CCL20 Biomarker Stratification for IL23 Antagonist Therapy
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Solution Overview
Problem
Current therapies for IL23-mediated diseases lack effective methods to identify specific patient populations suitable for treatment with IL23 antagonists, leading to variable treatment responses due to the heterogeneity of these diseases.
Innovation Solution
The use of CCL20 expression levels, alone or in combination with other biomarkers like IL22, LCN2, CRP, and FCP, to determine the appropriateness of administering an IL23 antagonist, guiding treatment decisions based on predetermined threshold levels in patient samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If IL23 antagonist therapy is administered to all patients with IL23-mediated diseases, then some patients may achieve clinical response, but treatment efficacy varies due to disease heterogeneity and lack of patient stratification
Solution Approach 1:
The patent applies preliminary action by measuring CCL20 expression levels in patient samples before administering IL23 antagonist therapy. This pre-treatment biomarker assessment allows clinicians to identify patients who are most likely to respond to IL23 antagonist therapy, enabling informed treatment decisions before therapy initiation. The method stratifies patients based on their baseline CCL20 levels, ensuring that therapy is directed toward the appropriate patient population.
Solution Approach 2:
The patent utilizes parameter changes by measuring and comparing CCL20 expression levels against predetermined threshold values. This quantitative approach transforms the heterogeneous patient population into stratified groups based on a specific measurable parameter (CCL20 level). Patients with CCL20 levels below the threshold are identified as likely responders, while those above the threshold are identified as unlikely responders, enabling precise treatment selection.
2Measurement precision
If patient populations are stratified using multiple biomarkers (CCL20, IL22, LCN2, CRP, FCP), then treatment prediction accuracy improves, but diagnostic complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the diagnostic approach into hierarchical levels. The primary and simplest method measures only CCL20 expression levels, which alone provides sufficient stratification capability. Optionally, additional biomarkers (IL22, LCN2, CRP, FCP) can be measured to further refine patient stratification. This segmented approach allows clinicians to start with a simple single-biomarker test and add complexity only when necessary for more precise patient characterization.
Solution Approach 2:
The patent demonstrates universality by developing a diagnostic system that can function at multiple levels of complexity. The same diagnostic platform can measure either just CCL20 or can simultaneously measure CCL20 plus additional biomarkers (IL22, LCN2, CRP, FCP), depending on the clinical need. This multi-functional approach allows the diagnostic system to adapt to different clinical scenarios, from basic patient stratification to more refined sub-group identification.
Data Source
AI summary
The present invention relates to the use of the Chemokine (C—C motif) ligand 20 (CCL20) as a biomarker to stratify or identify populations of patients suffering from interleukin-23 (IL23)-mediated diseases (e.g., Crohn's disease) responsive to treatment with an, anti-IL23 antagonist (including, e.g., anti-IL23 antibodies). Levels of CCL20 above or below a predetermined threshold can be used, for example, (i) to determine whether a patient with an IL23-mediated disease or disorder such a Crohn's disease is eligible or non-eligible for treatment with a therapeutic agent, (ii) to determine whether treatment with a certain agent should be commenced, suspended, or modified, (iii) to diagnose whether the IL23-mediated disease is treatable or not treatable with a specific therapeutic agent, or (iv) to predict the outcome of treating the IL23-mediated disease with a specific therapeutic agent. CCL20 can be used in combination with other IL23 pathway biomarkers such as IL22 and/or lipocalin-2 (LCN2).