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1. WO2020117795 - ASSESSMENT AND MONITORING OF MUCOSAL HEALING IN CHILDREN AND ADULTS WITH CROHN'S DISEASE

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[ EN ]

CLAIMS

WHAT IS CLAIMED IS:

1. A method of producing a Endoscopic Healing Index (EHI) score for a pediatric patient with Crohn’s Disease (CD), comprising:

obtaining biomarker levels in a sample from a pediatric patient under 18 years of age and having CD, the biomarkers comprising at least one of Ang1, Ang2, VEGFa, FGF2, CEACAM1, VCAM1, Alcam, a4b7, ICAM-1, MAdCAM, TGFa, BTC, EGF, SCF, AREG, ANXA13, EREG, HB-EGF, HGF, TGFb, IL-7, GM-CSF, IL-1b, IL-2, IL-5, IL-6, IL-10, IL-12/23p40, IL-13, IL-15, IL-17a, IL-17f, IL-22, IL-23, IL-31, IL-33, CRP, SAA1, ADA, TWEAK, IFN-g, EMMPRIN, MMP-1, MMP-2, MMP-3, MMP-9, or fibronectin;

for each biomarker level, generating a probability of the patient being in endoscopic remission or active disease by applying a model to the biomarker level, the model being derived from a training set of biomarker levels and SES-CD or CDEIS scores using random forest learning classification, logistic regression, quantile classification, ordinary least squares regression, or classification and regression trees;

providing a weight for the probability generated from each biomarker;

based on the weight for the probability generated from each biomarker, generating an overall probability of the patient being in endoscopic remission or active disease;

multiplying the overall probability by a factor, thereby producing an EHI score for the patient.

2. The method of claim 1, wherein the biomarkers comprise Ang1, Ang2, CEACAM1, VCAM1, TGFa, CRP, SAA1, MMP-1, MMP-2, MMP-3, MMP-9, EMMPRIN, and IL-7.

3. The method of claim 1, further comprising: determining that the patient is in remission or has mild endoscopic disease, or is likely to be in remission or have mild endoscopic disease, when the EHI score is less than or equal to 40 on a scale from 0 to 100.

4. The method of claim 3, wherein the remission corresponds to a Crohn's Disease Endoscopic Index of Severity (CDEIS) score of less than 3.

5. The method of claim 1, further comprising: determining that the patient is likely to have an endoscopically active disease when the EHI score is greater than or equal to 50 on a scale from 0 to 100.

6. The method of claim 5, wherein the endoscopically active disease corresponds to a CDEIS score of greater than or equal to 3.

7. The method of claim 1, further comprising, generating a second overall probability of the patient being in endoscopic remission or active disease by applying a second model to each biomarker level, and incorporating the second probability in the EHI score.

8. The method of claim 1, further comprising providing a CD therapy to the pediatric patient.

9. The method of claim 1, wherein the sample is serum.

10. The method of claim 1, wherein the pediatric patient is a human.

11. A method for monitoring a mucosal healing in a pediatric patient with Crohn’s Disease (CD) without performing an endoscopy on the patient, comprising:

obtaining biomarker levels in a first sample from a pediatric patient under 18 years of age and having CD, the biomarkers comprising at least one of Ang1, Ang2, VEGFa, FGF2, CEACAM1, VCAM1, Alcam, a4b7, ICAM-1, MAdCAM, TGFa, BTC, EGF, SCF, AREG, ANXA13, EREG, HB-EGF, HGF, TGFb, IL-7, GM-CSF, IL-1b, IL-2, IL-5, IL-6, IL-10, IL-12/23p40, IL-13, IL-15, IL-17a, IL-17f, IL-22, IL-23, IL-31, IL-33, CRP, SAA1, ADA, TWEAK, IFN-g, EMMPRIN, MMP-1, MMP-2, MMP-3, MMP-9, or fibronectin;

for each biomarker level, generating a probability of the patient being in endoscopic remission or active disease by applying a model to the biomarker level, the model being derived from a training set of biomarker levels and SES-CD or CDEIS scores using random forest learning classification, logistic regression, quantile classification, ordinary least squares regression, or classification and regression trees;

providing a weight for the probability generated from each biomarker;

based on the weight for the probability generated from each biomarker, generating an overall probability of the patient being in endoscopic remission or active disease;

multiplying the overall probability by a factor, thereby producing a first EHI score for the patient;

obtaining biomarker levels in a second sample from the pediatric patient at a later date; producing a second EHI score for the patient.

12. The method of claim 11, wherein the biomarkers comprise Ang1, Ang2, CEACAM1, VCAM1, TGFa, CRP, SAA1, MMP-1, MMP-2, MMP-3, MMP-9, EMMPRIN, and IL-7.

13. The method of claim 11, further comprising: determining that the patient is in remission or has mild endoscopic disease, or is likely to be in remission or have mild endoscopic disease, when the first or second EHI score is less than or equal to 40 on a scale from 0 to 100.

14. The method of claim 13, wherein the remission corresponds to a Crohn's Disease Endoscopic Index of Severity (CDEIS) score of less than 3.

15. The method of claim 11, further comprising: determining that the patient is likely to have an endoscopically active disease when the first or second EHI score is greater than or equal to 50 on a scale from 0 to 100.

16. The method of claim 15, wherein the endoscopically active disease corresponds to a CDEIS score of greater than or equal to 3.

17. The method of claim 11, further comprising, generating a second overall probability of the patient being in endoscopic remission or active disease by applying a second model to each biomarker level, and incorporating the second probability in the first or second EHI score.

18. The method of claim 11, further comprising providing a CD therapy to the pediatric patient.

19. The method of claim 11, wherein the first and second samples are serum.

20. The method of claim 11, wherein the pediatric patient is a human.