Week 6 Calprotectin Best Predicts Likelihood of Long-Term Endoscopic Healing in Crohn's Disease: A Post-Hoc Analysis of the UNITI/IM-UNITI Trials.

OBJECTIVES: There is need for biomarkers as predictors of outcome to medical treatment in Crohn's disease. The purpose of this study was to evaluate the predictive performance of fecal calprotectin for short- and long-term clinical and endoscopic outcomes.

METHODS: This post-hoc analysis of the UNITI/IM-UNITI studies (NCT01369329, NCT01369342, and NCT01369355; YODA #2019-4026) included 677 patients to evaluate the relationship of week 6 calprotectin cut-offs and changes from baseline assessments in calprotectin for prediction of outcomes at weeks 8, 32, and 52 using receiver operating characteristic curves with comparisons of areas under the curve (AUC). The relationship between clinical and biomarker assessments at week 6 and endoscopic remission (ER) at week 52 was evaluated using multivariate logistic regression models adjusted for confounders.

RESULTS: A week 6 calprotectin < 250 mg/kg demonstrated a significant ability to predict week 52 ER (AUC 0.709, 95% CI 0.566-0.852, p=0.014) with fair accuracy, and performed better than other calprotectin cut-offs and deltas from baseline for prediction of week 52 ER. When adjusted for covariates, patients with a week 6 fecal calprotectin < 250 mg/kg had 3.48 times (95% CI 1.31-9.28, p=0.013) increased odds of week 52 ER. No other week 6 clinical assessment (clinical remission or clinical response) or biomarker (CRP < 5 or drug level) had an association with week 52 ER.

CONCLUSIONS: In summary, the results of this post-hoc analysis suggest week 6 calprotectin levels < 250 mg/kg can be predictive of future endoscopic healing and may be more informative than clinical symptom improvement.