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Observational Study
. 2023 Jul;11(6):531-541.
doi: 10.1002/ueg2.12420. Epub 2023 Jun 15.

How many biomarker measurements are needed to predict prognosis in Crohn's disease patients under infliximab?-A prospective study

Fernando Magro  1   2   3   4 , Maria Manuela Estevinho  1   5 , Gaia Catalano  1 , Marta Patita  6 , Bruno Arroja  7 , Paula Lago  8 , Isadora Rosa  9 , Helena Tavares de Sousa  10   11 , Paula Ministro  12 , Irina Mocanu  6 , Ana Vieira  6 , Joana Castela  9 , Joana Moleiro  9 , Joana Roseira  10 , Eugénia Cancela  12 , Paula Sousa  12 , Francisco Portela  13 , Luís Correia  14 , Paula Moreira  4 , Mafalda Santiago  3   15 , Sandra Dias  15 , Joana Afonso  1 , Silvio Danese  16   17 , Laurent Peyrin-Biroulet  18 , Cláudia Camila Dias  3   19 ; GEDII (Grupo de Estudos da Doença Inflamatória Intestinal)
Affiliations
Observational Study

How many biomarker measurements are needed to predict prognosis in Crohn's disease patients under infliximab?-A prospective study

Fernando Magro et al. United European Gastroenterol J. 2023 Jul.

Abstract

Background: Timely stratification of Crohn's disease (CD) is essential for patients' management. The use of noninvasive accurate biomarkers is key to monitor treatment and to pursue mucosal healing, the ultimate treatment endpoint in CD.

Objective: We aimed to evaluate the performance of readily available biomarkers and develop risk matrices to predict CD progression.

Methods: Data from 289 CD patients receiving infliximab (IFX) maintenance therapy for 2 years was collected; those patients were included in DIRECT, a prospective multicenter observational study. Disease progression was evaluated using two composite outcomes incorporating clinical and drug-related factors, the first including IFX dose and/or frequency adjustments. Univariate and multivariable logistic regressions were used to calculate the odds ratios (OR) and to develop risk matrices.

Results: The isolated presence of anemia at least once during follow-up was a significant predictor of disease progression (OR 2.436 and 3.396 [p ≤ 0.001] for composite outcomes 1 and 2, respectively) regardless of confounding factors. Isolated highly elevated C-reactive protein (CRP; >10.0 mg/L) and fecal calprotectin (FC; >500.0 μg/g) in at least one visit were also significant predictors, while milder elevations (3.1-10.0 mg/L and 250.1-500.0 μg/g) were only relevant when detected in at least two visits (consecutive or not). The combination of biomarkers in risk matrices had good ability to predict progression; patients simultaneously presenting anemia, highly elevated CRP and FC at least once had 42%-63% probability of achieving the composite outcomes.

Conclusion: The combined evaluation of hemoglobin, CRP, and FC in at least one time point and their incorporation into risk matrices seems to be the optimal strategy for CD management, as data from additional visits did not meaningfully influence the predictions and may delay decision-making.

Keywords: Crohn's disease; biomarkers; calprotectin; infliximab.

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Conflict of interest statement

Fernando Magro served as a speaker and received honoraria from Abbvie, Biogen, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Lilly, Pfizer, Merck Sharp & Dohme, Sandoz, Takeda, UCB and Vifor. Helena Tavares de Sousa received fees for serving as a speaker for Takeda, AbbVie, Janssen, Pfizer, Ferring and Biogen. Isadora Rosa reports personal fees and/or non‐financial support from Abbvie, Ferring, Pharmakern, Janssen and Takeda, outside the submitted work, as well as research grants from Abbvie and Ferring. Silvio Danese served as a speaker, consultant and advisory board member for Schering Plough, Abbott (AbbVie) Laboratories, Merck, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alfa Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor and Johnson and Johnson. Laurent Peyrin‐Biroulet reports personal fees from Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boerhinger‐ Ingelheim, Lilly, HAC‐ Pharma, Index Pharmaceuticals, Amgen, Sandoz, Forward Pharma GmbH, Celgene, Biogen, Lycera, and Samsung Biosepsis. All other authors declare no competing interests.

Figures

FIGURE 1
FIGURE 1
Flowchart of patient enrollment and schematic representation of the monitoring schedule. CD, Crohn's disease; IFX, infliximab; UC, ulcerative colitis.
FIGURE 2
FIGURE 2
Risk matrix with presence of anemia, C‐reactive protein (CRP) and fecal calprotectin (FC) levels considered as variables. The mean probability (percentage) of achieving the two composite outcomes depending on the presence or absence of anemia and on whether the CRP and FC levels were above or below the defined cut‐off values is depicted. Individual squares are color‐coded according to the risk category for achieving the outcome. The number of patients and 95% confidence intervals for individual probabilities are shown in brackets.
See this image and copyright information in PMC

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