during maintenance treatment with biologics.