Methods for assessing mucosal healing in Crohn's disease patients
Inventors
Jain, Anjali • Kondragunta, Venkateswarlu • Hale, Michael
Assignees
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Publication Number
US-11162943-B2
Publication Date
2021-11-02
Expiration Date
Abstract
The present disclosure provides methods for assessing mucosal healing in a patient with Chron's Disease. The methods include detecting expression levels of analytes in a serum sample from a patient, and applying a mathematical algorithm to the expression levels, thereby producing a Mucosal Healing Index score for the patient. The present disclosure also provides kits that include two or more binding partners, each or which is capable of binding a different analyte measured in the disclosed mucosal healing assessment methods.
Core Innovation
The invention concerns a method for treating Crohn's Disease in a patient by determining a Mucosal Healing Index (MHI) score from serum expression levels of biomarkers consisting of Ang1, Ang2, CEACAM1, VCAM1, TGFα, CRP, SAA1, MMP-1, MMP-2, MMP-3, MMP-9, EMMPRIN, and IL-7. A mathematical algorithm is applied to the expression levels to produce the MHI score for the patient.
The method identifies the MHI score on a scale from 0 to 100 and uses the score to guide treatment by administering a therapeutically effective amount of a therapeutic agent based, at least in part, on the MHI score. One approach identifies patients having an MHI score between 50-100 and administers a therapeutically effective amount of the therapeutic agent to treat Crohn's Disease.
The disclosed index is tied to endoscopic assessment using Crohn's Disease Endoscopic Index of Severity (CDEIS). The disclosed ranges relate MHI to endoscopic disease states, including remission or mild endoscopic disease when the MHI score is less than or equal to 40 with CDEIS<3, and endoscopically active disease when the MHI score is greater than or equal to 50 with CDEIS≥3. The underlying algorithm may use two or more models to relate biomarker expression levels to an endoscopic score.
Claims Coverage
Two independent claims are identified: clm-00001 and clm-00011. Across these claims, the coverage centers on computing a Mucosal Healing Index (MHI) from serum biomarker expression via a mathematical algorithm and administering a therapeutically effective amount of a therapeutic agent based on MHI ranges tied to endoscopic severity.
Serum biomarker MHI determination for Crohn's Disease
Determining a Mucosal Healing Index (MHI) score for the patient by detecting in a serum sample expression levels of biomarkers consisting of Ang1, Ang2, CEACAM1, VCAM1, TGFα, CRP, SAA1, MMP-1, MMP-2, MMP-3, MMP-9, EMMPRIN, and IL-7, and applying a mathematical algorithm to the expression levels thereby producing the MHI score.
Treatment guided by MHI threshold for Crohn's Disease
Identifying the MHI score for the patient as comprising greater than or equal to 50 on a scale from 0 to 100 and administering a therapeutically effective amount of a therapeutic agent to treat Crohn's Disease based, at least in part, on the MHI score.
Identifying MHI range patients for therapeutic administration
Identifying a patient with Crohn's Disease having a Mucosal Healing Index (MHI) score of between 50-100 on a scale of 0-100, wherein the MHI score is determined by applying a mathematical algorithm to expression levels of biomarkers detected in a serum sample and administering a therapeutically effective amount of the therapeutic agent for treatment of Crohn's Disease.
The independent claims collectively cover serum-based measurement of a defined set of biomarkers followed by a mathematical algorithm to produce an MHI score and administration of a therapeutically effective therapeutic agent based on identifying patients within an MHI range of at least 50, or between 50-100. The disclosed claim framework also maps MHI ranges to CDEIS-defined endoscopic disease states.
Stated Advantages
Provides a serum-based mucosal-healing assessment for Crohn’s Disease using a Mucosal Healing Index (MHI).
Enables identification of remission or mild endoscopic disease and endoscopically active disease based on MHI thresholds tied to Crohn’s Disease Endoscopic Index of Severity (CDEIS).
Supports treatment of Crohn’s Disease by administering a therapeutically effective amount of a therapeutic agent based, at least in part, on the MHI score.
Documented Applications
Assessing therapeutic efficacy and monitoring mucosal status longitudinally in Crohn’s Disease using the MHI score.
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