The prognostic value of faecal calprotectin for long-term outcomes in ulcerative colitis

Lead Investigator: Shenghong Zhang, The first affiliated hospital of Sun Yat-sen University
Title of Proposal Research: The prognostic value of faecal calprotectin for long-term outcomes in ulcerative colitis
Vivli Data Request: 8266
Funding Source: This work was funded by the National Natural Science Foundation of China, grant/award number: 82070538 and 81870374.
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Ulcerative colitis (UC) is a chronic inflammatory disease affecting around 2% of the general population in North America and Western Europe, and its incidence is rising worldwide. UC is an inflammatory bowel disease, which causes irritation, inflammation, and ulcers in the lining of your large intestine. Patients with UC have heterogenous prognosis: some patients have good long-term outcomes after initiation treatment, while some will suffer from relapsing and exacerbated disease courses. Therefore, predicting the prognosis of UC patients is important for selecting optimal treatment approaches and conducting personalized management. Nowadays, identifying effective indicators for predicting the prognosis in UC is receiving more and more attention. Faecal calprotectin, is a protein that your body releases in your excrement when there is inflammation in your intestines. It is an inflammatory biomarker that can be used to assess disease activity and predict relapse in UC. However, the prognostic values of faecal calprotectin and corresponding thresholds for long-term outcomes are still unknown. This study aims at investigating the predictive ability and the threshold of faecal calprotectin for long-term outcomes in UC. This analysis will include data from four clinical trials (VISIBLE, MOMENTUM, GEMINI 1 and VARSITY). Analyses will be conducted to evaluate the relationship between faecal calprotectin and the outcomes of interest, and to assess the predictive ability of faecal calprotectin by determining the level at which one might expect a UC relapse. The results will help clinicians understand the prognostic value of faecal calprotectin and may help in selecting treatment approaches for patients with different prognosis.

Statistical Analysis Plan:

The selected studies were chosen because they detected concentration of faecal calprotectin after induction therapy and assessed endoscopic activity at week 52 in patients with UC.

Continuous and categorical variables are described as median (interquartile range, IQR) and proportion (percentage), respectively. The Mann-Whitney test and χ2 test are performed to evaluate the difference for continuous and categorical variables, respectively. A p-value less than 0.05 is considered as statistical significance. Univariate logistic analysis will be conducted to analyse the association of candidate predictors and outcomes. Multivariate logistic analysis will be performed on predictors with statistical significance in univariate analysis and potential confounders (like disease duration, treatment allocation). The receiver operating characteristic (ROC) analysis is performed to calculate the area under ROC curve (AUROC). The cut-off value is determined by the Youden index. AUROC, sensitivity, specificity, positive predictive value and negative predictive value are used to assess the predictive capacity of the predictors for predicting specific outcomes. Subgroup analysis for different trials will be performed to assess the predictive ability of FC. All statistical analysis was performed through R software.

Patient with missing value for faecal calprotectin after induction therapy will be excluded from this study. Patients with missing data for other variables will be omitted from the multivariate analysis.

Requested Studies:

A Phase 4, Open-label, Multicenter, Prospective Study to Evaluate the Effect of Remission Status on the Ability to Maintain or Achieve Clinical and Endoscopic Remission During a 12-Month, Long-term Maintenance Phase With 2.4g/Day MMX Mesalamine/Mesalazine Once Daily in Adult Subjects With Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT01124149
Sponsor ID: SPD476-409

A Randomized, Double-Blind, Double-Dummy, Multicenter, Active-Controlled Study to Evaluate the Efficacy and Safety of Vedolizumab IV Compared to Adalimumab SC in Subjects With Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT02497469
Sponsor ID: MLN0002-3026

A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study, With a Vedolizumab IV Reference Arm, to Evaluate the Efficacy and Safety of Vedolizumab Subcutaneous as Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy
Data Contributor: Takeda
Study ID: NCT02611830
Sponsor ID: MLN0002SC-3027

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by MLN0002 in Patients With Moderate to Severe Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT00783718
Sponsor ID: C13006

Public Disclosures:

Zheng, J., Zheng, D., Fan, Z., Li, L., Chen, R. and Zhang, S., 2024. Developing and Externally Validating a Simple Index Based on the Nonlinear Relationship of Fecal Calprotectin and Long-Term Outcomes in Ulcerative Colitis. Journal of Inflammation Research, pp.11247-11256. Doi : 10.2147/JIR.S497655